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Background: Stigma and masculinity represent persistent barriers in delivering successful HIV interventions to men. Our study examined community perceptions of HIV and anti-retroviral therapy (ART) and their implications for men on ART across the life course in Blantyre, Malawi.Methods: Our qualitative study is based on 72 face-to-face semi-structured interviews. Participants were selected purposively and included men on ART (with suppressed and unsuppressed viral loads), adult male community members irrespective of HIV status and other HIV stakeholders such as health personnel and program implementers. Interviews were conducted in Chichewa and English, transcribed verbatim and analyzed thematically in NVivo 12. We applied the socio-ecological model as our theoretical framework as well as a "life-course" perspective.Results: Our findings highlight lingering negative perceptions towards ART in general and towards PLHIV irrespective of viral load suppression. With intersecting notions of masculinity and stigma, men's descriptions of anticipated stigma in their relationships and when visiting health facilities dominated. Stigma was experienced at the personal, interpersonal, facility and community level. Yet, men living with HIV were perceived differently throughout the life-course, with young sexually active men seen as the most stigmatized group and older men seen as drawing resilience from a greater range of masculine norms. Some men of all ages displayed "transformative" masculinities independent of stigma and community expectations.Conclusions: We propose the "life-course" as a useful concept for studies on masculinity, HIV and stigma. Considering gendered constructions of "respectable" midlife-older age vis-à-vis younger age, and how they influence stigma as well as uptake and adherence to ART might lead to more targeted services for men that build on "transformative masculinities". [ABSTRACT FROM AUTHOR]

Objectives: Universal Test and Treat (UTT) strategies are being adopted across sub‐Saharan Africa based on clinical benefits to morbidity and mortality and to attain targets of the Joint United Nations Programme on HIV/AIDS (UNAIDS). Universal Test and Treat is expected to change the client population at clinics, due to more asymptomatic HIV clients initiating antiretroviral therapy (ART). We assessed the impact of UTT on client appointment adherence at 14 government‐managed health facilities in Eswatini's public sector health system. Methods: We assessed the impact of UTT on client adherence to appointment schedules from 2014 to 2017 in a stepped‐wedge trial. Repeated measures analysis was used to assess adherence to each scheduled appointment (primary definition: presenting for care within 7 days after the scheduled appointment), adjusting for time, age, sex, stage, marital status, ART status and facility. Results: Among 3354 clients (62.1% female; 57.4% < 35 years), a median (interquartile range) of 10 (6–15) appointments were scheduled during follow‐up. In a multivariable‐adjusted model, appointment adherence was significantly greater in clients who were female [odds ratio (OR) = 1.38, 95% confidence interval (CI): 1.25–1.52], older (e.g. 40 to < 50 years vs. < 20 years; OR = 1.45, 95% CI: 1.00–2.09), married (OR = 1.31, 95% CI: 1.19–1.44), had lower WHO stage at study enrolment (1–2 vs. 3–4: OR = 1.26, 95% CI: 1.13–1.41), and were currently on ART (OR = 3.55, 95% CI: 2.62–4.82). However, UTT strategy was not significantly associated with client adherence to scheduled appointments (OR = 1.02, 95% CI: 0.72–1.45). Conclusions: Despite transitioning to UTT, there was no change in visit adherence, a reassuring finding given the large volume of clients currently being initiated at earlier stages of HIV. [ABSTRACT FROM AUTHOR]

Copyright of AIDS & Behavior is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

We use a regression discontinuity design to estimate the causal effect of antiretroviral therapy (ART) eligibility according to national treatment guidelines of South Africa on two risk factors for cardiovascular disease, body mass index (BMI) and blood pressure. We combine survey data collected in 2010 in KwaZulu-Natal, South Africa, with clinical data on ART. We find that early ART eligibility significantly reduces systolic and diastolic blood pressure. We do not find any significant effects on BMI. The effect on blood pressure can be detected up to three years after becoming eligible for ART. [ABSTRACT FROM AUTHOR]

PrEPping to prevent HIV: Clinical trials have demonstrated that pre-exposure prophylaxis (PrEP) can prevent HIV infection in high-risk populations. Geldsetzer et al. conducted a randomized study of health care facilities in Eswatini to see whether promoting PrEP could increase uptake among the general population at high risk of acquiring HIV. They found that the promotion package resulted in a small increase in PrEP uptake, but only one third of at-risk adults, mostly women, agreed to participate in PrEP. Crucially, interviews with study participants and health care workers revealed that PrEP promotion activities needed to be expanded beyond health care facilities into community settings to raise awareness, particularly among men. Clinical trials have shown that antiretroviral drugs used as pre-exposure prophylaxis (PrEP) are highly effective for preventing HIV acquisition. PrEP efforts, including in sub-Saharan Africa, have almost exclusively focused on certain priority groups, particularly female sex workers, men having sex with men, pregnant women, serodiscordant couples, and young women. As part of a PrEP demonstration project involving the general population at six primary health care facilities in Eswatini (formerly Swaziland), we conducted a randomized trial of a health care facility–based PrEP promotion package designed to increase PrEP uptake. Over the 18-month study duration, 33.6% (517 of 1538) of adults identified by health care workers as being at risk of acquiring HIV took up PrEP, and 30.0% of these individuals attended all scheduled appointments during the first 6 months after initiation of PrEP. The PrEP promotion package was associated with a 55% (95% confidence interval, 15 to 110%; P = 0.036) relative increase in the number of individuals taking up PrEP, with an absolute increase of 2.2 individuals per month per health care facility. When asked how PrEP uptake could be improved in 217 accompanying in-depth qualitative interviews, interviewees recommended an expansion of PrEP promotion activities beyond health care facilities to communities. Although a health care facility–based promotion package improved PrEP uptake, both uptake and retention remained low. Expanding promotion activities to the community is needed to achieve greater PrEP coverage among adults at risk of HIV infection in Eswatini and similar settings. [ABSTRACT FROM AUTHOR]

Introduction: The WHO recommends antiretroviral treatment (ART) for all HIV‐positive patients regardless of CD4 count or disease stage, referred to as "Early Access to ART for All" (EAAA). The health systems effects of EAAA implementation are unknown. This trial was implemented in a government‐managed public health system with the aim to examine the "real world" impact of EAAA on care retention and viral suppression. Methods: In this stepped‐wedge randomized controlled trial, 14 public sector health facilities in Eswatini were paired and randomly assigned to stepwise transition from standard of care (SoC) to EAAA. ART‐naïve participants ≥18 years who were not pregnant or breastfeeding were eligible for enrolment. We used Cox proportional hazard models with censoring at clinic transition to estimate the effects of EAAA on retention in care and retention and viral suppression combined. Results: Between September 2014 and August 2017, 3405 participants were enrolled. In SoC and EAAA respectively, 12‐month HIV care retention rates were 80% (95% CI: 77 to 83) and 86% (95% CI: 83 to 88). The 12‐month combined retention and viral suppression endpoint rates were 44% (95% CI: 40 to 48) under SoC compared to 80% (95% CI: 77 to 83) under EAAA. EAAA increased both retention (HR: 1·60, 95% CI: 1·15 to 2·21, p = 0.005) and retention and viral suppression combined (HR: 4.88, 95% CI: 2.96 to 8.05, p < 0.001). We also identified significant gaps in current health systems ability to provide viral load (VL) monitoring with 80% participants in SoC and 66% in EAAA having a missing VL at last contact. Conclusions: The observed improvement in retention in care and on the combined retention and viral suppression provides an important co‐benefit of EAAA to HIV‐positive adults themselves, at least in the short term. Our results from this "real world" health systems trial strongly support EAAA for Eswatini and countries with similar HIV epidemics and health systems. VL monitoring needs to be scaled up for appropriate care management. [ABSTRACT FROM AUTHOR]

