Articles tagged as "Kenya"

Assisted partner services a safe, effective strategy to identify undiagnosed HIV cases in sub-Saharan Africa

Assisted partner services for HIV in Kenya: a cluster randomised controlled trial.

Cherutich P, Golden MR, Wamuti B, Richardson BA, Asbjornsdottir KH, Otieno FA, Ng'ang'a A, Mutiti PM, Macharia P, Sambai B, Dunbar M, Bukusi D, Farquhar C. Lancet HIV. 2016 Nov 29. pii: S2352-3018(16)30214-4. doi: 10.1016/S2352-3018(16)30214-4. [Epub ahead of print]

Background: Assisted partner services for index patients with HIV infections involves elicitation of information about sex partners and contacting them to ensure that they test for HIV and link to care. Assisted partner services are not widely available in Africa. We aimed to establish whether or not assisted partner services increase HIV testing, diagnoses, and linkage to care among sex partners of people with HIV infections in Kenya.

Methods: In this cluster randomised controlled trial, we recruited non-pregnant adults aged at least 18 years with newly or recently diagnosed HIV without a recent history of intimate partner violence who had not yet or had only recently linked to HIV care from 18 HIV testing services clinics in Kenya. Consenting sites in Kenya were randomly assigned (1:1) by the study statistician (restricted randomisation; balanced distribution in terms of county and proximity to a city) to immediate versus delayed assisted partner services. Primary outcomes were the number of partners tested for HIV, the number who tested HIV positive, and the number enrolled in HIV care, in those who were interviewed at 6 week follow-up. Participants within each cluster were masked to treatment allocation because participants within each cluster received the same intervention. This trial is registered with ClinicalTrials.gov, number NCT01616420.

Findings: Between Aug 12, 2013, and Aug 31, 2015, we randomly allocated 18 clusters to immediate and delayed HIV assisted partner services (nine in each group), enrolling 1305 participants: 625 (48%) in the immediate group and 680 (52%) in the delayed group. 6 weeks after enrolment of index patients, 392 (67%) of 586 partners had tested for HIV in the immediate group and 85 (13%) of 680 had tested in the delayed group (incidence rate ratio 4.8, 95% CI 3.7-6.4). 136 (23%) partners had new HIV diagnoses in the immediate group compared with 28 (4%) in the delayed group (5.0, 3.2-7.9) and 88 (15%) versus 19 (3%) were newly enrolled in care (4.4, 2.6-7.4). Assisted partner services did not increase intimate partner violence (one intimate partner violence event related to partner notification or study procedures occurred in each group).

Interpretation: Assisted partner services are safe and increase HIV testing and case-finding; implementation at the population level could enhance linkage to care and antiretroviral therapy initiation and substantially decrease HIV transmission.

Abstract access  

Editor’s notes: One of the greatest challenges to achieving goals such as the UNAIDS 90:90:90 treatment target is the development of more effective strategies to enable people undiagnosed living with HIV to be tested and engaged with care. One strategy for achieving this in high-income settings, albeit with a very limited evidence base, is assisted partner services. In this approach, health-care workers identify and attempt to contact the sexual partners of people recently diagnosed with HIV. These partners are then encouraged to be tested and engaged with care. This pragmatic cluster randomised study, conducted in Kenya, aimed to assess whether assisted partner services were feasible in a sub-Saharan African setting and if so, to measure the effectiveness in terms of additional individuals testing for HIV, receiving new HIV diagnoses and engaging with care as a result of the programme.

The results were striking, in that six weeks after enrolment almost five times as many partners of index cases in the immediate group (partners contacted  at enrolment) had been tested for HIV compared to the delayed group (partners contacted  six weeks after enrolment). There were five times as many new HIV diagnoses in the immediate group compared to the delayed group. There were also four times as many partners newly engaged with care in the immediate arm compared to the delayed arm. There was also no evidence that the tracing of sexual partners led to an increase in intimate partner violence.

These results illustrate that assisted partner services can make an important contribution to identifying people living with HIV who are undiagnosed, enabling people to get tested and engaged with care in a low-income setting. A major challenge, identified by the study authors, is whether the human resources would be available in already highly stretched settings to implement this strategy. They suggest that task shifting from professional healthcare providers to a less highly educated cadre of workers would be feasible and point to other areas of care such as safe male circumcision and ART delivery, where this has been successfully achieved. 

Africa
Kenya
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Thymidine analogue mutations associated with extensive resistance in African people failing on tenofovir

Occult HIV-1 drug resistance to thymidine analogues following failure of first-line tenofovir combined with a cytosine analogue and nevirapine or efavirenz in sub-Saharan Africa: a retrospective multi-centre cohort study.

Gregson J, Kaleebu P, Marconi VC, van Vuuren C, Ndembi N, Hamers RL, Kanki P, Hoffmann CJ, Lockman S, Pillay D, de Oliveira T, Clumeck N, Hunt G, Kerschberger B, Shafer RW, Yang C, Raizes E, Kantor R, Gupta RK. Lancet Infect Dis. 2016 Nov 30. pii: S1473-3099(16)30469-8. doi: 10.1016/S1473-3099(16)30469-8. [Epub ahead of print]

Background: HIV-1 drug resistance to older thymidine analogue nucleoside reverse transcriptase inhibitor drugs has been identified in sub-Saharan Africa in patients with virological failure of first-line combination antiretroviral therapy (ART) containing the modern nucleoside reverse transcriptase inhibitor tenofovir. We aimed to investigate the prevalence and correlates of thymidine analogue mutations (TAM) in patients with virological failure of first-line tenofovir-containing ART.

