Articles tagged as "HIV testing"

Phylogenetics - powerful new tools tied to ethical imperatives for key populations

Editor’s notes: There are now well over half a million HIV isolates that have been sequenced and the data stored in public accessible Genbank.  A systematic review by Hassan AS and colleagues of the methods used to define phylogenetic trees and clusters within them demonstrates the importance of using the correct criteria for the hypothesis being tested. Most articles use the pol sequence, since this is what is sequenced for drug resistance testing.  Most analyses have been done using a phylogenetic approach that uses a probability to assess the likelihood that isolates are clustered, and so depends on the cut-off value chosen.  For example, a well-studied outbreak of HIV among drug users in Finland is clearly linked to an earlier outbreak in Sweden, but because the Finnish isolates were collected later, they had already diverged somewhat from the Swedish ones.  If the threshold was set too high, they would not be recognized to be part of the same outbreak.  However for active transmission chains, a high threshold is needed to avoid falsely linking isolates.  There is no consensus on what methods to use, so caution is needed when comparing different studies.

Mark Wainberg, Professor of Medicine and of Microbiology at McGill University and a giant of Canadian HIV science, passed away this month.  So, as a tribute to his work, we have chosen a study from the McGill AIDS Centre by Brenner BG and colleagues.  The team used phylogenetic analysis to classify pre-treatment HIV isolates from 3901 men who have sex with men in Quebec according to the likelihood of being an acute or recent infection and the likelihood of clustering with other isolates.  Over the period from 2002-2015, a larger and larger proportion of the infections in this population could be linked to larger clusters, particularly involving younger men and men with recent infection, many of whom did not know their HIV status.  At least 40% of the onward spread of the epidemic in Quebec can be ascribed to just thirty clusters, varying in size from 20–140 individuals.

Using phylogenetics to understand transmission patterns requires careful attention to ethics, confidentiality and stigmatization.  A study in South Korea by Ahn MY and colleagues aimed to define the risk factors for clustering within clusters among 143 people living with HIV in four cities.  In eight out of the nine clusters identified participants did not report the same risk factors. Clusters were small, eight pairs and one quartet.  In the two tightest clusters, where the isolates were indistinguishable on the sequences examined, one man stated that he had sex with women, but the paired isolate came from another man and in the other pair, both men chose not to disclose their risk factors.  With small studies where information can sometimes be inferred even when not disclosed, it is perhaps not surprising that more than half the participants chose not to report their risk factors.

Other phylogenetic studies this month have explored the evolution of HIV recombination and the spread of different clades in communities in North-Eastern Brazil [Delatorre E et al.] and China.  In the North-Eastern states of Brazil, 72% of HIV isolates were subtype B, but rare subtypes such as D (1%) and CRF02_AG (1%) appear to be spreading within the population rather than being introduced from outside. In China studies from Sichuan [Wang Y et al.], Yunnan [Li Y and colleagues] and Zhejiang [Wang H et al.] have shown new recombinant forms of HIV with elements that suggest that viruses from different countries in the region have combined.  The widening diversity of HIV brings challenges for vaccine development, and potentially for HIV assays, such as those for recent infection that may differ in their sensitivity and specificity between different sub-types.  Understanding the migration of people and their viruses could be useful for providing better services, but careful attention to messaging will be needed to prevent such data from being used to discriminate further against migrants.

The final phylogenetic paper this month also comes from China, where Hao M and colleagues reported a study of students living with HIV in Beijing. The study demonstrated that transmitted drug resistance is still low in this setting, with just 0.8% of 237 students having virus that was resistant to non-nucleoside reverse transcriptase inhibitors that form part of the backbone of first line treatment in China.  A further 1.3% has resistance to protease inhibitors that are used in second line treatment.

Defining HIV-1 transmission clusters based on sequence data: a systematic review and perspectives.

Hassan AS, Pybus OG, Sanders EJ, Albert J, Esbjörnsson J. AIDS. 2017 Mar 28. doi: 10.1097/QAD.0000000000001470. [Epub ahead of print]

Understanding HIV-1 transmission dynamics is relevant to both screening and intervention strategies of HIV-1 infection. Commonly, HIV-1 transmission chains are determined based on sequence similarity assessed either directly from a sequence alignment or by inferring a phylogenetic tree. This review is aimed at both nonexperts interested in understanding and interpreting studies of HIV-1transmission, and experts interested in finding the most appropriate cluster definition for a specific dataset and research question. We start by introducing the concepts and methodologies of how HIV-1 transmission clusters usually have been defined. We then present the results of a systematic review of 105 HIV-1 molecular epidemiology studies summarizing the most popular methods and definitions in the literature. Finally, we offer our perspectives on how HIV-1 transmission clusters can be defined and provide some guidance based on examples from real life datasets.

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Large cluster outbreaks sustain the HIV epidemic among MSM in Quebec.

Brenner BG, Ibanescu RI, Hardy I, Stephens D, Otis J, Moodie E, Grossman Z,Vandamme AM, Roger M, Wainberg MA; and the Montreal PHI, SPOT cohorts. AIDS. 2017 Mar 13;31(5):707-717. doi: 10.1097/QAD.0000000000001383.

Objective: HIV-1 epidemics among MSM remain unchecked despite advances in treatment and prevention paradigms. This study combined viral phylogenetic and behavioural risk data to better understand underlying factors governing the temporal growth of the HIV epidemic among MSM in Quebec (2002-2015).

Methods: Phylogenetic analysis of pol sequences was used to deduce HIV-1transmission dynamics (cluster size, size distribution and growth rate) in first genotypes of treatment-naïve MSM (2002-2015, n = 3901). Low sequence diversity of first genotypes (0-0.44% mixed base calls) was used as an indication of early-stage infection. Behavioural risk data were obtained from the Montreal rapid testing site and primary HIV-1-infection cohorts.

Results: Phylogenetic analyses uncovered high proportion of clustering of new MSM infections. Overall, 27, 45, 48, 53 and 57% of first genotypes within one (singleton, n = 1359), 2-4 (n = 692), 5-9 (n = 367), 10-19 (n = 405) and 20+ (n = 1277) cluster size groups were early infections (<0.44% diversity). Thirty viruses within large 20+ clusters disproportionately fuelled the epidemic, representing 13, 25 and 42% of infections, first genotyped in 2004-2007 (n = 1314), 2008-2011 (n = 1356) and 2012-2015 (n = 1033), respectively. Of note, 35, 21 and 14% of MSM belonging to 20+, 2-19 and one (singleton) cluster groups were under 30 years of age, respectively. Half of persons seen at the rapid testing site (2009-2011, n = 1781) were untested in the prior year. Poor testing propensity was associated with fewer reported partnerships.

Conclusion: Addressing the heterogeneity in transmission dynamics among HIV-1-infected MSM populations may help guide testing, treatment and prevention strategies.

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HIV-1 transmission networks across South Korea.

Ahn MY, Wertheim JO, Kim WJ, Kim SW, Lee JS, Ann HW, Jeon Y, Ahn JY, Song JE, Oh DH, Kim YC, Kim EJ), Jung IY, Kim MH, Jeong W, Jeong SJ, Ku NS, Kim JM, Smith DM, Choi JY. AIDS Res Hum Retroviruses. 2017 Mar 27. doi: 10.1089/aid.2016.0212. [Epub ahead of print]

Molecular epidemiology can help clarify the properties and dynamics of HIV-1 transmission networks in both global and regional scales. We studied 143 HIV-1-infected individuals recruited from four medical centers of three cities in South Korea between April 2013 and May 2014. HIV-1 env V3 sequence data were generated (337-793 bp) and analyzed using a pairwise distance-based clustering approach to infer putative transmission networks. Participants whose viruses were ≤2.0% divergent according to Tamura-Nei 93 genetic distance were defined as clustering. We collected demographic, risk, and clinical data and analyzed these data in relation to clustering. Among 143 participants, we identified nine putative transmission clusters of different sizes (range 2-4 participants). The reported risk factor of participants were concordant in only one network involving two participants, that is, both individuals reported homosexual sex as their risk factor. The participants in the other eight networks did not report concordant risk factors, although they were phylogenetically linked. About half of the participants refused to report their risk factor. Overall, molecular epidemiology provides more information to understand local transmission networks and the risks associated with these networks.