Objectives: The HIV treatment cascade is a powerful framework for understanding progress from initial diagnosis to successful treatment. Data sources for cascades vary and often are based on clinical cohorts, population cohorts linked to clinics, or self-reported information. We use both biomarkers and self-reported data from a large population-based cohort of older South Africans to establish the first HIV cascade for this growing segment of the HIV-positive population and compare results using the different data sources.Methods: Data came from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) 2015 baseline survey of 5059 adults aged 40+ years. Dried blood spots (DBS) were screened for HIV, antiretroviral drugs and viral load. In-home surveys asked about HIV testing, diagnosis and antiretroviral therapy (ART) use. We calculated proportions and CIs for each stage of the cascade, conditional on attainment of the previous stage, using (1) biomarkers, (2) self-report and (3) both biomarkers and self-report, and compared with UNAIDS 90-90-90 targets.Results: 4560 participants had DBS results, among whom 1048 (23%) screened HIV-positive and comprised the denominator for each cascade. The biomarker cascade showed 63% (95% CI 60 to 66) on ART and 72% (95% CI 69 to 76) of those on ART with viral suppression. Self-reports underestimated testing, diagnosis and ART, with only 47% (95% CI 44 to 50) of HIV-positive individuals reporting ART use. The combined cascade indicated high HIV testing (89% (95% CI 87 to 91)), but lower knowledge of HIV-positive status (71% (95% CI 68 to 74)).Conclusions: Older South Africans need repeated HIV testing and sustained ART to reach 90-90-90 targets. HIV cascades relying on self-reports are likely to underestimate true cascade attainment, and biomarkers provide substantial improvements to cascade estimates. [ABSTRACT FROM AUTHOR]

The rapid scale-up of antiretroviral treatment (ART) for HIV since the mid-2000s, mostly through disease-specific or "vertical" programmes, has been a highly successful undertaking, which averted millions of deaths and prevented many new infections. However, the dynamics of the HIV epidemic and changing political and financial commitment to fight the disease will likely require new models for the delivery of ART over the coming decades if the promises of universal treatment are to be met. Delivery model innovations for ART are intended to improve both the effectiveness and efficiency of the HIV treatment cascade, reaching new people who require ART and providing ART to more people without an increase in resources. We describe twelve models for ART delivery, which could be achieved through five categories of delivery innovations: integrating ART ("vertical ART plus", "partially-integrated ART" and "fully-integrated ART"); modifying steps in the ART value chain ("professional task-shifted ART", "people task-shifted ART" and "technology-supported ART"); eliminating steps in the ART value chain ("immediate ART" and "less frequent ART pick-up"); changing ART locations ("private-sector ART", "traditional-sector ART" and "ART outside the health sector"); and keeping the status quo ("vertical ART"). The different delivery model innovations are not mutually exclusive and several could be combined, such as "vertical ART plus" with "task-shifted ART". Suitability of the models will highly depend on local and national contexts, including existing health systems resources, available funding, and type of HIV epidemic. Future implementation research needs to identify which models are the best fit for different contexts. [ABSTRACT FROM AUTHOR]

Background: There is robust clinical evidence to support offering early access to antiretroviral treatment (ART) to all HIV-positive individuals, irrespective of disease stage, to both improve patient health outcomes and reduce HIV incidence. However, as the global treatment guidelines shift to meet this evidence, it is still largely unknown if early access to ART for all (also referred to as "treatment as prevention" or "universal test and treat") is a feasible intervention in the resource-limited countries where this approach could have the biggest impact on the course of the HIV epidemics. The MaxART Early Access to ART for All (EAAA) implementation study was designed to determine the feasibility, acceptability, clinical outcomes, affordability, and scalability of offering early antiretroviral treatment to all HIV-positive individuals in Swaziland's public sector health system.Methods: This is a three-year stepped-wedge randomized design with open enrollment for all adults aged 18 years and older across 14 government-managed health facilities in Swaziland's Hhohho Region. Primary endpoints are retention and viral suppression. Secondary endpoints include ART initiation, adherence, drug resistance, tuberculosis, HIV disease progression, patient satisfaction, and cost per patient per year. Sites are grouped to transition two at a time from the control (standard of care) to intervention (EAAA) stage at each four-month step. This design will result in approximately one half of the total observation time to accrue in the intervention arm and the other half in the control arm. Our estimated enrolment number, which is supported by conservative power calculations, is 4501 patients over the course of the 36-month study period. A multidisciplinary, mixed-methods approach will be adopted to supplement the randomized controlled trial and meet the study aims. Additional study components include implementation science, social science, economic evaluation, and predictive HIV incidence modeling.Discussion: A stepped-wedge randomized design is a causally strong and robust approach to determine if providing antiretroviral treatment for all HIV-positive individuals is a feasible intervention in a resource-limited, public sector health system. We expect our study results to contribute to health policy decisions related to the HIV response in Swaziland and other countries in sub-Saharan Africa.Trial Registration: ClinicalTrials.gov, NCT02909218 . Registered on 10 July 2016. [ABSTRACT FROM AUTHOR]

There is increasing interest in home based testing and treatment of HIV to expand access to treatment in sub-Saharan Africa. Such programs rely on self-reported HIV history and use of antiretroviral therapy (ART). However, the accuracy of self-reported ART use in community settings is not well described. In this study, we compared self-reported ART (SR-ART) use in a home based survey against biological exposure to ART (BE-ART), in a population study of older adults in South Africa. Health and Aging in Africa: a Longitudinal Study of an INDEPTH community in South Africa (HAALSI) is a cohort of adults aged 40 +. The baseline home-based interview included self-reported HIV status and ART use. All participants also underwent biological testing for HIV antibodies, viral load and exposure to emtricitabine (FTC) or lamivudine (3TC), which are included in all first-line and second-line ART regimens in the public-sector South African HIV program. We calculated the performance characteristics for SR-ART compared to BE-ART and fit multivariable logistic regression models to identify correlates of invalid SR-ART responses. Of 4560 HAALSI participants with a valid HIV test result available, 1048 (23%) were HIV-positive and 734 [70% of people living with HIV (PLWH)] were biologically validated ART users (BE-ART). The sensitivity of SR-ART use was 64% (95% CI 61–68%) and the specificity was 94% (95% CI 91–96%); the positive predictive value (PPV) was 96% (95% CI 94–98%) and negative predictive value (NPV) was 52% (95% CI 48–56%). We found no sociodemographic predictors of accurate SR-ART use. Over one in three individuals with detectable ART in their blood denied current ART use during a home-based interview. These results demonstrate ongoing stigma related to HIV and its treatment, and have important implications for community health worker programs, clinical programs, and research studies planning community-based ART initiation in the region. [ABSTRACT FROM AUTHOR]