Methods: We retrospectively analysed patients from 20 studies within the TenoRes collaboration who had locally defined viral failure on first-line therapy with tenofovir plus a cytosine analogue (lamivudine or emtricitabine) plus a non-nucleoside reverse transcriptase inhibitor (NNRTI; nevirapine or efavirenz) in sub-Saharan Africa. Baseline visits in these studies occurred between 2005 and 2013. To assess between-study and within-study associations, we used meta-regression and meta-analyses to compare patients with and without TAMs for the presence of resistance to tenofovir, cytosine analogue, or NNRTIs.

Findings: Of 712 individuals with failure of first-line tenofovir-containing regimens, 115 (16%) had at least one TAM. In crude comparisons, patients with TAMs had lower CD4 counts at treatment initiation than did patients without TAMs (60.5 cells per µL [IQR 21.0-128.0] in patients with TAMS vs 95.0 cells per µL [37.0-177.0] in patients without TAMs; p=0.007) and were more likely to have tenofovir resistance (93 [81%] of 115 patients with TAMs vs 352 [59%] of 597 patients without TAMs; p<0.0001), NNRTI resistance (107 [93%] vs 462 [77%]; p<0.0001), and cytosine analogue resistance (100 [87%] vs 378 [63%]; p=0.0002). We detected associations between TAMs and drug resistance mutations both between and within studies; the correlation between the study-level proportion of patients with tenofovir resistance and TAMs was 0.64 (p<0.0001), and the odds ratio for tenofovir resistance comparing patients with and without TAMs was 1.29 (1.13-1.47; p<0.0001)

Interpretation: TAMs are common in patients who have failure of first-line tenofovir-containing regimens in sub-Saharan Africa, and are associated with multidrug resistant HIV-1. Effective viral load monitoring and point-of-care resistance tests could help to mitigate the emergence and spread of such strains.

Abstract  Full-text [free] access 

Editor’s notes: Since 2012, WHO has recommended that tenofovir should be included in first-line antiretroviral therapy, in place of the thymidine analogues, zidovudine and stavudine, which have more significant adverse effects. When therapy fails to maintain virologic control, tenofovir is associated with characteristic resistance mutations that are different from the thymidine analogue mutations (TAMs) associated with the older drugs. This study looked at the resistance patterns of people in Africa with virologic failure after starting on WHO recommended first-line combination including tenofovir and a non-nucleoside reverse transcriptase inhibitor (NNRTI).  TAMs were surprisingly common (16%) for a group who were not known to have received thymidine analogues. This is not what would be expected from this drug combination. The implication is that TAMs may have been present before tenofovir-containing treatment was started, possibly because of undeclared previous therapy. It is well known that TAMs make subsequent therapy with an NNRTI and nucleoside analogues very much more likely to fail. The presence of TAMs was associated with more extensive resistance to other drugs including lamivudine and NNRTIs, some of which may also have been present before the tenofovir based treatment.

Only people with treatment failure were studied. The total number entering into treatment is not recorded. However, based on other reports in Africa the authors speculate a failure rate of 15 to 35% and that they may therefore have found TAMs in two to six percent of people who started treatment. That seems a realistic figure for undeclared prior treatment and gives some perspective to the scale of this problem.

There is continuing concern about drug resistance in low- and middle-income countries.  As the thymidine analogues are phased out, people receiving them may be switched to tenofovir. In situations where there is no access to viral load monitoring, some people will have unrecognised virologic failure and may have developed resistance including TAMs. They are then likely to fail on tenofovir with additional resistance. Realistic strategies are necessary for the prompt detection of treatment failure.

Africa
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At the halfway mark? Community viral suppression in East Africa

Population levels and geographical distribution of HIV RNA in rural Ugandan and Kenyan communities, including serodiscordant couples: a cross-sectional analysis.

Jain V, Petersen ML, Liegler T, Byonanebye DM, Kwarisiima D, Chamie G, Sang N, Black D, Clark TD, Ladai A, Plenty A, Kabami J, Ssemmondo E, Bukusi EA, Cohen CR, Charlebois ED, Kamya MR, Havlir DV. Lancet HIV. 2016 Dec 15. pii: S2352-3018(16)30220-X. doi: 10.1016/S2352-3018(16)30220-X. [Epub ahead of print]

Background: As sub-Saharan Africa transitions to a new era of universal antiretroviral therapy (ART), up-to-date assessments of population-level HIV RNA suppression are needed to inform interventions to optimise ART delivery. We sought to measure population viral load metrics to assess viral suppression and characterise demographic groups and geographical locations with high-level detectable viraemia in east Africa.