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HIV-1 Genetic diversity in northeastern Brazil: high prevalence of non-B subtypes.

Delatorre E, Couto-Fernandez JC, Bello G.AIDS Res Hum Retroviruses. 2017 Mar 22. doi: 10.1089/AID.2017.0045. [Epub ahead of print]

The Northeastern Brazilian region has experienced a constant increase in the number of newly reported AIDS cases over the last decade, but the genetic diversity of HIV-1 strains currently disseminated in this region remains poorly explored. HIV-1 pol sequences were obtained from 140 patients followed at outpatient clinics from four Northeastern Brazilian states (Alagoas, Bahia, Ceará and Piauí) between 2014 and 2015. Subtype B was the most prevalent HIV-1 clade (72%) detected in the Northeastern region, followed by subtypes F1 (6%), C (5%) and D (1%). The remaining strains (16%) displayed a recombinant structure and were classified as: BF1 (11%), BC (4%), BCF1 (1%) and CRF02_AG-like (1%). The 20 HIV-1 BF1 and BC recombinant sequences detected were distributed among 11 lineages classified as: CRF28/29_BF-like (n = 5), CRF39_BF-like (n = 1), URFs_BF (n = 9) and URFs_BC (n = 5). Non-B subtypes were detected in all Northeastern Brazilian states, but with variable prevalence, ranging from 16% in Ceará to 55% in Alagoas. Phylogenetics analyses support that subtype D and CRF02_AG strains detected in the Northeastern region resulted from the expansion of autochthonous transmission networks, rather than from exogenous introductions from other countries. These results reveal that HIV-1 epidemic spreading in the Northeastern Brazilian region is comprised by multiple subtypes and recombinant strains and that the molecular epidemiologic pattern in this Brazilian region is much more complex than originally estimated.

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Identification of a novel HIV type 1 CRF01_AE/B'/C recombinant isolate in Sichuan, China.

Wang Y, Kong D, Xu W, Li F, Liang S, Feng Y, Zhang F, Shao Y, Ma L. AIDS Res Hum Retroviruses. 2017 Mar 13. doi: 10.1089/aid.2017.0002. [Epub ahead of print]

We report in this study a novel HIV-1 unique recombinant virus (XC2014EU01) isolated from an HIV-positive man who infected through heterosexual sex in Sichuan, China. The near full-length genome analyses showed that XC2014EU01 harbored one subtype B segment in pol region and two subtype C segments in gag-pol region in a CRF01_AE backbone. The unique mosaic structure was distinctly different from the other CRF01_AE/B'/C recombinant forms reported. Phylogenetic tree analyses revealed that the subtype B region originated from a Thailand subtype B' lineage, the subtype C regions were from an India C lineage, and the backbone was from CRF01_AE. XC2014EU01 was still identified as CCR5-tropic, and plasma of XC2014EU01 infected person had the media neutralizing activity. The emergence of XC2014EU01 may increase the complexity of the HIV-1 epidemic among high-risk populations and the difficulty of vaccine research and development.

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Identification of a novel HIV type 1 circulating recombinant form (CRF86_BC) among heterosexuals in Yunnan, China.

Li Y, Miao J, Miao Z, Song Y, Wen M, Zhang Y, Guo S, Zhao Y, Feng Y, Xia X. AIDS Res Hum Retroviruses. 2017 Mar;33(3):279-283. doi: 10.1089/AID.2016.0188. Epub 2016 Oct 18.

In recent years, multiple circulating recombinant forms (CRFs) and unique recombinant forms of human immunodeficiency virus type 1 (HIV-1) have been described in Yunnan, China. Here, we identified a novel HIV-1 CRF (CRF86_BC) isolated from three heterosexuals with no obvious epidemiologic linkage in western Yunnan (Baoshan prefecture) in China. CRF86_BC had a subtype C backbone with four subtype B fragments inserted into the pol, vpr, vpu, env, and nef gene regions, respectively. Furthermore, subregion tree analysis revealed that subtype C backbone originated from an Indian C lineage and subtype B segment inserted was from a Thai B lineage. They are different from previously documented B/C forms in its distinct backbone, inserted fragment size, and break points. This highlighted the importance of continual monitoring of genetic diversity and complexity of HIV-1 strains in this region.

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Near full-length genomic characterization of a novel HIV-1 unique recombinant (CRF55_01B/CRF07_BC) from a Malaysian immigrant worker in Zhejiang, China.

Wang H, Luo P, Zhu H, Wang N, Hu J, Mo Q, Yang Z, Feng Y. AIDS Res Hum Retroviruses. 2017 Mar;33(3):275-278.doi: 10.1089/AID.2016.0100. Epub 2016 Aug 17.

Recombinant forms contribute substantially to the genetic diversity of human immunodeficiency virus type 1 (HIV-1). Here we report a novel HIV-1 recombinant detected from a comprehensive HIV-1 molecular epidemiologic study among cross-border populations in China. Near full-length genome (NFLG) phylogenetic analysis showed that the novel HIV-1 recombinant ZJCIQ15005, which was isolated from a Malaysian immigrant worker in Zhejiang, China, clustered with CRF55_01B reference sequences but set up a distinct branch. Recombinant analysis showed that the NFLG of ZJCIQ15005 composed of CRF55_01B (as the backbone) and CRF07_BC,with 12 recombinant break points observed in the pol, vif, vpr, tat, rev, env,nef, and 3'LTR regions. This is the first detection of a novel HIV-1 recombinant (CRF55_01B/CRF07_BC) in immigrant workers in China. The emergence of this recombinant may increase the complexity of the HIV-1 epidemic in China and suggests the importance of continuous surveillance of the dynamic changes of HIV-1.

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Low rates of transmitted drug resistances among treatment-naive HIV-1 infected students in Beijing, China.

Hao M, Wang J, Xin R, Li X, Hao Y, Chen J, Ye J, Wang Y, He X, Huang C, Lu H. AIDS Res Hum Retroviruses. 2017 Mar 22. doi: 10.1089/AID.2017.0053. [Epub ahead of print]

Beijing has seen a rising epidemic of HIV among students. However, little information was known about the molecular epidemiologic data among HIV-infected students. In this study, the diversity and the prevalence of TDR in pol sequences deriving from 237 HIV-infected students were analyzed. TDR mutations were found in 5 MSM among students. The overall prevalence of TDR in students was 2.1%, comprised of 1.3% to protease inhibitors and 0.8 % to non-nucleoside reverse transcriptase inhibitors. Our finding indicates a low-level prevalence of TDR mutations among students in Beijing.

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Asia, Latin America, Northern America
Brazil, Canada, China, Republic of Korea
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Stigma and sex work

Editor’s notes: Two interesting studies this month looked at aspects of stigma.  There are big methodological challenges to the study of stigma.  Stigma comprises several different domains and few studies use standardized approaches to measurement that can be translated easily into other contexts.  A systematic review and meta-analysis concludes that people who feel more stigmatized are twice as likely to delay presenting for HIV care.  Gesesew HA and colleagues found only ten studies that met their pre-specified inclusion criteria, and five of these came from Ethiopia.  They acknowledge many of the challenges in combining the results of these ten studies into a single conclusion.  They recommend engagement of health care workers to try to reduce perceived stigma among people living with HIV.

The Nyblade L et al. study from Kenya emphasizes the perception of stigma among sex workers.  In a large sample of 497 females and 232 males, most reported experiencing stigma both verbal and measured from health care workers. For female sex workers, the anticipation of such stigma led to avoidance of health services for both HIV and non-HIV related conditions. In order to provide effective services for key populations, health care workers must be trained to be non-judgemental.  HIV services need to be provided in the context of an overall package of health care.