This study aims to characterize associations between depression symptom severity and HIV infection, both prior to and in years after ART initiation, among older adults. The Ugandan Non-Communicable Diseases & Aging Cohort Study (UGANDAC) is a study of 154 PLWH on ART and 142 community-based, HIV-negative controls. The Hopkins Checklist (HSCL), a 15-item depression scale, was used to screen for depression. We estimate differences in depressive symptoms by HIV and ART status and use multivariable log binomial regression to quantify differences in probable depression between PLWH on ART. HIV-infected and HIV-uninfected participants had a similar age (mean 52.0 vs. 51.9, p = 0.854) and sex distribution (47.4 vs. 47.9% female, p = 0.934). PLWH on ART had lower depression symptom severity than HIV-uninfected controls (mean score: 1.50 vs. 1.60, p = 0.006) and a lower prevalence of probable depression (21.4 vs. 33.8%, p = 0.017). Among 102 PLWH with pre-ART depression screening scores available, their mean depression symptom severity was similar to HIV-uninfected participants (mean 1.56 vs. 1.60, p = 0.512). In adjusted models, PLWH on ART had a lower prevalence of probable depression than HIV-negative controls [adjusted prevalence ratio: 0.68 (95% CI 0.47-0.99)]. In an observational cohort of PLWH over 40 on long-term ART and matched, community-based HIV-uninfected controls in rural Uganda, we found a lower prevalence of self-reported depression among aging PLWH on ART. [ABSTRACT FROM AUTHOR]

Background: With the increase in people living with HIV in sub-Saharan Africa and expanding eligibility criteria for antiretroviral therapy (ART), there is intense interest in the use of novel delivery models that allow understaffed health systems to successfully deal with an increasing demand for antiretroviral drugs (ARVs). This pragmatic randomized controlled trial in Dar es Salaam, Tanzania, evaluated a novel model of ARV community delivery: lay health workers (home-based carers [HBCs]) deliver ARVs to the homes of patients who are clinically stable on ART, while nurses and physicians deliver standard facility-based care for patients who are clinically unstable. Specifically, the trial aimed to assess whether the ARV community delivery model performed at least equally well in averting virological failure as the standard of care (facility-based care for all ART patients).Methods and Findings: The study took place from March 1, 2016, to October 27, 2017. All (48) healthcare facilities in Dar es Salaam that provided ART and had an affiliated team of public-sector HBCs were randomized 1:1 to either (i) ARV community delivery (intervention) or (ii) the standard of care (control). Our prespecified primary endpoint was the proportion of adult non-pregnant ART patients with virological failure at the end of the study period. The prespecified margin of non-inferiority was a risk ratio (RR) of 1.45. The mean follow-up period was 326 days. We obtained intent-to-treat (ITT) RRs using a log-binomial model adjusting standard errors for clustering at the level of the healthcare facility. A total of 2,172 patients were enrolled at intervention (1,163 patients) and control (1,009 patients) facilities. Of the 1,163 patients in the intervention arm, 516 (44.4%) were both clinically stable on ART and opted to receive ARVs in their homes or at another meeting point of their choosing in the community. At the end of the study period, 10.9% (95/872) of patients in the control arm and 9.7% (91/943) in the intervention arm were failing virologically. The ITT RR for virological failure demonstrated non-inferiority of the ARV community delivery model (RR 0.89 [1-sided 95% CI 0.00-1.18]). We observed no significant difference between study arms in self-reported patient healthcare expenditures over the last 6 months before study exit. Of those who received ARVs in the community, 97.2% (95% CI 94.7%-98.7%) reported being either "satisfied" or "very satisfied" with the program. Other than loss to follow-up (18.9% in the intervention and 13.6% in the control arm), the main limitation of this trial was that substantial decongestion of healthcare facilities was not achieved, thus making the logic for our preregistered ITT approach (which includes those ineligible to receive ARVs at home in the intervention sample) less compelling.Conclusions: In this study, an ARV community delivery model performed at least as well as the standard of care regarding the critical health indicator of virological failure. The intervention did not significantly reduce patient healthcare expenditures, but satisfaction with the program was high and it is likely to save patients time. Policy-makers should consider piloting, evaluating, and scaling more ambitious ARV community delivery programs that can reach higher proportions of ART patients.Trial Registration: ClinicalTrials.gov NCT02711293. [ABSTRACT FROM AUTHOR]

Estimation of causal effects from observational data is a primary goal of epidemiology. The use of multiple methods with different assumptions relating to exchangeability improves causal inference by demonstrating robustness across assumptions. We estimated the effect of antiretroviral therapy (ART) on mortality in rural KwaZulu-Natal, South Africa, from 2007 to 2011, using 2 methods with substantially different assumptions: the regression discontinuity design (RDD) and inverse-probability–weighted (IPW) marginal structural models (MSMs). The RDD analysis took advantage of a CD4-cell-count–based threshold for ART initiation (200 cells/μL). The 2 methods yielded consistent but nonidentical results for the effect of immediate initiation of ART (RDD intention-to-treat hazard ratio (HR) = 0.66, 95% confidence interval (CI): 0.35, 1.26; RDD complier average causal effect HR = 0.56, 95% CI: 0.41, 0.77; IPW MSM HR = 0.49, 95% CI: 0.42, 0.58). Although RDD and IPW MSM estimates have distinct identifying assumptions, strengths, and limitations in terms of internal and external validity, results in this application were similar. The differences in modeling approaches and the external validity of each method may explain the minor differences in effect estimates. The overall consistency of the results lends support for causal inference about the effect of ART on mortality from these data. [ABSTRACT FROM AUTHOR]

In a Perspective, Amitabh Suthar and Till Bärnighausen discuss progress made so far in reducing HIV-related mortality in South Africa and keys towards further population mortality reductions going forward. [ABSTRACT FROM AUTHOR]

Background: HIV self-testing allows HIV testing at any place and time and without health workers. HIV self-testing may thus be particularly useful for female sex workers (FSWs), who should test frequently but face stigma and financial and time barriers when accessing healthcare facilities.Methods and Findings: We conducted a cluster-randomized controlled health systems trial among FSWs in Kampala, Uganda, to measure the effect of 2 HIV self-testing delivery models on HIV testing and linkage to care outcomes. FSW peer educator groups (1 peer educator and 8 participants) were randomized to either (1) direct provision of HIV self-tests, (2) provision of coupons for free collection of HIV self-tests in a healthcare facility, or (3) standard of care HIV testing. We randomized 960 participants in 120 peer educator groups from October 18, 2016, to November 16, 2016. Participants' median age was 28 years (IQR 24-32). Our prespecified primary outcomes were self-report of any HIV testing at 1 month and at 4 months; our prespecified secondary outcomes were self-report of HIV self-test use, seeking HIV-related medical care and ART initiation. In addition, we analyzed 2 secondary outcomes that were not prespecified: self-report of repeat HIV testing-to understand the intervention effects on frequent testing-and self-reported facility-based testing-to quantify substitution effects. Participants in the direct provision arm were significantly more likely to have tested for HIV than those in the standard of care arm, both at 1 month (risk ratio [RR] 1.33, 95% CI 1.17-1.51, p < 0.001) and at 4 months (RR 1.14, 95% CI 1.07-1.22, p < 0.001). Participants in the direct provision arm were also significantly more likely to have tested for HIV than those in the facility collection arm, both at 1 month (RR 1.18, 95% CI 1.07-1.31, p = 0.001) and at 4 months (RR 1.03, 95% CI 1.01-1.05, p = 0.02). At 1 month, fewer participants in the intervention arms had sought medical care for HIV than in the standard of care arm, but these differences were not significant and were reduced in magnitude at 4 months. There were no statistically significant differences in ART initiation across study arms. At 4 months, participants in the direct provision arm were significantly more likely to have tested twice for HIV than those in the standard of care arm (RR 1.51, 95% CI 1.29-1.77, p < 0.001) and those in the facility collection arm (RR 1.22, 95% CI 1.08-1.37, p = 0.001). Participants in the HIV self-testing arms almost completely replaced facility-based testing with self-testing. Two adverse events related to HIV self-testing were reported: interpersonal violence and mental distress. Study limitations included self-reported outcomes and limited generalizability beyond FSWs in similar settings.Conclusions: In this study, HIV self-testing appeared to be safe and increased recent and repeat HIV testing among FSWs. We found that direct provision of HIV self-tests was significantly more effective in increasing HIV testing among FSWs than passively offering HIV self-tests for collection in healthcare facilities. HIV self-testing could play an important role in supporting HIV interventions that require frequent HIV testing, such as HIV treatment as prevention, behavior change for transmission reduction, and pre-exposure prophylaxis.Trial Registration: ClinicalTrials.gov NCT02846402. [ABSTRACT FROM AUTHOR]