Methods: The Sustainable East Africa Research in Community Health (SEARCH) study is a cluster-randomised controlled trial of an HIV test-and-treat strategy in 32 rural communities in Uganda and Kenya, selected on the basis of rural setting, having an approximate population of 10 000 people, and being within the catchment area of a President's Emergency Plan for AIDS Relief-supported HIV clinic. During the baseline population assessment in the SEARCH study, we did baseline HIV testing and HIV RNA measurement. We analysed stable adult (aged 15 years) community residents. We defined viral suppression as a viral load of less than 500 copies per mL. To assess geographical sources of transmission risk, we established the proportion of all adults (both HIV positive and HIV negative) with a detectable viral load (local prevalence of viraemia). We defined transmission risk hotspots as geopolitical subunits within communities with an at least 5% local prevalence of viraemia. We also assessed serodiscordant couples, measuring the proportion of HIV-positive partners with detectable viraemia. The SEARCH study is registered with ClinicalTrials.gov, number NCT01864603.

Findings: Between April 2, 2013, and June 8, 2014, of 303 461 stable residents, we enumerated 274 040 (90.3%), of whom 132 030 (48.2%) were adults. Of these, 117 711 (89.2%) had their HIV status established, of whom 11 964 (10.2%) were HIV positive. Of these, we measured viral load in 8828 (73.8%) people. Viral suppression occurred in 3427 (81.6%) of 4202 HIV-positive adults on ART and 4490 (50.9%) of 8828 HIV-positive adults. Regional viral suppression among HIV-positive adults occurred in 881 (48.2%) of 1827 people in west Uganda, 516 (45.0%) of 1147 in east Uganda, and 3093 (52.8%) of 5854 in Kenya. Transmission risk hotspots occurred in three of 21 parishes in west Uganda and none in east Uganda and in 24 of 26 Kenya geopolitical subunits. In Uganda, 492 (2.9%) of 16 874 couples were serodiscordant: in 287 (58.3%) of these couples, the HIV-positive partner was viraemic (and in 69 [14.0%], viral load was >100 000 copies per mL). In Kenya, 859 (10.0%) of 8616 couples were serodiscordant: in 445 (53.0%) of these couples, the HIV-positive partner was viraemic (and in 129 [15%], viral load was >100 000 copies per mL).

Interpretation: Before the start of the SEARCH trial, 51% of east African HIV-positive adults had viral suppression, reflecting ART scale-up efforts to date. Geographical hotspots of potential HIV transmission risk and detectable viraemia among serodiscordant couples warrant intensified interventions.

Abstract access  

Editor’s notes: Half of all people living with HIV with a valid viral load measurement in these East African communities had viral suppression (<500 copies/mL) at the start of this cluster randomised trial in 2013-14. These results already provided good evidence of the effectiveness and impact of antiretroviral programmes in East Africa. However, at the AIDS conference in July 2016 the study group presented updated results following two years of a universal test and treat (UTT) strategy with expansion of community-based HIV testing services (access abstract here). By this point, the UNAIDS 90-90-90 treatment target had been exceeded in the study communities and, overall, 82% of people living with HIV had viral suppression. 

These results highlight the role of community viral load metrics as indicators of programme impact. What gives rise to more debate is the role of these metrics in estimating the risk of ongoing HIV transmission in the community. Consensus seems to be emerging that the population prevalence of viraemia may be the metric best suited for this purpose. In this study, the estimated population prevalence of viraemia varied quite widely from 0.5 to 14.1% at the level of local communities (of between around 500 and 5000 people). This measure was also used to define several transmission hotspots, based on an arbitrary cut-off of five percent prevalence of viraemia.

Additional research is necessary in different epidemiological contexts to understand the association between these metrics and risk of HIV transmission. There is also some way to go to understand if such metrics can have practical public health implications for HIV prevention. Whether revealing such heterogeneity in transmission risk within generalized epidemics can inform the application of geographically focussed programmes is a question that now should be addressed.

Africa
Kenya, Uganda
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Is universal antenatal HIV testing still cost-effective?

Should HIV testing for all pregnant women continue? Cost-effectiveness of universal antenatal testing compared to focused approaches across high to very low HIV prevalence settings.

Ishikawa N, Dalal S, Johnson C, Hogan DR, Shimbo T, Shaffer N, Pendse RN, Lo YR, Ghidinelli MN, Baggaley R. J Int AIDS Soc. 2016 Dec 14;19(1):21212. doi: 10.7448/IAS.19.1.21212. eCollection 2016.

Introduction: HIV testing is the entry point for the elimination of mother-to-child transmission of HIV. Decreasing external funding for the HIV response in some low- and middle-income countries has triggered the question of whether a focused approach to HIV testing targeting pregnant women in high-burden areas should be considered. This study aimed at determining and comparing the cost-effectiveness of universal and focused HIV testing approaches for pregnant women across high to very low HIV prevalence settings.

Methods: We conducted a modelling analysis on health and cost outcomes of HIV testing for pregnant women using four country-based case scenarios (Namibia, Kenya, Haiti and Viet Nam) to illustrate high, intermediate, low and very low HIV prevalence settings. We used subnational prevalence data to divide each country into high-, medium- and low-burden areas, and modelled different antenatal and testing coverage in each.

