Articles tagged as "Zimbabwe"

Improving access to HIV testing—still the most important step to improve the lives of people living with HIV?

Editor’s notes: The target for HIV testing is very clear and well understood as the first 90 in the UNAIDS treatment targets. However, estimating the proportion of people living with HIV who know their status is not completely straightforward.  UNAIDS uses various data sources and a well described algorithm to make its annual estimates.  For some countries, population based surveys allow a random sample of the population to be interviewed and tested for HIV.  Nonetheless, such surveys only occur periodically and so data may be out of date.  People who were HIV-negative a few years ago may now be HIV positive and people who know that they were tested a few years ago and think that they know their status may in fact have acquired HIV in the meantime.  Staveteig and colleagues have used the most recent demographic and health surveys from 16 countries in sub-Saharan Africa to estimate the first 90 and to analyse the demographic characteristics associated with knowing one’s HIV status.  The authors discuss some of the challenges in the assumptions needed for this estimation process.  However, the surveys had excellent participation and a high rate of acceptance of HIV testing, so that out of more than 14 000 people living with HIV across the countries, the authors are able to state that 54% know their status.  The proportion in different countries ranges from 26% in Sierra Leone to 84% in Rwanda.  Their analysis does not present very surprising associations.  We have come to expect that men, young people and those with less than primary education are found to be less likely to know their status.  However, the study provides a direct estimate from survey data and as such helps to triangulate with other estimates from the region.

In general, the West and Central African region lags behind the East and Southern African region when it comes to access to HIV testing, linkage to treatment and viral suppression.  A catch-up plan has been developed and endorsed at high level political meetings in most countries in the region. The study by Inghels and colleagues from Côte d’Ivoire is therefore important.  They demonstrate that among 273 people recently diagnosed with HIV at the blood donors’ centre, almost half could have been diagnosed up to five years earlier if health care staff had followed guidelines to propose testing for indicator clinical conditions such as extreme weight loss, repeated fevers or shingles.  Approximately a quarter of people recently diagnosed with HIV had recognized risk factors for HIV (apart from their clinical presentation), but only approximately one-sixth, a small minority, of people had mentioned it to their heathcare professional.  If we are to catch up and ensure that 90% of people living with HIV have known their status by 2020, we need to maximize efforts to use a full range of differentiated HIV testing approaches.  Health care staff must offer HIV tests routinely to people with clinical indicator conditions. Staff at all levels of the health system must also promote an environment in which people with risk behaviours for HIV infection feel comfortable to be able to raise it and discuss it.

Reaching the 'first 90': gaps in coverage of HIV testing among people living with HIV in 16 African countries.

Staveteig S, Croft TN, Kampa KT, Head SK. PLoS One. 2017 Oct 12;12(10):e0186316. doi: 10.1371/journal.pone.0186316. eCollection 2017.

Background: UNAIDS has recently proposed a set of three ambitious targets that, if achieved, are predicted to end the AIDS epidemic by 2030. The targets, known as 90-90-90, call for 90% of people living with HIV (PLHIV) to know their status, 90% of PLHIV to receive antiretroviral therapy, and 90% of those on antiretroviral therapy to achieve viral suppression by the year 2020. We examine the first of these targets, focusing on sub-Saharan Africa, the region of the world most affected by HIV, to measure the proportion of PLHIV estimated to know their HIV status, and to identify background and behavioral characteristics significantly associated with gaps in ever testing among PLHIV.

Methods and findings: We analyze cross-sectional population-based data from the Demographic and Health Surveys (DHS) and AIDS Indicator Surveys (AIS) fielded since 2010 in 16 sub-Saharan African countries where voluntary serological testing was recently conducted: Burkina Faso, Cameroon, Chad, Cote d'Ivoire, Ethiopia, Gabon, Lesotho, Malawi, Namibia, Rwanda, Sierra Leone, Tanzania, Togo, Uganda, Zambia, and Zimbabwe. Survey response rates averaged 95.0% (range 89.3-99.5%), while consent to serotesting averaged 94.9% (range 88.7-99.6%). This study, which includes more than 14 000 respondents living with HIV, finds that 69% of PLHIV in the average study country have ever been tested for HIV (range 34-95%). Based on timing of the last test and on ART coverage, we estimate that 54% of PLHIV in the average country are aware of their status (range 26-84%). Adjusted logistic regression finds that men (median adjusted odds ratio [AOR] = 0.38), adults with less than primary education (median AOR = 0.31), and adolescents (median AOR = 0.32) are consistently less likely to have ever been tested for HIV than women, adults with secondary and above education, and adults age 30-39, respectively. In most countries unadjusted logistic regression also finds significant gaps in testing among the poorest groups and those reporting never having had sex.

Conclusion: The fact that an average of 54% of PLHIV in these 16 countries are estimated to know their status reflects encouraging progress. However, not only is this average far short of the 90% target set by UNAIDS for 2020, but it also implies that in the average study country nearly one-half of PLHIV are unable to access lifesaving care and treatment because they are unaware that they are HIV-positive. Several gaps in HIV testing coverage exist, particularly among adolescents, the least educated, and men. While the need to target demographic groups at greatest risk of HIV continues, additional interventions focused on reaching men and on reaching socially vulnerable populations such as adolescents, the poorest, and the least educated are essential.

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Missed opportunities for HIV testing among newly diagnosed HIV-infected adults in Abidjan, Côte d'Ivoire.

Inghels M, Niangoran S, Minga A, Yoboue JM, Dohoun L, Yao A, Eholié S, Anglaret X, Danel C. PLoS One. 2017 Oct 4;12(10):e0185117. doi: 10.1371/journal.pone.0185117. eCollection 2017

Background: HIV testing is crucial for starting ART earlier in HIV-infected people. We describe Missed Opportunities (MO) for HIV testing among adults newly diagnosed with HIV in Abidjan, Côte d'Ivoire.

Methods: Between April 2nd 2013 and April 1st 2014, a cross-sectional study was conducted among all adults newly diagnosed (< 1year) for HIV at the Blood Donors Medical Center of Abidjan with face to face questionnaire. An MO for HIV testing was defined as a medical consultation for a clinical indicator (e.g. symptoms, hospitalization, and pregnancy) or a non-clinical indicator (e.g. high-risk sexual behavior, HIV-infected partner) potentially related to an HIV infection but did not lead to HIV test proposal by a health care professional.

Results: Of the 341 patients who attended the center during this period, 273 (157 women and 116 men) were included in this analysis. 130 (47.6%) reported at least one medical consultation for an indicator relevant for a test proposal between 1 month and five years prior to their diagnosis. Among them, 92 (77.3%) experienced at least one MO for testing. The 273 included patients reported a total of 216 indicators; 146 (67.6%) were reported without test proposal and thus were MO. Hospitalization, extreme loss of weight, chronic or repeat fever and herpes zoster were the indicators with the largest number of MO. While 66 (24.2%) patients experienced non-clinical indicators relevant to risk of HIV infection, only 11 (4.0%) mentioned it to a health professional.

Conclusion: MO for HIV testing are frequent, even in situations for which testing is clearly recommended. Better train healthcare professionals and creating new opportunities of testing inside and, outside of medical settings are crucial to improve HIV control.

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Cryptoccal meningitis – the unacceptable consequence of leaving people behind during ART scale up

Editor’s notes: Cryptococcal meningitis is a severe disease that occurs in people with advanced immune suppression.  Its occurrence is an indicator that an HIV treatment programme is not working well, as it is rare in people whose CD4 count is above 100 cells per microlitre.  Rajasingham and colleagues have tried to estimate the current burden of disease.  This is not straightforward, as the number and proportion of people with advanced HIV disease is changing with the increasing scale up of antiretroviral therapy and earlier HIV diagnosis.  Nonetheless, severe immune suppression still occurs in those whose HIV infection remains undiagnosed or is diagnosed too late; among those who are not started on effective ARVs promptly and among those in whom ART fails and who are not managed effectively by the ART treatment programme.  The authors estimate that there could be more than 180 000 deaths from cryptococcal meningitis with the large majority (136 000) in Africa.  This makes Cryptococcus responsible for more than 15% of HIV-related deaths, second only to tuberculosis as a documented cause.  The authors emphasize the need for earlier diagnosis of HIV and better linkage to quality care programmes.  In the meantime, there are also advances in the screening, prophylaxis and treatment of Cryptococcus itself, which require investment in laboratory services and affordable medicines that can save lives until the effects of good ART improves the immune status.

Cassim and colleagues have developed a novel approach to costing different approaches to the roll out of technology for screening for cryptococcal antigen in the blood of people with advanced HIV infection.  Depending on the numbers of samples to be tested in the laboratory, a mix of single use lateral flow assays and automated enzyme immunoassays makes most sense.  The aim is to allow the more cost-effective high-volume sites to subsidize the low volume sites in order to ensure that as many people living with advanced HIV infection as possible can be screened.

Global burden of disease of HIV-associated cryptococcal meningitis: an updated analysis

Rajasingham R, Smith RM, Park BJ, Jarvis JN, Govender NP, Chiller TM, Denning DW, Loyse A, Boulware DR. Lancet Infect Dis. 2017 Aug;17(8):873-881. doi: 10.1016/S1473-3099(17)30243-8. Epub 2017 May 5.

Background: Cryptococcus is the most common cause of meningitis in adults living with HIV in sub-Saharan Africa. Global burden estimates are crucial to guide prevention strategies and to determine treatment needs, and we aimed to provide an updated estimate of global incidence of HIV-associated cryptococcal disease.

Methods: We used 2014 Joint UN Programme on HIV and AIDS estimates of adults (aged >15 years) with HIV and antiretroviral therapy (ART) coverage. Estimates of CD4 less than 100 cells per μL, virological failure incidence, and loss to follow-up were from published multinational cohorts in low-income and middle-income countries. We calculated those at risk for cryptococcal infection, specifically those with CD4 less than 100 cells/μL not on ART, and those with CD4 less than 100 cells per μL on ART but lost to follow-up or with virological failure. Cryptococcal antigenaemia prevalence by country was derived from 46 studies globally. Based on cryptococcal antigenaemia prevalence in each country and region, we estimated the annual numbers of people who are developing and dying from cryptococcal meningitis.

Findings: We estimated an average global cryptococcal antigenaemia prevalence of 6·0% (95% CI 5·8-6·2) among people with a CD4 cell count of less than 100 cells per μL, with 278 000 (95% CI 195 500-340 600) people positive for cryptococcal antigen globally and 223 100 (95% CI 150 600-282 400) incident cases of cryptococcal meningitis globally in 2014. Sub-Saharan Africa accounted for 73% of the estimated cryptococcal meningitis cases in 2014 (162 500 cases [95% CI 113 600-193 900]). Annual global deaths from cryptococcal meningitis were estimated at 181 100 (95% CI 119 400-234 300), with 135 900 (75%; [95% CI 93 900-163 900]) deaths in sub-Saharan Africa. Globally, cryptococcal meningitis was responsible for 15% of AIDS-related deaths (95% CI 10-19).

Interpretation: Our analysis highlights the substantial ongoing burden of HIV-associated cryptococcal disease, primarily in sub-Saharan Africa. Cryptococcal meningitis is a metric of HIV treatment programme failure; timely HIV testing and rapid linkage to care remain an urgent priority.

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Estimating the cost-per-result of a national reflexed cryptococcal antigenaemia screening program: Forecasting the impact of potential HIV guideline changes and treatment goals

Cassim N, Coetzee LM, Schnippel K, Glencross DK. PLoS One. 2017 Aug 22;12(8):e0182154. doi: 10.1371/journal.pone.0182154. eCollection 2017.

Introduction: During 2016, the National Health Laboratory Service (NHLS) introduced laboratory-based reflexed Cryptococcal antigen (CrAg) screening to detect early Cryptococcal disease in immunosuppressed HIV+ patients with a confirmed CD4 count of 100 cells/μl or less.

Objective: The aim of this study was to assess cost-per-result of a national screening program across different tiers of laboratory service, with variable daily CrAg test volumes. The impact of potential ART treatment guideline and treatment target changes on CrAg volumes, platform choice and laboratory workflow are considered.

Methods: CD4 data (with counts ≤ 100 cells/μl) from the fiscal year 2015/16 were extracted from the NHLS Corporate Date Warehouse and used to project anticipated daily CrAg testing volumes with appropriately-matched CrAg testing platforms allocated at each of 52 NHLS CD4 laboratories. A cost-per-result was calculated for four scenarios, including the existing service status quo (Scenario-I), and three other settings (as Scenarios II-IV) which were based on information from recent antiretroviral (ART) guidelines, District Health Information System (DHIS) data and UNAIDS 90/90/90 HIV/AIDS treatment targets. Scenario-II forecast CD4 testing offered only to new ART initiates recorded at DHIS. Scenario-III projected all patients notified as HIV+, but not yet on ART (recorded at DHIS) and Scenario-IV forecast CrAg screening in 90% of estimated HIV+ patients across South Africa (also DHIS). Stata was used to assess daily CrAg volumes at the 5th, 10th, 25th, 50th, 75th, 90th and 95th percentiles across 52 CD4-laboratories. Daily volumes were used to determine technical effort/ operator staff costs (% full time equivalent) and cost-per-result for all scenarios.

Results: Daily volumes ranged between 3 and 64 samples for Scenario-I at the 5th and 95th percentile. Similarly, daily volumes ranges of 1-12, 2-45 and 5-100 CrAg-directed samples were noted for Scenario's II, III and IV respectively. A cut-off of 30 CrAg tests per day defined use of either LFA or EIA platform. LFA cost-per-result ranged from $8.24 to $5.44 and EIA cost-per-result between $5.58 and $4.88 across the range of test volumes. The technical effort across scenarios ranged from 3.2-27.6% depending on test volumes and platform used.

Conclusion: The study reported the impact of programmatic testing requirements on varying CrAg test volumes that subsequently influenced choice of testing platform, laboratory workflow and cost-per-result. A novel percentiles approach is described that enables an overview of the cost-per-result across a national program. This approach facilitates cross-subsidisation of more expensive lower volume sites with cost-efficient, more centralized higher volume laboratories, mitigating against the risk of costing tests at a single site.

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HIV testing and the HIV epidemic –vitally important to prevent HIV becoming endemic

Editor’s notes: Epidemics refer to situations where the number of infections rises (and subsequently falls) more quickly than might be expected compared to a disease that is endemic.  Endemic implies a stable situation, with natural fluctuations in the number of cases.  Medley and Vassal have written a provocative article in Science that considers how differently individuals, communities and society react to epidemic rather than endemic diseases.  They choose to call HIV in 2017 endemic, which carries a serious risk. As the authors state, “The contained public response, and the concurrent shift of responsibility to individuals to protect themselves from risk, means that endemic disease embeds itself further, as those at risk are often the very same people who do not have the private resources to avoid risk or access treatment.”  There are in fact multiple separate epidemics of HIV in different regions and in different populations.  Some are rising and some are falling. The latest UNAIDS’ report emphasizes the heterogeneity of HIV infections in the world.  New HIV infections have fallen by 29% since 2010 in East and Southern Africa, the region with the highest rates.  On the other hand, new HIV infections have risen by an alarming 60% in Eastern Europe and Central Asia over the same period, albeit from a much lower baseline.  There is widespread political consensus to pursue the UN agenda endorsed at the High Level Meeting on Ending AIDS in New York last year.  Let’s not throw in the towel too soon!

HIV testing services remain central to the HIV strategy and, as usual, this month there are several important papers on aspects of HIV testing, many of which illustrate challenges that need to be overcome.

There are several reasons to encourage people living with HIV to know their status.  First and foremost, we know that the earlier treatment is started in the course of HIV, the better the outlook for the individual.  People who start treatment become much less likely to transmit HIV infection to sexual partners. People who know their HIV status are also able to make informed decisions about their lives and their partnerships.  A study this month by Escudero et al. from New York City used agent-based modelling to understand the testing and care continuum for people who inject drugs. Their results remind us of the key role of HIV testing.  They estimated that 53% of the HIV transmission events from people who inject drugs arose from people who did not know their status, and a further 37% from people who had not been started ART.  In other words, they estimate that only 10-11% of infections from people who inject drugs could be prevented by improving quality of care for people on treatment.  The need to find effective ways to encourage people at risk to know their status and start treatment is stark.

Guanzhou is one of the largest cities in China, with a high population of migrants both national and international.  It is among the most prosperous regions of Guangdong province and has the highest rates of HIV.   Chen et al. added some HIV testing related questions to a wider population based health survey in two districts and showed that approximately a quarter of adults had previously been tested for HIV.  HIV testing was almost all provided through free government facilities or blood transfusion centres.  Despite early steps to make HIV self-testing more available, none of the 666 participants who answered the relevant questions in the survey had used a self-test.  Distance from an HIV testing site was a key determinant of the likelihood of getting tested.  It was not clear that people who might be at higher risk were more likely to be tested, although the numbers and sampling focused on the general population rather than people at special risk.

Wang et al. explored the different HIV test kits used in the first line screening in Xi’an.  In line with Chinese guidelines, but not in line with WHO guidance on HIV testing algorithms for low prevalence settings, they used third- or fourth-generation rapid tests and repeated the positive tests.  WHO’s algorithm for low prevalence settings includes three different rapid tests based on different antigens.   Among 665 people found to be positive on rapid tests, only 559 were confirmed to be HIV-positive by Western blotting.  Subsequent follow up with additional Western blots showed that two of the individuals in whom the first Western blot was indeterminate were seroconverting but the other 104 were HIV-negative and had had false-positive results on the original rapid tests.  False positives were more likely with the fourth-generation test (22% of positive tests) compared to the various third-generation tests used (9-11% of positive tests).  Fourth-generation assays are known to be more sensitive, detecting people with HIV around a week or two earlier in the window period than third-generation assays.  However, the authors point out that in low prevalence settings like Xi’an, the known lack of specificity of fourth-generation assays means that they may not provide sufficient advantages to be used as the first line test.  Overall, the paper emphasizes the importance of using clearly defined algorithms.  The WHO algorithms no longer use Western blots, but do recommend using multiple tests based on different antigens for testing people at low risk of infection, and at least two different tests with different antigens for testing people at high risk of infection.  Everyone should have additional confirmatory tests done prior to starting ART.

Harbertson et al. also focused on the accuracy of rapid diagnostic tests.  They screened samples from 459 military personnel in seven African countries who had reported that they were HIV-positive.  Using the WHO algorithm, they compared the results of quality assured HIV testing to the self-reported HIV status of the participants.  They found that, in different country surveys, between three and 91% of people who said that they were living with HIV were in fact HIV-negative.  The authors point out that several studies have demonstrated the importance of following the WHO guidance, and that the positive predictive value of a test (or algorithm) will always fall as the overall prevalence falls.  They discuss possible limitations such as misunderstanding the question or the terminology used, but discount these possibilities as causing many of the false-positive reports, particularly given the highly variable results across different countries.  There was a strong association between the likelihood of a false positive report and lower education level. People whose understanding of HIV was less good were also more likely to report themselves to be positive falsely.  Overall, the authors assume that quality of testing services needs to be an important priority, while not discounting the challenges of using self-reports to collect information about HIV status.