A study from Europe used ecological data to explore structural risks for HIV among sex workers.  Reeves A and colleagues used regression modelling with data on sex work policies from 27 countries.  They showed a strong correlation between criminalisation of sex work and higher prevalence of HIV among sex workers.  Although they included other factors such as the level of economic development and using drugs, the relatively small number of data points does mean that there may be other confounding factors that could not be measured or adjusted for.

Significant association between perceived HIV related stigma and late presentation for HIV/AIDS care in low and middle-income countries: A systematic review and meta-analysis.

Gesesew HA, Tesfay Gebremedhin A, Demissie TD, Kerie MW, Sudhakar M, Mwanri L. PLoS One. 2017 Mar 30;12(3):e0173928. doi: 10.1371/journal.pone.0173928.eCollection 2017.

Background: Late presentation for human immunodeficiency virus (HIV) care is a major impediment for the success of antiretroviral therapy (ART) outcomes. The role that stigma plays as a potential barrier to timely diagnosis and treatment of HIV among people living with HIV/AIDS (acquired immunodeficiency syndrome) is ambivalent. This review aimed to assess the best available evidence regarding the association between perceived HIV related stigma and time to present for HIV/AIDS care.

Methods: Quantitative studies conducted in English language between 2002 and 2016 that evaluated the association between HIV related stigma and late presentation for HIV care were sought across four major databases. This review considered studies that included the following outcome: 'late HIV testing', 'late HIV diagnosis' and 'late presentation for HIV care after testing'. Data were extracted using a standardized Joanna Briggs Institute (JBI) data extraction tool. Meta- analysis was undertaken using Revman-5 software. I2 and chi-square test were used to assess heterogeneity. Summary statistics were expressed as pooled odds ratio with 95% confidence intervals and corresponding p-value.

Results: Ten studies from low- and middle- income countries met the search criteria, including six (6) and four (4) case control studies and cross-sectional studies respectively. The total sample size in the included studies was 3788 participants. Half (5) of the studies reported a significant association between stigma and late presentation for HIV care. The meta-analytical association showed that people who perceived high HIV related stigma had two times more probability of late presentation for HIV care than who perceived low stigma (pooled odds ratio = 2.4; 95%CI: 1.6-3.6, I2 = 79%).

Conclusions: High perceptions of HIV related stigma influenced timely presentation for HIV care. In order to avoid late HIV care presentation due the fear of stigma among patients, health professionals should play a key role in informing and counselling patients on the benefits of early HIV testing or early entry to HIV care. Additionally, linking the systems and positive case tracing after HIV testing should be strengthened.

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The relationship between health worker stigma and uptake of HIV counseling and testing and utilization of non-HIV health services: the experience of male and female sex workers in Kenya.

Nyblade L, Reddy A, Mbote D, Kraemer J, Stockton M, Kemunto C, Krotki K, Morla J, Njuguna S, Dutta A, Barker C. AIDS Care. 2017 Mar 22:1-9. doi: 10.1080/09540121.2017.1307922. [Epub ahead of print]

The barrier HIV-stigma presents to the HIV treatment cascade is increasingly documented; however less is known about female and male sex worker engagement in and the influence of sex-work stigma on the HIV care continuum. While stigma occurs in all spheres of life, stigma within health services may be particularly detrimental to health seeking behaviors. Therefore, we present levels of sex-work stigma from healthcare workers (HCW) among male and female sex workers in Kenya, and explore the relationship between sex-work stigma and HIV counseling and testing. We also examine the relationship between sex-work stigma and utilization of non-HIV health services. A snowball sample of 497 female sex workers (FSW) and 232 male sex workers (MSW) across four sites was recruited through a modified respondent-driven sampling process. About 50% of both male and female sex workers reported anticipating verbal stigma from HCW while 72% of FSW and 54% of MSW reported experiencing at least one of seven measured forms of stigma from HCW. In general, stigma led to higher odds of reporting delay or avoidance of counseling and testing, as well as non-HIV specific services. Statistical significance of relationships varied across type of health service, type of stigma and gender. For example, anticipated stigma was not a significant predictor of delay or avoidance of health services for MSW; however, FSW who anticipated HCW stigma had significantly higher odds of avoiding (OR = 2.11) non-HIV services, compared to FSW who did not. This paper adds to the growing evidence of stigma as a roadblock in the HIV treatment cascade, as well as its undermining of the human right to health. While more attention is being paid to addressing HIV-stigma, it is equally important to address the key population stigma that often intersects with HIV-stigma.

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National sex work policy and HIV prevalence among sex workers: an ecological regression analysis of 27 European countries.

Reeves A, Steele S, Stuckler D, McKee M, Amato-Gauci A, Semenza JC. Lancet HIV. 2017 Mar;4(3):e134-e140. doi: 10.1016/S2352-3018(16)30217-X. Epub2017 Jan 25.

Background: Sex workers are disproportionately affected by HIV compared with the general population. Most studies of HIV risk among sex workers have focused on individual-level risk factors, with few studies assessing potential structural determinants of HIV risk. In this Article, we examine whether criminal laws around sex work are associated with HIV prevalence among female sex workers.

Method: We estimate cross-sectional, ecological regression models with data from 27 European countries on HIV prevalence among sex workers from the European Centre for Disease Control; sex-work legislation from the US State Department's Country Reports on Human Rights Practices and country-specific legal documents; the rule of law and gross-domestic product per capita, adjusted for purchasing power, from the World Bank; and the prevalence of injecting drug use among sex workers. Although data from two countries include male sex workers, the numbers are so small that the findings here essentially pertain to prevalence in female sex workers.

Findings: Countries that have legalised some aspects of sex work (n=17) have significantly lower HIV prevalence among sex workers than countries that criminalise all aspects of sex work (n=10; β=-2·09, 95% CI -0·80 to -3·37;p=0·003), even after controlling for the level of economic development (β=-1·86; p=0·038) and the proportion of sex workers who are injecting drug users (-1·93;p=0·026). We found that the relation between sex work policy and HIV among sex workers might be partly moderated by the effectiveness and fairness of enforcement, suggesting legalisation of some aspects of sex work could reduce HIV among sex workers to the greatest extent in countries where enforcement is fair and effective.

Interpretation: Our findings suggest that the legalisation of some aspects of sex work might help reduce HIV prevalence in this high-risk group, particularly in countries where the judiciary is effective and fair.

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Infectious co-morbidities – why are people still dying of advanced HIV infections?

Editor’s notes: Tuberculosis remains the biggest reported killer of people living with HIV.  Studies from Guangxi, China and Nigeria examine risk factors for tuberculosis.  In the Chinese study, Cui Z and colleagues found almost one in six of 1019 people receiving care for HIV had active tuberculosis.  The risk factors that they found when comparing these 160 people with tuberculosis to matched controls living with HIV but without tuberculosis were well-known (low CD4 cell count, smoking and non-use of ART).  Long duration of HIV infection was also independently associated with developing tuberculosis, emphasising the need for tuberculosis specific measures in addition to ART.  The authors recommend standard approaches that need to be strengthened (active screening and case-finding with early initiation of ART; isoniazid preventive therapy and better infection control).  The most extraordinary statistic is how much higher the rate of tuberculosis is among this group of people receiving HIV care than it is among the general population of Guangxi.  173 times higher is pretty impressive!

The Pathmanathan I et al. study in Nigeria, carried out as part of a broader analysis of the outcomes of a nationally representative sample of people taking ART, is more optimistic.  The incidence rate for tuberculosis once people started on ART was 0.57 per 100 person years, which compares quite favourably with the estimated incidence for Nigeria from the WHO Global Tuberculosis 2016 report [link] of 0.32 per 100 person years.  Furthermore, most of the incident tuberculosis occurred soon after starting ART and (as might be expected) was most common in people with low CD4 count; previous tuberculosis or suspected but not diagnosed tuberculosis on starting ART.  Once people’s CD4 count was above 200 cells per ml, the incidence rate was 0.29 per 100 person-years.  This is encouraging, as it suggests that a good ART programme could have a significant impact on the overall risk of tuberculosis.  The aim of collaborative tuberculosis and HIV programme efforts must be to find people living with HIV before they are so immunocompromised.  In this study, the average CD4 count at enrolment was less than 200 cells per ml and around 5% of people already had tuberculosis at that time.