Results: When HIV testing services were only focused in high-burden areas within a country, mother-to-child transmission rates remained high ranging from 18 to 23%, resulting in a 25 to 69% increase in new paediatric HIV infections and increased future treatment costs for children. Universal HIV testing was found to be dominant (i.e. more QALYs gained with less cost) compared to focused approaches in the Namibia, Kenya and Haiti scenarios. The universal approach was also very cost-effective compared to focused approaches, with $ 125 per quality-adjusted life years gained in the Viet Nam-based scenario of very low HIV prevalence. Sensitivity analysis further supported the findings.

Conclusions: Universal approach to antenatal HIV testing achieves the best health outcomes and is cost-saving or cost-effective in the long term across the range of HIV prevalence settings. It is further a prerequisite for quality maternal and child healthcare and for the elimination of mother-to-child transmission of HIV.

Abstract  Full-text [free] access 

Editor’s notes: This paper describes research undertaken to support the consolidated guidelines on HIV testing services, published by World Health Organization in 2015. This analysis was conducted in response to growing questions as to whether focused HIV testing in high prevalence areas can improve value for money in investment for HIV testing.

A model was parameterized to represent four scenarios with high, intermediate, low, and very low HIV prevalence settings (Namibia, Kenya, Haiti, and Viet Nam). Three approaches to HIV testing in antenatal care are considered in comparison with current coverage in each setting. These three approaches were: a very focused approach, a targeted approach, and a universal testing approach for all pregnant women.  The authors estimate the costs and effects of each scenario, including the future costs of treating paediatric HIV for 20 years. Universal testing was found to be cost-saving in Namibia, Kenya and Haiti and was found to be cost-effective in Viet Nam ($125 per QALY gained).  The targeted testing approach was also more cost-effective than current coverage in all settings.

The clear policy implication from this analysis is that HIV testing for pregnant women saves both money and lives in the long term. Universal HIV testing in antenatal care can be regarded as a good investment in almost any HIV prevalence setting. However, it is also important to note that targeted testing was more cost-effective than current coverage in all settings. Countries that are currently struggling to provide testing in antenatal care may need to consider factors other than cost-effectiveness in their planning and strategy for scaling up. This is important in order to address HIV at a national scale.  

Africa, Asia, Latin America
Haiti, Kenya, Namibia, Viet Nam
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Improving ART adherence: what works?

Interventions to improve adherence to antiretroviral therapy: a systematic review and network meta-analysis.

Kanters S, Park JJ, Chan K, Socias ME, Ford N, Forrest JI, Thorlund K, Nachega JB, Mills EJ. Lancet HIV. 2017 Jan;4(1):e31-e40. doi: 10.1016/S2352-3018(16)30206-5. Epub 2016 Nov 16.

Background: High adherence to antiretroviral therapy is crucial to the success of HIV treatment. We evaluated comparative effectiveness of adherence interventions with the aim of informing the WHO's global guidance on interventions to increase adherence.

Methods: For this systematic review and network meta-analysis, we searched for randomised controlled trials of interventions that aimed to improve adherence to antiretroviral therapy regimens in populations with HIV. We searched Cochrane Central Register of Controlled Trials, Embase, and MEDLINE for reports published up to July 16, 2015, and searched major conference abstracts from Jan 1, 2013, to July 16, 2015. We extracted data from eligible studies for study characteristics, interventions, patients' characteristics at baseline, and outcomes for the study populations of interest. We used network meta-analyses to compare adherence and viral suppression for all study settings (global network) and for studies in low-income and middle-income countries only (LMIC network).

Findings: We obtained data from 85 trials with 16 271 participants. Short message service (SMS; text message) interventions were superior to standard of care in improving adherence in both the global network (odds ratio [OR] 1.48, 95% credible interval [CrI] 1.00-2.16) and in the LMIC network (1.49, 1.04-2.09). Multiple interventions showed generally superior adherence to single interventions, indicating additive effects. For viral suppression, only cognitive behavioural therapy (1.46, 1.05-2.12) and supporter interventions (1.28, 1.01-1.71) were superior to standard of care in the global network; none of the interventions improved viral response in the LMIC network. For the global network, the time discrepancy (whether the study outcome was measured during or after intervention was withdrawn) was an effect modifier for both adherence to antiretroviral therapy (coefficient estimate -0.43, 95% CrI -0.75 to -0.11) and viral suppression (-0.48; -0.84 to -0.12), suggesting that the effects of interventions wane over time.

Interpretation: Several interventions can improve adherence and viral suppression; generally, their estimated effects were modest and waned over time.

Abstract access  

Editor’s notes: Maintaining adherence to self-administered medications is difficult. On average, people who are prescribed medications for chronic diseases take fewer than half the prescribed doses. Evidence suggests that in most settings adherence to antiretroviral therapy (ART) is better than this, but there will always be people that struggle to maintain the high levels of adherence required for durable virologic suppression. In this analysis, there was some evidence that specific activities or combinations of activities improved virologic suppression. However, the effect sizes were small and when the analysis was confined to studies in low-income and middle-income countries, there was no evidence to suggest an effect on virologic suppression. Overall the evidence to support any particular activity or combination of activities was not compelling.     