As more and more people chose to know their HIV status, it may be possible to use routine data from the health service to track the epidemiology of HIV, rather than to use special surveys. Traditionally surveys of antenatal mothers have been used to monitor trends in the HIV epidemic over time.  With the widespread adoption of routine testing for mothers, a large proportion of women have an HIV test.  However, the assays used vary.  For surveillance purposes, samples are often stored and transported as dried blood spots and assays are run in batches using automated ELISA technology.  Routine testing (as discussed above) is often done using an algorithm based on a number of different rapid tests.   Pereira et al. have explored the differences between these approaches among almost 40 000 Brazilian mothers who participated in the antenatal surveillance exercise.  They interviewed mothers and linked their routine ANC results to the surveillance database.  Overall the prevalence of HIV among expectant mothers in Brazil was similar whichever approach was used (0.36% or 0.38%).  However, there were interesting differences.  The performance accuracy in those found positive in the surveillance exercise (which was taken as the gold standard) was only 84% overall and varied between regions from 43% to 100%.  So these 14 false negative results among the 88 individuals who were truly positive were compensated for in the overall prevalence estimates by a similar number (18) of false positive results among around 30 000 individuals who were truly negative. This highlights the challenges of providing accurate results to people in low prevalence settings. The 13% of mothers who slipped through the routine services and were not tested or refused to be tested were significantly more likely to be HIV-positive (0.56%), reinforcing the potential biases involved.  Finding 90% of people living with HIV will require considerable attention to the detail and the quality of HIV testing services.

Adolescents are often a population left behind, and regular reports show that adolescents living with HIV are less likely to know their status or to be on treatment or virally supressed.  Simms et al. used provider initiated testing and counselling (PITC) in primary care clinics in Harare, Zimbabwe.  For two years, the research team supported the routine offer of HIV testing to all six to 15 year olds presenting to seven clinics in a well-defined area of Harare.  The authors then conducted a population-based survey to find out how many eight to 17 year olds (who had had two years of exposure to the intervention) were aware of their status. 141 (2.6%) were living with HIV and more than one-third of these were undiagnosed.  Some had rarely been to the clinic, and others had been taken to the clinic by a guardian who was unable to consent to HIV testing on behalf of the child or the child’s parents.  Others had slipped through the PITC net, possibly because, as Lightfoot et al. in an accompanying comment suggest, providers still find it hard to offer HIV tests to everyone, as they assume that people living with HIV will not appear healthy.  This fits with the researchers’ findings that adolescents living with HIV who were currently healthy, had no skin or other problems and had parents who were alive were less likely to be diagnosed.  Both papers suggest that community based testing is needed to find adolescents. However, this also raises challenges in settings with lower prevalence than the high-density suburbs of Harare chosen for this project.  As prevalence falls lower than the 2.6% observed, a huge testing effort is needed, with attendant costs, but also (as explored above) with the risks of inaccurate results and of the very people that we want to find most, not being around for testing at the right moment. 

 

When an emerging disease becomes endemic.

Medley GF, Vassall A. Science. 2017 Jul 14;357(6347):156-158. doi: 10.1126/science.aam8333.

Epidemics, such as HIV in the early 1980s and Ebola in 2014, inspire decisive government investment and action, and individual and societal concern, sometimes bordering on panic. By contrast, endemic diseases, such as HIV in 2017 and tuberculosis, struggle to maintain the same attention. For many, the paradox is that endemic disease, in its totality, continues to impose a far higher public health burden than epidemic disease. Overall, the swift political response to epidemics has resulted in success. It has proven possible to eradicate epidemic diseases, often without the availability of vaccines and other biomedical technologies. In recent times, only HIV has made the transition from epidemic to endemic, but diseases that have existed for centuries continue to cause most of the infectious disease burden.

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The risk of HIV transmission at each step of the HIV care continuum among people who inject drugs: a modeling study.

Escudero DJ, Lurie MN, Mayer KH, King M, Galea S, Friedman SR, Marshall BL. BMC Public Health. 2017 Jul 25;17(1):614. doi: 10.1186/s12889-017-4528-9.

Background: People who inject drugs (PWID) are at continued risk for HIV in the U.S., and experience disparities across the HIV care continuum compared to other high-risk groups. Estimates of the risk of HIV transmission at each stage of the care continuum may assist in identifying public health priorities for averting incident infections among PWID, in addition to transmissions to sexual partners of PWID.

Methods: We created an agent-based model simulating HIV transmission and the HIV care continuum for PWID in New York City (NYC) in 2012. To account for sexual transmission arising from PWID to non-PWID, the simulation included the entire adult NYC population. Using surveillance data and estimates from the National HIV Behavioral Surveillance system, we simulated a dynamic sexual and injecting network. We estimated the proportion of HIV transmission events attributable to PWID in the following categories, those: without an HIV diagnosis ('Undiagnosed'); diagnosed but not on antiretroviral therapy (ART) ('Diagnosed - not on ART'); those who initiated ART but were not virally suppressed ('Unsuppressed'); and, those who achieved viral suppression ('Suppressed').

Results: We estimated HIV incidence among PWID to be 113 per 100 000 person-years in 2012, with an overall incidence rate for the entire adult NYC population of 33 per 100 000 person-years. Despite accounting for only 33% of the HIV-infected PWID population, the Undiagnosed were associated with 52.6% (95% simulation interval [95% SI]: 47.1-57.0%) of total transmission events. The Diagnosed - not on ART population contributed the second-largest proportion of HIV transmissions, with 36.6% (95% SI: 32.2-41.5%). The Unsuppressed population contributed 8.7% (95% SI: 5.6-11.8%), and Suppressed 2.1% (95% SI: 1.1-3.9%), relatively little of overall transmission.

Conclusion: Among PWID in NYC, more than half (53%) of transmissions were from those who were unaware of their infection status and more than 36% were due to PWID who knew their status, but were not on treatment. Our results indicate the importance of early diagnosis and interventions to engage diagnosed PWID on treatment to further suppress population-level HIV transmission. Future HIV prevention research should focus on the elimination of identified and potential barriers to the testing, diagnosis, and retention of PWID on HIV treatment.

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Is there a relationship between geographic distance and uptake of HIV testing services? A representative population-based study of Chinese adults in Guangzhou, China.

Chen W, Zhou F, Hall BJ, Tucker JD, Latkin C, Renzaho AMN, Ling L. PLoS One. 2017 Jul 20;12(7):e0180801. doi: 10.1371/journal.pone.0180801. eCollection 2017.

Achieving high coverage of HIV testing services is critical in many health systems, especially where HIV testing services remain centralized and inconvenient for many. As a result, planning the optimal spatial distribution of HIV testing sites is increasingly important. We aimed to assess the relationship between geographic distance and uptake of HIV testing services among the general population in Guangzhou, China. Utilizing spatial epidemiological methods and stratified household random sampling, we studied 666 adults aged 18-59. Computer-assisted interviews assessed self-reported HIV testing history. Spatial scan statistic assessed the clustering of participants who have ever been tested for HIV, and two-level logistic regression models assessed the association between uptake of HIV testing and the mean driving distance from the participant's residence to all HIV testing sites in the research sites. The percentage of participants who have ever been tested for HIV was 25.2% (168/666, 95%CI: 21.9%, 28.5%), and the majority (82.7%) of participants tested for HIV in Centres for Disease Control and Prevention, public hospitals or STIs clinics. None reported using self-testing. Spatial clustering analyses found a hotspot included 48 participants who have ever been tested for HIV and 25.8 expected cases (Rate Ratio = 1.86, P = 0.002). Adjusted two-level logistic regression found an inverse relationship between geographic distance (kilometers) and ever being tested for HIV (aOR = 0.90, 95%CI: 0.84, 0.96). Married or cohabiting participants (aOR = 2.14, 95%CI: 1.09, 4.20) and those with greater social support (aOR = 1.04, 95%CI: 1.01, 1.07) were more likely to be tested for HIV. Our findings underscore the importance of considering the geographical distribution of HIV testing sites to increase testing. In addition, expanding HIV testing coverage by introducing non-facility based HIV testing services and self-testing might be useful to achieve the goal that 90% of people living with HIV knowing their HIV status by the year 2020.

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The characteristics of screening and confirmatory test results for HIV in Xi'an, China.

Wang L, Zhou KH, Zhao HP, Wang JH, Zheng HC, Yu Y, Chen W. PLoS One. 2017 Jul 7;12(7):e0180071. doi: 10.1371/journal.pone.0180071. eCollection 2017.

Objectives: Individuals with recent or acute HIV infection are more infectious than those with established infection. Our objective was to analyze the characteristics of detection among HIV infections in Xi'an.

Methods: A 4th-generation kit (Architect HIV Ag/Ab Combo) and three 3rd-generationEIA kits (WanTai, XinChuang and Livzon) were used for HIV screening. Overall, 665 individuals were identified as positive and were tested by western blotting (WB). The characteristics of the screening and confirmatory tests were analyzed, including the band patterns, the early detection performance and the false-positive rates.

Results: In total, 561 of the 665 patients were confirmed as having HIV-1 infection, and no HIV-2 specific band was observed. Among these 561 WB-positive cases, reactivity to greater than or equal to 9 antigens was the most commonly observed pattern (83.18%), and the absence of reactivity to p17, p31 and gp41 was detected in 6.44%, 5.9% and 2.86% of the cases, respectively. Two cases were positive by the 4th-generation assay but negative by the 3rd-generation assay for HIV screening and had seroconversion. The false-positive rate of the Architect HIV Ag/Ab Combo (22.01%) was significantly higher than those of WanTai (9.88%), XinChuang (10.87%) and Livzon (8.93%), p<0.05

Conclusion: HIV infection in Xi'an is mainly caused by HIV-1, and individuals are rarely identified at the early phase. Although the false-positive rate of the 4th-generation assay was higher than that of the 3rd-generation assay, it is still recommended for use as the initial HIV screening test for high-risk individuals. In Xi'an, a 3rd-generation assay for screening could be considered.

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Self-reported HIV-positive status but subsequent HIV-negative test result using rapid diagnostic testing algorithms among seven sub-Saharan African military populations.

Harbertson J, Hale BR, Tran BR, Thomas AG, Grillo M, Jacobs MB, McAnany J, Shaffer RA. PLoS One. 2017 Jul 7;12(7):e0180796. doi: 10.1371/journal.pone.0180796. eCollection 2017.

HIV rapid diagnostic tests (RDTs) combined in an algorithm are the current standard for HIV diagnosis in many sub-Saharan African countries, and extensive laboratory testing has confirmed HIV RDTs have excellent sensitivity and specificity. However, false-positive RDT algorithm results have been reported due to a variety of factors, such as suboptimal quality assurance procedures and inaccurate interpretation of results. We conducted HIV serosurveys in seven sub-Saharan African military populations and recorded the frequency of personnel self-reporting HIV positivity, but subsequently testing HIV-negative during the serosurvey. The frequency of individuals who reported they were HIV-positive but subsequently tested HIV-negative using RDT algorithms ranged from 3.3 to 91.1%, suggesting significant rates of prior false-positive HIV RDT algorithm results, which should be confirmed using biological testing across time in future studies. Simple measures could substantially reduce false-positive results, such as greater adherence to quality assurance guidelines and prevalence-specific HIV testing algorithms as described in the World Health Organization's HIV testing guidelines. Other measures to improve RDT algorithm specificity include classifying individuals with weakly positive test lines as HIV indeterminate and retesting. While expansion of HIV testing in resource-limited countries is critical to identifying HIV-infected individuals for appropriate care and treatment, careful attention to potential causes of false HIV-positive results are needed to prevent the significant medical, psychological, and fiscal costs resulting from individuals receiving a false-positive HIV diagnosis.

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Transitioning from antenatal surveillance surveys to routine HIV testing: a turning point in the mother-to-child transmission prevention programme for HIV surveillance in Brazil.

Pereira GFM, Sabidó M, Caruso A, Benzaken AS. BMC Infect Dis. 2017 Jul 5;17(1):469. doi: 10.1186/s12879-017-2540-4.

Background: In Brazil, due to the rapid increase in programmes for the prevention of mother-to-child transmission (PMTCT), routine programme data are widely available. The objective of this study was to assess the utility of programmatic data to replace HIV surveillance based on the antenatal care (ANC) surveillance survey (SS).

Methods: We analysed ANC SS data from 219 maternity service clinics. PMTCT variables were extracted from the ANC SS data collection form, which allowed us to capture and compare the ANC SS data and PMTCT HIV test results for each pregnant woman who completed the ANC SS. Both the PMTCT programme and the ANC SS tested for HIV using sequential ELISA and western blot for confirmation. We assessed the completeness (% missing) of the PMTC data included in the ANC SS.

Results: Of the 36 713 pregnant women who had ANC SS HIV tests performed, 30 588 also underwent PMTCT HIV testing. The HIV prevalence rate from routine PMTCT testing was 0.36%, compared to 0.38% from the ANC SS testing (relative difference -0.05%; absolute difference -0.02%). The relative difference in prevalence rates between pregnant women in northern Brazil and pregnant women central-west Brazil was -0.98 and 0.66, respectively. Of the 29 856 women who had HIV test results from both the PMTCT and ANC SS, the positive percent agreement of the PMTCT versus the surveillance test was 84.1% (95% confidence interval [CI]: 74.8-91.0), and the negative percent agreement was 99.9% (95% CI: 99.9-100.0). The PMTCT HIV testing uptake was 86.4%. The ANC SS HIV prevalence was 0.33% among PMTCT non-refusers and 0.59% among refusers, with a percent bias of -10.80% and a differential prevalence ratio of 0.56. Syphilis and HIV testing results were complete in 98% and 97.6% of PMTCT reports, respectively. The reported HIV status for the women at clinic entry was missing.

Conclusion: Although there were consistent HIV prevalence estimates from the PMTCT data and the ANC SS, the overall positive percent agreement of 84.1% falls below the World Health Organization benchmark of 94.7%. Therefore, Brazil must continue to reinforce data collection practices and ensure the quality of recently introduced rapid HIV testing before replacing the PMTCT data with surveillance techniques. However, some regions with better results could be prioritized to pilot the use of PMTCT data for surveillance.

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Community burden of undiagnosed HIV infection among adolescents in Zimbabwe following primary healthcare-based provider-initiated HIV testing and counselling: A cross-sectional survey.

Simms V, Dauya E, Dakshina S, Bandason T, McHugh G, Munyati S, Chonzi P, Kranzer K, Ncube G, Masimirembwa C, Thelingwani R, Apollo T, Hayes R, Weiss HA, Ferrand RA. PLoS Med. 2017 Jul 25;14(7):e1002360. doi: 10.1371/journal.pmed.1002360. eCollection 2017 Jul.

Background: Children living with HIV who are not diagnosed in infancy often remain undiagnosed until they present with advanced disease. Provider-initiated testing and counselling (PITC) in health facilities is recommended for high-HIV-prevalence settings, but it is unclear whether this approach is sufficient to achieve universal coverage of HIV testing. We aimed to investigate the change in community burden of undiagnosed HIV infection among older children and adolescents following implementation of PITC in Harare, Zimbabwe.

Methods and Findings: Over the course of 2 years (January 2013-January 2015), 7 primary health clinics (PHCs) in southwestern Harare implemented optimised, opt-out PITC for all attendees aged 6-15 years. In February 2015-December 2015, we conducted a representative cross-sectional survey of 8-17-year-olds living in the 7 communities served by the study PHCs, who would have had 2 years of exposure to PITC. Knowledge of HIV status was ascertained through a caregiver questionnaire, and anonymised HIV testing was carried out using oral mucosal transudate (OMT) tests. After 1 participant taking antiretroviral therapy was observed to have a false negative OMT result, from July 2015 urine samples were obtained from all participants providing OMTs and tested for antiretroviral drugs to confirm HIV status. Children who tested positive through PITC were identified from among survey participants using gender, birthdate, and location. Of 7146 children in 4251 eligible households, 5486 (76.8%) children in 3397 households agreed to participate in the survey, and 141 were HIV positive. HIV prevalence was 2.6% (95% CI 2.2%-3.1%), and over a third of participants with HIV were undiagnosed (37.7%; 95% CI 29.8%-46.2%). Similarly, among the subsample of 2643 (48.2%) participants with a urine test result, 34.7% of those living with HIV were undiagnosed (95% CI 23.5%-47.9%). Based on extrapolation from the survey sample to the community, we estimated that PITC over 2 years identified between 18% and 42% of previously undiagnosed children in the community. The main limitation is that prevalence of undiagnosed HIV was defined using a combination of 3 measures (OMT, self-report, and urine test), none of which were perfect.

Conclusions: Facility-based approaches are inadequate in achieving universal coverage of HIV testing among older children and adolescents. Alternative, community-based approaches are required to meet the Joint United Nations Programme on HIV/AIDS (UNAIDS) target of diagnosing 90% of those living with HIV by 2020 in this age group.

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Old fashioned AIDS is still with us – shocking in 2017

Editor’s notes: The term AIDS refers to advanced HIV disease with a CD4 count below 200 cells per microl. or with one of several typical opportunistic infections. It is more than twenty years since the revolutionary discovery of highly active combination antiretroviral therapy.  While deaths due to HIV have fallen steadily over the past two decades, it is shocking that so many people are still dying from AIDS.  In part this is due to the same issues of HIV testing discussed above.  The Centers for Disease Control and Prevention (CDC) published their most recent report on surveillance in the United States of America (USA).  The authors show very gradual progress in the right direction. But, still more than 20% of people are diagnosed with HIV infection in the USA when they already have AIDS.  In fact, in a further 20% of people, the stage of infection was not reported to CDC, so as a proportion of those with a known stage at diagnosis, as many as one quarter were diagnosed with AIDS. As might be expected, there are disparities between states with District of Columbia and California doing a little better.  There are big disparities by age (with over one third of people diagnosed at age greater than 45 years having AIDS) but surprisingly little difference by ethnicity.

Médecins sans Frontières (MSF) recently released a report highlighting the challenge of advanced disease, which was picked up in a commentary in the British Medical Journal by Cousins.  The report points out that in hospital settings in Democratic Republic of Congo, Guinea, Kenya, and Malawi, MSF are still seeing an alarmingly high mortality rate, with one third of deaths occurring within the first 48 hours of admission.  As many as three quarters of the patients had been on antiretroviral therapy (ART), suggesting that their advanced disease was not a consequence of late presentation, but rather of failure of the health system to deliver quality care.  The importance of detecting treatment failure early and changing to effective second (or third) line ART was emphasized.  Once patients do present to hospital with advanced HIV disease, it is a clinical emergency and urgent effective care may make a big difference.  WHO has recently issued guidance on managing advanced HIV disease, and the Journal of the International AIDS Society has recently released a useful supplement on Differentiated Care and HIV.

Back in the USA, Braunstein et al. used existing laboratory and other data to construct a retrospective analysis of what happened in the intervenable period during which different treatment approaches might have prevented more than 11 000 people from dying with HIV between 2007 and 2013.  The intervenable period was defined as the 12 months before the last three months of life.  The authors pointed out that in the last three months of life, people might be in care that was not typical of their engagement during the preceding year.  So the intervenable period is therefore more important to see where change could happen.  Like the MSF team, they found that a substantial proportion of people were not properly treated, as shown by the finding that 60% of people did not have a suppressed viral load in the period analysed.  This was despite 98% having some engagement with the health system as shown by laboratory records, 80% being defined as linked to care, and 76% being prescribed ART. The challenge seemed to be to provide high quality care with continuity of care and decisions made promptly according to the findings in the laboratory.