Background: Loss to follow-up is high among HIV patients not yet receiving antiretroviral therapy (ART). Clinical trials have demonstrated the clinical efficacy of early ART; however, these trials may miss an important real-world consequence of providing ART at diagnosis: its impact on retention in care.Methods and Findings: We examined the effect of immediate (versus deferred) ART on retention in care using a regression discontinuity design. The analysis included all patients (N = 11,306) entering clinical HIV care with a first CD4 count between 12 August 2011 and 31 December 2012 in a public-sector HIV care and treatment program in rural South Africa. Patients were assigned to immediate versus deferred ART eligibility, as determined by a CD4 count < 350 cells/μl, per South African national guidelines. Patients referred to pre-ART care were instructed to return every 6 months for CD4 monitoring. Patients initiated on ART were instructed to return at 6 and 12 months post-initiation and annually thereafter for CD4 and viral load monitoring. We assessed retention in HIV care at 12 months, as measured by the presence of a clinic visit, lab test, or ART initiation 6 to 18 months after initial CD4 test. Differences in retention between patients presenting with CD4 counts just above versus just below the 350-cells/μl threshold were estimated using local linear regression models with a data-driven bandwidth and with the algorithm for selecting the bandwidth chosen ex ante. Among patients with CD4 counts close to the 350-cells/μl threshold, having an ART-eligible CD4 count (<350 cells/μl) was associated with higher 12-month retention than not having an ART-eligible CD4 count (50% versus 32%), an intention-to-treat risk difference of 18 percentage points (95% CI 11 to 23; p < 0.001). The decision to start ART was determined by CD4 count for one in four patients (25%) presenting close to the eligibility threshold (95% CI 20% to 31%; p < 0.001). In this subpopulation, having an ART-eligible CD4 count was associated with higher 12-month retention than not having an ART-eligible CD4 count (91% versus 21%), a complier causal risk difference of 70 percentage points (95% CI 42 to 98; p < 0.001). The major limitations of the study are the potential for limited generalizability, the potential for outcome misclassification, and the absence of data on longer-term health outcomes.Conclusions: Patients who were eligible for immediate ART had dramatically higher retention in HIV care than patients who just missed the CD4-count eligibility cutoff. The clinical and population health benefits of offering immediate ART regardless of CD4 count may be larger than suggested by clinical trials. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization recommends initiating antiretroviral therapy (ART) regardless of CD4 count. We assessed the effect of ART eligibility on treatment uptake and simulated the impact of WHO’s recommendations in South Africa. Methods: We conducted an empirical analysis of cohort data using a regression discontinuity design, and then used this model for policy simulation. We enrolled all patients (n = 19,279) diagnosed with HIV between August 2011 and December 2013 in the Hlabisa HIV Treatment and Care Programme in rural South Africa. Patients were ART-eligible with CD4<350 cells/mm3 or Stage III/IV illness. We estimated: (1) distribution of first CD4 counts in 2013; (2) probability of initiating ART ≤6 months of HIV diagnosis under existing criteria at each CD4 count; (3) probability of initiating ART by CD4 count if thresholds were eliminated; and (4) number of expected new initiators if South Africa eliminates thresholds. Findings: In 2013, 38.9% of patients diagnosed had a CD4 count ≥500. 8.0% of these patients initiated even without eligible CD4 counts. If CD4 criteria were eliminated, we project that an additional 19.2% of patients with CD4 ≥500 would initiate ART; 72.8% would not initiate ART despite being eligible. Eliminating CD4 criteria would increase the number starting ART by 26.7%. If these numbers hold nationally, this would represent an additional 164,000 initiators per year, a 5.2% increase in patients receiving ART and 5.3% increase in programme costs. Conclusions: Removing CD4 criteria alone will modestly increase timely uptake of ART. However, our results suggest the majority of newly-eligible patients will not initiate. Improved testing, linkage, and initiation procedures are needed to achieve 90-90-90 targets. [ABSTRACT FROM AUTHOR]

Jan Hontelez and colleagues argue that the cost-effectiveness studies of HIV treatment scale-up need to include health system constraints to be more informative. [ABSTRACT FROM AUTHOR]

Background: A consequence of the widespread uptake of anti-retroviral therapy (ART) is that the older South African population will experience an increase in life expectancy, increasing their risk for cardiometabolic diseases (CMD), and its risk factors. The long-term interactions between HIV infection, treatment, and CMD remain to be elucidated in the African population. The HAALSI cohort was established to investigate the impact of these interactions on CMD morbidity and mortality among middle-aged and older adults.Methods: We recruited randomly selected adults aged 40 or older residing in the rural Agincourt sub-district in Mpumalanga Province. In-person interviews were conducted to collect baseline household and socioeconomic data, self-reported health, anthropometric measures, blood pressure, high-sensitivity C-reactive protein (hsCRP), HbA1c, HIV-status, and point-of-care glucose and lipid levels.Results: Five thousand fifty nine persons (46.4% male) were enrolled with a mean age of 61.7 ± 13.06 years. Waist-to-hip ratio was high for men and women (0.92 ± 0.08 vs. 0.89 ± 0.08), with 70% of women and 44% of men being overweight or obese. Blood pressure was similar for men and women with a combined hypertension prevalence of 58.4% and statistically significant increases were observed with increasing age. High total cholesterol prevalence in women was twice that observed for men (8.5 vs. 4.1%). The prevalence of self-reported CMD conditions was higher among women, except for myocardial infarction, and women had a statistically significantly higher prevalence of angina (10.82 vs. 6.97%) using Rose Criteria. The HIV- persons were significantly more likely to have hypertension, diabetes, or be overweight or obese than HIV+ persons. Approximately 56% of the cohort had at least 2 measured or self-reported clinical co-morbidities, with HIV+ persons having a consistently lower prevalence of co-morbidities compared to those without HIV. Absolute 10-year risk cardiovascular risk scores ranged from 7.7-9.7% for women and from 12.5-15.3% for men, depending on the risk score equations used.Conclusions: This cohort has high CMD risk based on both traditional risk factors and novel markers like hsCRP. Longitudinal follow-up of the cohort will allow us to determine the long-term impact of increased lifespan in a population with both high HIV infection and CMD risk. [ABSTRACT FROM AUTHOR]

