Agnès Fiamma

Removing barriers to knowing HIV status: Same-day mobile HIV testing in Zimbabwe

Objectives:We developed a mobile HIV voluntary counseling testing (VCT) strategy. Our aims were (1) to describe those using the services, (2) to assess the acceptability of such services, (3) to assess reasons for not testing previously, and (4) to compare those who used the services with those who did not to determine how to increase acceptability. Methods:We provided free anonymous mobile VCT using 2 rapid HIV tests in 12 marketplaces in Epworth and Seke, Zimbabwe. Qualitative interviews were conducted to assess motivations for and barriers to testing. A subsample of HIV testers and individuals near testing vans who declined testing (nontesters) completed a questionnaire. Results:A total of 1099 individuals participated in mobile VCT between March 2002 and August 2003. The proportion of participants infected with HIV was 29.2%. Overall, 98.8% of participants elected to receive HIV test results the same day. Reasons for not testing previously were often logistic (eg, inconvenience of hours [25.6%] and location [20.7%] or cost [8%]). Those who used the same-day mobile testing services (testers vs. nontesters) perceived themselves at higher risk for HIV infection (adjusted odds ratio [AOR] = 1.8) but were less likely to have known people with HIV (AOR = 0.49) or where to get tested (AOR = 0.57). Conclusions:Same-day HIV testing in community settings seems to be acceptable in sub-Saharan Africa. Barriers to HIV testing are often logistic and can be overcome with community-based strategies. These strategies need to be refined to address the needs of those not using mobile testing services.

Male circumcision and HIV/AIDS: challenges and opportunities

2enrolled in the respective studies. The Kenya and Uganda trials replicated the landmark fi ndings of the South African Orange Farm study, the fi rst randomised controlled trial to report a greater than 50% protective benefi t of male circumcision. 3 Before the availability of data from these three African randomised controlled trials, multiple observational studies correlated male circumcision with reduced risk of HIV infection. 4–9 Systematic reviews and meta-analysis of observational studies provide further evidence of the association of male circumcision with reduced risk of HIV infection 10–12 and a plausible explanation for the biological mechanism for reduced risk of infection has been suggested. 13 Recently released longitudinal evidence of the range of health benefi ts that male circumcision provides, 14

Heterosexual anal intercourse increases risk of HIV infection among young South African men.

Data from a nationally representative household survey of South African youth aged 15–24 years found that sexually active men reporting anal intercourse were nearly twice as likely to be HIV infected as men reporting only vaginal sex (OR 1.7, 95% CI 1.0–3.0). The associated risk was more pronounced among men aged 15–19 years (OR 4.3, 95% CI 1.5–12.1). The association among women was not significant (OR 1.2, 95% CI 0.7–2.0).

Effect of community-based voluntary counselling and testing on HIV incidence and social and behavioural outcomes (NIMH Project Accept; HPTN 043): a cluster-randomised trial

BACKGROUND Although several interventions have shown reduced HIV incidence in clinical trials, the community-level effect of effective interventions on the epidemic when scaled up is unknown. We investigated whether a multicomponent, multilevel social and behavioural prevention strategy could reduce HIV incidence, increase HIV testing, reduce HIV risk behaviour, and change social and behavioural norms. METHODS For this phase 3 cluster-randomised controlled trial, 34 communities in four sites in Africa and 14 communities in Thailand were randomly allocated in matched pairs to receive 36 months of community-based voluntary counselling and testing for HIV (intervention group) or standard counselling and testing alone (control group) between January, 2001, and December, 2011. The intervention was designed to make testing more accessible in communities, engage communities through outreach, and provide support services after testing. Randomisation was done by a computer-generated code and was not masked. Data were collected at baseline (n=14 567) and after intervention (n=56.683) by cross-sectional random surveys of community residents aged 18-32 years. The primary outcome was HIV incidence and was estimated with a cross-sectional multi-assay algorithm and antiretroviral drug screening assay. Thailand was excluded from incidence analyses because of low HIV prevalence. This trial is registered at ClinicalTrials.gov, number NCT00203749. FINDINGS The estimated incidence of HIV in the intervention group was 1.52% versus 1.81% in the control group with an estimated reduction in HIV incidence of 13.9% (relative risk [RR] 0.86, 95% CI 0.73-1.02; p=0.082). HIV incidence was significantly reduced in women older than 24 years (RR=0.70, 0.54-0.90; p=0.0085), but not in other age or sex subgroups. Community-based voluntary counselling and testing increased testing rates by 25% overall (12-39; p=0.0003), by 45% (25-69; p<0·0001) in men and 15% (3-28; p=0.013) in women. No overall effect on sexual risk behaviour was recorded. Social norms regarding HIV testing were improved by 6% (95% CI 3-9) in communities in the intervention group. INTERPRETATION These results are sufficiently robust, especially when taking into consideration the combined results of modest reductions in HIV incidence combined with increases in HIV testing and reductions in HIV risk behaviour, to recommend the Project Accept approach as an integral part of all interventions (including treatment as prevention) to reduce HIV transmission at the community level. FUNDING US National Institute of Mental Health, the Division of AIDS of the US National Institute of Allergy and Infectious Diseases, and the Office of AIDS Research of the US National Institutes of Health.

