Do tests devised to detect recent HIV-1 infection provide reliable estimates of incidence in Africa?

International audienceThe objective of this study was to assess the performance of 4 biologic tests designed to detect recent HIV-1 infections in estimating incidence in West Africa (BED, Vironostika, Avidity, and IDE-V3). These tests were assessed on a panel of 135 samples from 79 HIV-1-positive regular blood donors from Abidjan, C?d'Ivoire, whose date of seroconversion was known (Agence Nationale de Recherches sur le SIDA et les H?tites Virales 1220 cohort). The 135 samples included 26 from recently infected patients (180 days), and 15 from patients with clinical AIDS. The performance of each assay in estimating HIV incidence was assessed through simulations. The modified commercial assays gave the best results for sensitivity (100% for both), and the IDE-V3 technique gave the best result for specificity (96.3%). In a context like Abidjan, with a 10% HIV-1 prevalence associated with a 1% annual incidence, the estimated test-specific annual incidence rates would be 1.2% (IDE-V3), 5.5% (Vironostika), 6.2% (BED), and 11.2% (Avidity). Most of the specimens falsely classified as incident cases were from patients infected for >180 days but <1 year. The authors conclude that none of the 4 methods could currently be used to estimate HIV-1 incidence routinely in C?d'Ivoire but that further adaptations might enhance their accuracy

Fitting a vaccine into the HIV prevention landscape

International audienceNo abstract availabl

Universal Test and Treat is not associated with sub-optimal antiretroviral therapy adherence in rural South Africa: the ANRS 12249 TasP trial

Introduction HIV treatment guidelines now recommend antiretroviral therapy (ART) initiation regardless of CD4 count to maximise benefit both for the individual and society. It is unknown whether the initiation of ART at higher CD4 counts would affect adherence levels. We investigated whether initiating ART at higher CD4 counts was associated with sub-optimal adherence (<95%) during the first 12 months of ART. Methods A prospective cohort study nested within a two-arm cluster-randomised trial of universal test and treat implemented March 2012 - June 2016 to measure impact of ART on HIV incidence in rural KwaZulu-Natal. ART was initiated regardless of CD4 count in the intervention arm and according to national guidelines in the control arm. ART adherence was measured monthly using a visual analogue scale (VAS) and pill counts (PC). HIV viral load was measured at ART initiation, 3 and 6 months, and six monthly thereafter. We pooled data from participants in both arms and used random-effects logistic regression models to examine the association between CD4 count at ART initiation and sub-optimal adherence, and assessed if adherence levels were associated with virological suppression. Results Among 900 individuals who initiated ART ≥ 12 months before study end, median (IQR) CD4 at ART initiation was 350 cells/mm3 (234, 503); median age was 34.6 years (IQR 27.4-46.4) and 71.7% were female. Adherence was sub-optimal in 14.7% of visits as measured by VAS and 20.7% by PC. In both the crude analyses and after adjusting for potential confounders, adherence was not significantly associated with CD4 count at ART initiation (adjusted OR for linear trend in sub-optimal adherence with every 100 cells/mm3 increase in CD4 count: 1.00, 95% CI 0.95-1.05, for VAS, and 1.03, 95%CI 0.99-1.07, for PC). Virological suppression at 12 months was 97%. Optimal adherence by both measures was significantly associated with virological suppression (p<0.001 for VAS; p=0.006 for PC). Conclusions We found no evidence that higher CD4 counts at ART initiation were associated with sub-optimal ART adherence in the first 12 months. Our findings should alleviate concerns about adherence in individuals initiating ART at higher CD4 counts, however long-term outcomes are needed

Evaluation of the impact of immediate versus WHO recommendations-guided antiretroviral therapy initiation on HIV incidence: the ANRS 12249 TasP (Treatment as Prevention) trial in Hlabisa sub-district, KwaZulu-Natal, South Africa: study protocol for a cluster randomised controlled trial