The package of interventions recommended by WHO in their guidance for people presenting with advanced HIV disease includes screening, treatment and/or prophylaxis for major opportunistic infections, rapid ART initiation and intensified adherence support interventions.  Additional support for this approach comes from the REALITY randomized trial conducted by Hakim and colleagues in Uganda, Zimbabwe, Malawi, and Kenya.  In this trial, people with advanced HIV infection, judged by their CD4 count, were randomized in a factorial design.  1805 participants were randomized to different ART regimens; to nutritional support or not; and to a package of prophylaxis.  This paper reports on the differences seen according to whether or not participants were randomized to receive the enhanced prophylaxis.  The package consisted of at least 12 weeks of co-trimoxazole (against pneumocystis, malaria, and various bacterial and protozoal infections), co-formulated with isoniazid and pyridoxine (against tuberculosis), along with fluconazole (against cryptococcus, candida and other fungi) also for 12 weeks and azithromycin (against a broader range of invasive bacteria including salmonella) for five days.  The enhanced prophylaxis led to a 27% reduction in mortality six months after entering the study, and there was still a clear difference after one year, by when 127 people had died in the standard of care group compared to 98 in the enhanced prophylaxis group.  Nonetheless, the death rate was still considerable.  It is also worth noting that many of the people in whom the CD4 count was extremely low did not complain of any symptoms.  So CD4 testing is still needed at the point of clinical care to determine who needs urgent differentiated care for advanced HIV infection.

The final paper in this section is a randomised trial from GHESKIO in Haiti (Koenig et al.).  The investigators randomized 701 people diagnosed with HIV, to start ART on the same day as their diagnosis, or to wait for three weeks, as is standard of care at the centre.  12 months later, viral suppression was somewhat better in people who started ART on the same day (61% vs. 52% at a cut-off of 1000 copies per ml.).  The authors point out that this was a single centre study, and results from GHESKIO might not be generalizable to other treatment sites in Haiti.  Although there were still substantial losses to follow up, there was clearly no evidence that the policy to start people on HIV treatment immediately was too hasty.

 

Missed opportunities: adapting the HIV care continuum to reduce HIV-related deaths

Braunstein SL, Robbins RS, Daskalakis DC. J Acquir Immune Defic Syndr. 2017 Jul 26. doi: 10.1097/QAI.0000000000001509. [Epub ahead of print]

Introduction: With advances in HIV care, persons with HIV/AIDS (PWHA) can lead healthy lives, but avoidable, HIV-related deaths continue to occur in New York City (NYC).

Methods: We selected PWHA from our surveillance registry who died between 2007-2013, resided in NYC, and survived ≥15 months post-diagnosis to generate an HIV Mortality Reduction Continuum of Care (HMRCC) describing pre-death care patterns among PWHA. We used HIV laboratory test reports to measure care outcomes during an "intervenable period" (IP) during which deaths may have been avoided. The continuum was stratified by underlying cause of death (COD) (HIV-related vs. other), and the HIV-related HMRCC was stratified by demographic characteristics.

Results: 11 187 analysis-eligible PWHA died during 2007-2013. 98% linked to care; 80% were retained in care during the IP; 66% were prescribed ART; 47% had VL≤1500 copies/mL; 40% achieved viral suppression (VS). Half (47%) of deaths were HIV-related. Retention was higher among HIV-related COD (83% vs. 78%), but VS was lower (34% vs. 46%). The HIV-related HMRCC revealed disparities in VS. Despite comparable retention rates, Whites had the highest VS (42%, vs. 32% Blacks and 33% Latinos/Hispanics). Additionally, retention and VS increased with increasing age. People with a history of injection drug use had relatively high rates of retention (88%) and VS (37%).

Discussion: The HMRCC is a novel framework for evaluating pre-death care patterns among PWHA and identifying opportunities to reduce preventable deaths. In NYC, reducing mortality will require increasing VS among those already in care, particularly for Blacks and Latinos/Hispanics.

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Enhanced prophylaxis plus antiretroviral therapy for advanced HIV infection in Africa

Hakim J, Musiime V, Szubert AJ, Mallewa J, Siika A, Agutu C, Walker S, Pett SL, Bwakura-Dangarembizi M, Lugemwa A, Kaunda S, Karoney M, Musoro G, Kabahenda S, Nathoo K, Maitland K, Griffiths A, Thomason MJ, Kityo C, Mugyenyi P, Prendergast AJ, Walker AS, Gibb DM; REALITY Trial Team. N Engl J Med. 2017 Jul 20;377(3):233-245. doi: 10.1056/NEJMoa1615822.

Background: In sub-Saharan Africa, among patients with advanced human immunodeficiency virus (HIV) infection, the rate of death from infection (including tuberculosis and cryptococcus) shortly after the initiation of antiretroviral therapy (ART) is approximately 10%.

Methods: In this factorial open-label trial conducted in Uganda, Zimbabwe, Malawi, and Kenya, we enrolled HIV-infected adults and children 5 years of age or older who had not received previous ART and were starting ART with a CD4+ count of fewer than 100 cells per cubic millimeter. They underwent simultaneous randomization to receive enhanced antimicrobial prophylaxis or standard prophylaxis, adjunctive raltegravir or no raltegravir, and supplementary food or no supplementary food. Here, we report on the effects of enhanced antimicrobial prophylaxis, which consisted of continuous trimethoprim-sulfamethoxazole plus at least 12 weeks of isoniazid-pyridoxine (co-formulated with trimethoprim-sulfamethoxazole in a single fixed-dose combination tablet), 12 weeks of fluconazole, 5 days of azithromycin, and a single dose of albendazole, as compared with standard prophylaxis (trimethoprim-sulfamethoxazole alone). The primary end point was 24-week mortality.

Results: A total of 1805 patients (1733 adults and 72 children or adolescents) underwent randomization to receive either enhanced prophylaxis (906 patients) or standard prophylaxis (899 patients) and were followed for 48 weeks (loss to follow-up, 3.1%). The median baseline CD4+ count was 37 cells per cubic millimeter, but 854 patients (47.3%) were asymptomatic or mildly symptomatic. In the Kaplan-Meier analysis at 24 weeks, the rate of death with enhanced prophylaxis was lower than that with standard prophylaxis (80 patients [8.9% vs. 108 [12.2%]; hazard ratio, 0.73; 95% confidence interval [CI], 0.55 to 0.98; P=0.03); 98 patients (11.0%) and 127 (14.4%), respectively, had died by 48 weeks (hazard ratio, 0.76; 95% CI, 0.58 to 0.99; P=0.04). Patients in the enhanced-prophylaxis group had significantly lower rates of tuberculosis (P=0.02), cryptococcal infection (P=0.01), oral or esophageal candidiasis (P=0.02), death of unknown cause (P=0.03), and new hospitalization (P=0.03). However, there was no significant between-group difference in the rate of severe bacterial infection (P=0.32). There were nonsignificantly lower rates of serious adverse events and grade 4 adverse events in the enhanced-prophylaxis group (P=0.08 and P=0.09, respectively). Rates of HIV viral suppression and adherence to ART were similar in the two groups.

Conclusion: Among HIV-infected patients with advanced immunosuppression, enhanced antimicrobial prophylaxis combined with ART resulted in reduced rates of death at both 24 weeks and 48 weeks without compromising viral suppression or increasing toxic effects.

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Same-day HIV testing with initiation of antiretroviral therapy versus standard care for persons living with HIV: A randomized unblinded trial

Koenig SP, Dorvil N, Dévieux JG, Hedt-Gauthier BL, Riviere C, Faustin M, Lavoile K, Perodin C, Apollon A, Duverger L, McNairy ML, Hennessey KA, Souroutzidis A, Cremieux PY, Severe P, Pape JW. PLoS Med. 2017 Jul 25;14(7):e1002357. doi: 10.1371/journal.pmed.1002357. eCollection 2017 Jul.

Background: Attrition during the period from HIV testing to antiretroviral therapy (ART) initiation is high worldwide. We assessed whether same-day HIV testing and ART initiation improves retention and virologic suppression.

Methods and Findings: We conducted an unblinded, randomized trial of standard ART initiation versus same-day HIV testing and ART initiation among eligible adults ≥18 years old with World Health Organization Stage 1 or 2 disease and CD4 count ≤500 cells/mm3. The study was conducted among outpatients at the Haitian Group for the Study of Kaposi's Sarcoma and Opportunistic infections (GHESKIO) Clinic in Port-au-Prince, Haiti. Participants were randomly assigned (1:1) to standard ART initiation or same-day HIV testing and ART initiation. The standard group initiated ART 3 weeks after HIV testing, and the same-day group initiated ART on the day of testing. The primary study endpoint was retention in care 12 months after HIV testing with HIV-1 RNA <50 copies/ml. We assessed the impact of treatment arm with a modified intention-to-treat analysis, using multivariable logistic regression controlling for potential confounders. Between August 2013 and October 2015, 762 participants were enrolled; 59 participants transferred to other clinics during the study period, and were excluded as per protocol, leaving 356 in the standard and 347 in the same-day ART groups. In the standard ART group, 156 (44%) participants were retained in care with 12-month HIV-1 RNA <50 copies, and 184 (52%) had <1000 copies/ml; 20 participants (6%) died. In the same-day ART group, 184 (53%) participants were retained with HIV-1 RNA <50 copies/ml, and 212 (61%) had <1000 copies/ml; 10 (3%) participants died. The unadjusted risk ratio (RR) of being retained at 12 months with HIV-1 RNA <50 copies/ml was 1.21 (95% CI: 1.04, 1.38; p = 0.015) for the same-day ART group compared to the standard ART group, and the unadjusted RR for being retained with HIV-1 RNA <1000 copies was 1.18 (95% CI: 1.04, 1.31; p = 0.012). The main limitation of this study is that it was conducted at a single urban clinic, and the generalizability to other settings is uncertain.

Conclusions: Same-day HIV testing and ART initiation is feasible and beneficial in this setting, as it improves retention in care with virologic suppression among patients with early clinical HIV disease.

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Women know what they want, but need more reproductive health choices

Editor’s notes: Eliminating new HIV infections among children is often seen as a useful barometer of the overall success of the health systems as it relates to HIV.  Combination prevention approaches that include structural, behavioural and biomedical elements reduce the chance of women becoming HIV-positive.  Effective provision of a range of choices of modern contraceptive technology allow women to choose whether and when to have babies.  The option B+ approach should ensure that all pregnant women living with HIV are offered lifelong ART, which minimises the chance of mother to child transmission of HIV infection.  Continuing ART treatment for life keeps the mother healthy and allows her to support the development of her infant.

New HIV infections in children have declined by 46% since 2010, but there were still an estimated 160 000 new infections in 2016.  We know that in many settings the health system barometer is still forecasting plenty of clouds among the bright spells.  This month saw a range of papers describing reproductive health choices and HIV, as well as reflections on how option B+ is working, now that it is standard of care.

Contraceptive choices for women at high risk of HIV or living with HIV are complicated.  WHO recently reclassified long-acting progestin injections, such as DMPA, for women at high risk of HIV infection as category 2 in the Medical Eligibility for Contraception guidance. Category 2 means that, although the method is generally safe to use, clinical judgment and careful follow up may be required.  While the evidence comes from meta-analyses of observational studies, with inherent limitations, there is a reliable association between new HIV infection and the use of injectable progestins.  The ongoing randomized ECHO trial will provide higher quality evidence of causality, but results will not be reported until 2019. 

Mayhew et al. found that women living with HIV attending clinics in Kenya, were quite clear about their fertility intentions.  Many did not want more children, although they acknowledged pressure from partners and others.  Stigma around breast-feeding, worries about money and about possible health consequences of pregnancy were all reasons to decide not to have further children. The large majority used various sorts of contraception, but despite this 40% of pregnancies during the study were unintended.  The authors felt that the advice given by the clinics was not adequate and that choice of contraceptive method was limited.  In particular reliable long-acting methods, both reversible and not, were rarely taken up by the younger women.  Overall 16% of women used long-acting methods, and no pregnancies occurred in this group.

Chanda et al. focused on female sex workers in Zambia and found similar results.  Almost half the women had had terminations of pregnancies, and 62% of pregnancies were not planned.  Interestingly the availability of condoms at their places of work reduced the chances of unwanted pregnancy.  Approximately 39% used injectable long-acting contraceptives and only 18% used dual protection with a barrier in addition to a non-barrier method.  Less than one-third of the women reported that condoms were available often or always at work, and 23% reported using no contraception.  Providing access to condoms for sex workers in the highest transmission areas of countries like Zambia seems such an obvious pre-requisite for HIV programmes that it is extraordinary that in 2017 we still do not manage to do so.

Finally on this theme, Salters et al. demonstrate that contraceptive choice for women living with HIV is not only a challenge in sub-Saharan Africa.  The authors followed women in the Canadian HIV Women's Sexual and Reproductive Health Cohort Study and showed that 61% of reported pregnancies were unintended. Women with unintended pregnancies tended to be younger, single and born in Canada compared to women with planned pregnancies.  To support the second prong of the strategy to eliminate HIV infections in children, we need to improve on the integration between services for sexual and reproductive health and rights and services for women living with HIV.

Once women living with HIV are pregnant, the focus shifts to the third and fourth prong – preventing transmission to the infant and keeping the mother and infant healthy.  Option B+ has transformed the approach in most antenatal clinics with high rates of coverage of HIV testing and most women receiving ART during pregnancy.  In the One Stop Clinic in Ifakara, Tanzania, Gamell et al. show that almost all pregnant women, who do not already know that they are living with HIV, are offered an HIV test and that 94% accept it.  Retesting late in pregnancy is not yet routine, and only 3% were re-tested, of whom one (2%) had seroconverted.  Since acute HIV infection has such an important impact on the risk of transmission, re-testing later in pregnancy is now routine in many countries.  Coverage is far from complete, so it is not always clear whether the high rates of seroconversion observed reflect a selection bias in choosing women who are at particularly high risk.  This is an important area for research if we are to continue to drive down the already low transmission rates.  Similarly the authors found that women who slipped through the net and presented in labour, were not always tested and did have a higher prevalence of infection - 5.2% vs. 3.1%. The other significant finding in Ifakara was that, as in many cohort studies, women were happy to take ART during pregnancy to protect their infants, but retention in care thereafter was much less impressive.  Of women newly diagnosed with HIV infection during pregnancy, 27% were lost to follow up at the time of the analysis.

Chadambuka et al. used qualitative methods to understand what impact the shift to option B+ has had in their study area in Zimbabwe.  Overall, the women interviewed were very positive about treatment.  They believed that it was good for their babies and also good for them, making them look healthy and thus avoiding stigma.  However, women pointed out that their male partners are not exposed to as much information at the clinic or in the community.  As a result, many men are less keen to be tested and sometimes not keen for their partners to be taking medicine despite appearing healthy.  As one woman put it: “Very few men are supportive. You have to be strong. The men base their judgment on how healthy you appear to be as you carry yourself around and he also compares to how healthy he feels and opts to delay testing. But delaying only brings further harm. So when those men tell you to stop taking your medication, you need to tell them that they can stop if they want to, whilst you continue with your treatment.”  Within the power dynamics of many relationships, such a forthright approach may not be easy for all women.  So we need continued attention on how to engage men in the process and how to empower women to act as agents of change within their communities.

 

Fertility intentions and contraceptive practices among clinic-users living with HIV in Kenya: a mixed methods study

Mayhew SH, Colombini M, Kimani JK, Tomlin K, Warren CE; Integra Initiative, Mutemwa R. BMC Public Health. 2017 Jul 5;17(1):626. doi: 10.1186/s12889-017-4514-2.

Background: Preventing unwanted pregnancies in Women Living with HIV (WLHIV) is a recognised HIV-prevention strategy. This study explores the fertility intentions and contraceptive practices of WLHIV using services in Kenya.

Methods: Two hundred forty women self-identifying as WLHIV who attended reproductive health services in Kenya were interviewed with a structured questionnaire in 2011; 48 were also interviewed in-depth. STATA SE/13.1, Nvivo 8 and thematic analysis were used.

Results: Seventy one percent participants did not want another child; this was associated with having at least two living children and being the bread-winnerFP use was high (92%) but so were unintended pregnancies (40%) while living with HIV. 56 women reported becoming pregnant "while using FP": all were using condoms or short-term methods. Only 16% participants used effective long-acting reversible contraceptives or permanent methods (LARC-PM). Being older than 25 years and separated, widowed or divorced were significant predictors of long-term method use. Qualitative data revealed strong motivation among WLHIV to plan or prevent pregnancies to avoid negative health consequences. Few participants received good information about contraceptive choices.

Conclusions: WLHIV need better access to FP advice and a wider range of contraceptives including LARC to enable informed choices that will protect their fertility intentions, ensure planned pregnancies and promote safe child-bearing.

Trial registration: Integra is a non-randomised pre-post intervention trial registered with Current Controlled Trials ID: NCT01694862.

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Contraceptive use and unplanned pregnancy among female sex workers in Zambia

Chanda MM, Ortblad KF, Mwale M, Chongo S, Kanchele C, Kamungoma N, Barresi LG, Harling G, Bärnighausen T, Oldenburg CE. Contraception. 2017 Sep;96(3):196-202. doi: 10.1016/j.contraception.2017.07.003. Epub 2017 Jul 12.

Objectives: Access to reproductive healthcare, including contraceptive services, is an essential component of comprehensive healthcare for female sex workers (FSW). Here, we evaluated the prevalence of and factors associated with contraceptive use, unplanned pregnancy, and pregnancy termination among FSW in three transit towns in Zambia.

Study design: Data arose from the baseline quantitative survey from a randomized controlled trial of HIV self-testing among FSW. Eligible participants were 18 years of age or older, exchanged sex for money or goods at least once in the past month, and were HIV-uninfected or status unknown without recent HIV testing (<3 months). Logistic regression models were used to assess factors associated with contraceptive use and unplanned pregnancy.

Results: Of 946 women eligible for this analysis, 84.1% had been pregnant at least once, and among those 61.6% had an unplanned pregnancy, and 47.7% had a terminated pregnancyIncarceration was associated with decreased odds of dual contraception use (aOR=0.46, 95% CI 0.32-0.67) and increased odds of unplanned pregnancy (aOR=1.75, 95% CI 1.56-1.97). Condom availability at work was associated with increased odds of using condoms only for contraception (aOR=1.74, 95% CI 1.21-2.51) and decreased odds of unplanned pregnancy (aOR=0.63, 95% CI 0.61-0.64).

Conclusions: FSW in this setting have large unmet reproductive health needs. Structural interventions, such as increasing condom availability in workplaces, may be useful for reducing the burden of unplanned pregnancy.

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Pregnancy incidence and intention after HIV diagnosis among women living with HIV in Canada

Salters K, Loutfy M, de Pokomandy A, Money D, Pick N, Wang L, Jabbari S, Carter A, Webster K, Conway T, Dubuc D, O'Brien N, Proulx-Boucher K, Kaida A; CHIWOS Research Team. PLoS One. 2017 Jul 20;12(7):e0180524. doi: 10.1371/journal.pone.0180524. eCollection 2017.

Background: Pregnancy incidence rates among women living with HIV (WLWH) have increased over time due to longer life expectancy, improved health status, and improved access to and HIV prevention benefits of combination antiretroviral therapy (cART). However, it is unclear whether intended or unintended pregnancies are contributing to observed increases.

Methods: We analyzed retrospective data from the Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS). Kaplan-Meier methods and GEE Poisson models were used to measure cumulative incidence and incidence rate of pregnancy after HIV diagnosis overall, and by pregnancy intention. We used multivariable logistic regression models to examine independent correlates of unintended pregnancy among the most recent/current pregnancy.

Results: Of 1165 WLWH included in this analysis, 278 (23.9%) women reported 492 pregnancies after HIV diagnosis, 60.8% of which were unintendedUnintended pregnancy incidence (24.6 per 1000 women-years (WYs); 95% CI: 21.0, 28.7) was higher than intended pregnancy incidence (16.6 per 1000 WYs; 95% CI: 13.8, 20.1) (Rate Ratio: 1.5, 95% CI: 1.2-1.8). Pregnancy incidence among WLWH who initiated cART before or during pregnancy (29.1 per 1000 WYs with 95% CI: 25.1, 33.8) was higher than among WLWH not on cART during pregnancy (11.9 per 1000 WYs; 95% CI: 9.5, 14.9) (Rate Ratio: 2.4, 95% CI: 2.0-3.0). Women with current or recent unintended pregnancy (vs. intended pregnancy) had higher adjusted odds of being single (AOR: 1.94; 95% CI: 1.10, 3.42), younger at time of conception (AOR: 0.95 per year increase, 95% CI: 0.90, 0.99), and being born in Canada (AOR: 2.76, 95% CI: 1.55, 4.92).