Background: Poor clinical record keeping hinders health systems monitoring and patient care in many low resource settings. We develop and validate a novel method to impute dates of antiretroviral treatment (ART) initiation from routine laboratory data in South Africa's public sector HIV program. This method will enable monitoring of the national ART program using real-time laboratory data, avoiding the error potential of chart review.Methods: We developed an algorithm to impute ART start dates based on the date of a patient's "ART workup", i.e. the laboratory tests used to determine treatment readiness in national guidelines, and the time from ART workup to initiation based on clinical protocols (21 days). To validate the algorithm, we analyzed data from two large clinical HIV cohorts: Hlabisa HIV Treatment and Care Programme in rural KwaZulu-Natal; and Right to Care Cohort in urban Gauteng. Both cohorts contain known ART initiation dates and laboratory results imported directly from the National Health Laboratory Service. We assessed median time from ART workup to ART initiation and calculated sensitivity (SE), specificity (SP), positive predictive value (PPV), and negative predictive value (NPV) of our imputed start date vs. the true start date within a 6 month window. Heterogeneity was assessed across individual clinics and over time.Results: We analyzed data from over 80,000 HIV-positive adults. Among patients who had a workup and initiated ART, median time to initiation was 16 days (IQR 7,31) in Hlabisa and 21 (IQR 8,43) in RTC cohort. Among patients with known ART start dates, SE of the imputed start date was 83% in Hlabisa and 88% in RTC, indicating this method accurately predicts ART start dates for about 85% of all ART initiators. In Hlabisa, PPV was 95%, indicating that for patients with a lab workup, true start dates were predicted with high accuracy. SP (100%) and NPV (92%) were also very high.Conclusions: Routine laboratory data can be used to infer ART initiation dates in South Africa's public sector. Where care is provided based on protocols, laboratory data can be used to monitor health systems performance and improve accuracy and completeness of clinical records. [ABSTRACT FROM AUTHOR]

Introduction: In South Africa, older adults make up a growing proportion of people living with HIV. HIV programmes are likely to reach older South Africans in home-based interventions where testing is not always feasible. We evaluate the accuracy of self-reported HIV status, which may provide useful information for targeting interventions or offer an alternative to biomarker testing. Methods: Data were taken from the Health and Aging in Africa: A Longitudinal Study of an INDEPTH Community in South Africa (HAALSI) baseline survey, which was conducted in rural Mpumalanga province, South Africa. A total of 5059 participants aged ≥40 years were interviewed from 2014 to 2015. Self-reported HIV status and dried bloodspots for HIV biomarker testing were obtained during at-home interviews. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for self-reported status compared to "gold standard" biomarker results. Logbinomial regression explored associations between demographic characteristics, antiretroviral therapy (ART) status and sensitivity of self-report. Results: Most participants (93%) consented to biomarker testing. Of those with biomarker results, 50.9% reported knowing their HIV status and accurately reported it. PPV of self-report was 94.1% (95% confidence interval (CI): 92.0-96.0), NPV was 87.2% (95% CI: 86.2-88.2), sensitivity was 51.2% (95% CI: 48.2-54.3) and specificity was 99.0% (95% CI: 98.7-99.4). Participants on ART were more likely to report their HIV-positive status, and participants reporting false-negatives were more likely to have older HIV tests. Conclusions: The majority of participants were willing to share their HIV status. False-negative reports were largely explained by lack of testing, suggesting HIV stigma is retreating in this setting, and that expansion of HIV testing and retesting is still needed in this population. In HIV interventions where testing is not possible, self-reported status should be considered as a routine first step to establish HIV status. [ABSTRACT FROM AUTHOR]

Background: Although domestic HIV/AIDS financing is increasing, international HIV/AIDS financing has plateaued. Providing incentives for the health system (i.e. performance-based financing [PBF]) may help countries achieve more with available resources. We systematically reviewed effects of PBF on HIV/AIDS service delivery to inform WHO guidelines.Methods: PubMed, WHO Index Medicus, conference databases, and clinical trial registries were searched in April 2015 for randomised trials, comparative contemporaneous studies, or time-series studies. Studies evaluating PBF in people with HIV were included when they reported service quality, access, or cost. Meta-analyses were not possible due to limited data. This study is registered with PROSPERO, number CRD42015023207.Results: Four studies, published from 2009 to 2015 and including 173,262 people, met the eligibility criteria. All studies were from Sub-Saharan Africa. PBF did not improve individual testing coverage (relative risk [RR], 1.00, 95% confidence interval [CI] 0.89 to 1.13), improved couples testing coverage (RR 1.11, 95% CI 1.02 to 1.20), and improved pregnant women testing coverage (RR 1.29, 95% CI 1.28-1.30). PBF improved coverage of antiretrovirals in pregnant women (RR 1.55, 95% CI 1.50 to 1.59), infants (RR 1.92, 95% CI 1.84 to 2.01), and adults (RR 1.74, 1.64 to 1.85). PBF reduced attrition (RR 0.84, 95% CI 0.74 to 0.96) and treatment failure (odds ratio 0.55, 95% CI 0.32 to 0.97). Potential harms were not reported.Conclusions: Although the limited data suggests PBF positively affected HIV service access and quality, critical health system and governance knowledge gaps remain. More research is needed to inform national policymaking. [ABSTRACT FROM AUTHOR]

Objective: Clinic-based studies have shown that patients with human immunodeficiency virus (HIV) gain weight after initiation of antiretroviral therapy (ART). This study aimed to determine whether the scale-up of ART was associated with a population-level increase in body mass index (BMI) and blood pressure (BP) in a community with high HIV and obesity prevalence.Methods: A household survey was conducted in rural KwaZulu-Natal before ART scale-up (in 2004) and when ART coverage had reached 25% (in 2010). Anthropometric data was linked with HIV surveillance data.Results: Mean BMI decreased in women from 29.9 to 29.1 kg/m2 (P = 0.002) and in men from 24.2 to 23.0 kg/m2 (P < 0.001). Similarly, overweight and obesity prevalence declined significantly in both sexes. Mean systolic BP decreased from 123.0 to 118.2 mm Hg (P < 0.001) among women and 128.4 to 123.2 mm Hg (P < 0·001) among men.Conclusions: Large-scale ART provision is likely to have caused a decline in BMI at the population level, because ART has improved the survival of those with substantial HIV-related weight loss. The ART scale-up may have created an unexpected opportunity to sustain population-level weight loss in communities with high HIV and obesity prevalence though targeted lifestyle and nutrition interventions. [ABSTRACT FROM AUTHOR]