Late HIV diagnosis was also the subject of a study from Jiangsu province in China.  Hu H and colleagues looked at the trends in HIV testing and presentation to care before the CD4 count fell below 350 cells per ml.  From 2011-2014 in cross-sectional annual community based surveys among around 2500 men who have sex with men (MSM), there was a modest decline in the proportion who had had an HIV test within the last 12 months from 60% to 53%, and late presentation remained stable around 40%.  We have to shift from this plateau and the authors point out that HIV self-tests seem highly acceptable to MSM in China and that social media and internet based advocacy might also help.

There is increasing interest in co-infections with hepatitis B and C viruses in people living with HIV.  Hepatitis B is widespread in many countries in sub-Saharan Africa with “horizontal” transmission occurring in childhood.  Vaccination is now included as part of some countries programmes on expanded immunisation.  Co-infection with HIV and Hepatitis B leads to more rapid progression of liver damage and to liver cancer. Seremba E and colleagues tested stored sera from people living with HIV in the Rakai community and found that around half had already been infected with hepatitis B (in line with the high prevalence of infection in children).  During the follow up samples from people who were hepatitis B negative, new infections with hepatitis B occurred in 39 individuals, giving an incidence rate of 1.2 per 100 person years.  While hepatitis B vaccine is recommended for people living with HIV who are not infected, this study shows that ART is also protective, particularly if it contains lamivudine or tenofovir.  So this may be an added benefit of the wider scale-up of ART.

Despite advance in ART, too many people still die with HIV-associated infections that are only seen at low CD4 cell counts.  An important example is cryptococcal meningitis, which causes an insidious onset of symptoms. By the time patients are seen at the hospital with severe headache and signs of raised intracranial pressure it is often too late to prevent them from dying. This is because the best medicines (liposomal amphotericin and flucytosine) are expensive and often not available.  So WHO recommends pre-emptive treatment for people who are first seen at the health service with CD4 counts less than 100 cells per ml and with cryptococcal antigen (CRAG) detectable in the blood.  A modelling study by Ramachandran A et al. from Uganda and the US considered the likely costs and benefits of using a new lateral flow assay for CRAG for people living with HIV with a low CD4 count, with pre-emptive treatment with fluconazole for people found to be CRAG-positive. The results, including various sensitivity tests, are strongly in favour of widespread implementation of this strategy. The authors calculate that it would cost Uganda around US$650 000 per year and would avert more than a thousand deaths.  Like the tuberculosis discussions above, the real aim is to prevent people living with HIV reaching the stage where “old-fashioned” opportunistic infections can cause such misery.  However in the medium term, we are likely to continue to see many people presenting late in the course of their infections, and CRAG (and tuberculosis) screening and management are key ways to prevent mortality.

Risk factors associated with Tuberculosis (TB) among people living with HIV/AIDS: A pair-matched case-control study in Guangxi, China.

Cui Z, Lin M, Nie S, Lan R. PLoS One. 2017 Mar 30;12(3):e0173976. doi:10.1371/journal.pone.0173976.eCollection 2017.

Background: As one of the poorest provinces in China, Guangxi has a high HIV and TB prevalence, with the annual number of TB/HIV cases reported by health department among the highest in the country. However, studies on the burden of TB-HIV co-infection and risk factors for active TB among HIV-infected persons in Guangxi have rarely been reported.

Objective: To investigate the risk factors for active TB among people living with HIV/AIDS in Guangxi Zhuang autonomous region, China.

Methods: A surveillance survey was conducted of 1019 HIV-infected patients receiving care at three AIDS prevention and control departments between 2013 and 2015. We investigated the cumulative prevalence of TB during 2 years. To analyze risk factors associated with active TB, we conducted a 1:1 pair-matched case-control study of newly reported active TB/HIV co-infected patients. Controls were patients with HIV without active TB, latent TB infection or other lung disease, who were matched with the case group based on sex and age (± 3 years).

Results: A total of 1019 subjects were evaluated. 160 subjects (15.70%) were diagnosed with active TB, including 85 clinically diagnosed cases and 75 confirmed cases. We performed a 1:1 matched case-control study, with 82 TB/HIV patients and 82 people living with HIV/AIDS based on surveillance site, sex and age (±3) years. According to multivariate analysis, smoking (OR = 2.996, 0.992-9.053), lower CD4+ T-cell count (OR = 3.288, 1.161-9.311), long duration of HIV-infection (OR = 5.946, 2.221-15.915) and non-use of ART (OR = 7.775, 2.618-23.094) were independent risk factors for TB in people living with HIV/AIDS.

Conclusion: The prevalence of active TB among people living with HIV/AIDS in Guangxi was 173 times higher than general population in Guangxi. It is necessary for government to integrate control planning and resources for the two diseases. Medical and public health workers should strengthen health education for TB/HIV prevention and treatment and promote smoking cessation. Active TB case finding and early initiation of ART is necessary to minimize the burden of disease among patients with HIV, as is IPT and infection control in healthcare facilities.

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Incidence and predictors of tuberculosis among HIV-infected adults after initiation of antiretroviral therapy in Nigeria, 2004-2012.

Pathmanathan I, Dokubo EK, Shiraishi RW, Agolory SG, Auld AF, Onotu D, Odafe S, Dalhatu I, Abiri O, Debem HC, Bashorun A, Ellerbrock T. PLoS One. 2017 Mar 10;12(3):e0173309. doi: 10.1371/journal.pone.0173309.eCollection 2017.

Background: Nigeria had the most AIDS-related deaths worldwide in 2014 (170 000), and 46% were associated with tuberculosis (TB). Although treatment of people living with HIV (PLHIV) with antiretroviral therapy (ART) reduces TB-associated morbidity and mortality, incident TB can occur while on ART. We estimated incidence and characterized factors associated with TB after ART initiation in Nigeria.

Methods: We analyzed retrospective cohort data from a nationally representative sample of adult patients on ART. Data were abstracted from 3496 patient records, and analyses were weighted and controlled for a complex survey design. We performed domain analyses on patients without documented TB disease and used a Cox proportional hazard model to assess factors associated with TB incidence after ART.

Results: At ART initiation, 3350 patients (95.8%) were not receiving TB treatment. TB incidence after ART initiation was 0.57 per 100 person-years, and significantly higher for patients with CD4<50/μL (adjusted hazard ratio [AHR]:4.2, 95% confidence interval [CI]: 1.4-12.7) compared with CD4≥200/μL. Patients with suspected but untreated TB at ART initiation and those with a history of prior TB were more likely to develop incident TB (AHR: 12.2, 95% CI: 4.5-33.5 and AHR: 17.6, 95% CI: 3.5-87.9, respectively).

Conclusion: Incidence of TB among PLHIV after ART initiation was low, and predicted by advanced HIV, prior TB, and suspected but untreated TB. Study results suggest a need for improved TB screening and diagnosis, particularly among high-risk PLHIV initiating ART, and reinforce the benefit of early ART and other TB prevention efforts.

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Trends in late HIV diagnosis among men who have sex with men in Jiangsu province, China: Results from four consecutive community-based surveys, 2011-2014.

Hu H, Yan H, Liu X, Xu X, Xu J, Qiu T, Shi LE, Fu G, HuanX, McFarland W, Wei C). PLoS One. 2017 Mar 9;12(3):e0172664. doi:10.1371/journal.pone.0172664.eCollection 2017.

Objectives: To examine trends in HIV testing, late HIV diagnosis and associated factors among men who have sex with men (MSM) in Jiangsu province, China.

Methods: Four consecutive community-based cross-sectional surveys were conducted among MSM from 2011 to 2014 in eight cities in the province. Participants were recruited from MSM venues and via the internet. HIV bio-behavioral surveys were conducted to collect demographic and behavioral data and measure HIV infection. HIV-infected participants with CD4 counts less than 350 cells/µL were defined as having a late HIV diagnosis. Chi-square trend tests were used to compare temporal changes over the years and multivariable logistic regression analyses were used to identify factors associated with late diagnosis.