Conclusion: Nearly one-quarter of women reported pregnancy after HIV diagnosis, with 61% of all pregnancies reported as unintended. Integrated HIV and reproductive health care programming is required to better support WLWH to optimize pregnancy planning and outcomes and to prevent unintended pregnancy.

Abstract  Full-text [free] access

 

Prevention of mother-to-child transmission of HIV Option B+ cascade in rural Tanzania: the One Stop Clinic model

Gamell A, Luwanda LB, Kalinjuma AV, Samson L, Ntamatungiro AJ, Weisser M, Gingo W, Tanner M, Hatz C, Letang E, Battegay M; KIULARCO Study Group. PLoS One. 2017 Jul 12;12(7):e0181096. doi: 10.1371/journal.pone.0181096. eCollection 2017.

Background: Strategies to improve the uptake of Prevention of Mother-To-Child Transmission of HIV (PMTCT) are needed. We integrated HIV and maternal, newborn and child health services in a One Stop Clinic to improve the PMTCT cascade in a rural Tanzanian setting.

Methods: The One Stop Clinic of Ifakara offers integral care to HIV-infected pregnant women and their families at one single place and time. All pregnant women and HIV-exposed infants attended during the first year of Option B+ implementation (04/2014-03/2015) were includedPMTCT was assessed at the antenatal clinic (ANC), HIV care and labour ward, and compared with the pre-B+ period. We also characterised HIV-infected pregnant women and evaluated the MTCT rate.

Results: 1579 women attended the ANC. Seven (0.4%) were known to be HIV-infectedOf the remainder, 98.5% (1548/1572) were offered an HIV test94% (1456/1548) accepted and 38 (2.6%) tested HIV-positive51 were re-screened for HIV during late pregnancy and one had seroconvertedThe HIV prevalence at the ANC was 3.1% (46/1463). Of the 39 newly diagnosed women, 35 (90%) were linked to care. HIV test was offered to >98% of ANC clients during both the pre- and post-B+ periods. During the post-B+ period, test acceptance (94% versus 90.5%, p<0.0001) and linkage to care (90% versus 26%, p<0.0001) increasedTen additional women diagnosed outside the ANC were linked to care. 82% (37/45) of these newly-enrolled women started antiretroviral treatment (ART). After a median time of 17 months, 27% (12/45) were lost to follow-up. 79 women under HIV care became pregnant and all received ART. After a median follow-up time of 19 months, 6% (5/79) had been lost. 5727 women delivered at the hospital, 20% (1155/5727) had unknown HIV serostatus. Of these, 30% (345/1155) were tested for HIV, and 18/345 (5.2%) were HIV-positive. Compared to the pre-B+ period more women were tested during labour (30% versus 2.4%, p<0.0001). During the study, the MTCT rate was 2.2%.

Conclusions: The implementation of Option B+ through an integrated service delivery model resulted in universal HIV testing in the ANC, high rates of linkage to care, and MTCT below the elimination threshold. However, HIV testing in late pregnancy and labour, and retention during early ART need to be improved.

Abstract  Full-text [free] access

 

Acceptability of lifelong treatment among HIV-positive pregnant and breastfeeding women (Option B+) in selected health facilities in Zimbabwe: a qualitative study

Chadambuka A, Katirayi L, Muchedzi A, Tumbare E, Musarandega R, Mahomva AI, Woelk G BMC Public Health. 2017 Jul 25;18(1):57. doi: 10.1186/s12889-017-4611-2.

Background: Zimbabwe's Ministry of Health and Child Care (MOHCC) adopted 2013 World Health Organization (WHO) prevention of mother-to-child HIV transmission (PMTCT) guidelines recommending initiation of HIV-positive pregnant and breastfeeding women (PPBW) on lifelong antiretroviral treatment (ART) irrespective of clinical stage (Option B+). Option B+ was officially launched in Zimbabwe in November 2013; however the acceptability of life-long ART and its potential uptake among women was not known.

Methods: A qualitative study was conducted at selected sites in Harare (urban) and Zvimba (rural) to explore Option B+ acceptability; barriers, and facilitators to ART adherence and service uptake. In-depth interviews (IDIs), focus group discussions (FGDs) and key informant interviews (KIIs) were conducted with PPBW, healthcare providers, and community members. All interviews were audio-recorded, transcribed, and translated; data were coded and analyzed in MaxQDA v10.

Results: Forty-three IDIs, 22 FGDs, and five KIIs were conducted. The majority of women accepted lifelong ART. There was however, a fear of commitment to taking lifelong medication because they were afraid of defaulting, especially after cessation of breastfeeding. There was confusion around dosage; and fear of side effects, not having enough food to take drugs, and the lack of opportunities to ask questions in counseling. Participants reported the need for strengthening community sensitization for Option B+. Facilitators included receiving a simplified pill regimen; ability to continue breastfeeding beyond 6 months like HIV-negative women; and partner, community and health worker support. Barriers included distance of health facility, non-disclosure of HIV status, poor male partner support and knowing someone who had negative experience on ART.

Conclusions: This study found that Option B+ is generally accepted among PPBW as a means to strengthen their health and protect their babies. Consistent with previous literature, this study demonstrated the importance of male partner and community support in satisfactory adherence to ART and enhancing counseling techniques. Strengthening community sensitization and male knowledge is critical to encourage women to disclose their HIV status and ensure successful adherence to ART. Targeting and engaging partners of women will remain key determinants to women's acceptance and adherence on ART under Option B+

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Africa, Northern America
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Technology is advancing rapidly, but are we making the most of it?

Editor’s notes: HIV self-testing was a key area of discussion in the Paris IAS meeting.  UNITAID signed the next phase of the STAR Initiative that is working with six countries in Southern Africa to transform the market for self-testing and understand the impact of different delivery systems.  The Bill and Melinda Gates Foundation are using their resources to lower prices of self-test kits.  Following WHO’s decision to prequalify an oral fluid test, many countries are including self-test commodities within their PEPFAR Country Operation Plans and Global Fund concept notes. WHO have issued guidance on self-testing and assisted partner notification. So we can expect to see more and more self-tests out there in the field!

In Malawi, Choko et al. reported on qualitative research done prior to a cluster randomized trial that involves providing self-tests to women attending antenatal care (ANC) for them to take home to their partners.  Although couples are welcomed at ANC clinics and couple testing is certainly beneficial, many men still feel that the clinic is not a place for them.  As one participant said: “Considering what happens here at the ANC clinic, I don’t see my husband escorting me anymore because you find he is alone among many women and he has to listen to some things concerning birth. . . .”

In contrast, many women and men engaged in conversations about how providing self-test kits could help communication, stigma, privacy, control and time pressure among other aspects of involving men in HIV testing.  Some concerns were raised around violence and it is clear that this approach will suit some but not all couples, so it needs to be delivered in a way that respects autonomy with no coercion.

In a very different context, Jamil et al. have conducted a randomized trial among Australian gay men and men who have sex with men.  The trial enrolled “high risk” men who reported multiple partners and condomless sex over the past months.  A central premise of public health strategies to control the HIV epidemic is to find people who have acquired HIV as early as possible.  So the trial aimed to determine whether the offer of free oral fluid self-tests led to earlier testing and more frequent testing.  They found that compared with standard care, availability of free oral-fluid self-testing increased testing frequency both in men who had not tested recently and in men who had not tested at all in the past years. Importantly there was no decline in facility-based testing for HIV or sexually transmitted infections, which might have implied replacement.  The men commented that self-testing was highly acceptable and easy to do.

Self-tests are not a panacea.  Oral fluid tests do have a slightly lower sensitivity than blood based tests.  This may be important when HIV-antibody levels are not high, particularly in people taking ART (either as treatment or as PrEP), or early in the course of infection.  Furthermore, both oral fluid and blood based test rely on visual identification of bands on the test strip that may be faint, leading to some people assuming that they are negative or failing to see the positive band.  Curlin et al. examined the performance of oral fluid tests in people seroconverting to HIV during three specific trials.  They found a considerable number of false negative results and a long delay before some individuals became positive on oral fluid tests.  There was also a clear suggestion that some test operators were less good than others at performing the test and the possibility that one batch of the test kits were less sensitive.  Overall they concluded that “caution must be exercised when interpreting a negative oral fluid test in settings where acute infection is likely, and where PrEP use, ART induced viral suppression, or profound immunosuppression may result in low HIV-specific antibody titers.”  However, as an additional screening tool to be used in populations where many of whom are “missing” from the first 90 are to be found, self-tests have much to offer.  Many of these people will have acquired HIV some time ago and by definition will not be taking ART.  So the cautions raised by Curlin et al. may be less relevant for the primary intended purpose of self-tests.  Nonetheless, they make it very clear that oral fluid self-tests are not an appropriate technology to follow people on treatment or on PrEP.  Nor are they recommended for the diagnosis of acute infection.

While self-tests may increase the proportion of adults knowing their HIV status, different technology is needed for infants.  Nucleic acid amplification is used to detect pro-viral DNA or viral RNA in samples from infants.  The technology is more complex and often centralized, leading to delays and loss to follow up in mother-infant pairs.  Several systems now aim to provide testing close to the point of care and the evaluation of the SAMBA HIV-1 Qual Whole Blood Test from Ondiek et al. is an encouraging report.  Sensitivity and specificity were high (98.5% and 99.8% on 745 infant samples) and comparable to the standard approach used in centralized labs.  Samples from those with discrepant results were rechecked by assays based on multiple targets and suggested that the SAMBA test and the standard approach were each responsible for some of the few false positive and negatives seen.  The advantages of the SAMBA system is that it has been designed to be used in peripheral health systems.  All the reagents are freeze dried and stable without refrigeration. Turnaround time is approximately 2 hours with minimal sample handling once the sample is put into the machine.  Costs will still need to come down, but competition with other manufacturers may help.

The SAMBA technology that was evaluated is a qualitative assay aimed at diagnosis of infants.  A larger market is for viral load assays that are central to the monitoring of the effectiveness of HIV treatment and form the indicator for UNAIDS’s third 90.  However, at the moment viral load assays are still too expensive. As a result the optimal strategy for their use remains uncertain within programmes that have to make difficult decisions about where their limited resources should be spent.

Negoescu et al. have built an interesting model to explore the economic trade-offs between different frequencies of performing viral load assays.  More importantly they explore models of adapting the frequency of assays according to characteristics of the person taking ART.  People who have been on treatment for longer periods, or are older, or report fewer problems with adherence could be selected for less frequent assays.  This could save resources, without compromising health outcomes.  However, for countries like Uganda, which was used as the example to calibrate the model, the best approach seems to still be a viral load assay once per year, regardless of other factors.  And indeed, many resource limited countries are having to make difficult choices about how to allocate stretched budgets between expansion of access to viral load assays to the possible detriment of basic prevention programmes such as male circumcision and condoms.  As more resources become available (or as the cost of viral load assays fall) countries may well choose to do more frequent viral load assays.  The authors showed that monthly assays were more expensive but did (unsurprisingly) lead to benefits in terms of earlier detection of virological failure.  Given the renewed attention to drug resistance and the role of late detection of HIV treatment failure in propagating it, such models may become increasingly important.  Adapting the viral load assay frequency to the characteristics of the person taking HIV treatment could be a sensible approach in middle and higher income settings.

For some years, WHO has recommended that nucleic acid amplification should also be used as the first line test for tuberculosis among people living with HIV.  The GeneXpert® system has been taken up quite widely in many countries where HIV is common among people with tuberculosis, most notably in South Africa.  However, Hermans et al. remind us that technology is only one part of the solution.  Although there is no doubt that Xpert is considerably more sensitive than sputum microscopy and considerably quicker than mycobacterial culture, incorporating the technology into routine practice is not always straightforward.  At the Infectious Disease Institute in Kampala, Uganda, where there are well trained clinicians and better resources than in much of the rest of Uganda, Xpert was made available at no cost for the diagnosis of tuberculosis in a one stop combined HIV-TB clinic.  In a cohort of people living with HIV with symptoms suggestive of possible tuberculosis and whose sputum smear microscopy result was negative, many clinicians still preferred to treat on the basis of their clinical judgement and chest radiography.  Xpert™ was requested in less than half the patients.  Similar numbers of people were started on treatment for tuberculosis regardless of whether Xpert was requested (22% vs 21%).  And among those in whom an Xpert™ was performed, more were started on anti-tuberculosis treatment who had had a negative test than a positive one.  So it was not really clear that Xpert was useful in the diagnosis and management of HIV-related tuberculosis in this setting.  Xpert is not 100% sensitive, so many clinicians will choose to treat patients who might have tuberculosis regardless of the results of new technology.  Xpert also give a result that includes resistance to rifampicin, but this was not such a major issue in Kampala and was not an objective of this study.  Those treated without a confirmed test result were more likely to die during the next 12 months, but the authors point out that there are many possible reasons for this.  Many clinicians are aware of the high rates of undiagnosed tuberculosis found at autopsy in people with HIV. Thus, empirical treatment is often given to those who are critically unwell, even when there is no clear evidence of tuberculosis.

GeneXpert® was also the technology used in another study of tuberculosis contact tracing among school children in Swaziland (Ustero et al.).  Despite a rapid and extensive response to look for additional cases in schools where a confirmed case of tuberculosis had been found, no secondary cases were identified.  In household contacts of the same children, they found an additional two cases.  WHO recommends contacts tracing in households of infectious tuberculosis patients.  Although there is still a large and important gap in the estimated number of tuberculosis cases and the number who are notified and treated by national programmes, the best ways to find the missing cases are not well established.  Even in settings where both infections are among the most important causes of mortality, tuberculosis is much less prevalent than HIV.  So the challenge for case-finding and screening approaches for tuberculosis is to select the populations most at risk. An alternative would be to develop tools that are so sensitive, specific and cheap that they can be used for widespread screening. GeneXpert® is not that tool.

While tuberculosis remains the single most important cause of mortality among people living with HIV in low resource settings, there is welcome and increasing attention being paid to human papillomaviruses (HPV).  Certain types of HPV are the cause of cervical cancer.  This is an AIDS-defining illness both because it is more common among women living with HIV and because it has such a high mortality when only detected at the late stages.  At the Paris conference there was a morning session on how to do more about cervical cancer and in particular how to build on the synergies of both HPV and HIV programmes to provide more integrated services for women who are at risk of both infections.  The most important types of HPV that cause cervical cancer can be prevented by vaccination.  However, to be most effective the vaccine has to be given prior to becoming infected with the relevant HPV strain.  So the study by Sudenga et al. in South Africa is useful as it demonstrates how many younger women aged 16-24 years in the Western Cape Province had antibodies against four of the important types included in the quadrivalent vaccine that they were testing.  The majority of participants (64%) had antibodies to two or more types present at enrolment and 12% had antibodies to all four.  Furthermore, among those participants who received placebo injections, the seroconversion rates were alarming high at 23% for HPV16 and 5% for HPV6 over the 7 months of the study among baseline seronegative participants.  South Africa has been a leader in the region in HPV vaccination for schoolgirls.  It is clear that vaccination needs to happen at a young enough age to catch most girls before they become sexually active.  This is in contrast to the offer of pre-exposure prophylaxis, which should be focused on young women who are already sexually active and at higher risk of acquiring HIV.  The specificities of synergies and integration need to be clearly delineated if we are to maximize efficiency.

HPV is also the principal cause of anal carcinoma, which is a significant problem among gay men and men who have sex with men.  Jin et al. have been building on the progress in cervical cancer screening, where new technologies such as nucleic acid detection or oncoprotein detection are leading to big improvements in some settings and replacing cytology as the first line screen for women.  The authors determined whether similar biomarkers including both nucleic acids and cellular markers could be used instead of anal cytology.  As with most advances in diagnostic technology, there is a trade-off between sensitivity and specificity.  Tests that do not miss any cases of neoplastic change are also likely to lead to many people being unnecessarily referred for further assessment and treatment.  However, both new approaches seem to be able to be calibrated in this Australian population to allow fewer referrals while still maintaining a similar sensitivity to the current cytological approach.

Acceptability of woman-delivered HIV self-testing to the male partner, and additional interventions: a qualitative study of antenatal care participants in Malawi.

Choko AT, Kumwenda MK, Johnson CC, Sakala DW, Chikalipo MC, Fielding K, Chikovore J, Desmond N, Corbett EL. J Int AIDS Soc. 2017 Jun 26;20(1):1-10. doi: 10.7448/IAS.20.1.21610.

Introduction: In the era of ambitious HIV targets, novel HIV testing models are required for hard-to-reach groups such as men, who remain underserved by existing services. Pregnancy presents a unique opportunity for partners to test for HIV, as many pregnant women will attend antenatal care (ANC). We describe the views of pregnant women and their male partners on HIV self-test kits that are woman-delivered, alone or with an additional intervention.

Methods: A formative qualitative study to inform the design of a multi-arm multi-stage cluster-randomized trial, comprised of six focus group discussions and 20 in-depth interviews, was conducted. ANC attendees were purposively sampled on the day of initial clinic visit, while men were recruited after obtaining their contact information from their female partners. Data were analysed using content analysis, and our interpretation is hypothetical as participants were not offered self-test kits.

Results: Providing HIV self-test kits to pregnant women to deliver to their male partners was highly acceptable to both women and men. Men preferred this approach compared with standard facility-based testing, as self-testing fits into their lifestyles which were characterized by extreme day-to-day economic pressures, including the need to raise money for food for their household daily. Men and women emphasized the need for careful communication before and after collection of the self-test kits in order to minimize the potential for intimate partner violence although physical violence was perceived as less likely to occur. Most men stated a preference to first self-test alone, followed by testing as a couple. Regarding interventions for optimizing linkage following self-testing, both men and women felt that a fixed financial incentive of approximately USD$2 would increase linkage. However, there were concerns that financial incentives of greater value may lead to multiple pregnancies and lack of child spacing. In this low-income setting, a lottery incentive was considered overly disappointing for those who receive nothing. Phone call reminders were preferred to short messaging service.

Conclusions: Woman-delivered HIV self-testing through ANC was acceptable to pregnant women and their male partners. Feedback on additional linkage enablers will be used to alter pre-planned trial arms.

Abstract  Full-text [free] access

 

Effect of availability of HIV self-testing on HIV testing frequency in gay and bisexual men at high risk of infection (FORTH): a waiting-list randomised controlled trial.

Jamil MS, Prestage G, Fairley CK, Grulich AE, Smith KS, Chen M, Holt M, McNulty AM, Bavinton BR, Conway DP, Wand H, Keen P,Bradley J, Kolstee J, Batrouney C, Russell D, Law M, Kaldor JM, Guy RJ. Lancet HIV. 2017 Jun;4(6):e241-e250. doi: 10.1016/S2352-3018(17)30023-1. Epub 2017 Feb 17.

Background: Frequent testing of individuals at high risk of HIV is central to current prevention strategies. We aimed to determine if HIV self-testing would increase frequency of testing in high-risk gay and bisexual men, with a particular focus on men who delayed testing or had never been tested before.