Background: Mother-to-child transmission (MTCT) of HIV remains a major source of new HIV infections in children. Prevention of mother-to-child transmission of HIV (PMTCT) using lifelong antiretroviral treatment (ART) for all pregnant and breastfeeding women living with HIV (Option B+) is the major strategy for eliminating paediatric HIV. Ensuring that patients are satisfied with PMTCT services is important for optimizing uptake, adherence and retention in treatment. Methods: We conducted a facility based quantitative cross-sectional survey in Dar-es-Salaam, Tanzania, between March and April 2014, when the country was transitioning to the implementation of PMTCT Option B+. We interviewed 595 pregnant and breastfeeding women living with HIV, who received PMTCT care in 36 public health facilities. Predictors of overall dissatisfaction with PMTCT services were identified using a multiple logistic regression. Results: Overall 8% of the patients expressed dissatisfaction with PMTCT services. Patients who perceived health care workers (HCW) communication skills as poor, had a 5-fold (OR 4.9, 95% CI 1.8–13.4) increased risk of dissatisfaction and those who perceived HCW capacity to understand client concerns as poor, had a 6-fold (OR 5.7, 95% CI 2.3–14.0) increased risk. Having a total visit time longer than two hours was associated with a 2-fold increased risk of being dissatisfied (OR 2.3, 95% CI 1.1–4.7). Every 30-minute increment in total visit time was associated with a 10% higher (OR 1.1, 95% CI 1.0–1.2) risk of being dissatisfied. The probability of being dissatisfied ranged from 4% (95% CI 2% - 6%) in the presence of patient-perceived good communication, good understanding of patient concerns, and a total visit time below two hours, to 70% (95% CI 47% - 86%) if HCW failed in all of these aspects. Conclusion: Patient dissatisfaction with PMTCT services was generally low; reflecting that quality of care was maintained during Tanzania’s transition to Option B+ strategy aiming to increase the number of women initiating life-long ART in PMTCT clinics. Improved HCW communication with clients, their understanding of patient concerns and a reduction of the total visit time would further optimize women’s overall satisfaction with PMTCT services in Tanzania. [ABSTRACT FROM AUTHOR]

Shortages of human resources for treating HIV/AIDS (HRHA) are a fundamental barrier to reaching universal antiretroviral treatment (ART) coverage in developing countries. Previous studies suggest that recruiting HRHA to attain universal ART coverage poses an insurmountable challenge as ART significantly increases survival among HIV-infected individuals. While new evidence about ART’s prevention benefits suggests fewer infections may mitigate the challenge, new policies such as treatment-as-prevention (TasP) will exacerbate it. We develop a mathematical model to analytically study the net effects of these countervailing factors. Using South Africa as a case study, we find that contrary to previous results, universal ART coverage is achievable even with current HRHA numbers. However, larger health gains are possible through a surge-capacity policy that aggressively recruits HRHA to reach universal ART coverage quickly. Without such a policy, TasP roll-out can increase health losses by crowding out sicker patients from treatment, unless a surge capacity exclusively for TasP is also created. [ABSTRACT FROM AUTHOR]

Background: The World Health Organization's (WHO) antiretroviral therapy (ART) guidelines have generally been adopted rapidly and with high fidelity by countries in sub-Saharan Africa. Thus far, however, WHO has not published specific guidance on nutritional care and support for (non-pregnant) adults living with HIV despite a solid evidence base for some interventions. This offers an opportunity for a case study on whether national clinical guidelines in sub-Saharan Africa provide concrete recommendations in the face of limited guidance by WHO. This study, therefore, aims to determine if national HIV treatment guidelines in sub-Saharan Africa contain specific guidance on nutritional care and support for non-pregnant adults living with HIV. Methods: We identified the most recent national HIV treatment guidelines in sub-Saharan African countries with English as an official language. Using pre-specified criteria, we determined for each guideline whether it provides guidance to clinicians on each of five components of nutritional care and support for adults living with HIV: assessment of nutritional status, dietary counseling, micronutrient supplementation, ready-to-use therapeutic or supplementary foods, and food subsidies. Results: We found that national HIV treatment guidelines in sub-Saharan Africa generally do not contain concrete recommendations on nutritional care and support for non-pregnant adults living with HIV. Conclusions: Given that decisions on nutritional care and support are inevitably being made at the clinician-patient level, and that clinicians have a relative disadvantage in systematically identifying, summarizing, and weighing up research evidence compared to WHO and national governments, there is a need for more specific clinical guidance. In our view, such guidance should at a minimum recommend daily micronutrient supplements for adults living with HIV who are in pre-ART stages, regular dietary counseling, periodic assessment of anthropometric status, and additional nutritional management of undernourished patients. More broadly, our findings suggest that countries in sub-Saharan Africa look to WHO for guidance in translating evidence into clinical guidelines. It is, thus, likely that the development of concrete recommendations by WHO on nutritional interventions for people living with HIV would lead to more specific guidelines at the country-level and, ultimately, better clinical decisions and treatment outcomes. [ABSTRACT FROM AUTHOR]

Background: High BMI and blood pressure are leading chronic disease risk factors in South Africa. Longterm effects of HIV and ART on adiposity and blood pressure are poorly understood, and direct comparisons of risk factor trajectories in HIV- versus HIV+ populations are rare. Methods: In 2003 and 2010, height, weight, and blood pressure were recorded in a study population (n = 505) in KwaZulu-Natal, South Africa (30% adult HIV prevalence). We modeled change in BMI and BP longitudinally in HIV- individuals (n = 315), seroconverters (n = 32), HIV+ patients not on ART (HIV+ART−; n = 52), HIV+ patients on ART for 0–<2 years as of 2010 (HIV+ART0–<2 yrs; n = 18), patients on ART for 2–5 years (HIV+ART2–5yrs; n = 44), and a subgroup with unknown HIV status (n = 44). Difference-in-differences were assessed in reference to the HIV- population. Results: Between 2003 and 2010, BMI increased significantly in the HIV- group, by 0.874 (95% CI 0.339, 1.41; p = 0.001), to 30.4. BMI drop was significantly greater in HIV+ART0-<2yrs than in HIV+ART2–5yrs (p = 0.005). DID in BMI in HIV+ART0-<2yrs versus the reference was -5.21 (95% CI -7.53, -2.90; p = 0.001), and DID in HIV+ART2–5yrs versus reference was -1.35 (95% CI -2.89, 0.189; p = 0.086). DID in SBP in HIV+ART−vs HIV- DID was -7.55 mmHg (95% CI -13.2 to -1.90; p = 0.009). Conclusion: Short-term ART (0–<2 years) was associated with larger weight loss than either no ART or long-term ART. Once on ART for 2+ years, individuals ‘caught up’ on weight gain with the HIV- population. Our results showcase the importance of health system readiness to address the burgeoning double burden of disease in South Africa. [ABSTRACT FROM AUTHOR]

Background: The effect of the rapid scale-up of vertical antiretroviral treatment (ART) programs for HIV in sub-Saharan Africa on the overall health system is under intense debate. Some have argued that these programs have reduced access for people suffering from diseases unrelated to HIV because ART programs have drained human and physical resources from other parts of the health system; others have claimed that the investments through ART programs have strengthened the general health system and the population health impacts of ART have freed up health care capacity for the treatment of diseases that are not related to HIV. To establish the population-level impact of ART programs on health care utilization in the public-sector health system, we compared trends in health care utilization among HIV-infected people receiving and not receiving ART with HIV-uninfected people during a period of rapid ART scale-up. Methods and Findings: We used data from the Wellcome Trust Africa Centre for Population Health, which annually elicited information on health care utilization from all surveillance participants over the period 2009–2012 (N = 32,319). We determined trends in hospitalization, and public-sector and private-sector primary health care (PHC) clinic visits for HIV-infected and -uninfected people over a time period of rapid ART scale-up (2009–2012) in this community. We regressed health care utilization on HIV status and ART status in different calendar years, controlling for sex, age, and area of residence. The proportion of people who reported to have visited a public-sector primary health care (PHC) clinic in the last 6 months increased significantly over the period 2009–2012, for both HIV-infected people (from 59% to 67%; p<0.001), and HIV-uninfected people (from 41% to 47%; p<0.001). In contrast, the proportion of HIV-infected people visiting a private-sector PHC clinic declined from 22% to 12% (p<0.001) and hospitalization rates declined from 128 to 82 per 1000 PY (p<0.001). For HIV-uninfected people, the proportion visiting a private-sector PHC clinic declined from 16% to 9%, and hospitalization rates declined from 78 to 44 per 1000 PY (p<0.001). After controlling for potential confounding factors, all trends remained of similar magnitude and significance. Conclusions: Our results indicate that the ART scale-up in this high HIV prevalence community has shifted health care utilization from hospitals and private-sector primary care to public-sector primary care. Remarkably, this shift is observed for both HIV-infected and -uninfected populations, supporting and extending hypotheses of ‘therapeutic citizenship’ whereby HIV-infected patients receiving ART facilitate primary care access for family and community members. One explanation of our findings is that ART has improved the capacity or quality of primary care in this community and, as a consequence, increasingly met overall health care needs at the primary care level rather than at the secondary level. Future research needs to confirm this causal interpretation of our findings using qualitative work to understand causal mechanisms or quasi-experimental quantitative studies to increase the strength of causal inference. [ABSTRACT FROM AUTHOR]