Results: A total of 2441, 2677, 2591 and 2610 participants were enrolled in 2011, 2012, 2013 and 2014, respectively. Testing for HIV in the last 12 months decreased over the time period, from 59.9% to 52.5% (p<0.001). Late HIV diagnosis remained high and steady, ranging from 33.3% to 44.2% over the years with no significant change over time (p = 0.418). MSM who were older than 24 years (aOR =1.748, p = 0.020 for 25-39 years old; aOR = 3.148, p<0.001 for 40 years old or older), were recruited via internet (aOR = 1.596, p = 0.024), and did not have an HIV test in the past 12 months (aOR = 3.385, p<0.001) were more likely to be late diagnosed.

Conclusions: Our study showed a plateau in HIV testing among MSM in China, in parallel to high levels of late diagnosis. Emerging and innovative strategies such as HIV self-testing and reaching more MSM by internet, both highly acceptable to MSM in China, may reduce late diagnosis.

Abstract  Full-text [free] access 

Hepatitis B incidence and prevention with antiretroviral therapy among HIV-positive individuals in Uganda.

Seremba E, Ssempijja V, Kalibbala S, Gray RH, Wawer MJ, Nalugoda F, Casper C, Phipps W, Ocama P, Serwadda D, Thomas DL, Reynolds SJ. 123. AIDS. 2017 Mar 27;31(6):781-786. doi: 10.1097/QAD.0000000000001399.

Objective: Antiretroviral therapy (ART) may interfere with replication of hepatitis B virus (HBV), raising the hypothesis that HBV infection might be prevented by ART. We investigated the incidence and risk factors associated with HBV among HIV-infected adults in Rakai, Uganda.

Methods: We screened stored sera from 944 HIV-infected adults enrolled in the Rakai Community Cohort Study between September 2003 and March 2015 for evidence of HBV exposure. Serum from participants who tested anti-hepatitis B core-negative (497) at baseline were tested over 3-7 consecutive survey rounds for incident HBV. Poisson incidence methods were used to estimate incidence of HBV with 95% confidence intervals (CIs), whereas Cox proportional regression methods were used to estimate hazard ratios (HRs).

Results: Thirty-nine HBV infections occurred over 3342 person-years, incidence1.17/100 person-years. HBV incidence was significantly lower with ART use: 0.49/100 person-years with ART and 2.3/100 person-years without ART [adjusted HR (aHR) 0.25, 95% CI 0.1-0.5, P < 0.001], and with lamivudine (3TC) use: (0.58/100 person-years) with 3TC and 2.25/100 person-years without 3TC (aHR 0.32, 95% CI0.1-0.7, P =  < 0.007). No new HBV infections occurred among those on tenofovir-based ART. HBV incidence also decreased with HIV RNA suppression: 0.6/100 person-years with 400 copies/ml or less and 4.0/100 person-years with more than 400 copies/ml (aHR, 6.4, 95% CI 2.2-19.0, P < 0.001); and with age: 15-29 years versus 40-50 years (aHR 3.2, 95% CI 1.2-9.0); 30-39 years versus 40-50 years (aHR 2.1, 95% CI 0.9-5.3).

Conclusion: HBV continues to be acquired in adulthood among HIV-positive Ugandans and HBV incidence is dramatically reduced with HBV-active ART. In addition to widespread vaccination, initiation of ART may prevent HBV acquisition among HIV-positive adults in sub-Saharan Africa.

Abstract access 

Cost-effectiveness of CRAG-LFA screening for cryptococcal meningitis among people living with HIV in Uganda.

Ramachandran A(1), Manabe Y(1,)(2), Rajasingham R(3), Shah M(4).141. BMC Infect Dis. 2017 Mar 23;17(1):225. doi: 10.1186/s12879-017-2325-9.

Background: Cryptococcal meningitis (CM) constitutes a significant source of mortality in resource-limited regions. Cryptococcal antigen (CRAG) can be detected in the blood before onset of meningitis. We sought to determine the cost-effectiveness of implementing CRAG screening using the recently developed CRAG lateral flow assay in Uganda compared to current practice without screening.

Methods: A decision-analytic model was constructed to compare two strategies for cryptococcal prevention among people living with HIV with CD4 < 100 in Uganda: No cryptococcal screening vs. CRAG screening with WHO-recommended preemptive treatment for CRAG-positive patients. The model was constructed to reflect primary HIV clinics in Uganda, with a cohort of HIV-infected patients withCD4 < 100 cells/µL. Primary outcomes were expected costs, DALYs, and incremental cost-effectiveness ratios (ICERs). We evaluated varying levels of programmatic implementation in secondary analysis.

Results: CRAG screening was considered highly cost-effective and was associated with an ICER of $6.14 per DALY averted compared to no screening (95% uncertainty range: $-20.32 to $36.47). Overall, implementation of CRAG screening was projected to cost $1.52 more per person, and was projected to result in a 40% relative reduction in cryptococcal-associated mortality. In probabilistic sensitivity analysis, CRAG screening was cost-effective in 100% of scenarios and cost saving (ie cheaper and more effective than no screening) in 30% of scenarios. Secondary analysis projected a total cost of $651 454 for 100%implementation of screening nationally, while averting 1228 deaths compared to no screening.

Conclusion: CRAG screening for PLWH with low CD4 represents excellent value for money with the potential to prevent cryptococcal morbidity and mortality in Uganda.

Abstract  Full-text [free] access

Africa, Asia
China, Nigeria, Uganda
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Keeping up appearances – the reasons people living with HIV who are not yet ill, give for starting ART

Factors that motivated otherwise healthy HIV-positive young adults to access HIV testing and treatment in South Africa.

Lambert RF, Orrell C, Bangsberg DR, Haberer JE. AIDS Behav. 2017 Feb 11. doi: 10.1007/s10461-017-1704-y. [Epub ahead of print]

The World Health Organization recommends early initiation of HIV antiretroviral therapy (ART) for all those infected with the virus at any CD4 count. Successfully reaching individuals with relatively high CD4 counts depends in large part on healthy individuals seeking testing and treatment; however, little is known about factors motivating this decision. We conducted a qualitative study to explore this issue among 25 young HIV-positive adults (age 18-35) with a CD4 count >350 cells/mm3 who recently started or made the decision to start ART in Gugulethu, South Africa. Using an inductive content analytical approach, we found that most individuals sought testing and treatment early in the disease progression because of a desire to appear healthy thereby avoiding stigma associated with AIDS. Other factors included social support, responsibilities and aspirations, normalcy of having HIV, and accessible services. These findings suggest that maintenance of physical appearance should be included in the development of novel testing and treatment interventions.

Abstract access  

Editor’s notes: A lot has been written on why people delay entry into care, when they are living with HIV. The guidance that all people living with HIV should now start treatment means that many people who are healthy are being offered treatment. The authors of this paper found that in a small sample of people in South Africa, looking healthy mattered. There was a value in the message that ART could maintain health, and in the words of one participant in their study, to ‘remain beautiful’. In addition, other positive anticipated results of taking ART emerged from the data. Young people saw the benefit in maintaining their health so they can help their family in the future, for example. However, despite the positive messages on appearance and a future role for the family and society, many concerns remained. Participants wanted privacy to live with HIV without others knowing. Fears of stigma, fears of an altered appearance and faltering strength haunted participants. The authors stress the value of the positive messaging of ART as an aid to sustaining a healthy appearance. They suggest that this messaging could be used to encourage people to start ART promptly. 

Africa
South Africa
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Only a quarter of people living with HIV in South Africa virally suppressed

The continuum of HIV care in South Africa: implications for achieving the second and third UNAIDS 90-90-90 targets.

Takuva S, Brown AE, Pillay Y, Delpech V, Puren AJ. AIDS. 2017 Feb 20;31(4):545-552. doi: 10.1097/QAD.0000000000001340.