Background: Antiretroviral therapy (ART) suppresses HIV viral load in all body compartments and so limits the risk of HIV transmission. It has been suggested that ART not only contributes to preventing transmission at individual but potentially also at population level. This trial aims to evaluate the effect of ART initiated immediately after identification/diagnosis of HIV-infected individuals, regardless of CD4 count, on HIV incidence in the surrounding population. The primary outcome of the overall trial will be HIV incidence over two years. Secondary outcomes will include i) socio-behavioural outcomes (acceptability of repeat HIV counselling and testing, treatment acceptance and linkage to care, sexual partnerships and quality of life); ii) clinical outcomes (mortality and morbidity, retention into care, adherence to ART, virologic failure and acquired HIV drug resistance), iii) cost-effectiveness of the intervention. The first phase will specifically focus on the trial's secondary outcomes.Methods/design: A cluster-randomised trial in 34 (2 × 17) clusters within a rural area of northern KwaZulu-Natal (South Africa), covering a total population of 34,000 inhabitants aged 16 years and above, of whom an estimated 27,200 would be HIV-uninfected at start of the trial. The first phase of the trial will include ten (2 × 5) clusters. Consecutive rounds of home-based HIV testing will be carried out. HIV-infected participants will be followed in dedicated trial clinics: in intervention clusters, they will be offered immediate ART initiation regardless of CD4 count and clinical stage; in control clusters they will be offered ART according to national treatment eligibility guidelines (CD4 <350 cells/μL, World Health Organisation stage 3 or 4 disease or multidrug-resistant/extensively drug-resistant tuberculosis). Following proof of acceptability and feasibility from the first phase, the trial will be rolled out to further clusters.Discussion: We aim to provide proof-of-principle evidence regarding the effectiveness of Treatment-as-Prevention in reducing HIV incidence at the population level. Data collected from the participants at home and in the clinics will inform understanding of socio-behavioural, economic and clinical impacts of the intervention as well as feasibility and generalizability. © 2013 Iwuji et al.; licensee BioMed Central Ltd

JMIR Res Protoc

BACKGROUND: Effective antiretroviral therapy has greatly reduced HIV-related morbidity and mortality, dramatically changing the demographics of the population of people living with HIV. The majority of people living with HIV in France are well cared for insofar as their HIV infection is concerned but remain at risk for age-associated comorbidities. Their long-term, potentially complex, and growing care needs make the routine, longitudinal assessment of health-related quality of life and other patient-reported outcomes of relevance in the current treatment era. OBJECTIVE: We aim to describe the development of a Web-based electronic patient-reported outcomes system for people living with HIV linked to the ANRS CO3 Aquitaine cohort's data capture and visualization system (ARPEGE) and designed to facilitate the electronic collection of patient-reported data and ultimately promote better patient-physician communication and quality of care (both patient satisfaction and health outcomes). METHODS: Participants who meet the eligibility criteria will be invited to engage with the Web-based electronic patient-reported outcomes system and provided with the information necessary to create a personal patient account. They will then be able to access the electronic patient-reported outcomes system and complete a set of standardized validated questionnaires covering health-related quality of life (World Health Organization's Quality of Life Instrument in HIV infection, named WHOQOL-HIV BREF) and other patient-reported outcomes. The information provided via questionnaires will ultimately be presented in a summary format for clinicians, together with the patient's HIV care history. RESULTS: The prototype of the Web-based electronic patient-reported outcome system will be finalized and the first 2 formative research phases of the study (prototyping and usability testing) will be conducted from December 2017 to May 2018. We describe the sequential processes planned to ensure that the proposed electronic patient-reported outcome system is ready for formal pilot testing, referred to herein as phases 1a and 1b. We also describe the planned pilot-testing designed to evaluate the acceptability and use of the system from the patient's perspective (phase 2). CONCLUSIONS: As the underlying information technology solution, ARPEGE, has being developed in-house, should the feasibility study presented here yield promising results, the panel of services provided via the proposed portal could ultimately be expanded and used to experiment with health-promoting interventions in aging people living with HIV in hospital-based care or adapted for use in other patient populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03296202; https://clinicaltrials.gov/ct2/show/NCT03296202 (Archived by WebCite at http://www.webcitation.org/6zgOBArps). REGISTERED REPORT IDENTIFIER: RR1-10.2196/9439