Findings from this analysis have been incorporated into most recent consolidated ART guidelines from the World Health Organization. Trying to summarize complex evidence in this way creates many challenges. Trials were conducted in different populations. Some with all people starting ART, others with people considered to have high risk of suboptimal adherence, and others with people who already had adherence problems. The trials also naturally would have differed in content and quality of the usual package of care to support adherence (the comparator for most programme). 60% of the trials were conducted exclusively in the United States, while others were conducted across different settings.

These are just some of the things that make it difficult to synthesize this evidence into guidance that can be applicable to people living with HIV worldwide. HIV programmes in countries have to decide whether or not to adopt any of these activities that are recommended by WHO on the basis of relatively weak evidence. Would we expect activities aimed at improving adherence to be generalizable across different settings? One might argue probably not. Adherence is a multifactorial, dynamic process and there is unlikely to be a ‘one size fits all’ approach to supporting adherence. In the absence of better evidence for any specific activity, we should perhaps focus on improving the quality of the basic package of adherence support offered to all people receiving ART, while also developing better ways to identify when certain people might benefit from enhanced support.        

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Closing the HIV testing gap with partner-delivered self-testing

Promoting partner testing and couples testing through secondary distribution of HIV self-tests: a randomized clinical trial.

Masters SH, Agot K, Obonyo B, Napierala Mavedzenge S, Maman S, Thirumurthy H. PLoS Med. 2016 Nov 8;13(11):e1002166. doi: 10.1371/journal.pmed.1002166. eCollection 2016.

Background: Achieving higher rates of partner HIV testing and couples testing among pregnant and postpartum women in sub-Saharan Africa is essential for the success of combination HIV prevention, including the prevention of mother-to-child transmission. We aimed to determine whether providing multiple HIV self-tests to pregnant and postpartum women for secondary distribution is more effective at promoting partner testing and couples testing than conventional strategies based on invitations to clinic-based testing.

Methods and findings: We conducted a randomized trial in Kisumu, Kenya, between June 11, 2015, and January 15, 2016. Six hundred antenatal and postpartum women aged 18-39 y were randomized to an HIV self-testing (HIVST) group or a comparison group. Participants in the HIVST group were given two oral-fluid-based HIV test kits, instructed on how to use them, and encouraged to distribute a test kit to their male partner or use both kits for testing as a couple. Participants in the comparison group were given an invitation card for clinic-based HIV testing and encouraged to distribute the card to their male partner, a routine practice in many health clinics. The primary outcome was partner testing within 3 mo of enrollment. Among 570 participants analyzed, partner HIV testing was more likely in the HIVST group (90.8%, 258/284) than the comparison group (51.7%, 148/286; difference = 39.1%, 95% CI 32.4% to 45.8%, p < 0.001). Couples testing was also more likely in the HIVST group than the comparison group (75.4% versus 33.2%, difference = 42.1%, 95% CI 34.7% to 49.6%, p < 0.001). No participants reported intimate partner violence due to HIV testing. This study was limited by self-reported outcomes, a common limitation in many studies involving HIVST due to the private manner in which self-tests are meant to be used.

Conclusions: Provision of multiple HIV self-tests to women seeking antenatal and postpartum care was successful in promoting partner testing and couples testing. This approach warrants further consideration as countries develop HIVST policies and seek new ways to increase awareness of HIV status among men and promote couples testing.

Trial registration: ClinicalTrials.gov NCT02386215.

Abstract  Full-text [free] access 

Editor’s notes: Despite scale-up of HIV testing services, two in every five people living with HIV remain undiagnosed. World Health Organization (WHO) has just issued updated guidance on HIV testing services (HTS). In an effort to plug this testing gap, it strengthened the recommendation that HIV self-testing (HIVST) should be offered as one of the approaches to HTS. This paper adds to the body of evidence supporting that recommendation and provides more insight into the specific role of partner-delivered self-testing.     

There are challenges with conducting clinical trials of HIVST, one of which is selecting an appropriate outcome measure. In this trial, the primary outcome was participant report of male partner testing within three months of enrolment. Overall, uptake of male partner testing as reported by the participants was surprisingly high. It is worth noting that the participants and their partners may not have been particularly hard-to-reach groups. Almost all were married. The female participants were frequent testers. On average, they had tested three times in the past year. Most participants also reported that their male partner had tested at least once in the past year. It should also be noted that many women that were screened chose not to participate, so the participants may have to some extent pre-selected themselves as more interested and more likely to benefit from the activity.   

There were very few male partners reported as testing HIV positive during follow-up. This study was not able to determine how effectively people linked to care after HIVST. This is one of a number of research questions that remain around the delivery and impact of HIVST. Many of these are being addressed by the large HIV Self-Testing Africa (STAR) Project (http://hivstar.lshtm.ac.uk/). What seems to be beyond debate now though is that HIVST can and should play a role in helping us to achieve the UNAIDS 90-90-90 treatment target.   

Africa
Kenya
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Comparing different methods to measure HIV incidence in a sub-Saharan African population

Estimating HIV incidence using a cross-sectional survey: comparison of three approaches in a hyperendemic setting, Ndhiwa sub-county, Kenya, 2012.