Background: We characterize engagement with HIV care in South Africa in 2012 to identify areas for improvement towards achieving global 90-90-90 targets.

Methods: Over 3.9 million CD4 cell count and 2.7 million viral load measurements reported in 2012 in the public sector were extracted from the national laboratory electronic database. The number of persons living with HIV (PLHIV), number and proportion in HIV care, on antiretroviral therapy (ART) and with viral suppression (viral load <400 copies/ml) were estimated and stratified by sex and age group. Modified Poisson regression approach was used to examine associations between sex, age group and viral suppression among persons on ART.

Results: We estimate that among 6 511 000 PLHIV in South Africa in 2012, 3 300 000 individuals (50.7%) accessed care and 32.9% received ART. Although viral suppression was 73.7% among the treated population in 2012, the overall percentage of persons with viral suppression among all PLHIV was 23.8%. Linkage to HIV care was lower among men (38.5%) than among women (57.2%). Overall, 47.1% of those aged 0-14 years and 47.0% of those aged 15-49 years were linked to care compared with 56.2% among those aged above 50 years.

Conclusion: Around a quarter of all PLHIV have achieved viral suppression in South Africa. Men and younger persons have poorer linkage to HIV care. Expanding HIV testing, strengthening prompt linkage to care and further expansion of ART are needed for South Africa to reach the 90-90-90 target. Focus on these areas will reduce the transmission of new HIV infections and mortality in the general population.

Abstract access 

Editor’s notes: To maximise the impact of ART, people living with HIV should be diagnosed early, enrolled and initiated on antiretroviral therapy (ART) and retained in ART care. Long-term adherence to achieve and maintain viral load suppression is the last step in the continuum of HIV care. Engagement along the complete treatment cascade will determine the long-term success of the global response to HIV.

In this manuscript, the authors used a combination of national HIV prevalence estimates and routine data collected through the National Health Laboratory Service to construct and characterize the different stages of the HIV care continuum in South Africa.

They estimate that, despite the expansion of the ART programme in South Africa, only about a quarter of people living with HIV were virally suppressed in 2012, contrasting with recent estimates from Botswana where about 70% of people living with HIV were reported to be virally suppressed. They estimate that only about half of all people living with HIV accessed care, but report that, once in care, the ART programme proves to be effective with three-quarters of people on ART achieving virologic suppression. Not surprisingly they found that men and younger persons have poorer linkage to care. They recommend that HIV testing needs to be expanded, and linkage to care needs to be promoted for people testing HIV-positive, if the UNAIDS 90-90-90 treatment target is to be reached.

This paper illustrates how, in the context of a national public sector laboratory diagnostic service, routine laboratory data can be used to monitor the public health response to HIV at a national level. 

Africa
South Africa
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A cohort-based approach to the HIV treatment cascade finds linkage the major bottleneck

From HIV infection to therapeutic response: a population-based longitudinal HIV cascade-of-care study in KwaZulu-Natal, South Africa.

Haber N, Tanser F, Bor J, Naidu K, Mutevedzi T, Herbst K, Porter K, Pillay D, Barnighausen T. Lancet HIV. 2017 Jan 30. pii: S2352-3018(16)30224-7. doi: 10.1016/S2352-3018(16)30224-7. [Epub ahead of print]

Background: Standard approaches to estimation of losses in the HIV cascade of care are typically cross-sectional and do not include the population stages before linkage to clinical care. We used individual-level longitudinal cascade data, transition by transition, including population stages, both to identify the health-system losses in the cascade and to show the differences in inference between standard methods and the longitudinal approach.

Methods: We used non-parametric survival analysis to estimate a longitudinal HIV care cascade for a large population of people with HIV residing in rural KwaZulu-Natal, South Africa. We linked data from a longitudinal population health surveillance (which is maintained by the Africa Health Research Institute) with patient records from the local public-sector HIV treatment programme (contained in an electronic clinical HIV treatment and care database, ARTemis). We followed up all people who had been newly detected as having HIV between Jan 1, 2006, and Dec 31, 2011, across six cascade stages: three population stages (first positive HIV test, HIV status knowledge, and linkage to care) and three clinical stages (eligibility for antiretroviral therapy [ART], initiation of ART, and therapeutic response). We compared our estimates to cross-sectional cascades in the same population. We estimated the cumulative incidence of reaching a particular cascade stage at a specific time with Kaplan-Meier survival analysis.

Findings: Our population consisted of 5205 individuals with HIV who were followed up for 24 031 person-years. We recorded 598 deaths. 4539 individuals gained knowledge of their positive HIV status, 2818 were linked to care, 2151 became eligible for ART, 1839 began ART, and 1456 had successful responses to therapy. We used Kaplan-Meier survival analysis to adjust for censorship due to the end of data collection, and found that 8 years after testing positive in the population health surveillance, 16% had died. Among living patients, 82% knew their HIV status, 45% were linked to care, 39% were eligible for ART, 35% initiated ART, and 33% had reached therapeutic response. Median times to transition for these cascade stages were 52 months, 52 months, 20 months, 3 months, and 9 months, respectively. Compared with the population stages in the cascade, the transitions across the clinical stages were fast. Over calendar time, rates of linkage to care have decreased and patients presenting for the first time for care were, on average, healthier.

Interpretation: HIV programmes should focus on linkage to care as the most important bottleneck in the cascade. Cascade estimation should be longitudinal rather than cross-sectional and start with the population stages preceding clinical care.

Abstract access  

Editor’s notes: The HIV treatment cascade outlines the stages required to effectively treat HIV, starting with HIV testing and ending with viral suppression. The cascade has become a widely-used framework to evaluate the performance of HIV care programmes, to measure progress towards universal treatment coverage, and to identify gaps in care. However, methods for constructing the HIV treatment cascade vary considerably. The majority of cascade analyses rely on cross-sectional data obtained from different sources. The authors present the first analysis of the HIV treatment cascade that follows individuals longitudinally from the time of HIV infection across all stages of the cascade. By linking data from a demographic surveillance system with electronic clinical records, they are able to describe the cascade for a large population-based cohort of people living with HIV in rural KwaZulu-Natal, South Africa.  They demonstrate that, once people became eligible for ART, the rates of ART initiation, and of viral suppression after initiation, were high. Half of individuals started ART within three months of becoming eligible, and 94% of people on therapy achieved virologic suppression. In addition, retention in care improved over time. However, a key finding is that rates of HIV diagnosis and linkage to care worsened over time, and less than 50% of people had linked to care within eight years of HIV infection, despite 82% being aware of their status. As illustrated by cascade analyses in other settings, increasing linkage to care remains a major challenge for reaching the UNAIDS 90-90-90 treatment target in sub-Saharan Africa.  

In addition to highlighting linkage as the most important bottleneck in the HIV care cascade in this part of rural KwaZulu-Natal, the study illustrates some of the weaknesses in traditional cascade analyses based on cross-sectional data. The cross-sectional cascade is constructed from snapshots of different groups of people in a particular moment in time, rather than describing what happens to the same group of people over time. The authors illustrate how a cross-sectional analysis can give a misleading impression of improvement in the cascade over time, because it fails to take account of changes in the population. The longitudinal cascade, by following the same group of people, provides important insights into the true progression of the cascade over time, and identification of losses along each stage. However, the individual-level longitudinal data necessary for this type of analysis requires a large investment in data collection, and is unlikely to be feasible in most resource-limited settings.

Africa
South Africa
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Adolescents and PMTCT services: where are the gaps?

PMTCT service uptake among adolescents and adult women attending antenatal care in selected health facilities in Zimbabwe.

Musarandega R, Machekano R, Chideme M, Muchuchuti C, Mushavi A, Mahomva A, Guay L. J Acquir Immune Defic Syndr. 2017 Feb 20. doi: 10.1097/QAI.0000000000001327. [Epub ahead of print]

Background: Age-disaggregated analyses of prevention of mother-to-child transmission (PMTCT) program data to assess the uptake of HIV services by pregnant adolescent women are limited but are critical to understanding the unique needs of this vulnerable, high risk population.