Estimation of HIV incidence in a large, community-based, randomized clinical trial: NIMH project accept (HIV Prevention Trials Network 043).

Background National Institute of Mental Health Project Accept (HIV Prevention Trials Network [HPTN] 043) is a large, Phase III, community-randomized, HIV prevention trial conducted in 48 matched communities in Africa and Thailand. The study intervention included enhanced community-based voluntary counseling and testing. The primary endpoint was HIV incidence, assessed in a single, cross-sectional, post-intervention survey of >50,000 participants. Methods HIV rapid tests were performed in-country. HIV status was confirmed at a central laboratory in the United States. HIV incidence was estimated using a multi-assay algorithm (MAA) that included the BED capture immunoassay, an avidity assay, CD4 cell count, and HIV viral load. Results Data from Thailand was not used in the endpoint analysis because HIV prevalence was low. Overall, 7,361 HIV infections were identified (4 acute, 3 early, and 7,354 established infections). Samples from established infections were analyzed using the MAA; 467 MAA positive samples were identified; 29 of those samples were excluded because they contained antiretroviral drugs. HIV prevalence was 16.5% (range at study sites: 5.93% to 30.8%). HIV incidence was 1.60% (range at study sites: 0.78% to 3.90%). Conclusions In this community-randomized trial, a MAA was used to estimate HIV incidence in a single, cross-sectional post-intervention survey. Results from this analysis were subsequently used to compare HIV incidence in the control and intervention communities. Trial Registration ClinicalTrials.gov NCT00203749

Development of Methods for Cross-Sectional HIV Incidence Estimation in a Large, Community Randomized Trial

Background Accurate methods of HIV incidence determination are critically needed to monitor the epidemic and determine the population level impact of prevention trials. One such trial, Project Accept, a Phase III, community-randomized trial, evaluated the impact of enhanced, community-based voluntary counseling and testing on population-level HIV incidence. The primary endpoint of the trial was based on a single, cross-sectional, post-intervention HIV incidence assessment. Methods and Findings Test performance of HIV incidence determination was evaluated for 403 multi-assay algorithms [MAAs] that included the BED capture immunoassay [BED-CEIA] alone, an avidity assay alone, and combinations of these assays at different cutoff values with and without CD4 and viral load testing on samples from seven African cohorts (5,325 samples from 3,436 individuals with known duration of HIV infection [1 month to >10 years]). The mean window period (average time individuals appear positive for a given algorithm) and performance in estimating an incidence estimate (in terms of bias and variance) of these MAAs were evaluated in three simulated epidemic scenarios (stable, emerging and waning). The power of different test methods to detect a 35% reduction in incidence in the matched communities of Project Accept was also assessed. A MAA was identified that included BED-CEIA, the avidity assay, CD4 cell count, and viral load that had a window period of 259 days, accurately estimated HIV incidence in all three epidemic settings and provided sufficient power to detect an intervention effect in Project Accept. Conclusions In a Southern African setting, HIV incidence estimates and intervention effects can be accurately estimated from cross-sectional surveys using a MAA. The improved accuracy in cross-sectional incidence testing that a MAA provides is a powerful tool for HIV surveillance and program evaluation.

Can HIV incidence testing be used for evaluating HIV intervention programs? A reanalysis of the Orange Farm male circumcision trial (ANRS-1265)

BackgroundThe objective of this study was to estimate the effect of male circumcision (MC) on HIV acquisition estimated using HIV incidence assays and to compare it to the effect measured by survival analysis.MethodsWe used samples collected during the MC randomized controlled trial (ANRS-1265) conducted in Orange Farm (South Africa) among men aged 18 to 24. Among the 2946 samples collected at the last follow-up visit, 194 HIV-positive samples were tested using two incidence assays: Calypte HIV-EIA (BED) and an avidity assay based on the BioRad HIV1/2+O EIA (AI). The results of the assays were also combined (BED-AI). The samples included the 124 participants (4.2% of total) who were HIV-positive at randomization. The protective effect was calculated as one minus the intention-to-treat incidence rate ratio in an uncorrected manner and with correction for misclassifications, with simple theoretical formulae. Theoretical calculations showed that the uncorrected intention-to-treat effect was approximately independent of the value of the incidence assay window period and was the ratio of the number tested recent seroconverters divided by the number tested HIV-negative between the randomization groups. We used cut-off values ranging from 0.325 to 2.27 for BED, 31.6 to 96 for AI and 0.325-31.6 to 1.89-96 for BED-AI. Effects were corrected for long-term specificity using a previously published formula. 95% Confidence intervals (CI) were estimated by bootstrap resampling.ResultsWith the highest cut-off values, the uncorrected protective effects evaluated by BED, AI and BED-AI were 50% (95%CI: 27% to 66%), 50% (21% to 69%) and 63% (36% to 81%). The corrections for misclassifications were lower than 50% of the number of tested recent. The corrected effects were 53% (30% to 70%), 55% (25% to 77%) and 67% (38% to 86%), slightly higher than the corresponding uncorrected values. These values were consistent with the previously reported protective effect of 60% (34% to 76%) obtained with survival analysis.ConclusionsHIV incidence assays may be employed to assess the effect of interventions using cross-sectional data.