Methods: In this randomised trial, HIV-negative high-risk gay and bisexual men who reported condomless anal intercourse or more than five male sexual partners in the past 3 months were recruited at three clinical and two community-based sites in Australia. Enrolled participants were randomly assigned (1:1) to the intervention (free HIV self-testing plus facility-based testing) or standard care (facility-based testing only). Participants completed a brief online questionnaire every 3 months, which collected the number of self-tests used and the number and location of facility-based tests, and HIV testing was subsequently sourced from clinical records. The primary outcome of number of HIV tests over 12 months was assessed overall and in two strata: recent (last test ≤2 years ago) and non-recent (>2 years ago or never tested) testers. A statistician who was masked to group allocation analysed the data; analyses included all participants who completed at least one follow-up questionnaire. After the 12 month follow-up, men in the standard care group were offered free self-testing kits for a year. This trial is registered with the Australian New Zealand clinical trials registry, number actrn12613001236785.

Findings: Between Dec 1, 2013, and Feb 5, 2015, 182 men were randomly assigned to self-testing, and 180 to standard care. The analysis population included 178 (98%) men in the self-testing group (174 person-years) and 165 (92%) in the standard care group (162 person-years). Overall, men in the self-testing group had 701 HIV tests (410 self-tests; mean 4·0 tests per year), and men in the standard care group had 313 HIV tests (mean 1·9 tests per year); rate ratio (rr) 2·08 (95% ci 1·82-2·38; p<0·0001). Among recent testers, men in the self-testing group had 627 tests (356 self-tests; mean 4·2 per year), and men in the standard care group had 297 tests (mean 2·1 per year); rr 1·99 (1·73-2·29; p<0·0001). Among non-recent testers, men in the self-testing group had 74 tests (54 self-tests; mean 2·8 per year), and men in the standard care group had 16 tests (mean 0·7 per year); rr 3·95 (2·30-6·78; p<0·0001). The mean number of facility-based HIV tests per year was similar in the self-testing and standard care groups (mean 1·7 vs 1·9 per year, respectively; rr 0·86, 0·74-1·01; P=0·074). No serious adverse events were reported during follow-up.

Interpretation: HIV self-testing resulted in a two times increase in frequency of testing in gay and bisexual men at high risk of infection, and a nearly four times increase in non-recent testers, compared with standard care, without reducing the frequency of facility-based HIV testing. HIV self-testing should be made more widely available to help increase testing and earlier diagnosis.

Abstract access

 

Analysis of false-negative human immunodeficiency virus rapid tests performed on oral fluid in 3 international clinical research studies.

Curlin ME, Gvetadze R, Leelawiwat W, Martin M, Rose C, Niska RW, Segolodi TM, Choopanya K, Tongtoyai J, Holtz TH, Samandari T, McNicholl JM; OraQuick Study Group. Clin Infect Dis. 2017 Jun 15;64(12):1663-1669. doi: 10.1093/cid/cix228.

Background: The OraQuick Advance Rapid HIV-1/2 Test is a point-of-care test capable of detecting human immunodeficiency virus (HIV)-specific antibodies in blood and oral fluid. To understand test performance and factors contributing to false-negative results in longitudinal studies, we examined results of participants enrolled in the Botswana TDF/FTC Oral HIV Prophylaxis Trial, the Bangkok Tenofovir Study, and the Bangkok MSM Cohort Study, 3 separate clinical studies of high-risk, HIV-negative persons conducted in Botswana and Thailand.

Methods: In a retrospective observational analysis, we compared oral fluid OraQuick (OFOQ) results among participants becoming HIV infected to results obtained retrospectively using enzyme immunoassay and nucleic acid amplification tests on stored specimens. We categorized negative OFOQ results as true-negative or false-negative relative to nucleic acid amplification test and/or enzyme immunoassay, and determined the delay in OFOQ conversion relative to the estimated time of infection. We used log-binomial regression and generalized estimating equations to examine the association between false-negative results and participant, clinical, and testing-site factors.

Results: Two-hundred thirty-three false-negative OFOQ results occurred in 80 of 287 seroconverting individuals.  Estimated OFOQ conversion delay ranged from 14.5 to 547.5 (median, 98.5) days. Delayed OFOQ conversion was associated with clinical site and test operator (P < .05), preexposure prophylaxis (P = .01), low plasma viral load (P < .02), and time to kit expiration (P < .01). Participant age, sex, and HIV subtype were not associated with false-negative results. Long OFOQ conversion delay time was associated with antiretroviral exposure and low plasma viral load.

Conclusions: Failure of OFOQ to detect HIV-1 infection was frequent and multifactorial in origin. In longitudinal trials, negative oral fluid results should be confirmed via testing of blood samples.

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Multi-country validation of SAMBA - A novel molecular point-of- care test for HIV-1 detection in resource-limited setting.

Ondiek J, Namukaya Z, Mtapuri-Zinyowera S, Balkan S, Elbireer A, Ushiro Lumb I, Kiyaga C, Goel N, Ritchie A, Ncube P, Omuomu K, Ndiege K, Kekitiinwa A,Mangwanya D, Fowler MG, Nadala L, Lee H. J Acquir Immune Defic Syndr. 2017 Jun 9. doi: 10.1097/QAI.0000000000001476. [Epub ahead of print]

Introduction: Early diagnosis of HIV-1 infection and the prompt initiation of antiretroviral therapy are critical to achieving a reduction in the morbidity and mortality of infected infants. The SAMBA HIV-1 Qual Whole Blood Test was developed specifically for early infant diagnosis and prevention of mother-to-child transmission programs implemented at the point-of-care in resource-limited settings.

Methods: We have evaluated the performance of this test run on the SAMBA I semi-automated platform with fresh whole blood specimens collected from 202 adults and 745 infants in Kenya, Uganda, and Zimbabwe. Results were compared with those obtained with the Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) HIV-1 assay as performed with fresh whole blood or dried blood spots of the same subjects, and discrepancies were resolved with alternative assays.

Results: The performance of the SAMBA and CAP/CTM assays evaluated at five laboratories in the three countries was similar for both adult and infant samples. The clinical sensitivity, specificity, and positive and negative predictive values for the SAMBA test were 100%, 99.2%, 98.7%, and 100%, respectively, with adult samples, and 98.5%, 99.8%, 99.7%, and 98.8%, respectively, with infant samples.

Discussion: Our data suggest that the SAMBA HIV-1 Qual Whole Blood Test would be effective for early diagnosis of HIV-1 infection in infants at point-of care settings in sub-Saharan Africa.

Abstract access

 

Differentiated human immunodeficiency virus RNA monitoring in resource-limited settings: an economic analysis.

Negoescu DM, Zhang Z, Bucher HC, Bendavid E; Swiss HIV Cohort Study. Clin Infect Dis. 2017 Jun 15;64(12):1724-1730. doi: 10.1093/cid/cix177.

Background: Viral load (VL) monitoring for patients receiving antiretroviral therapy (ART) is recommended worldwide. However, the costs of frequent monitoring are a barrier to implementation in resource-limited settings. The extent to which personalized monitoring frequencies may be cost-effective is unknown.

Methods: We created a simulation model parameterized using person-level longitudinal data to assess the benefits of flexible monitoring frequencies. Our data-driven model tracked human immunodeficiency virus (HIV)-infected individuals for 10 years following ART initiation. We optimized the interval between viral load tests as a function of patients' age, gender, education, duration since ART initiation, adherence behavior, and the cost-effectiveness threshold. We compared the cost-effectiveness of the personalized monitoring strategies to fixed monitoring intervals every 1, 3, 6, 12, and 24 months.

Results: Shorter fixed VL monitoring intervals yielded increasing benefits (6.034 to 6.221 discounted quality-adjusted life-years [QALYs] per patient with monitoring every 24 to 1 month over 10 years, respectively, standard error = 0.005 QALY), at increasing average costs: US$3445 (annual monitoring) to US$5393 (monthly monitoring) per patient, respectively (standard error = US$3.7). The adaptive policy optimized for low-income contexts achieved 6.142 average QALYs at a cost of US$3524, similar to the fixed 12-month policy (6.135 QALYs, US$3518). The adaptive policy optimized for middle-income resource settings yields 0.008 fewer QALYs per person, but saves US$204 compared to monitoring every 3 months.

Conclusions: The benefits from implementing adaptive vs fixed VL monitoring policies increase with the availability of resources. In low- and middle-income countries, adaptive policies achieve similar outcomes to simpler, fixed-interval policies.

Abstract  Full-text [free] access

 

Treatment decisions and mortality in HIV-positive presumptive smear-negative TB in the Xpert™ MTB/RIF era: a cohort study.

Hermans SM, Babirye JA, Mbabazi O, Kakooza F, Colebunders R, Castelnuovo B, Sekaggya-Wiltshire C, Parkes-Ratanshi R, Manabe YC. BMC Infect Dis. 2017 Jun 16;17(1):433. doi: 10.1186/s12879-017-2534-2.

Background: The Xpert™ MTB/RIF (XP) has a higher sensitivity than sputum smear microscopy (70% versus 35%) for TB diagnosis and has been endorsed by the WHO for TB high burden countries to increase case finding among HIV co-infected presumptive TB patients. Its impact on the diagnosis of smear-negative TB in a routine care setting is unclear. We determined the change in diagnosis, treatment and mortality of smear-negative presumptive TB with routine use of Xpert MTB/RIF (XP).

Methods: Prospective cohort study of HIV-positive smear-negative presumptive TB patients during a 12-month period after XP implementation in a well-staffed and trained integrated TB/HIV clinic in Kampala, Uganda. Prior to testing clinicians were asked to decide whether they would treat empirically prior to Xpert result; actual treatment was decided upon receipt of the XP result. We compared empirical and XP-informed treatment decisions and all-cause mortality in the first year.

Results: Of 411 smear-negative presumptive TB patients, 175 (43%) received an XP; their baseline characteristics did not differ. XP positivity was similar in patients with a pre-XP empirical diagnosis and those without (9/29 [17%] versus 14/142 [10%], P = 0.23). Despite XP testing high levels of empirical treatment prevailed (18%), although XP results did change who ultimately was treated for TB. When adjusted for CD4 count, empirical treatment was not associated with higher mortality compared to no or microbiologically confirmed treatment.

Conclusions: XP usage was lower than expected. The lower sensitivity of XP in smear-negative HIV-positive patients led experienced clinicians to use XP as a "rule-in" rather than "rule-out" test, with the majority of patients still treated empirically.

Keywords: Empirical treatment; HIV Infections/complications; Molecular diagnostic techniques/methods; Tuberculosis, pulmonary/diagnosis; Tuberculosis, pulmonary/epidemiology

Abstract  Full-text [free] access 

 

School and household tuberculosis contact investigations in Swaziland: Active TB case finding in a high HIV/TB burden setting.

Ustero PA, Kay AW, Ngo K, Golin R, Tsabedze B, Mzileni B,Glickman J, Wisile Xaba M, Mavimbela G, Mandalakas AM. PLoS One. 2017 Jun 5;12(6):e0178873. doi: 10.1371/journal.pone.0178873.eCollection 2017.

Background: Investigation of household contacts exposed to infectious tuberculosis (TB) is widely recommended by international guidelines to identify secondary cases of TB and limit spread. There is little data to guide the use of contact investigations outside of the household, despite strong evidence that most TB infections occur outside of the home in TB high burden settings. In older adolescents, the majority of infections are estimated to occur in school. Therefore, as part of a project to increase active case finding in Swaziland, we performed school contact investigations following the identification of a student with infectious TB.

Methods: The Butimba Project identified 7 adolescent TB index cases (age 10-20) with microbiologically confirmed disease attending 6 different schools between June 2014 and March 2015. In addition to household contact investigations, Butimba Project staff worked with the Swaziland School Health Programme (SHP) to perform school contact investigations. At 6 school TB screening events, between May and October 2015, selected students underwent voluntary TB screening and those with positive symptom screens provided sputum for TB testing.

Results: Among 2015 student contacts tested, 177 (9%) screened positive for TB symptoms, 132 (75%) produced a sputum sample, of which zero tested positive for TB. Household contact investigations of the same index cases yielded 40 contacts; 24 (60%) screened positive for symptoms; 19 produced a sputum sample, of which one case was confirmed positive for TB. The odds ratio of developing TB following household vs. school contact exposure was significantly lower (OR 0.0, 95% CI 0.0 to 0.18, P = 0.02) after exposure in school.

Conclusion: School-based contact investigations require further research to establish best practices in TB high burden settings. In this case, a symptom-based screening approach did not identify additional cases of tuberculosis. In comparison, household contact investigations yielded a higher percentage of contacts with positive TB screens and an additional tuberculosis case.

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HPV serostatus pre- and post-vaccination in a randomized phase II preparedness trial among young Western Cape, South African women: the EVRI trial.

Sudenga SL, Torres BN, Botha MH, Zeier M, Abrahamsen ME, Glashoff RH, Engelbrecht S, Schim Van der Loeff MF, Van der Laan LE, Kipping S, Taylor D, Giuliano AR. Papillomavirus Res. 2017 Jun;3:50-56. doi: 10.1016/j.pvr.2017.02.001. Epub 2017 Feb 16.

Background: HPV antibodies are a marker of past exposure to the virus. Our objective was to assess HPV serostatus pre- and post-vaccination among HIV-negative women.

Methods: Women aged 16-24 years old were randomized in a placebo controlled trial utilizing the 4-valent HPV (4vHPV) vaccine (NCT01489527, clinicaltrials.gov). Participants (n=389) received the 4vHPV vaccine or placebo following a three dose schedule. Sera were collected at Day 1 and Month 7 for assessment of HPV 6, 11, 16, and 18 neutralizing antibody levels using a multiplex competitive Luminex immunoassay (Merck) based on detecting the L1 capsid antigen for each HPV type.

Results: Seroprevalence was 73% for HPV6, 47% for HPV11, 33% for HPV16, and 44% for HPV18. Seroprevalence for any HPV type did not significantly differ by age or lifetime number of partners. The majority of participants (64%) had two or more 4vHPV antibodies present at enrollment and 12% had antibodies to all four. Among women in the vaccine arm, those that were seropositive for HPV16 at enrollment had higher titers at month 7 compared to women that were seronegative for HPV16 at enrollment; this trend holds for the other HPV types as well. Seroconversion among baseline seronegative participants in the placebo group ranged from 5% for HPV16 to 23% for HPV6.

Conclusion: HPV seroprevalence was high in this population, emphasizing the need to vaccinate prior to sexual debut.

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The performance of human papillomavirus biomarkers in predicting anal high-grade squamous intraepithelial lesions in gay and bisexual men.

Jin F, Roberts JM, Grulich AE, Poynten IM, Machalek DA, Cornall A, Phillips S, Ekman D, McDonald RL, Hillman RJ, Templeton DJ, Farnsworth A, Garland SM, Fairley CK, Tabrizi SN; SPANC Research Team. AIDS. 2017 Jun 1;31(9):1303-1311. doi: 10.1097/QAD.0000000000001462.

Background: We evaluate the performance of human papillomavirus (HPV) biomarkers in prediction of anal histological high-grade squamous intraepithelial lesions in gay and bisexual men (GBM) in Sydney, Australia.

Design: Baseline analysis of a 3-year cohort study.

Methods: The study of the prevention of anal cancer is natural history study of anal HPV infection in GBM aged at least 35 years. All participants completed cytological and histological assessments. Stored ThinPrep PreservCyt residua were tested for HPV genotyping (Linear Array and Cobas 4800) and viral load, E6/E7 mRNA expression (NucliSENS easyQ HPV v1) and dual cytology staining of p16/Ki 67 antibodies (CINtecPLUS). Performance of each biomarker was compared with liquid-based anal cytology. The hypothetical referral rates were defined as the proportion of men who had abnormal cytology or tested positive to each of the biomarkers.

Results: The median age of the 617 participants was 49 years (range: 35-79), and 35.7% were HIV-positive. All biomarkers were strongly associated with the grade of HPV-associated anal lesions (P < 0.001 for all). High-risk HPV (HR-HPV) viral load with a 33% cut-off and HR-HPV E6/E7 mRNA had similar sensitivity to anal cytology (78.4 and 75.4 vs. 83.2%, respectively), improved specificity (68.0 and 69.4 vs. 52.4%, respectively) and lower referral rates (47.0 and 45.0 vs. 59.2%, respectively). Specificity was significantly higher in the HIV-negative for HR-HPV viral load (72.3 vs. 58.2%, P = 0.005).

Conclusion: HR-HPV viral load and E6/E7 mRNA had similar sensitivity and higher specificity in predicting histological anal high-grade squamous intraepithelial lesion with lower referrals in GBM than anal cytology.

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Africa, Asia, Europe, Oceania
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Age-disparate sexual partnerships - it’s more complicated than sugar daddies and blessers

Editor’s notes: Sugar daddies and blessers are men who provide gifts, money or other benefits to much younger women in exchange for sex.  These relationships are inevitably complex and are often seen as an important mode of transmission for HIV, particularly in Southern and East Africa.  Health education campaigns have raised the issue and aimed to discourage young women from having sex with older men.  However, the research on age-disparate relationships has been harder to interpret. Some studies show that having older partners is not necessarily an independent risk factor for HIV acquisition and others demonstrate a clear age difference in some couples where phylogenetics makes transmission seem very likely.  Nor do all age-disparate relationships involve sugar daddies or blessers.  Many women choose partners who are a few years older than themselves without such clear cut transactional motives.

This month saw Akulian et al. conclude that “age of sexual partner is a major risk factor for HIV acquisition” with frighteningly high rates of HIV incidence of 9.7 per 100 person years occurring among women aged 15-24 years old reporting partnerships with men aged 30-34 years old.  Yet the same research group (Harling et al.), in the same geographic community three years ago, concluded that “partner age disparity did not predict HIV acquisition” and cautioned against using resources for public health campaigns to reduce such partnerships.  A recent paper (de Oliveira et al.) from another research setting, also in KwaZulu-Natal, used phylogenetics to link isolates that were likely to be transmission pairs.  They too found that younger women (aged younger than 25 years) were more likely to have older male partners.  On average in the couples linked by phylogenetics the age difference was 8.7 years when the woman was younger than 25 but only 1.1 years when she was older than 25 years.

This month Schaefer et al. also demonstrated that in the Manicaland cohort in Zimbabwe, where incidence is somewhat lower than in KwaZulu-Natal, young women aged 15-24 years in partnerships with older men were likely to become  HIV positive .  They note that even the introduction of ART has not changed this observed finding, suggesting that the failure to reach men as effectively as we are reaching women, may be a significant reason for ongoing transmission.

The Akullian et al. paper used statistical techniques to smooth the observations from more than 1000 seroconversions observed in more than 25 000 person years of follow-up.  Harling et al. followed the cohort of women aged 15-29 years in the study area and observed 458 seroconversions over 5913 woman years of observation.  Although age-disparate relationships were common, age disparity was not an independent risk factor for HIV infection.  Akullian et al. explain that the real risk is from men aged 25-34 years.  Men in this age group are more likely to have recently acquired HIV, as it is the peak age group for incidence in males.  They are therefore likely to be particularly infectious with higher viral loads. They are also a group that has a low uptake of HIV testing and linkage to ART. 

The rates of ART use and HIV prevalence of older male partners for young women was explored by Evans et al. using data from the South African 2012 National HIV survey.  They found that male partners who were considerably older were more likely to be taking ART and so were likely to transmit fewer infections to their partners, which would tie in well with the Akullian et al. hypothesis of the highest risk being men aged 25-34 years.  The highest incidence is among young women, and these women are most likely to have partners in the 25-34 year old age band.  So we must be careful not to over-generalize.  This helps to explain the apparently differing results from these various studies.  If all age-disparate relationships are included in epidemiological studies, the important impact of transmission from recently infected and untreated 25-34 year old men to their younger female partners aged younger than 25 years may be diluted.