Methods: We conducted a retrospective analysis of patient-level PMTCT data collected from 2011 to 2013 in 36 health facilities in 5 districts of Zimbabwe using an electronic database. We compared uptake proportions for PMTCT services between adolescent (< 19 years) and adult (> 19 years) women. Multivariable binomial regression analysis was used to estimate the association of the women's age group with each PMTCT service indicator.

Results: The study analysed data from 22 215 women aged 12 to 50 years (22.5% adolescents). Adolescents were more likely to present to ANC before 14 weeks gestational age compared to older women (adjusted relative risk (aRR)=1.34; 95% confidence interval (CI): 1.22-1.47) with equally low rates of completion of four ANC visits. Adolescents were less likely to present with known HIV status (aRR=0.34; 95% CI: 0.29-0.41) but equally likely to be HIV tested in ANC. HIV prevalence was 5.5% in adolescents versus 20.1% in adults. While > 84% of both HIV-positive groups received ARVs for PMTCT, 44% of eligible adolescents were initiated on ART versus 51.3% of eligible adults, though not statistically significant.

Conclusions: Pregnant adolescents must be a priority for primary HIV prevention services and expanded HIV treatment services among pregnant women to achieve an AIDS-free generation in Zimbabwe and similar high HIV burden countries.

Abstract access  

Editor’s notes: Young women continue to be a key population at risk of acquiring HIV, and contribute approximately one-third of all new infections in sub-Saharan Africa. Young women face multiple legal, economic and social vulnerabilities that place them not only at higher risk of acquiring HIV but may also have an impact on their ability to access antenatal care (ANC) services and programmes to prevent mother-to-child HIV transmission (PMTCT) if they get pregnant. This in turn has implications for the goal of eliminating paediatric HIV infection.

This retrospective study compared the uptake of PMTCT services between adolescents (people aged 19 years and below) and older women accessing ANC in 36 public sector services across Zimbabwe. The study was conducted between 2011 and 2013, when PMTCT guidelines recommended Option A. Option A called for life-long antiretroviral therapy (ART) for women who were ART-eligible based on immunological or clinical criteria; or, for people ineligible, zidovudine monotherapy through pregnancy followed by single dose nevirapine at the onset of labour. It is no longer formally recommended by World Health Organization (WHO), although it is still used in some countries.      

Nearly a quarter of all women were adolescents and over 80% were on their first pregnancy or primigravid. Adolescent women were 34% more likely to attend their first ANC visit by 14 weeks of gestational age compared to adult women. But among both groups, only about 10% attended their first ANC visit in the first trimester and less than 40% attended the four antenatal visits recommended by WHO. Notably, knowledge of HIV status prior to the first ANC attendance was 66% lower in adolescent women, even after adjusting for parity and facility type, with only 3.1% aware of their HIV status. In addition, the proportion of women who were known HIV-positive and taking ART was also lower, although this may be due partly to fewer adolescents being eligible for ART. The uptake of HIV testing (over 95%) and uptake of zidovudine prophylaxis was high among all women. However, there was a suggestion that adolescents were less likely than older women to start ART if they were eligible, although this was not statistically significant. Indeed, several studies in the region have demonstrated lower levels of ART initiation among pregnant adolescents compared to older women.  

Older women would have been more likely to have undergone HIV testing in previous pregnancies. However, even after adjusting for parity, this study demonstrates that adolescents are less likely to have previously accessed HIV testing. Common barriers to testing highlighted by other studies include lack of information, unavailability of HIV testing services, unfriendly HIV testing environments in health facilities and the need for parental consent. Lack of knowledge of HIV status prior to pregnancy is also a missed opportunity for family planning, and initiation of ART prior to pregnancy. The substantial difference in HIV prevalence among adolescents compared to older women highlights the critical need for implementing prevention programmes such as pre-exposure prophylaxis among young women in high HIV prevalence settings. While adolescents are less likely to be tested for HIV in the general population than adults, this study illustrates that when HIV testing is offered in appropriate, supportive environments, uptake is high.

Overall, the uptake of HIV testing and of prophylaxis were high, demonstrating the potential for eliminating infections in children. A major limitation is that this analysis was limited to women who had sought antenatal care. Promoting early ANC attendance is important to allow early ART initiation, to reduce the risk of intrauterine HIV transmission. Following a positive HIV test result, particular attention is necessary to ensure linkage to care and support for sustained adherence to ART.

Africa
Zimbabwe
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Peer led activities increase HIV testing uptake among MSM

Effectiveness of peer-led interventions to increase HIV testing among men who have sex with men: a systematic review and meta-analysis.

Shangani S, Escudero D, Kirwa K, Harrison A, Marshall B, Operario D. AIDS Care. 2017 Feb 2:1-11. doi: 10.1080/09540121.2017.1282105. [Epub ahead of print]

HIV testing constitutes a key step along the continuum of HIV care. Men who have sex with men (MSM) have low HIV testing rates and delayed diagnosis, especially in low-resource settings. Peer-led interventions offer a strategy to increase testing rates in this population. This systematic review and meta-analysis summarizes evidence on the effectiveness of peer-led interventions to increase the uptake of HIV testing among MSM. Using a systematic review protocol that was developed a priori, we searched PubMed, PsycINFO and CINAHL for articles reporting original results of randomized or non-randomized controlled trials (RCTs), quasi-experimental interventions, and pre- and post-intervention studies. Studies were eligible if they targeted MSM and utilized peers to increase HIV testing. We included studies published in or after 1996 to focus on HIV testing during the era of combination antiretroviral therapy. Seven studies encompassing a total of 6205 participants met eligibility criteria, including two quasi-experimental studies, four non-randomized pre- and-post intervention studies, and one cluster randomized trial. Four studies were from high-income countries, two were from Asia and only one from sub-Saharan Africa. We assigned four studies a "moderate" methodological rigor rating and three a "strong" rating. Meta-analysis of the seven studies found HIV testing rates were statistically significantly higher in the peer-led intervention groups versus control groups (pooled OR 2.00, 95% CI 1.74-2.31). Among randomized trials, HIV testing rates were significantly higher in the peer-led intervention versus control groups (pooled OR: 2.48, 95% CI 1.99-3.08). Among the non-randomized pre- and post-intervention studies, the overall pooled OR for intervention versus control groups was 1.71 (95% CI 1.42-2.06), with substantial heterogeneity among studies (I2 = 70%, p < 0.02). Overall, peer-led interventions increased HIV testing among MSM but more data from high-quality studies are needed to evaluate effects of peer-led interventions on HIV testing among MSM in low- and middle-income countries.

Abstract access  

Editor’s notes: A key driver of the HIV epidemic is low uptake of HIV testing in many settings. This leads to a high proportion of individuals living with HIV being unaware of their status, failing to engage with care and treatment and hence being at risk of transmitting HIV to others. Recent reviews have illustrated that programmes led by members of the same peer group can be effective in promoting HIV-associated behavioural change and improving clinical outcomes. Gay men and other men who have sex with men can experience specific challenges associated with engagement with HIV care. This problem is particularly acute in resource poor regions due to very high levels of stigma.

This systematic review is the first to look specifically at the effectiveness of peer-led activities among gay men and other men who have sex with men. Seven studies were found which fulfilled the inclusion criteria of assessing the impact of peer-led activities on HIV testing uptake among gay men and other men who have sex with men. Four of these were in high income settings, and the others in Peru, Taiwan and Kenya. Each study illustrated a positive effect of peer-led activities on increasing HIV testing rates, and meta-analyses illustrated consistent effects when data were stratified by sub-groups (study methodology, study quality or setting). However, the generalizability of these studies to the entire population of gay men and other men who have sex with men is a concern recognized by the authors as the majority used gay-centric community venues to recruit participants. This is likely to exclude individuals who do not self-identify as being part of this community. Two studies, one in Taiwan and the other in Peru, used social-media as a mechanism of recruitment. This approach may lead to a wider recruitment, although not accessible to people without access to the internet.