Near-perfect adherence to antiretroviral therapy (ART) is required to achieve the best possible prevention and treatment outcomes. Yet, there have been particular concerns about the challenges of adherence among patients living in resource-limited settings in sub-Saharan Africa. The primary objective of this study was to explore adherence in a low-resourced, rural community of high HIV prevalence in South Africa and to identify specific individual and structural factors that can either challenge or support adherence in this context. We applied digital stories as a qualitative research tool to gain insights into personal contexts of HIV and ART adherence. Through an inductive thematic analysis of twenty story texts, soundtracks and drawings, we explored experiences, understandings, and contexts of the participants and identified potential barriers and facilitators for those on lifelong treatment. We found that many of the stories reflected a growing confidence in the effectiveness of ART, which should be viewed as a key facilitator to successful adherence since this attitude can promote disclosure and boost access to social support. Nevertheless, stories also highlighted the complexity of the issues that individuals and households face as they deal with HIV and ART in this setting and it is clear that an overburdened local healthcare system has often struggled to meet the demands of a rapidly expanding epidemic and to provide the necessary medical and emotional support. Our analysis suggests several opportunities for further research and the design of novel health interventions to support optimal adherence. Firstly, future health promotion campaigns should encourage individuals to test together, or at least accompany each other for testing, to encourage social support from the outset. Additionally, home-based testing and ART club interventions might be recommended to make it easier for individuals to adhere to their treatment regimens and to provide a sense of support and solidarity. [ABSTRACT FROM AUTHOR]

Background: Women have better patient outcomes in HIV care and treatment than men in sub-Saharan Africa. We assessed--at the population level--whether and to what extent mass HIV treatment is associated with changes in sex disparities in adult life expectancy, a summary metric of survival capturing mortality across the full cascade of HIV care. We also determined sex-specific trends in HIV mortality and the distribution of HIV-related deaths in men and women prior to and at each stage of the clinical cascade.Methods and Findings: Data were collected on all deaths occurring from 2001 to 2011 in a large population-based surveillance cohort (52,964 women and 45,688 men, ages 15 y and older) in rural KwaZulu-Natal, South Africa. Cause of death was ascertained by verbal autopsy (93% response rate). Demographic data were linked at the individual level to clinical records from the public sector HIV treatment and care program that serves the region. Annual rates of HIV-related mortality were assessed for men and women separately, and female-to-male rate ratios were estimated in exponential hazard models. Sex-specific trends in adult life expectancy and HIV-cause-deleted adult life expectancy were calculated. The proportions of HIV deaths that accrued to men and women at different stages in the HIV cascade of care were estimated annually. Following the beginning of HIV treatment scale-up in 2004, HIV mortality declined among both men and women. Female adult life expectancy increased from 51.3 y (95% CI 49.7, 52.8) in 2003 to 64.5 y (95% CI 62.7, 66.4) in 2011, a gain of 13.2 y. Male adult life expectancy increased from 46.9 y (95% CI 45.6, 48.2) in 2003 to 55.9 y (95% CI 54.3, 57.5) in 2011, a gain of 9.0 y. The gap between female and male adult life expectancy doubled, from 4.4 y in 2003 to 8.6 y in 2011, a difference of 4.3 y (95% CI 0.9, 7.6). For women, HIV mortality declined from 1.60 deaths per 100 person-years (95% CI 1.46, 1.75) in 2003 to 0.56 per 100 person-years (95% CI 0.48, 0.65) in 2011. For men, HIV-related mortality declined from 1.71 per 100 person-years (95% CI 1.55, 1.88) to 0.76 per 100 person-years (95% CI 0.67, 0.87) in the same period. The female-to-male rate ratio for HIV mortality declined from 0.93 (95% CI 0.82-1.07) in 2003 to 0.73 (95% CI 0.60-0.89) in 2011, a statistically significant decline (p = 0.046). In 2011, 57% and 41% of HIV-related deaths occurred among men and women, respectively, who had never sought care for HIV in spite of the widespread availability of free HIV treatment. The results presented here come from a poor rural setting in southern Africa with high HIV prevalence and high HIV treatment coverage; broader generalizability is unknown. Additionally, factors other than HIV treatment scale-up may have influenced population mortality trends.Conclusions: Mass HIV treatment has been accompanied by faster declines in HIV mortality among women than men and a growing female-male disparity in adult life expectancy at the population level. In 2011, over half of male HIV deaths occurred in men who had never sought clinical HIV care. Interventions to increase HIV testing and linkage to care among men are urgently needed. [ABSTRACT FROM AUTHOR]

Background: The Universal HIV Test and Treat (UTT) strategy represents a challenge for science, but is also a challenge for individuals and societies. Are repeated offers of provider-initiated HIV testing and immediate antiretroviral therapy (ART) socially-acceptable and can these become normalized over time? Can UTT be implemented without potentially adding to individual and community stigma, or threatening individual rights? What are the social, cultural and economic implications of UTT for households and communities? And can UTT be implemented within capacity constraints and other threats to the overall provision of HIV services? The answers to these research questions will be critical for routine implementation of UTT strategies. Methods/design: A social science research programme is nested within the ANRS 12249 Treatment-as-Prevention (TasP) cluster-randomised trial in rural South Africa. The programme aims to inform understanding of the (i) social, economic and environmental factors affecting uptake of services at each step of the continuum of HIV prevention, treatment and care and (ii) the causal impacts of the TasP intervention package on social and economic factors at the individual, household, community and health system level. We describe a multidisciplinary, multi-level, mixed-method research protocol that includes individual, household, community and clinic surveys, and combines quantitative and qualitative methods. Discussion: The UTT strategy is changing the overall approach to HIV prevention, treatment and care, and substantial social consequences may be anticipated, such as changes in social representations of HIV transmission, prevention, HIV testing and ART use, as well as changes in individual perceptions and behaviours in terms of uptake and frequency of HIV testing and ART initiation at high CD4. Triangulation of social science studies within the ANRS 12249 TasP trial will provide comprehensive insights into the acceptability and feasibility of the TasP intervention package at individual, community, patient and health system level, to complement the trial's clinical and epidemiological outcomes. It will also increase understanding of the causal impacts of UTT on social and economic outcomes, which will be critical for the long-term sustainability and routine UTT implementation. [ABSTRACT FROM AUTHOR]