All these studies come from South Africa (usually KwaZulu-Natal) and Zimbabwe and so further detailed epidemiology supported by phylogenetics would be welcome from elsewhere.  Nonetheless, these various studies do translate into a clear message for action.  We need to work hard to find better ways to engage men aged 25-34 years, encourage them to get tested for HIV (see the HIV self-testing approaches above for instance) and link them to care and effective treatment much more efficiently than we are doing at present. 

Sexual partnership age pairings and risk of HIV acquisition in rural South Africa.

Akullian A, Bershteyn A, Klein D, Vandormael A, Bärnighausen T, Tanser F. AIDS. 2017 Jul 31;31(12):1755-1764. doi: 10.1097/QAD.0000000000001553.

Objective: To quantify the contribution of specific sexual partner age groups to the risk of HIV acquisition in men and women in a hyperendemic region of South Africa.

Design: We conducted a population-based cohort study among women (15-49 years of age) and men (15-55 years of age) between 2004 and 2015 in KwaZulu-Natal, South Africa.

Methods: Generalized additive models were used to estimate smoothed HIV incidence rates across partnership age pairings in men and women. Cox proportional hazards regression was used to estimate the relative risk of HIV acquisition by partner age group.

Results: A total of 882 HIV seroconversions were observed in 15  935 person-years for women, incidence rate = 5.5 per 100 person-years [95% confidence interval (CI), 5.2-5.9] and 270 HIV seroconversions were observed in 9372 person-years for men, incidence rate = 2.9 per 100 person-years (95% CI, 2.6-3.2). HIV incidence was highest among 15-24-year-old women reporting partnerships with 30-34-year-old men, incidence rate = 9.7 per 100 person-years (95% CI, 7.2-13.1). Risk of HIV acquisition in women was associated with male partners aged 25-29 years (adjusted hazard ratio; aHR = 1.44, 95% CI, 1.02-2.04) and 30-34 years (aHR = 1.50, 95% CI, 1.08-2.09) relative to male partners aged 35 and above. Risk of HIV acquisition in men was associated with 25-29-year-old (aHR = 1.72, 95% CI, 1.02-2.90) and 30-34-year-old women (aHR = 2.12, 95% CI, 1.03-4.39) compared to partnerships with women aged 15-19 years.

Conclusion: Age of sexual partner is a major risk factor for HIV acquisition in both men and women, independent of one's own age. Partner age pairings play a critical role in driving the cycle of HIV transmission.

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Do age-disparate relationships drive HIV incidence in young women? Evidence from a population cohort in rural KwaZulu-Natal, South Africa.

Harling G, Newell ML, Tanser F, Kawachi I, Subramanian SV, Bärnighausen T.J Acquir Immune Defic Syndr. 2014 Aug 1;66(4):443-51. doi: 10.1097/QAI.0000000000000198.

Background: Based on ethnographic investigations and mathematical models, older sexual partners are often considered a major risk factor for HIV for young women in sub-Saharan Africa. Numerous public health campaigns have been conducted to discourage young women from relationships with older men. However, longitudinal evidence relating sex partner age disparity to HIV acquisition in women is limited.

Methods: Using data from a population-based open cohort in rural KwaZulu-Natal, South Africa, we studied 15- to 29-year-old women who were HIV seronegative at first interview between January 2003 and June 2012 (n = 2444). We conducted proportional hazards analysis to establish whether the age disparity of women's most recent sexual partner, updated at each surveillance round, was associated with subsequent HIV acquisition.

Results: A total of 458 HIV seroconversions occurred over 5913 person-years of follow-up (incidence rate: 7.75 per 100 person-years). Age disparate relationships were common in this cohort; 37.7% of women reported a partner 5 or more years older than themselves. The age disparity of women's partners was not associated with HIV acquisition when measured either continuously [hazard ratio (HR) for 1-year increase in partner's age: 1.00, 95% confidence interval (CI): 0.97 to 1.03] or categorically (man ≥5 years older: HR, 0.98; 95% CI: 0.81 to 1.20; man ≥10 years older: HR, 0.98; 95% CI: 0.67 to 1.43). These results were robust to adjustment for known sociodemographic and behavioral HIV risk factors and did not vary significantly by women's age, marital status, education attainment, or household wealth.

Conclusions: HIV incidence in young women was very high in this rural community in KwaZulu-Natal. Partner age disparity did not predict HIV acquistion. Campaigns to reduce age-disparate sexual relationships may not be a cost-effective use of HIV prevention resources in this setting.

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Transmission networks and risk of HIV infection in KwaZulu-Natal, South Africa: a community-wide phylogenetic study.

de Oliveira T, Kharsany AB, Gräf T, Cawood C, Khanyile D, Grobler A, Puren A, Madurai S, Baxter C, Karim QA, Karim SS. Lancet HIV. 2017 Jan;4(1):e41-e50. doi: 10.1016/S2352-3018(16)30186-2. Epub 2016 Dec 1.

Background: The incidence of HIV infection in young women in Africa is very high. We did a large-scale community-wide phylogenetic study to examine the underlying HIV transmission dynamics and the source and consequences of high rates of HIV infection in young women in South Africa.

Methods: We did a cross-sectional household survey of randomly selected individuals aged 15-49 years in two neighbouring subdistricts (one urban and one rural) with a high burden of HIV infection in KwaZulu-Natal, South Africa. Participants completed structured questionnaires that captured general demographic, socioeconomic, psychosocial, and behavioural data. Peripheral blood samples were obtained for HIV antibody testing. Samples with HIV RNA viral load greater than 1000 copies per mL were selected for genotyping. We constructed a phylogenetic tree to identify clusters of linked infections (defined as two or more sequences with bootstrap or posterior support ≥90% and genetic distance ≤4·5%).

Findings: From June 11, 2014, to June 22, 2015, we enrolled 9812 participants, 3969 of whom tested HIV positive. HIV prevalence (weighted) was 59·8% in 2835 women aged 25-40 years, 40·3% in 1548 men aged 25-40 years, 22·3% in 2224 women younger than 25 years, and 7·6% in 1472 men younger than 25 years. HIV genotyping was done in 1589 individuals with a viral load of more than 1000 copies per mL. In 90 transmission clusters, 123 women were linked to 103 men. Of 60 possible phylogenetically linked pairings with the 43 women younger than 25 years, 18 (30·0%) probable male partners were younger than 25 years, 37 (61·7%) were aged 25-40 years, and five (8·3%) were aged 41-49 years: mean age difference 8·7 years (95% CI 6·8-10·6; p<0·0001). For the 92 possible phylogenetically linked pairings with the 56 women aged 25-40 years, the age difference dropped to 1·1 years (95% CI -0·6 to 2·8; p=0·111). 16 (39·0%) of 41 probable male partners linked to women younger than 25 years were also linked to women aged 25-40 years. Of 79 men (mean age 31·5 years) linked to women younger than 40 years, 62 (78·5%) were unaware of their HIV-positive status, 76 (96·2%) were not on antiretroviral therapy, and 29 (36·7%) had viral loads of more than 50 000 copies per mL.

Interpretation: Sexual partnering between young women and older men, who might have acquired HIV from women of similar age, is a key feature of the sexual networks driving transmission. Expansion of treatment and combination prevention strategies that include interventions to address age-disparate sexual partnering is crucial to reducing HIV incidence and enabling Africa to reach the goal of ending AIDS as a public health threat.

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Age-disparate relationships and HIV incidence in adolescent girls and young women: evidence from Zimbabwe.

Schaefer R, Gregson S, Eaton JW, Mugurungi O, Rhead R, Takaruza A, Maswera R, Nyamukapa C. AIDS. 2017 Jun 19;31(10):1461-1470. doi: 10.1097/QAD.0000000000001506.

Objective: Age-disparate sexual relationships with older men may drive high rates of HIV acquisition in young women in sub-Saharan Africa, but evidence is limited. We investigate the association between age-disparate relationships and HIV incidence in Manicaland, Zimbabwe.

Design: A general-population open-cohort study (six surveys) (1998-2013).

Methods: A total of 3746 young women aged 15-24 years participated in consecutive surveys and were HIV-negative at the beginning of intersurvey periods. Last sexual partner age difference and age-disparate relationships [intergenerational (≥10 years age difference) and intragenerational (5-9 years) versus age-homogeneous (0-4 years)] were tested for associations with HIV incidence in Cox regressions. A proximate determinants framework was used to explore factors possibly explaining variations in the contribution of age-disparate relationships to HIV incidence between populations and over time.

Results: About 126 HIV infections occurred over 8777 person-years (1.43 per 100 person-years; 95% confidence interval = 1.17-1.68). Sixty-five percent of women reported partner age differences of at least 5 years. Increasing partner age differences were associated with higher HIV incidence [adjusted hazard ratio (aHR) = 1.05 (1.01-1.09)]. Intergenerational relationships tended to increase HIV incidence [aHR = 1.78 (0.96-3.29)] but not intragenerational relationships [aHR = 0.91 (0.47-1.76)]. Secondary education was associated with reductions in intergenerational relationships [adjusted odds ratio (aOR) = 0.49 (0.36-0.68)]. Intergenerational relationships were associated with partners having concurrent relationships [aOR = 2.59 (1.81-3.70)], which tended to increase HIV incidence [aHR = 1.74 (0.96-3.17)]. Associations between age disparity and HIV incidence did not change over time.

Conclusion: Sexual relationships with older men expose young women to increased risk of HIV acquisition in Manicaland, which did not change over time, even with introduction of antiretroviral therapy.

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HIV prevalence and ART use among men in partnerships with 15-29 year old women in South Africa: HIV risk implications for young women in age-disparate partnerships.

Evans M, Maughan-Brown B, Zungu N, George G. AIDS Behav. 2017 Aug;21(8):2533-2542. doi: 10.1007/s10461-017-1741-6.

This study assesses whether men's ART use mitigates HIV-risk within age-disparate partnerships. Using data from the 2012 South African National HIV survey, we analyzed differences in HIV prevalence and ART use between men in age-disparate and age-similar partnerships with young women aged 15-29 using multiple logistic regression analyses. Within partnerships involving women 15-24 years old, men in age-disparate partnerships were more likely to be HIV-positive (5-9 year age-gap: aOR 2.8, 95%CI 1.4-5.2; p < 0.01; 10+ year age-gap: aOR 2.2, 95%CI 1.0-4.6; p < 0.05). Men in age-disparate partnerships who were 5-9 years older were significantly more likely to be HIV-positive and ART-naïve (aOR 2.4, 95%CI 1.2-4.8; p < 0.05), while this was not the case for men 10+ years older (aOR 1.5, 95%CI 0.7-3.6; p = 0.32). No evidence was found that 25-29 year old women were at greater HIV-risk in age-disparate partnerships. Our results indicate that young women aged 15-24 have a greater likelihood of exposure to HIV through age-disparate partnerships, but ART use among men 10+ years older could mitigate risk.

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Africa
South Africa, Zimbabwe
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How are we going to get to our prevention targets? Old tools, new tools and a more nuanced understanding of transmission dynamics.

Editor’s notes: By 2020, the Fast-Track strategy is aiming to reduce new HIV infections to 200 000 per year.  There is increasing recognition that if we are to succeed, we will need to do much more than simply putting people onto HIV treatment.  Despite the massive impact of ART on infectiousness, the decline in new infections at the community level is still not fast enough, even in countries like Botswana (see above) where 90-90-90 has almost been reached.  Renewed enthusiasm for primary prevention has also followed key trials of biomedical prevention tools including voluntary medical male circumcision and ARV-based prevention.  It is all too easy for us to forget the crucial role that condoms have played from the early days of the epidemic.  More recently, with HIV seen as a less terrifying infection, many programmes suffer from “condom fatigue”.  So it is good to see papers on the key importance of condoms as well as perspectives on how they are perceived by young men.

The magic of ARVs does not end with treatment.  We are finally moving to wider use of pre-exposure prophylaxis (PrEP).  There is no doubt that PrEP works when taken, but there are still plenty of questions for policy-makers about how to adopt it whole-heartedly into their national strategic plans and for financiers about how to pay for it.  Papers this month cover a range of experiences with PrEP from the US, where the huge majority of PrEP users still live, to Europe and Australia, where policies are finally moving towards wider use.  Long acting PrEP remains a key objective for many, as it might improve regular adherence, which has proved the Achilles’ heel of oral and topical PrEP in several of the large studies.

One of the ways to make PrEP most cost-effective is to ensure that it is available to people who are most likely to acquire HIV.  So the hope continues that phylogenetic analyses will allow more sophisticated understanding of the dynamics of the multiple overlapping networks of HIV transmission in communities.  Papers this month cover Australia and the PANGEA consortium of African research sites along with a cautionary comment about establishing the ethical framework for such studies, particularly among populations who are already subject to discrimination and criminalization.

When used correctly and consistently, condoms are highly effective not only to prevent HIV but also to prevent pregnancy and to prevent sexually transmitted infections.  Stover and colleagues have tried to capture all three benefits in one model.  They explore three potential scenarios for condom programming between now and 2030 in 81 countries that are priorities for family planning or HIV programmers or both.  The benefits of greater investment in condoms are huge.  In their most optimistic scenario, the authors suggest that if the entire gap between people who would like to use condoms and people who currently use them was filled (almost 11 billion condoms over the period), this could prevent up to 400 million unwanted pregnancies; 16.8 million new HIV infections and more than 700 million sexually transmitted infections.  The costs are quite modest, and at $115 per DALY averted this is an investment that everyone should support.  There are of course limitations in such a broad brush model, but it provides an excellent starting point.

The challenges in provision of condoms to young people go well beyond the cost and effectiveness considerations that underpin the previous analysis.  In an interesting qualitative study in South Africa, de Bruin and Panday-Soobrayan report their findings from focus group discussions with learners in 33 public schools.  Most of the learners were not in favour of provision of condoms at school, although they were keen on more youth friendly sexual and reproductive health and rights services within the public sector.  Many thought that provision of condoms would lead to earlier and more frequent sexual contacts, despite considerable experience showing that this is not the case in other settings.

Multiple trials have shown that PrEP is extremely effective when it is used consistently and correctly.  Many countries in all continents are now beginning to work out where it fits within their combination prevention package.  To date, the large majority of PrEP users are in the United States of America (USA), where more than 140 000 people have started.  It is much harder to measure how many are still taking it regularly.  Patel and colleagues analysed utilization at three months after the initial prescription of PrEP in three major PrEP clinics in three states in the USA.  18% of the 201 people (90% male) seen at baseline did not use their PrEP and this was strongly predicted by insurance status, with around a four-fold risk of dropping out among those who were not insured.  Although the numbers are small, this is an important study.  The authors suggest that increased insurance cover might make PrEP have a greater impact.  More broadly it raises the challenge that PrEP is often needed most by people least able to access it.  This will be a real challenge in countries where people most at risk, such as gay men and other men who have sex with men and sex workers, are criminalized or discriminated against in many health care settings.

In Australia, PrEP has been provided through large demonstration projects while awaiting decisions about how to include it in routine practice.  Lal and colleagues report results from 114 (one transgender woman, the rest male) people taking PrEP in the Victorian PrEP Demonstration project.  Participants have to pay an equivalent of an insurance co-payment, in order to make the situation more like the “real world”.  The participants were recruited because they were at high risk of HIV engaging in condomless anal sex with partners who were known to be living with HIV or of unknown status.  Adherence to PrEP was excellent as measured by a variety of reported and biological measures.  They observed one seroconversion in a man with exposure two weeks before starting PrEP who was already in the process of seroconverting and whose virus was found to be resistant to emtricitabine.  The only other seroconversion occurred in someone who had not yet started PrEP.  The authors found a substantial increase in rates of gonorrhoea and chlamydia once participants were “stable” on PrEP after three months.  There was also a significant reduction in condom use with both regular and casual partners.  This is one of the first studies to document important risk compensation among PrEP users.  Of course, preventing HIV is a huge benefit that generally outweighs the harms of additional treatment for sexually transmitted infections.  However, the study emphasizes the importance of enhancing sexual health services alongside PrEP and reminds us that people most at risk of HIV are also at high risk of other infections (and also of pregnancy in the context of heterosexual transmission.)  If PrEP is integrated within a broad sexual health service, there could be considerable synergistic benefits.

Gay men and men who have sex with men who enrolled in the PrEP demonstration project in Amsterdam also had high concomitant rates of hepatitis C virus (HCV).  Hoorenborg and colleagues found that around 5% of the 375 men enrolled in the project were co-infected.  The HCV found among these men were genetically similar to those circulating in the population of gay men and other men who have sex with men living with HIV, and more distinct from HCV from other risk groups.  This is good evidence that HCV and HIV both circulate in this population, and emphasizes once again the need for more integrated services, including hepatitis screening.

The ÉCLAIR study is a phase 2a trial of cabotegravir injections in healthy HIV-negative male volunteers.  As noted, adherence is a major challenge in many PrEP trials; although notably less of a problem when people choose to take PrEP in demonstration projects.  It is hoped that cabotegravir could be the first long acting PrEP.  Markowitz and colleagues presented the results of this study at CROI 2017.  The authors point out that although the injections are painful, many men stated that they would be happy to continue if the injections were effective.  No serious safety challenges emerged. The pharmacokinetics suggests that a dose given more frequently will be needed – and subsequent trials will use a two monthly regimen. 

One group for whom PrEP has been recommended by WHO for some years are serodiscordant couples (SDCs).  The Partners PrEP study, which forms one of the cornerstones for the evidence that PrEP works for both men and women, was conducted in SDCs.  The idea is to protect the HIV-negative partner from infection until such time as the partner living with HIV has been on ART consistently and suppressed their viral load.  So a study from the Centers for Disease Control USA is relevant to discussions of PrEP.  Crepaz and colleagues found that around 6000 new HIV infections occur each year in the USA among men and women having heterosexual sex and are aware that their partner is living with HIV.  They point out that viral suppression is achieved by only around 50% of heterosexuals living with HIV and that an additional proportion does not know their HIV status.  So the importance of HIV testing, and of focusing efforts on serodiscordant couples is clear.  Such efforts include both improving HIV treatment effectiveness, and providing a range of prevention choices including PrEP until viral suppression is achieved.

While the study above used traditional epidemiological surveillance reports, phylogenetics may provide additional insights into the dynamics of transmission.  In Australia, where notifications with HIV are rising steadily,  Castley and colleagues have examined the sequence data from almost 5000 viruses collected across the country from 2005-2012.  This sample is drawn from around 1200 new HIV infections per year (and around 27 000 people living with HIV).  The sample is not random, but reflects samples that were sent for sequencing to determine drug resistance.  Around one quarter of sequences are found in tight clusters (pairs, triplets or more) with other sequences, making it likely that they are closely connected by transmission.  Of course, all HIV sequences have been transmitted, so a longer time period and complete sampling would be expected to give a much higher proportion in clusters.  Indeed the more recent samples are around twice as likely to be in clusters as those collected at the start of the time period. Nonetheless, the large sample and the time period of collection allows some clear observations to be made.  In all states, the proportion of non-B subtypes is increasing, which must relate to travel and migration to and from Asia and Africa.  There is little evidence that the C subtypes (originally from Africa) are found in all male clusters suggesting little spill over into the community of gay men and other men having sex with men.  Larger clusters are more common among younger, all male networks. Like most molecular epidemiological studies, there are a small number of large clusters which represent highly active transmission.  These clusters are also most likely to be all male.  Taken together, the results suggest that the steady rise in notifications in Australia is probably due to increasing migration and travel and to ongoing active transmission networks among young gay men.  The challenge is to turn this sort of analysis into clear policy recommendations that can improve HIV prevention.