Blaizot S, Kim AA, Zeh C, Riche B, Maman D, DeCock K, Etard JF, Ecochard R. AIDS Res Hum Retroviruses. 2016 Dec 13. [Epub ahead of print]

Objectives: Estimating HIV incidence is critical for identifying groups at risk for HIV infection, planning and targeting interventions, and evaluating these interventions over time. The use of reliable estimation methods for HIV incidence is thus of high importance. The aim of this study was to compare methods for estimating HIV incidence in a population-based cross-sectional survey.

Design/methods: The incidence estimation methods evaluated included assay-derived methods, a testing history-derived method, and a probability-based method applied to data from the Ndhiwa HIV Impact in Population Survey (NHIPS). Incidence rates by sex and age and cumulative incidence as a function of age were presented.

Results: HIV incidence ranged from 1.38 [95% confidence interval (CI) 0.67-2.09] to 3.30 [95% CI 2.78-3.82] per 100 persons-years overall; 0.59 [95% CI 0.00-1.34] to 2.89 [95% CI 0.11-5.68] in men; and 1.62 [95% CI 0.16-6.04] to 4.03 [95% CI 3.30-4.77] per 100 persons-years in women. Women had higher incidence rates than men for all methods. Incidence rates were highest among women aged 15-24 and 25-34 years and highest among men aged 25-34 years.

Conclusion: Comparison of different methods showed variations in incidence estimates, but they were in agreement to identify most-at-risk groups. The use and comparison of several distinct approaches for estimating incidence are important to provide the best-supported estimate of HIV incidence in the population.

Abstract access

Editor’s notes: The estimation of HIV incidence is important both for planning effective HIV prevention strategies, and also to provide a proximal measure of changes in HIV epidemics both in general populations and in higher risk sub-groups. Further development of methods for accurately measuring HIV incidence that can be applied in routine monitoring settings is necessary.

This study compares three assay-based incidence estimation methods with approaches using self-reported testing history and a probabilistic technique on age and sex stratified sero-prevalence data. Two of the assays, BioRad and Lag, use antibody markers and a recent infection testing algorithm (RITA). The BioRad assay allowed for a longer time window for detection post-infection than the Lag. Recent infections were reclassified using results from HIV viral load tests and self-reported ART use, as appropriate. The other assay detected trace levels of HIV RNA in HIV seronegative individuals. The results for the two RITA assays were very similar at 1.38 [95% CI 0.67 – 2.09] infections per 100 person years (PY) for the BioRad and 1.46 [95% CI 0.71 – 2.22] per 100 PY for Lag. Combining these with HIV-RNA results led to small increases in each incidence estimate. The results for the probability-based incidence assays were very close to those derived from the combination of the RITA and HIV-RNA assays. However, the testing history-derived approach estimated incidence as almost double that from the other methods and this is likely to be in large part due to reporting/recall bias.

Despite the limitations of the methods, it was possible to identify population sub-groups defined by age and sex at higher risk of HIV infection. 

Africa
Kenya
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Using HIV testing infrastructure for other diseases can be very low cost

Implementation and operational research: cost and efficiency of a hybrid mobile multidisease testing approach with high HIV testing coverage in east Africa.

Chang W, Chamie G, Mwai D, Clark TD, Thirumurthy H, Charlebois ED, Petersen M, Kabami J, Ssemmondo E, Kadede K, Kwarisiima D, Sang N, Bukusi EA, Cohen CR, Kamya M, Havlir DV, Kahn JG. J Acquir Immune Defic Syndr. 2016 Nov 1;73(3):e39-e45.

Background: In 2013-2014, we achieved 89% adult HIV testing coverage using a hybrid testing approach in 32 communities in Uganda and Kenya (SEARCH: NCT01864603). To inform scalability, we sought to determine: (1) overall cost and efficiency of this approach; and (2) costs associated with point-of-care (POC) CD4 testing, multidisease services, and community mobilization.

Methods: We applied microcosting methods to estimate costs of population-wide HIV testing in 12 SEARCH trial communities. Main intervention components of the hybrid approach are census, multidisease community health campaigns (CHC), and home-based testing for CHC nonattendees. POC CD4 tests were provided for all HIV-infected participants. Data were extracted from expenditure records, activity registers, staff interviews, and time and motion logs.

Results: The mean cost per adult tested for HIV was $20.5 (range: $17.1-$32.1) (2014 US$), including a POC CD4 test at $16 per HIV+ person identified. Cost per adult tested for HIV was $13.8 at CHC vs. $31.7 by home-based testing. The cost per HIV+ adult identified was $231 ($87-$1245), with variability due mainly to HIV prevalence among persons tested (ie, HIV positivity rate). The marginal costs of multidisease testing at CHCs were $1.16/person for hypertension and diabetes, and $0.90 for malaria. Community mobilization constituted 15.3% of total costs.

Conclusions: The hybrid testing approach achieved very high HIV testing coverage, with POC CD4, at costs similar to previously reported mobile, home-based, or venue-based HIV testing approaches in sub-Saharan Africa. By leveraging HIV infrastructure, multidisease services were offered at low marginal costs.