Refocusing and prioritizing HIV programmes in conflict and post-conflict settings: funding recommendations.

Conflict and post-conflict settings pose specific challenges to HIV prevention and care efforts. Whereas armed conflicts have decreased very considerably in number, the interactions between HIV epidemiology and conflict remain problematic. This review describes factors that affect HIV in conflict and post-conflict settings, identifies challenges to addressing HIV, and presents actionable and measurable programming and funding recommendations that can be implemented immediately. Funding priorities include prevention and care efforts such as the provision and monitoring of universal precautions for HIV infection, health services for sexual violence and antiretroviral therapy. Policy efforts should prioritize enforcing appropriate conduct by peacekeepers and aid workers, interventions targeted at specific phases and contexts of conflicts, supporting the continuity of programmes from emergency to post emergency and reconstruction efforts and simplifying and accelerating funding mechanisms.

HIV Surveillance in a Large, Community-Based Study: Results from the Pilot Study of Project Accept (HIV Prevention Trials Network 043)

BackgroundProject Accept is a community randomized, controlled trial to evaluate the efficacy of community mobilization, mobile testing, same-day results, and post-test support for the prevention of HIV infection in Thailand, Tanzania, Zimbabwe, and South Africa. We evaluated the accuracy of in-country HIV rapid testing and determined HIV prevalence in the Project Accept pilot study.MethodsTwo HIV rapid tests were performed in parallel in local laboratories. If the first two rapid tests were discordant (one reactive, one non-reactive), a third HIV rapid test or enzyme immunoassay was performed. Samples were designated HIV NEG if the first two tests were non-reactive, HIV DISC if the first two tests were discordant, and HIV POS if the first two tests were reactive. Samples were re-analyzed in the United States using a panel of laboratory tests.ResultsHIV infection status was correctly determined based on-in country testing for 2,236 (99.5%) of 2,247 participants [7 (0.37%) of 1,907 HIV NEG samples were HIV-positive; 2 (0.63%) of 317 HIV POS samples were HIV-negative; 2 (8.3%) of 24 HIV DISC samples were incorrectly identified as HIV-positive based on the in-country tie-breaker test]. HIV prevalence was: Thailand: 0.6%, Tanzania: 5.0%, Zimbabwe 14.7%, Soweto South Africa: 19.4%, Vulindlela, South Africa: 24.4%, (overall prevalence: 14.4%).ConclusionsIn-country testing based on two HIV rapid tests correctly identified the HIV infection status for 99.5% of study participants; most participants with discordant HIV rapid tests were not infected. HIV prevalence varied considerably across the study sites (range: 0.6% to 24.4%).Trial RegistrationClinicalTrials.gov registry number NCT00203749.

Overestimation of the South African HIV incidence using the BED IgG Assay

We thank Rehle et al. for their important study of HIV incidence in South Africa which we read with great interest. We agree with the authors that the incidence of HIV in South Africa is probably extremely high particularly among young women and believe that the study will help us focus HIV prevention efforts on appropriate subgroups. We have serious concerns however about the applicability of the BED IgG assay to the South African HIV epidemic. In light of recent evidence we are concerned that Rehle et al. have overstated the true absolute incidence of HIV in South Africa. As the name implies the BED assay was developed using sequences from HIV subtypes B D and E. To compensate for imperfect sensitivity and specificity Rehle et al. use a correction factor based on McDougal et al.s study of subtype B virus. Given that the majority of HIV infections considered by Rehle et al. were (apparently) of subtype C the applicability of the McDougal correction and indeed of the BED assay itself to these samples is problematic. More questions arise in light of a recent report by Karita et al. that the BED assay does not perform well in subtype C virus infections; investigators found a specificity of 71% (95% confidence interval (CI) 54 - 84%) substantially different from one estimate of specificity used in the McDougal correction (94% for infections more than 360 days in the past). In addition Karita et al. found that using the BED assay with the McDougal correction resulted in overestimation of incidence in prospective Ugandan samples (subtype not available but probably A and D) reporting a corrected BED incidence of 6.4% and a true incidence of 1.3 - 1.7%.4 We are therefore concerned that the incidence figures reported by Rehle et al. may be overestimates. If indeed these figures are incorrect this will make future comparisons with more accurate measures of incidence difficult and could lead to spurious conclusions with regard to the course of the epidemic. Given these concerns and the currentUNAIDS recommendation against using the BED assay for incidence estimation it would be helpful if the authors clarified their findings with a quantitative sensitivity analysis of their estimates. Until the BED assay has been further validated we believe that BED-derived estimates of HIV incidence must be interpreted with caution. (full-text)