UNAIDS joined an interesting meeting on the ethics of phylogenetic studies in Africa organised by the PANGEA consortium.  Many of the issues discussed are also covered in a comment by Cohen on the importance of thinking through the risks inherent in these studies.  A key issue is to ensure that systems are reinforced to monitor any unexpected harms and to establish mitigation strategies to minimize them.  The challenges are not necessarily different to traditional epidemiological studies which may highlight networks and locations of groups that are criminalized or discriminated against.  In community consultations, prior to agreeing to go forward with phylogenetic studies, some potential participants even say that they would be keen to “know who infected them” in order to punish them.  This is clearly NOT the aim of such studies and emphasizes the importance of clear information about the limitations of the techniques which cannot usually rule out the possibility of additional links in the transmission chain.  Issues of anonymised information and what to do if clinically relevant results such as drug resistance mutations are uncovered as incidental findings also need to be discussed.

Furthermore, Ratmann and colleagues, reporting on the first 4000 sequences from the PANGEA consortium (largely from the Rakai project in Uganda), also emphasize some of the technical challenges that may lead to erroneous results in creating phylogenies.  There is little doubt that as the cost of sequencing falls and as the technologies and software become increasingly straightforward, we will see more and more studies of sequence data.  It is likely that analysis of these data will lead to more nuanced approaches to HIV prevention, particularly as the overall incidence falls, and sharper tools are needed to dissect the pathways of ongoing transmission.

The case for investing in the male condom

Stover J, Rosen JE, Carvalho MN, Korenromp EL, Friedman HS, Cogan M, Deperthes B. PLoS One. 2017 May 16;12(5):e0177108. doi: 10.1371/journal.pone.0177108. eCollection 2017.

When used correctly and consistently, the male condom offers triple protection from unintended pregnancy and the transmission of sexually transmitted infections (STIs) and human immunodeficiency virus (HIV). However, with health funding levels stagnant or falling, it is important to understand the cost and health impact associated with prevention technologies. This study is one of the first to attempt to quantify the cost and combined health impact of condom use, as a means to prevent unwanted pregnancy and to prevent transmission of STIs including HIV. This paper describes the analysis to make the case for investment in the male condom, including the cost, impact and cost-effectiveness by three scenarios (low in which 2015 condom use levels are maintained; medium in which condom use trends are used to predict condom use from 2016-2030; and high in which condom use is scaled up, as part of a package of contraceptives, to meet all unmet need for family planning by 2030 and to 90% for HIV and STI prevention by 2016) for 81 countries from 2015-2030. An annual gap between current and desired use of 10.9 billion condoms was identified (4.6 billion for family planning and 6.3 billion for HIV and STIs). Under a high scenario that completely reduces that gap between current and desired use of 10.9 billion condoms, we found that by 2030 countries could avert 240 million DALYs. The additional cost in the 81 countries through 2030 under the medium scenario is $1.9 billion, and $27.5 billion under the high scenario. Through 2030, the cost-effectiveness ratios are $304 per DALY averted for the medium and $115 per DALY averted for the high scenario. Under the three scenarios described above, our analysis demonstrates the cost-effectiveness of the male condom in preventing unintended pregnancy and HIV and STI new infections. Policy makers should increase budgets for condom programming to increase the health return on investment of scarce resources.

Abstract  Full-text [free] access

Learners' perspectives on the provision of condoms in South African public schools.

de Bruin WE, Panday-Soobrayan S. AIDS care. 2017 May 16:1-4. doi: 10.1080/09540121.2017.1327647. [Epub ahead of print]

A stubborn health challenge for learners in South African public schools concerns sexual and reproductive health and rights (SRHR). In 2015, the Department of Basic Education (DBE) proposed the provision of condoms and SRHR-services to learners in schools. This study aimed to contribute to the finalisation and implementation of DBE's policy by exploring learners' perspectives on the provision of condoms and SRHR-services in schools. Sixteen focus group discussions were conducted with learners (n = 116) from 33 public schools, to assess their attitudes, social influences, and needs and desires regarding condom provision and SRHR-services in schools. The majority of learners did not support condom provision in schools as they feared that it may increase sexual activity. Contrarily, they supported the provision of other SRHR-services as clinics fail to offer youth-friendly services. Learners' sexual behaviour and access to SRHR-services are strongly determined by their social environment, including traditional norms and values, and social-pressure from peers and adults. Learners' most pressing needs and desires to access condoms and SRHR-services in school concerned respect, privacy and confidentiality of such service provision. Implementation of DBE's policy must be preceded by an evidence-informed advocacy campaign to debunk myths about the risk of increased sexual activity, to advocate for why such services are needed, to shift societal norms towards open discussion of adolescent SRHR and to grapple with the juxtaposition of being legally empowered but socially inhibited to protect oneself from HIV, STIs and early pregnancy. Provision of condoms and other SRHR-services in schools must be sensitive to learners' privacy and confidentiality to minimise stigma and discrimination.

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Impact of insurance coverage on utilization of pre-exposure prophylaxis for HIV prevention

Patel RR, Mena L, Nunn A, McBride T, Harrison LC, Oldenburg CE, Liu J, Mayer KH, Chan PA.  PLoS One. 2017 May 30;12(5):e0178737 . doi: 10.1371/journal.pone.0178737. eCollection 2017.

Pre-exposure prophylaxis (PrEP) can reduce U.S. HIV incidence. We assessed insurance coverage and its association with PrEP utilization. We reviewed patient data at three PrEP clinics (Jackson, Mississippi; St. Louis, Missouri; Providence, Rhode Island) from 2014-2015. The outcome, PrEP utilization, was defined as patient PrEP use at three months. Multivariable logistic regression was performed to determine the association between insurance coverage and PrEP utilization. Of 201 patients (Jackson: 34%; St. Louis: 28%; Providence: 28%), 91% were male, 51% were White, median age was 29 years, and 21% were uninsured; 82% of patients reported taking PrEP at three months. Insurance coverage was significantly associated with PrEP utilization. After adjusting for Medicaid-expansion and individual socio-demographics, insured patients were four times as likely to use PrEP services compared to the uninsured (OR: 4.49, 95% CI: 1.68-12.01; p = 0.003). Disparities in insurance coverage are important considerations in implementation programs and may impede PrEP utilization.

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Medication adherence, condom use and sexually transmitted infections in Australian PrEP users: interim results from the Victorian PrEP demonstration project

Lal L, Audsley J, Murphy D, Fairley CK, Stoove M, Roth N, Moore R, Tee BK, Puratmaja N, Anderson PL, Leslie D, Grant RM, De Wit J, Wright E; VicPrEP Study Team. AIDS. 2017 May 1 doi: 10.1097/QAD.0000000000001519. [Epub ahead of print]

Objective: HIV Pre-exposure prophylaxis (PrEP) decreases risk of HIV acquisition however its efficacy is closely dependent on adherence. There is also concern that the preventive effect of PrEP may be offset by risk compensation, notably an increase in condomless anal sex.

Design: Multi-site, open-label demonstration study that recruited people at current or recent risk of HIV infection in Melbourne, Australia.

Methods: Participants were recruited from three general practice clinics and one sexual health clinic in Melbourne and consented to take daily tenofovir/emtricitabine for 30 months. Sexual practice data, HIV and sexually transmitted infection (STI) test results were collected at baseline and 3-monthly during follow up. PrEP adherence was evaluated by self-report at clinical visits, online surveys, refill-based assessments and dried blood spot (DBS) testing. We present a 12-month interim analysis.

Results: 114 people were recruited. We observed a significant decline in condom use which occurred concomitantly with a significant increase in STIs over the first 12 months of PrEP. Incidence (per 100PY) of any STI was 43.2 and 119.8 at m0-3 and M3-12, respectively (IRR 2.77 (1.52, 5.56)). Adherence to PrEP medication was high by all measures, including six month TDF-FTC levels in DBS.

Conclusions: We found significant reduction in condom use and an increase STIs over the first 12 months of follow-up. High medication adherence rates coupled with a decline in condom use and a rise in STIs, suggests that prevention, early detection and treatment of STIs is a chief research priority in the current era of HIV PrEP.

Abstract

Men who have sex with men starting pre-exposure prophylaxis (PrEP) are at risk of HCV infection: evidence from the Amsterdam PrEP study

Hoornenborg E, Achterbergh RC, Van Der Loeff MF, Davidovich U, Hogewoning A, de Vries HJ, Schinkel J, Prins M, Laar TJWV; Amsterdam PrEP Project team in the HIV Transmission Elimination AMsterdam Initiative, MOSAIC study group. AIDS. 2017 May 1. doi: 10.1097/QAD.0000000000001522. [Epub ahead of print].

Objectives and Design: Hepatitis C virus (HCV) has been recognised as an emerging sexually transmitted infection (STI) among HIV-positive men who have sex with men (MSM). However, HIV-negative MSM at high risk for HIV might also be at increased risk for HCV. We studied the HCV prevalence in HIV-negative MSM who start pre-exposure prophylaxis (PrEP) in Amsterdam. Phylogenetic analysis was used to compare HCV strains obtained from HIV-negative and HIV-positive MSM.

Methods: At enrolment in the Amsterdam PrEP (AMPrEP) demonstration project, HIV-negative MSM were tested for the presence of HCV antibodies and HCV RNA. If positive for HCV RNA, an HCV NS5B gene fragment (709 bp) was sequenced and compared with HCV isolates from HIV-positive MSM (n = 223) and risk groups other than MSM (n = 153), using phylogenetic analysis.

Results: Of 375 HIV-negative MSM enrolled in AMPrEP, 18 (4.8%, 95%CI 2.9%-7.5%) of participants were anti-HCV and/or HCV RNA positive at enrolment; 15/18 (83%) had detectable HCV RNA. HCV genotyping showed genotype 1a (73%), 4d (20%) and 2b (7%). All HCV-positive MSM starting PrEP were part of MSM-specific HCV clusters containing MSM with and without HIV.

Conclusion: HCV prevalence among HIV-negative MSM who started PrEP was higher than previously reported. All HIV-negative HCV-positive MSM were infected with HCV strains already circulating among HIV-positive MSM. The increasing overlap between sexual networks of HIV-positive and HIV-negative MSM might result in an expanding HCV-epidemic irrespective of HIV-status. Hence, routine HCV testing should be offered to MSM at high risk for HIV, especially for those enrolling in PrEP programs.

Abstract

Safety and tolerability of long-acting cabotegravir injections in HIV-uninfected men (ECLAIR): a multicentre, double-blind, randomised, placebo-controlled, phase 2a trial.

Markowitz M, Frank I, Grant RM, Mayer KH, Elion R, Goldstein D, Fisher C, Sobieszczyk ME, Gallant JE, Van Tieu H, Weinberg W, . Margolis DA, Hudson KJ, Stancil BS, Ford SL, Patel P, Gould E, Rinehart AR, Smith KY, Spreen WR. Lancet HIV. 2017 May 22. pii: S2352-3018(17)30068-1. doi: 10.1016/S2352-3018(17)30068-1. [Epub ahead of print]

Background: Cabotegravir (GSK1265744) is an HIV-1 integrase strand transfer inhibitor with potent antiviral activity and a long half-life when administered by injection that prevented simian-HIV infection upon repeat intrarectal challenge in male macaques. We aimed to assess the safety, tolerability, and pharmacokinetics of long-acting cabotegravir injections in healthy men not at high risk of HIV-1 infection.

Methods: We did this multicentre, double-blind, randomised, placebo-controlled, phase 2a trial at ten sites in the USA. Healthy men (aged 18-65 years) deemed not at high risk of acquiring HIV-1 at screening were randomly assigned (5:1), via computer-generated central randomisation schedules, to receive cabotegravir or placebo. Participants received oral cabotegravir 30 mg tablets or matching placebo once daily during a 4 week oral lead-in phase, followed by a 1 week washout period and, after safety assessment, three intramuscular injections of long-acting cabotegravir 800 mg or saline placebo at 12 week intervals. Study site staff and participants were masked to treatment assignment from enrolment through week 41 (time of the last injection). The primary endpoint was safety and tolerability from the first injection (week 5) to 12 weeks after the last injection. We did analysis in the safety population, defined as all individuals enrolled in the study who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov identifier, NCT02076178.

Findings: Between March 27, 2014, and Feb 23, 2016, we randomly assigned 127 participants to receive cabotegravir (n=106) or placebo (n=21); 126 (99%) participants comprised the safety population. Most participants were men who have sex with men (MSM; n=106 [83%]) and white (n=71 [56%]). 87 (82%) participants in the cabotegravir group and 20 (95%) participants in the placebo group completed the injection phase. Adverse events (n=7 [7%]) and injection intolerability (n=4 [4%]) were the main reasons for withdrawal in the cabotegravir group. The frequency of grade 2 or higher adverse events was higher in participants in the long-acting cabotegravir group (n=75 [80%]) than in those in the placebo group (n=10 [48%]; p=0·0049), mostly due to injection-site pain (n=55 [59%]). No significant differences were noted in concomitant medications, laboratory abnormalities, electrocardiogram, and vital sign assessments. Geometric mean trough plasma concentrations were 0·302 μg/mL (95% CI 0·237-0·385), 0·331 μg/mL (0·253-0·435), and 0·387 μg/mL (0·296-0·505) for injections one, two, and three, respectively, indicating lower than predicted exposure. The geometric mean apparent terminal phase half-life estimated after the third injection was 40 days. Two (2%) MSM acquired HIV-1 infection, one in the placebo group during the injection phase and one in the cabotegravir group 24 weeks after the final injection when cabotegravir exposure was well below the protein-binding-adjusted 90% inhibitory concentration.

Interpretation: Despite high incidence of transient, mild-to-moderate injection-site reactions, long-acting cabotegravir was well tolerated with an acceptable safety profile. Pharmacokinetic data suggest that 800 mg administered every 12 weeks is a suboptimal regimen; alternative dosing strategies are being investigated. Our findings support further investigation of long-acting injectable cabotegravir as an alternative to orally administered pre-exposure prophylaxis regimens.

Abstract

Examination of HIV infection through heterosexual contact with partners who are known to be HIV infected in the United States, 2010-2015

Crepaz N, Dong B, Chen M, Hall I. AIDS. 2017 Jul 17;31(11):1641-1644. doi: 10.1097/QAD.0000000000001526.

Using data from the National HIV Surveillance System, we examined HIV infections diagnosed between 2010 and 2015 attributed to heterosexual contact with partners previously known to be HIV infected. More than four in 10 HIV infections among heterosexual males and five in 10 HIV infections among heterosexual women were attributed to this group. Findings may inform the prioritization of prevention and care efforts and resource allocation modeling for reducing new HIV infection among discordant partnerships.

Abstract

A national study of the molecular epidemiology of HIV-1 in Australia 2005–2012

Castley A, Sawleshwarkar S, Varma R, Herring B, Thapa K, Dwyer D, Chibo D, Nguyen N, Hawke K, Ratcliff R, Garsia R, Kelleher A, Nolan D; Australian Molecular Epidemiology Network-HIV (AMEN-HIV).. PLoS One. 2017 May 10;12(5):e0170601. doi: 10.1371/journal.pone.0170601. eCollection 2017.

Introduction: Rates of new HIV-1 diagnoses are increasing in Australia, with evidence of an increasing proportion of non-B HIV-1 subtypes reflecting a growing impact of migration and travel. The present study aims to define HIV-1 subtype diversity patterns and investigate possible HIV-1 transmission networks within Australia.

Methods: The Australian Molecular Epidemiology Network (AMEN) HIV collaborating sites in Western Australia, South Australia, Victoria, Queensland and western Sydney (New South Wales), provided baseline HIV-1 partial pol sequence, age and gender information for 4873 patients who had genotypes performed during 2005-2012. HIV-1 phylogenetic analyses utilised MEGA V6, with a stringent classification of transmission pairs or clusters (bootstrap ≥98%, genetic distance ≤1.5% from at least one other sequence in the cluster).

Results: HIV-1 subtype B represented 74.5% of the 4873 sequences (WA 59%, SA 68.4%, w-Syd 73.8%, Vic 75.6%, Qld 82.1%), with similar proportion of transmission pairs and clusters found in the B and non-B cohorts (23% vs 24.5% of sequences, p = 0.3). Significantly more subtype B clusters were comprised of ≥3 sequences compared with non-B clusters (45.0% vs 24.0%, p = 0.021) and significantly more subtype B pairs and clusters were male-only (88% compared to 53% CRF01_AE and 17% subtype C clusters). Factors associated with being in a cluster of any size included; being sequenced in a more recent time period (p<0.001), being younger (p<0.001), being male (p = 0.023) and having a B subtype (p = 0.02). Being in a larger cluster (>3) was associated with being sequenced in a more recent time period (p = 0.05) and being male (p = 0.008).

Conclusion: This nationwide HIV-1 study of 4873 patient sequences highlights the increased diversity of HIV-1 subtypes within the Australian epidemic, as well as differences in transmission networks associated with these HIV-1 subtypes. These findings provide epidemiological insights not readily available using standard surveillance methods and can inform the development of effective public health strategies in the current paradigm of HIV prevention in Australia

Abstract  Full-text [free] access

HIV-1 full-genome phylogenetics of generalized epidemics in sub-Saharan Africa: impact of missing nucleotide characters in next-generation sequences.

Ratmann O, Wymant C, Colijn C, Danaviah S, Essex M, Frost SD, Gall A, Gaiseitsiwe S, Grabowski M, Gray R, Guindon S, von Haeseler A, Kaleebu P, Kendall M, Kozlov A, Manasa J, Minh BQ, Moyo S, Novitsky V, Nsubuga R, Pillay S, Quinn TC, Serwadda D, Ssemwanga D, Stamatakis A, Trifinopoulos J, Wawer M, Leigh Brown A, de Oliveira T, Kellam P, Pillay D, Fraser C.. AIDS Res Hum Retroviruses. 2017 May 25. doi: 10.1089/AID.2017.0061. [Epub ahead of print].

To characterize HIV-1 transmission dynamics in regions where the burden of HIV-1 is greatest, the 'Phylogenetics and Networks for Generalised HIV Epidemics in Africa' consortium (PANGEA-HIV) is sequencing full-genome viral isolates from across sub-Saharan Africa. We report the first 3985 PANGEA-HIV consensus sequences from four cohort sites (Rakai Community Cohort Study, n=2833; MRC/UVRI Uganda, n=701; Mochudi Prevention Project, n=359; Africa Health Research Institute Resistance Cohort, n=92). Next-generation sequencing success rates varied: more than 80% of the viral genome from the gag to the nef genes could be determined for all sequences from South Africa, 75% of sequences from Mochudi, 60% of sequences from MRC/UVRI Uganda, and 22% of sequences from Rakai. Partial sequencing failure was primarily associated with low viral load, increased for amplicons closer to the 3' end of the genome, was not associated with subtype diversity except HIV-1 subtype D, and remained significantly associated with sampling location after controlling for other factors. We assessed the impact of the missing data patterns in PANGEA-HIV sequences on phylogeny reconstruction in simulations. We found a threshold in terms of taxon sampling below which the patchy distribution of missing characters in next-generation sequences has an excess negative impact on the accuracy of HIV-1 phylogeny reconstruction, which is attributable to tree reconstruction artifacts that accumulate when branches in viral trees are long. The large number of PANGEA-HIV sequences provides unprecedented opportunities for evaluating HIV-1 transmission dynamics across sub-Saharan Africa and identifying prevention opportunities. Molecular epidemiological analyses of these data must proceed cautiously because sequence sampling remains below the identified threshold and a considerable negative impact of missing characters on phylogeny reconstruction is expected.