Measuring retention in care for HIV-positive pregnant women in Prevention of Mother-to-Child Transmission of HIV (PMTCT) option B+ programs: the Mozambique experience

Background Failure to retain HIV-positive pregnant women on antiretroviral therapy (ART) leads to increased mortality for the mother and her child. This study evaluated different retention measures for women’s engagement along the continuum of care for prevention of mother-to-child transmission (PMTCT) option B+ services in Mozambique. Methods We compared ‘point’ retention (patient’s presence in care 12-month post-ART initiation or any time thereafter) with the following definitions: alive and in care 12 month post-ART initiation (Ministry of Health; MOH); attendance at a health facility up to 15-month post-ART initiation (World Health Organization; WHO); alive and in treatment at 1-, 2-, 3-, 6-, 9-, and 12-month post-ART initiation (Inter-Agency Task Team; IATT); and alive and in care 12-month post-ART initiation with ≥75% appointment adherence during follow-up (i.e. ‘appointment adherence’ retention) or with ≥75% of appointments met on time during follow-up (i.e. ‘on-time adherence’ retention). Kaplan-Meier survival curves were produced to assess variability in retention rates. We used ‘on-time adherence’ retention as our reference to estimate sensitivity, specificity, and proportion of misclassified patients. Results Considering the ‘point’ retention definition, 16,840 HIV-positive pregnant women enrolled in option B+ PMTCT services were identified as ‘retained in care’ 12-month post-ART initiation. Of these, 60.3% (95% CI 59.6–61.1), 84.8% (95% CI 84.2–85.3), and 16.4% (95% CI 15.8–17.0) were classified as ‘retained in care’ using MOH, WHO, and IATT definitions, respectively, and 1.2% (95% CI 1.0–1.4) were classified as ‘retained in care’ using the ‘≥75% on-time adherence’ definition. All definitions provided specificity rates of ≥98%. The sensitivity rates were 3.0% with 78% of patients misclassified according to the WHO definition and 4.3% with 54% of patients misclassified according to the MOH definition. The ‘point’ retention definition misclassified 97.6% of patients. Using IATT and ‘appointment adherence’ retention definitions, sensitivity rates (9.0 and 11.7%, respectively) were also low; however, the proportion of misclassified patients was smaller (15.9 and 18.3%, respectively). Conclusion More stringent definitions indicated lower retention rates for PMTCT programs. Policy makers and program managers should include attendance at follow-up visits when measuring retention in care to better guide planning, scale-up, and monitoring of interventions

BMC Public Health

Background Failure to retain HIV-positive pregnant women on antiretroviral therapy (ART) leads to increased mortality for the mother and her child. This study evaluated different retention measures for women’s engagement along the continuum of care for prevention of mother-to-child transmission (PMTCT) option B+ services in Mozambique. Methods We compared ‘point’ retention (patient’s presence in care 12-month post-ART initiation or any time thereafter) with the following definitions: alive and in care 12 month post-ART initiation (Ministry of Health; MOH); attendance at a health facility up to 15-month post-ART initiation (World Health Organization; WHO); alive and in treatment at 1-, 2-, 3-, 6-, 9-, and 12-month post-ART initiation (Inter-Agency Task Team; IATT); and alive and in care 12-month post-ART initiation with ≥75% appointment adherence during follow-up (i.e. ‘appointment adherence’ retention) or with ≥75% of appointments met on time during follow-up (i.e. ‘on-time adherence’ retention). Kaplan-Meier survival curves were produced to assess variability in retention rates. We used ‘on-time adherence’ retention as our reference to estimate sensitivity, specificity, and proportion of misclassified patients. Results Considering the ‘point’ retention definition, 16,840 HIV-positive pregnant women enrolled in option B+ PMTCT services were identified as ‘retained in care’ 12-month post-ART initiation. Of these, 60.3% (95% CI 59.6–61.1), 84.8% (95% CI 84.2–85.3), and 16.4% (95% CI 15.8–17.0) were classified as ‘retained in care’ using MOH, WHO, and IATT definitions, respectively, and 1.2% (95% CI 1.0–1.4) were classified as ‘retained in care’ using the ‘≥75% on-time adherence’ definition. All definitions provided specificity rates of ≥98%. The sensitivity rates were 3.0% with 78% of patients misclassified according to the WHO definition and 4.3% with 54% of patients misclassified according to the MOH definition. The ‘point’ retention definition misclassified 97.6% of patients. Using IATT and ‘appointment adherence’ retention definitions, sensitivity rates (9.0 and 11.7%, respectively) were also low; however, the proportion of misclassified patients was smaller (15.9 and 18.3%, respectively). Conclusion More stringent definitions indicated lower retention rates for PMTCT programs. Policy makers and program managers should include attendance at follow-up visits when measuring retention in care to better guide planning, scale-up, and monitoring of interventions