Overall, this review emphasizes the potential of peer-led activities to overcome barriers to engage with testing and treatment experienced by gay men and other men who have sex with men and other hard to reach and high-risk sub-populations. It also illustrated the very limited current evidence available to assess such programmes.

 

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Outcomes on ART among children and adolescents in Latin America

Mortality in children with human immunodeficiency virus initiating treatment: a six-cohort study in Latin America.

Luque MT, Jenkins CA, Shepherd BE, Padgett D, Rouzier V, Succi RC, Machado DM, McGowan CC, Vermund SH, Pinto JA. J Pediatr. 2017 Jan 9. pii: S0022-3476(16)31433-0. doi: 10.1016/j.jpeds.2016.12.034. [Epub ahead of print]

Objectives: To assess the risks of and factors associated with mortality, loss to follow-up, and changing regimens after children with HIV infected perinatally initiate combination antiretroviral therapy (cART) in Latin America and the Caribbean.

Study design: This 1997-2013 retrospective cohort study included 1174 antiretroviral therapy-naive, perinatally infected children who started cART when they were younger than 18 years of age (median 4.7 years; IQR 1.7-8.8) at 1 of 6 cohorts from Argentina, Brazil, Haiti, and Honduras, within the Caribbean, Central and South America Network for HIV Epidemiology. Median follow-up was 5.6 years (IQR 2.3-9.3). Study outcomes were all-cause mortality, loss to follow-up, and major changes/interruption/stopping of cART. We used Cox proportional hazards models stratified by site to examine the association between predictors and times to death or changing regimens.

Results: Only 52% started cART at younger than 5 years of age; 19% began a protease inhibitor. At cART initiation, median CD4 count was 472 cells/mm3 (IQR 201-902); median CD4% was 16% (IQR 10-23). Probability of death was high in the first year of cART: 0.06 (95% CI 0.04-0.07). Five years after cART initiation, the cumulative mortality incidence was 0.12 (95% CI 0.10-0.14). Cumulative incidences for loss to follow-up and regimen change after 5 years were 0.16 (95% 0.14-0.18) and 0.30 (95% 0.26-0.34), respectively. Younger children had the greatest risk of mortality, whereas older children had the greatest risk of being lost to follow-up or changing regimens.

Conclusions: Innovative clinical and community approaches are needed for quality improvement in the pediatric care of HIV in the Americas.

Abstract access

Editor’s notes: Despite the dramatic declines in mortality with antiretroviral therapy (ART), mortality rates among children living with HIV still remain substantially higher than in the general paediatric population in high-income settings, such as in the United States of America. Mortality rates after ART initiation are even higher in sub-Saharan Africa, likely because children initiate ART at older ages and at more advanced stages of disease. There are, however, no data available for Latin America and the Caribbean, which has had a mostly stable epidemic with a slowly declining adult HIV incidence over the past decade.

In this retrospective cohort study, the authors investigate mortality, loss-to-follow-up (LTFU) and regimen change among children who acquired HIV in the perinatal period from Argentina, Haiti, Honduras and Brazil. They initiated ART aged below 18 years. About half of all children started ART aged over five years, and a third had clinical AIDS by the time they initiated ART. This would suggest that paediatric HIV programmes in this region face similar challenges to those seen in African programmes, including failure of prevention of mother-to-child HIV transmission (PMTCT) programmes and late diagnosis of children.

As expected, a low baseline CD4 count and clinical AIDS at baseline were both associated with an increased risk of mortality. Importantly, younger age at starting ART was also associated with an increased hazard of death, as was being an adolescent (although the association was weaker). The most likely reason for this is that the youngest children placed on ART may have been initiated following presentation with fast-progressing disease, and would therefore have a higher risk of death than comparatively healthier and stable older children. The higher risk of death among the adolescents likely reflects delayed diagnosis of slow-progressors in adolescence.   

Another important finding was the significantly higher risk of LTFU and regimen change in adolescents compared to younger children. This finding, also noted in African and high-income setting cohorts, highlights the challenges of retaining adolescents in care, addressing treatment fatigue, and possibly increased risk of attrition from care during transitioning from paediatric to adult services. 

In summary, HIV care outcomes in children in Latin America and the Caribbean appear to be similar to those reported in other settings. Together, they highlight the pressing need for strengthening prevention of mother-to-child HIV transmission programmes, particularly follow-up and prompt testing of HIV-exposed infants. It also emphasizes the need for innovative approaches to support children to stay in care and maintain long-term adherence. 

Latin America
Argentina, Brazil, Haiti, Honduras
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HIV Self-testing acceptable to vocational students in South Africa

High acceptability of HIV self-testing among technical vocational education and training college students in Gauteng and North West province: what are the implications for the scale up in South Africa?

Mokgatle MM, Madiba S. PLoS One. 2017 Jan 31;12(1):e0169765. doi: 10.1371/journal.pone.0169765. eCollection 2017.

Background: Although HIV self-testing (HIVST) is globally accepted as an important complement to existing HIV testing approaches, South Africa has lagged behind in its adoption. As a result, data on the acceptability and uptake of HIVST is limited. The study investigated the acceptability of HIVST among students in Technical Vocational Education and Training (TVET) colleges in two provinces in South Africa.

Methods: A cross-sectional survey using a self-administered structured questionnaire was used to collect data among 3662 students recruited from 13 TVET colleges.

Results: The mean age of the students was 21.9 years. The majority (80.9%) were sexually active; while 66.1% reported that they had one sexual partner, and 33.9% had two or more sexual partners in the past year, and 66.5% used condoms during the last sexual act. Three-quarters tested for HIV in the past year but less than half knew about HIVST prior to the survey. The acceptability of HIVST was high; about three-quarters showed a willingness to purchase a self-test kit and a majority would self-test with partners. Acceptability of HIVST was associated with being sexually active (OR = 1.73, p = 0.02, confidence interval (CI): 1.08-2.75), having ever been tested for HIV (OR = 1.74, p = 0.001, CI: 1.26-2.38), and having multiple sexual partners (OR = 0.61, p = 0.01, CI: 0.42-0.88). Three-quarters would confirm test results at a local health facility. In terms of counselling, telephone hotlines were acceptable to only 39.9%, and less than half felt that test-kit leaflets would provide sufficient information to self-test.

Interpretations: The high acceptability of HIVST among the students calls for extensive planning and preparation for the scaling up of HIVST in South Africa. In addition, campaigns similar to those conducted to promote HIV counselling and testing (HCT) should be considered to educate communities about HIVST.

Abstract  Full-text [free] access  

Editor’s notes: The percentage of people living with HIV who know their status (the first 90 of the UNAIDS 90:90:90 treatment target) has been consistently well below the stated target in national HIV treatment cascades. HIV self-testing is an exciting strategy being used to increase the uptake of testing, and has recently been adopted in South Africa. This study had two aims; firstly to assess the participants attitudes to currently available HIV counselling and testing services and secondly to assess the level of acceptability of HIV self-testing. The study population were students in technical and vocational education and training colleges in South Africa.

Among people who had not tested for HIV in the past year, reasons given for non-uptake of testing (other than a low perception of risk) included a fear of stigma associated with a positive test or a lack of comfort with testing in a hospital setting. Less than half of participants had heard of HIV self-testing, but when the concept was explained to them, around 80% expressed a willingness to use it if it was available, and 70% were willing to purchase the self-test kit. These results are consistent with other studies of HIV self-testing uptake and acceptability in sub-Saharan Africa.

The stated willingness of participants to present at a clinic for a confirmatory test is encouraging. However, this may not reflect actual behaviour, especially in a setting where there is currently no plan or system to link people with positive HIV self-test results to a clinic for confirmatory testing. However, the drive to improve counselling and linkage around self-testing needs to be balanced against the fundamental principle for HIV self-testing to allow choice for users to test without the need for a health worker to be present, and the privacy associated with this. Further work may include assessing acceptability of using remote services to complement HIV self-testing such as telephone hotlines or other counselling strategies. 

Africa
South Africa
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