Abstract  Full-text [free] access

 

Africa, Asia, Europe, Northern America, Oceania
Afghanistan, Angola, Australia, Azerbaijan, Bangladesh, Benin, Bolivia, Botswana, Brazil, Burkina Faso, Burundi, Cambodia, Cameroon, Central African Republic, Chad, China, Comoros, Congo, Côte d'Ivoire, Democratic People's Republic of Korea, Democratic Republic of the Congo, Djibouti, Egypt, Equatorial Guinea, Eritrea, Ethiopia, Gabon, Gambia, Ghana, Guatemala, Guinea, Guinea-Bissau, Haiti, India, Indonesia, Iran (Islamic Republic of), Iraq, Jamaica, Kenya, Kyrgyzstan, Lao People's Democratic Republic, Lesotho, Liberia, Madagascar, Malawi, Mauritania, Mexico, Morocco, Mozambique, Myanmar, Namibia, Nepal, Netherlands, Niger, Nigeria, Pakistan, Papua New Guinea, Peru, Philippines, Russian Federation, Rwanda, Sao Tome and Principe, Senegal, Sierra Leone, Solomon Islands, Somalia, South Africa, South Sudan, Sudan, Swaziland, Tajikistan, Togo, Turkmenistan, Uganda, Ukraine, United Republic of Tanzania, United States of America, Uzbekistan, Viet Nam, Yemen, Zambia, Zimbabwe
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Do people take more risks when they know they are “protected”?

Editor’s notes: Risk compensation is a phenomenon well known to behavioural scientists.  When car-drivers wear seat belts, they may drive faster because they feel safer.  Despite some evidence to the contrary, a commonly voiced concern about PrEP is that people who take it will take more risks with their sexual health.  So it is reassuring to see two studies that examine partnership dynamics and condom use among people on antiretroviral therapy (ART) and among men who have been circumcised.

McGrath and Grapsa studied relationships and reported sexual behaviour among 632 people living with HIV and enrolled in an ongoing cohort study in KwaZulu Natal during the period, when only those with lower CD4 counts were eligible for ART.  They interviewed participants every 6 months, in person or by phone, for up to 36 months. This was in order to follow which relationships were formed and which dissolved and to determine how often participants were having sex and how often they were having condomless sex.  The authors clearly document (perhaps unsurprisingly) that many relationships dissolved (192 out of 565 partnerships at some time in the study) or formed (161 out of 132 individuals who were single at some time in the study).  Partnerships dissolved more frequently among people who had only been in a relationship for less than a year; people who drank alcohol and in partnerships where the participant described the relationship as being of “poor quality”.  New partners were more common for people who were younger; had not disclosed their HIV status; drank alcohol or reported having more than 3 lifetime sexual partners at the start of the study.  There was no suggestion that being on ART affected the likelihood of forming or leaving a partnership. This is important for mathematical models of HIV transmission in the era of universal treatment policies.

Sex was more frequently reported in people in more recent partnerships; people who knew their partners’ HIV status and among people who wanted more children.  Sex was less frequent and more often protected by a condom among people who did not trust their partner’s fidelity or where the couple did not live together.  People who were eligible for ART tended to use condoms more regularly during the follow up than people who were still “waiting for treatment”.  Other factors associated with more condom use included more equitable gender norms; HIV status disclosure and not living together.  Condoms were used less often in partnerships that included alcohol, partner violence or where the couple wanted more children.  Overall, the authors estimated that around 5.5% of sex acts were “risky” (that is unprotected with a partner who was HIV negative or where the HIV status was unknown) among those eligible for ART and around 13.2% for those not yet eligible.  Around one third of the participants reported having condomless sex at least once, but in almost half of these, they knew that their partner was also living with HIV.

Taking effective ART regularly means that people living with HIV are no longer infectious once their viral load is reliably suppressed.  However, it is clear that not everyone achieves viral load suppression.  This study provides useful prospective information about partnerships and sexual behaviour in the context of very high HIV transmission.  It is reassuring in showing that on the whole, sexual behaviour seems less risky, even before taking the huge effect of ART into account.  There was no evidence to suggest that risk compensation occurred in those offered ART.

In order to maximize the preventive benefits of ART, it is essential that people are supported to take their medicines regularly.  In crowded urban facilities in high prevalence settings, long waiting times, and challenges in stock management mean that people living with HIV have to be quite determined to negotiate the systems and minimize treatment interruptions.  Although it is national policy in Zambia and some other highly burden countries to provide three-month supplies to people whose HIV is stable and well controlled, McCarthy and colleagues found that less than half of people who should be getting three-month refills were doing so.  They instituted a cluster randomized trial of a quality improvement programme across 16 health facilities in Lusaka.  Each clinic follows around 4-5000 people on ART of whom around 1000 are stable and eligible for three-monthly refills.  The key element was for a focal point in each of the eight intervention clinics to be designated as a quality improvement officer and to be supported with materials to plan and monitor drug stocks and support local changes.  This is to ensure that stable patients did not have to spend long periods in the clinic or go away with less medicine than they needed.  The District Health Management team supported the quality improvement officers when the challenges identified were beyond their responsibilities or capabilities to change.  The programme led to a statistically significant 15% increase in the proportion of appropriate people receiving three-month refills (reaching 69%).  On average the intervention clinics became less congested (35 fewer visits per day compared to the controls) and had shorter waiting times (20 minutes shorter per visit) although these results did not reach statistical significance.

Another study exploring risk compensation was carried out by Shi and colleagues.  The authors used data from recent demographic and health surveys from countries that are part of the scale-up of voluntary medical male circumcision in East and Southern Africa.  Circumcision was most prevalent in Kenya (88% and 94% before and after 2008, when scale-up was pushed) and lowest in Zimbabwe (12% and 11% respectively). Overall condom usage increased in both circumcised and uncircumcised men.  Reports of condom use at last sex averaged around 15-16% before 2008 across the ten countries surveyed and rose to around 21% after 2008.  There was no suggestion that men who were circumcised were any less likely to use a condom than men who were not.  Similarly, there was no suggestion that circumcised men were more likely to have non-cohabiting partners.

The study also highlights big differences between countries, and between different groups.  Even among men with no regular partner, the use of a condom at last sex is often less than 50% with differences as expected also seen by age, education, religion and residence.  Promoting circumcision remains a hugely cost-effective approach to HIV prevention.  This study therefore provides important reassurance that the possibility of risk compensation is not serious for circumcision programmes.  Nonetheless we still have plenty of work to do to reach our targets and prevent HIV.

Does ART change partnership dynamics and HIV risk behaviours among PLWH? A cohort study in KwaZulu-Natal, South Africa.

McGrath N, Grapsa E. AIDS. 2017 Apr 10. doi: 10.1097/QAD.0000000000001502. [Epub ahead of print]

Objective: We explore the impact of antiretroviral therapy (ART) on partnership acquisition and dissolution rates and changes in sexual behaviours among HIV-infected adults.

Design: Using detailed longitudinal data from a prospective cohort of HIV-infected adults with CD4<200 cell/ml (ART-eligible) or CD4>500 cell/ml (pre-ART) conducted in rural KwaZulu-Natal, South Africa, 2009-2012.

Methods: Partnership acquisition and dissolution are explored through survival analysis methods, while generalized linear models were fitted for the sexual behaviour outcomes with interaction terms to allow the association with ART to vary over time. Throughout, the primary comparison of interest for each outcome is differences between the two ART groups.

Results: ART is not associated with partner acquisition or relationship dissolution. During follow-up, the two ART groups do not differ in the odds of being sexually active nor the number of sex acts, while the odds of unprotected sex are significantly lower for partnerships of ART-eligible participants, a0R = 0.26, 95%CI(0.15,0.43). Relationship-level characteristics including cohabitation status and wanting more children with that partner are associated with higher odds and increased frequency of sexual activity, increased odds of unprotected sex; while living with partner, higher relationship quality and longer relationship duration are associated with lower risk of partnership dissolution.

Conclusion: Being on ART was not associated with increased sexual risk behaviours, a reassuring finding given the WHO recommends ART initiation upon HIV diagnosis. The importance of relationship-level characteristics provides evidence that HIV care services should offer routine support for HIV disclosure and sexual risk reduction, and promotion of couples-testing and positive couple-relationships.

Abstract access 

Quality improvement intervention to increase adherence to ART prescription policy at HIV treatment clinics in Lusaka, Zambia: A cluster randomized trial.

McCarthy EA, Subramaniam HL, Prust ML, Prescott MR, Mpasela F, Mwango A, Namonje L, Moyo C, Chibuye B, van den Broek JW, Hehman L, Moberley S. PLoS One. 2017 Apr 18;12(4):e0175534. doi: 10.1371/journal.pone.0175534. eCollection 2017.

Introduction: In urban areas, crowded HIV treatment facilities with long patient wait times can deter patients from attending their clinical appointments and picking up their medications, ultimately disrupting patient care and compromising patient retention and adherence.

Methods: Formative research at eight facilities in Lusaka revealed that only 46% of stable HIV treatment patients were receiving a three-month refill supply of antiretroviral drugs, despite it being national policy for stable adult patients. We designed a quality improvement intervention to improve the operationalization of this policy. We conducted a cluster-randomized controlled trial in sixteen facilities in Lusaka with the primary objective of examining the intervention's impact on the proportion of stable patients receiving three-month refills. The secondary objective was examining whether the quality improvement intervention reduced facility congestion measured through two proxy indicators: daily volume of clinic visits and average clinic wait times for services.

Results: The mean change in the proportion of three-month refills among control facilities from baseline to endline was 10% (from 38% to 48%), compared to a 25% mean change (an increase from 44% to 69%) among intervention facilities. This represents a significant 15% mean difference (95% CI: 2%-29%; P = 0.03) in the change in proportion of patients receiving three-month refills. On average, control facilities had 15 more visits per day in the endline than in the baseline, while intervention facilities had 20 fewer visits per day in endline than in baseline, a mean difference of 35 fewer visits per day (P = 0.1). The change in the mean facility total wait time for intervention facilities dropped 19 minutes between baseline and endline when compared to control facilities (95% CI: -10.2-48.5; P = 0.2).

Conclusion: A more patient-centred service delivery schedule of three-month prescription refills for stable patients is viable. We encourage the expansion of this sustainable intervention in Zambia's urban clinics.

Abstract Full-text [free] access

Evidence that promotion of male circumcision did not lead to sexual risk compensation in prioritized sub-Saharan countries.

Shi CF, Li M, Dushoff J. PLoS One. 2017 Apr 25;12(4):e0175928. doi: 10.1371/journal.pone.0175928. eCollection 2017.

Background: WHO and UNAIDS prioritized 14 eastern and southern African countries with high HIV and low male circumcision prevalence for a voluntary medical male circumcision (VMMC) scale-up in 2007. Because circumcision provides only partial protection against HIV infection to men, the issue of possible risk compensation in response to VMMC campaigns is of particular concern. In this study, we looked at population-level survey data from the countries prioritized by WHO for a VMMC scale-up. We compared the difference in sexual risk behaviours (SRB) between circumcised and uncircumcised men before and after the WHO's official VMMC promotion.

Materials and Methods: Ten countries (Kenya, Lesotho, Malawi, Mozambique, Namibia, Rwanda, Tanzania, Uganda, Zambia and Zimbabwe) participating in the WHO's VMMC scale-up had available data from the Demographic and Health Surveys (DHS). We used cumulative-link mixed models to investigate interactions between survey period and circumcision status in predicting SRB, in order to evaluate whether the difference between the behavior of the two groups changed before and after the scale-up, while controlling for socio-demographic and knowledge-related covariates. The main responses were condom use at last sex and number of non-cohabiting sexual partners, both in the last 12 months.

Results: There was little change in condom use by circumcised men relative to uncircumcised men from before the VMMC scale up to after the scale up. The relative odds ratio is 1.06 (95% CI, 0.95-1.18; interaction P = 0.310). Similarly, there was little change in the number of non-cohabiting partners in circumcised men (relative to uncircumcised men): the relative odds ratio of increasing the number of partners is 0.95 (95% CI, 0.86-1.05; interaction P = 0.319). Age, religion, education, job, marital status, media use and HIV knowledge also showed statistically significant association with the studied risk behaviours. We also found significant differences among countries, while controlling for covariates.

Conclusions: Overall, we find no evidence of sexual risk compensation in response to VMMC campaigns in countries prioritized by WHO. Changes in relative partner behaviour and the relative odds of condom use were small (and of uncertain sign). In fact, our estimates, though not significant, both suggest slightly less risky behavior. We conclude that sexual risk compensation in response to VMMC campaigns has not been a serious problem to date, but urge continued attention to local context, and to promulgating accurate messages about circumcision within and beyond the VMMC context.

Abstract   Full-text [free] access 

Africa
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Increasing HIV testing by sharing the load and updating tasks and traditions for traditional birth attendants and lay providers

Editor’s notes: Nigeria still has the highest number of new HIV infections among children in the world, around 40 000 annually, with the large majority arising from mother to child transmission.  In Nigeria, less than 20% of pregnant women receive HIV testing. This is due to several issues which include a limited number of HIV testing service delivery points and a limited number of deliveries taking place at health facilities.  Around two thirds of deliveries take place at home, traditionally supported by traditional birth attendants (TBAs).  Many TBAs in Nigeria have little knowledge of either the benefits or practice of HIV testing, nor of ways to reduce transmission of HIV to infants.

Chizoba and colleagues have developed and tested a model of antenatal care that aims to integrate TBAs within the government primary health care (PHC) network.  The intervention consisted of PHC clinics identifying a few TBAs who operated in the catchment area of the clinic. Between one and five of these TBAs was invited to the PHC clinic for a one-day training on HIV point of care testing, and asked to refer all women found to be positive to the clinic for confirmation and follow up.  Once a month TBAs came to the clinic for encouragement and to provide data on tests performed.  Once a quarter, the clinic visited the TBAs to provide supervision, mentoring and quality improvement training.  The TBAs were also paid $2 for every pregnant woman whom they tested for HIV, in order to compensate them for any loss of earnings from pregnant women living with HIV who would now be seen in the clinic rather than delivering at home. 

The authors used a quasi-experimental design for this study. Out of the 74 PEPFAR supported PHC clinics that provided HIV services in their antenatal clinics in Ebonyi state of Nigeria, 34 were interested in this new integrated approach, whereas 40 expressed no interest.  20 clinics were chosen at random from each of these categories, to avoid additional selection bias.  (Although as the authors state, there may already be considerable differences between the clinics that were interested and clinics that were not).  Comparisons were made before and after the programme was put in place, and also between clinics in the intervention group and those in the group that had not been interested to integrate services with the TBAs.

Despite this non-randomized design, the results are quite striking with more than twice as many women receiving HIV testing in the intervention clinics in the six months after the intervention began (going up from 2501 to 5346 across the 20 clinics).  There was no such increase in the non-intervention areas (which saw a change from 1770 to 1892 across the 20 clinics).  Furthermore the large majority of the increase was among women who had been tested by the TBAs. 

While this is hugely encouraging and a big increase, it will be important to see if the increase can be sustained as it is a significant change in the way that the TBAs and the PHC clinic staff work.  It is also not clear how much the increase is a result of the integration model and how much it relates to the additional payment that TBAs receive, which seems to amount to around $100 per TBA over the 6 month period of the assessment.

A thorough review of the role of trained lay providers in performing HIV tests was carried out as part of the WHO process that led to the guidance in 2015 that “Lay providers who are trained and supervised to use rapid diagnostic tests (RDTs) can independently conduct safe and effective HIV testing services.” Kennedy and colleagues now present the details of that systematic review.

Many national policies, particularly in African countries allow for HIV testing by trained lay providers using rapid diagnostic tests (RDTs) and even more allow lay providers to perform pre- and post-test counselling (around 80% of African countries in one survey of policies).  However, some countries limit these roles to trained healthcare providers due to concerns about lay providers’ ability to perform the tests accurately and reliably and to deliver high quality pre- and post-test counselling, linkage to appropriate prevention and clinical care services, and coordination with laboratory services to ensure the delivery of correct test results.

Despite widespread use of lay providers, there are actually rather few studies that directly compare the outcomes of testing between lay and professional providers.  The authors reviewed over 6000 titles, abstracts or full articles and found only five that allowed a direct comparison, while an additional six studies allowed the values and preferences of clients and providers to be assessed.

While this evidence base is very limited, findings from the single randomized trial (in the US) and one observational study (in Malawi), that compared pre- and post-intervention time periods, suggest that using trained lay providers can increase HIV testing uptake.  Three studies compared the quality of testing between lay providers and professional providers and found that both can achieve similar testing quality. Unfortunately, no studies measured adverse events following testing, nor linkage to care. The six values and preferences studies, also found support for lay providers.

This is the key evidence that underpins the strong recommendation from WHO and now also from many national authorities, that trained lay providers are an essential component in the efforts to scale up HIV testing in order to reach the first 90.

Increasing HIV testing among pregnant women in Nigeria: evaluating the traditional birth attendant and primary health center integration (TAP-In) model.

Chizoba AF, Pharr JR, Oodo G, Ezeobi E, Ilozumb J, Egharevba J, Ezeanolue EE, Nwandu A. AIDS Care. 2017 Apr 18:1-5. doi: 10.1080/09540121.2017.1317325. [Epub ahead of print]

Engaging Traditional Birth Attendants (TBAs) may be critical to preventing mother-to-child transmission of HIV (PMTCT) in Nigeria. We integrated TBAs into Primary Health Centers (PHCs) and provided the TBAs with HIV counseling and testing (HCT) training for PMTCT (TAP-In). The purpose of this study was to evaluate the impact of TAP-In on HCT uptake among pregnant women. A quasi-experimental design was used for this study. Twenty PHCs were assigned to the intervention group that integrated TAP-In and 20 were assigned to the control group. Data were collected six months prior to the initiation of TAP-In and six months post, using antenatal clinic registries. Intervention PHCs more than doubled the number of pregnant women who received HCT in their catchment area post TAP-In while control PHCs had no significant change. After initiating TAP-In, intervention PHCs provided almost three times more HCT than the control PHCs (p < 0.01) with TBA provided over half of the HCT post TAP-In. The TAP-In model was effective for increasing HCT among pregnant women.

Abstract access 

Should trained lay providers perform HIV testing? A systematic review to inform World Health Organization guidelines.

Kennedy CE, Yeh PT, Johnson C, Baggaley R. AIDS Care. 2017 Apr 24:1-7. doi:10.1080/09540121.2017.1317710. [Epub ahead of print.]

New strategies for HIV testing services (HTS) are needed to achieve UN 90-90-90 targets, including diagnosis of 90% of people living with HIV. Task-sharing HTS to trained lay providers may alleviate health worker shortages and better reach target groups. We conducted a systematic review of studies evaluating HTS by lay providers using rapid diagnostic tests (RDTs). Peer-reviewed articles were included if they compared HTS using RDTs performed by trained lay providers to HTS by health professionals, or to no intervention. We also reviewed data on end-users' values and preferences around lay providers preforming HTS. Searching was conducted through 10 online databases, reviewing reference lists, and contacting experts. Screening and data abstraction were conducted in duplicate using systematic methods. Of 6113 unique citations identified, 5 studies were included in the effectiveness review and 6 in the values and preferences review. One US-based randomized trial found patients' uptake of HTS doubled with lay providers (57% vs. 27%, percent difference: 30, 95% confidence interval: 27-32, p < 0.001). In Malawi, a pre/post study showed increases in HTS sites and tests after delegation to lay providers. Studies from Cambodia, Malawi, and South Africa comparing testing quality between lay providers and laboratory staff found little discordance and high sensitivity and specificity (≥98%). Values and preferences studies generally found support for lay providers conducting HTS, particularly in non-hypothetical scenarios. Based on evidence supporting using trained lay providers, a WHO expert panel recommended lay providers be allowed to conduct HTS using HIV RDTs. Uptake of this recommendation could expand HIV testing to more people globally.

Abstract  Full-text [free] access

Africa, Asia
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