Abstract access  

Editor’s notes: The scale up of HIV testing services over recent years has meant that infrastructure for HIV testing is, in many places, much stronger than that of other diseases. This study assessed the costs and cost-effectiveness of both HIV testing services and additional multi disease testing in 32 communities of Uganda and Kenya. As has been found in other studies, testing people through community health campaigns cost less than home-based testing. However, the cost per HIV positive person identified varied widely according to the underlying HIV prevalence. The costs of including additional disease testing services – for hypertension, diabetes and malaria – were low. A more holistic approach to health testing could lead to substantial health benefits for relatively low cost.

Africa
Kenya, Uganda
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Invasive cervical cancers preventable by HPV vaccines: a comparison of HIV-positive and negative women

Effect of HIV infection on human papillomavirus types causing invasive cervical cancer in Africa.

Clifford GM, de Vuyst H, Tenet V, Plummer M, Tully S, Franceschi S. J Acquir Immune Defic Syndr. 2016 Nov 1;73(3):332-339.

Objectives: HIV infection is known to worsen the outcome of cervical human papillomavirus (HPV) infection and may do so differentially by HPV type.

Design: Twenty-one studies were included in a meta-analysis of invasive cervical cancers (ICC) among women infected with HIV in Africa.

Method: Type-specific HPV DNA prevalence was compared with data from a similar meta-analysis of HIV-negative ICC using prevalence ratios (PR).

Results: HPV detection was similar in 770 HIV-positive (91.2%) and 3846 HIV-negative (89.6%) ICC, but HIV-positive ICC harbored significantly more multiple HPV infections (PR = 1.75, 95% confidence intervals: 1.18 to 2.58), which were significantly more prevalent in ICC tested from cells than from biopsies. HPV16 was the most frequently detected type in HIV-positive ICC (42.5%), followed by HPV18 (22.2%), HPV45 (14.4%), and HPV35 (7.1%). Nevertheless, HIV-positive ICC were significantly less frequently infected with HPV16 than HIV-negative ICC (PR = 0.88, 95% confidence intervals: 0.79 to 0.99). Other high-risk types were significantly more prevalent in HIV-positive ICC, but only for HPV18 was there a significantly higher prevalence of both single and multiple infections in HIV-positive ICC. Increases for other high-risk types were primarily accounted for by multiple infections. The proportion of HPV-positive ICC estimated attributable to HPV16/18 (71.8% in HIV positive, 73.4% in HIV negative) or HPV16/18/31/33/45/52/58 (88.8%, 89.5%) was not affected by HIV.

Conclusions: HIV alters the relative carcinogenicity of HPV types, but prophylactic HPV16/18 vaccines may nevertheless prevent a similar proportion of ICC, irrespective of HIV infection.

Abstract access  

Editor’s notes: Invasive cervical cancer (ICC) is one of the most common cancers in low and middle income countries. In the African region the prevalence of both ICC and HIV are high. Compared to HIV-negative women, HIV-positive women are at increased risk of oncogenic high-risk (HR) human papillomavirus (HPV) incidence and persistence, and cervical lesion incidence and progression. Current HPV vaccines offer potential for cervical cancer prevention by targeting the HR-HPV types associated with ICC. Although there is no data yet available on HPV vaccine efficacy among HIV-positive persons, HPV vaccines have been reported to be safe and immunogenic in HIV-positive children, female adolescents and adults. 

This systematic review compared the HPV type distribution and the HPV vaccine type distribution in ICC biopsy and cervical cell specimens of 770 HIV-positive and 3846 HIV-negative women from 21 studies in 12 African countries.

The authors report that the fraction of ICC attributable to the HPV types included in the current bivalent (HPV16/18) and nonavalent (HPV16/18/31/33/45/52/58) vaccines was similar among HIV-positive and HIV-negative women (bivalent: 61.7% and 67.3%; nonavalent: 88.9% and 89.5%, respectively). However, a non-negligible proportion of ICC from both HIV-positive and HIV-negative women were infected with non-vaccine types in the absence of any of the vaccine types (7.0% and 7.9% of ICC from HIV-positive and HIV-negative women, respectively), and this was highest for HPV35.

These findings confirm that the currently available HPV vaccines could prevent a similar proportion of ICC cases in HIV-positive as in HIV-negative women. ICC remains an important co-morbidity among HIV-positive women even in the antiretroviral era. Given that HIV-positive women are at greater risk of HR-HPV persistence and cervical lesion incidence and faster progression to high-grade cervical lesions, primary prevention of HPV infection through vaccination could reduce HPV infection and HPV-associated disease in Africa. However, cervical cancer screening will continue to remain important for both HIV-positive and HIV-negative women as there remain a proportion of ICC cases that may not be preventable by currently available vaccines. 

Comorbidity, Epidemiology
Africa
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School-based HIV prevention programmes appear ineffective

School-based interventions for preventing HIV, sexually transmitted infections, and pregnancy in adolescents.

Mason-Jones AJ, Sinclair D, Mathews C, Kagee A, Hillman A, Lombard C. Cochrane Database Syst Rev. 2016 Nov 8;11:CD006417.