Cost-Effectiveness of World Health Organization 2010 Guidelines for Prevention of Mother-to-Child HIV Transmission in Zimbabwe

Background. In 2010, the World Health Organization (WHO) released revised guidelines for prevention of mother-to-child human immunodeficiency virus (HIV) transmission (PMTCT). We projected clinical impacts, costs, and cost-effectiveness of WHO-recommended PMTCT strategies in Zimbabwe. Methods. We used Zimbabwean data in a validated computer model to simulate a cohort of pregnant, HIV-infected women (mean age, 24 years; mean CD4 count, 451 cells/µL; subsequent 18 months of breastfeeding). We simulated guideline-concordant care for 4 PMTCT regimens: single-dose nevirapine (sdNVP); WHO-recommended Option A, WHO-recommended Option B, and Option B+ (lifelong maternal 3-drug antiretroviral therapy regardless of CD4). Outcomes included maternal and infant life expectancy (LE) and lifetime healthcare costs (2008 US dollars [USD]). Incremental cost-effectiveness ratios (ICERs, in USD per year of life saved [YLS]) were calculated from combined (maternal + infant) discounted costs and LE. Results. Replacing sdNVP with Option A increased combined maternal and infant LE from 36.97 to 37.89 years and would reduce lifetime costs from $5760 to$5710 per mother–infant pair. Compared with Option A, Option B further improved LE (38.32 years), and saved money within 4 years after delivery ($5630 per mother–infant pair). Option B+ (LE, 39.04 years; lifetime cost,$6620 per mother–infant pair) improved maternal and infant health, with an ICER of $1370 per YLS compared with Option B. Conclusions. Replacing sdNVP with Option A or Option B will improve maternal and infant outcomes and save money; Option B increases health benefits and decreases costs compared with Option A. Option B+ further improves maternal outcomes, with an ICER (compared with Option B) similar to many current HIV-related healthcare interventions

Health Facility Characteristics and Their Relationship to Coverage of PMTCT of HIV Services across Four African Countries: The PEARL Study

Background: Health facility characteristics associated with effective prevention of mother-to-child transmission of HIV (PMTCT) coverage in sub-Saharan are poorly understood. Methodology/Principal Findings: We conducted surveys in health facilities with active PMTCT services in Cameroon, Cote d’Ivoire, South Africa, and Zambia. Data was compiled via direct observation and exit interviews. We constructed composite scores to describe provision of PMTCT services across seven topical areas: antenatal quality, PMTCT quality, supplies available, patient satisfaction, patient understanding of medication, and infrastructure quality. Pearson correlations and Generalized Estimating Equations (GEE) to account for clustering of facilities within countries were used to evaluate the relationship between the composite scores, total time of visit and select individual variables with PMTCT coverage among women delivering. Between July 2008 and May 2009, we collected data from 32 facilities; 78 % were managed by the government health system. An opt-out approach for HIV testing was used in 100 % of facilities in Zambia, 63 % in Cameroon, and none in Côte d’Ivoire or South Africa. Using Pearson correlations, PMTCT coverage (median of 55%, (IQR: 33–68) was correlated with PMTCT quality score (rho = 0.51; p = 0.003); infrastructure quality score (rho = 0.43; p = 0.017); time spent at clinic (rho = 0.47