Background: School-based sexual and reproductive health programmes are widely accepted as an approach to reducing high-risk sexual behaviour among adolescents. Many studies and systematic reviews have concentrated on measuring effects on knowledge or self-reported behaviour rather than biological outcomes, such as pregnancy or prevalence of sexually transmitted infections (STIs).

Objectives: To evaluate the effects of school-based sexual and reproductive health programmes on sexually transmitted infections (such as HIV, herpes simplex virus, and syphilis), and pregnancy among adolescents.

Search methods: We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for published peer-reviewed journal articles; and ClinicalTrials.gov and the World Health Organization's (WHO) International Clinical Trials Registry Platform for prospective trials; AIDS Education and Global Information System (AEGIS) and National Library of Medicine (NLM) gateway for conference presentations; and the Centers for Disease Control and Prevention (CDC), UNAIDS, the WHO and the National Health Service (NHS) centre for Reviews and Dissemination (CRD) websites from 1990 to 7 April 2016. We hand searched the reference lists of all relevant papers.

Selection criteria: We included randomized controlled trials (RCTs), both individually randomized and cluster-randomized, that evaluated school-based programmes aimed at improving the sexual and reproductive health of adolescents.

Data collection and analysis: Two review authors independently assessed trials for inclusion, evaluated risk of bias, and extracted data. When appropriate, we obtained summary measures of treatment effect through a random-effects meta-analysis and we reported them using risk ratios (RR) with 95% confidence intervals (CIs). We assessed the certainty of the evidence using the GRADE approach.

Main results: We included eight cluster-RCTs that enrolled 55,157 participants. Five trials were conducted in sub-Saharan Africa (Malawi, South Africa, Tanzania, Zimbabwe, and Kenya), one in Latin America (Chile), and two in Europe (England and Scotland). Sexual and reproductive health educational programmes. Six trials evaluated school-based educational interventions. In these trials, the educational programmes evaluated had no demonstrable effect on the prevalence of HIV (RR 1.03, 95% CI 0.80 to 1.32, three trials; 14 163 participants; low certainty evidence), or other STIs (herpes simplex virus prevalence: RR 1.04, 95% CI 0.94 to 1.15; three trials, 17 445 participants; moderate certainty evidence; syphilis prevalence: RR 0.81, 95% CI 0.47 to 1.39; one trial, 6977 participants; low certainty evidence). There was also no apparent effect on the number of young women who were pregnant at the end of the trial (RR 0.99, 95% CI 0.84 to 1.16; three trials, 8280 participants; moderate certainty evidence). Material or monetary incentive-based programmes to promote school attendance. Two trials evaluated incentive-based programmes to promote school attendance. In these two trials, the incentives used had no demonstrable effect on HIV prevalence (RR 1.23, 95% CI 0.51 to 2.96; two trials, 3805 participants; low certainty evidence). Compared to controls, the prevalence of herpes simplex virus infection was lower in young women receiving a monthly cash incentive to stay in school (RR 0.30, 95% CI 0.11 to 0.85), but not in young people given free school uniforms (data not pooled, two trials, 7229 participants; very low certainty evidence). One trial evaluated the effects on syphilis and the prevalence was too low to detect or exclude effects confidently (RR 0.41, 95% CI 0.05 to 3.27; one trial, 1291 participants; very low certainty evidence). However, the number of young women who were pregnant at the end of the trial was lower among those who received incentives (RR 0.76, 95% CI 0.58 to 0.99; two trials, 4200 participants; low certainty evidence). Combined educational and incentive-based programmes. The single trial that evaluated free school uniforms also included a trial arm in which participants received both uniforms and a programme of sexual and reproductive education. In this trial arm herpes simplex virus infection was reduced (RR 0.82, 95% CI 0.68 to 0.99; one trial, 5899 participants; low certainty evidence), predominantly in young women, but no effect was detected for HIV or pregnancy (low certainty evidence).

Authors' conclusions: There is a continued need to provide health services to adolescents that include contraceptive choices and condoms and that involve them in the design of services. Schools may be a good place in which to provide these services. There is little evidence that educational curriculum-based programmes alone are effective in improving sexual and reproductive health outcomes for adolescents. Incentive-based interventions that focus on keeping young people in secondary school may reduce adolescent pregnancy but further trials are needed to confirm this.

Abstract  Full-text [free] access 

Editor’s notes: School-based HIV prevention programmes are widespread worldwide. These programmes use educational institutions as a venue to reach a population that is entering sexual maturity. Several systematic reviews have found beneficial effects of these programmes on HIV-associated knowledge and behaviours, though a subsequent effect of reduced HIV incidence remains unconfirmed. In this systematic review and meta-analysis, the authors included eight randomized controlled trials from sub-Saharan Africa, Europe, and Latin America. Whether using a curriculum- or incentive-based programme, the trials did not provide evidence of an effect of school-based programmes on reducing HIV infection. Nor was there compelling evidence of an effect of these programmes on reducing sexually transmitted infection or pregnancy. This paper highlights the difficulty of translating knowledge and reported behaviors into reductions in HIV infection and other biological outcomes. Further thought is necessary to deliver effective sexual and reproductive health programmes in schools – possibly including incentives, which show some promise but need further evidence on effectiveness. 

Africa, Europe, Latin America
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