We assess depression rates and investigate whether depression among HIV-infected adults receiving antiretroviral treatment (ART) is associated with social support and HIV coping strategies in rural South Africa (SA). The study took place in a decentralised public-sector ART programme in a poor, rural area of KwaZulu-Natal, SA, with high-HIV prevalence and high-ART coverage. The 12-item General Health Questionnaire (GHQ12), validated in this setting, was used to assess depression in 272 adults recently initiated on ART. Estimates of depression prevalence ranged from 33% to 38%, depending on the method used to score the GHQ12. Instrumental social support (providing tangible factors for support, such as financial assistance, material goods or services), but not emotional social support (expressing feelings, such as empathy, love, trust or acceptance, to support a person), was significantly associated with lower likelihood of depression [adjusted odds ratio (aOR) = 0.65, 95% confidence interval (CI) 0.52–0.81,P< 0.001], when controlling for sex, age, marital status, education, household wealth and CD4 cell count. In addition, using “avoidance of people” as a strategy to cope with HIV was associated with an almost three times higher odds of depression (aOR = 2.79, CI: 1.34–5.82,P= 0.006), whereas none of the other five coping strategies we assessed was significantly associated with depression. In addition to antidepressant drug treatment, interventions enhancing instrumental social support and behavioural therapy replacing withdrawal behaviours with active HIV coping strategies may be effective in reducing the burden of depression among patients on ART. [ABSTRACT FROM PUBLISHER]

: In light of changing WHO guidelines for HIV treatment, Till Bärnighausen and colleagues consider how large-scale HIV treatment-as-prevention trials can be adapted so that they can remain viable. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

: Using nine structurally different models, Jan Hontelez and colleagues investigate timeframes for HIV elimination in South Africa using a universal test and treat strategy. Please see later in the article for the Editors' Summary [ABSTRACT FROM AUTHOR]

Background: Little is known about the variability of CD4 counts in the general population of sub-Saharan Africa countries affected by the HIV epidemic. We investigated factors associated with CD4 counts in a rural area in South Africa with high HIV prevalence and high antiretroviral treatment (ART) coverage. Methods: CD4 counts, health status, body mass index (BMI), demographic characteristics and HIV status were assessed in 4990 adult resident participants of a demographic surveillance in rural KwaZulu-Natal in South Africa; antiretroviral treatment duration was obtained from a linked clinical database. Multivariable regression analysis, overall and stratified by HIV status, was performed with CD4 count levels as outcome. Results: Median CD4 counts were significantly higher in women than in men overall (714 vs. 630 cells/µl, p<0.0001), both in HIV-uninfected (833 vs. 683 cells/µl, p<0.0001) and HIV-infected adults (384.5 vs. 333 cells/µl, p<0.0001). In multivariable regression analysis, women had 19.4% (95% confidence interval (CI) 16.1–22.9) higher CD4 counts than men, controlling for age, HIV status, urban/rural residence, household wealth, education, BMI, self-reported tuberculosis, high blood pressure, other chronic illnesses and sample processing delay. At ART initiation, HIV-infected adults had 21.7% (95% CI 14.6–28.2) lower CD4 counts than treatment-naive individuals; CD4 counts were estimated to increase by 9.2% (95% CI 6.2–12.4) per year of treatment. Conclusions: CD4 counts are primarily determined by sex in HIV-uninfected adults, and by sex, age and duration of antiretroviral treatment in HIV-infected adults. Lower CD4 counts at ART initiation in men could be a consequence of lower CD4 cell counts before HIV acquisition. [ABSTRACT FROM AUTHOR]

Beliefs about antiretroviral treatment (ART) are crucial for treatment success but not well documented in sub-Sahara African countries. We studied the frequency of false beliefs about ART in 389 ART patients in Livingstone, Zambia. Despite intensive pre-ART counseling, we find that more than half of the patients hold at least one false belief about ART effectiveness, side effects, or the consequences of ART non-retention or non-adherence. Commonly held false beliefs-e.g., pastors can cure HIV infection through prayer and ART can be stopped without harmful effects while taking immune-boosting herbs-are likely to decrease ART adherence and retention. [ABSTRACT FROM AUTHOR]

The HIV Prevention Trials Network (HPTN) 052 study, which showed the effectiveness of antiretroviral treatment in reducing HIV transmission, has been hailed as a "game changer" in the fight against HIV, prompting calls for scaling up treatment as prevention (TasP). However, it is unclear how TasP can be financed, given flat-lining support for global HIV programs. We assess whether TasP is indeed a game changer or if comparable benefits are obtainable at similar or lower cost by increasing coverage of medical male circumcision (MMC) and antiretroviral treatment (ART) at CD4 <350/μL. We develop a new mathematical model and apply it to South Africa, finding that high ART coverage combined with high MMC coverage provides approximately the same HIV incidence reduction as TasP, for $5 billion less over 2009-2020. MMC outperforms ART significantly in cost per infection averted ($1,096 vs. $6,790) and performs comparably in cost per death averted ($5,198 vs. $5,604). TasP is substantially less cost effective at $8,375 per infection and $7,739 per death averted. The prevention benefits of HIV treatment are largely reaped with high ART coverage. The most cost-effective HIV prevention strategy is to expand MMC coverage and then scale up ART, but the most cost-effective HIV-mortality reduction strategy is to scale up MMC and ART jointly. TasP is cost effective by commonly used absolute benchmarks but it is far less cost effective than MMC and ART. Given South Africa's current annual ART spending, the $5 billion in savings offered by MMC and ART over TasP in the next decade, for similar health benefits, challenges the widely hailed status of TasP as a game changer. [ABSTRACT FROM AUTHOR]

Despite extraordinary global progress in increasing coverage of antiretroviral treatment (ART), the majority of people needing ART currently are not receiving treatment. Both the number of people needing ART and the average ART price per patient-year are expected to increase in coming years, which will dramatically raise funding needs for ART. Several international organizations are using interventions in ART markets to decrease ART price or to improve ART quality, delivery and innovation, with the ultimate goal of improving population health. These organizations need to select those market interventions that are most likely to substantially affect population health outcomes (ex ante assessment) and to evaluate whether implemented interventions have improved health outcomes (ex post assessment).We develop a framework to structure ex ante and ex post assessment of the population health impact of market interventions, which is transmitted through effects in markets and health systems. Ex ante assessment should include evaluation of the safety and efficacy of the ART products whose markets will be affected by the intervention; theoretical consideration of the mechanisms through which the intervention will affect population health; and predictive modelling to estimate the potential population health impact of the intervention. For ex post assessment, analysts need to consider which outcomes to estimate empirically and which to model based on empirical findings and understanding of the economic and biological mechanisms along the causal pathway from market intervention to population health. We discuss methods for ex post assessment and analyse assessment issues (unintended intervention effects, interaction effects between different interventions, and assessment impartiality and cost). We offer seven recommendations for ex ante and ex post assessment of population health impact of market interventions. [ABSTRACT FROM PUBLISHER]

Objective To provide a broad and up-to-date picture of the effect of antiretroviral therapy (ART) provision on population-level mortality in Southern and East Africa. Methods Data on all-cause, AIDS and non-AIDS mortality among 15-59 year olds were analysed from demographic surveillance sites (DSS) in Karonga (Malawi), Kisesa (Tanzania), Masaka (Uganda) and the Africa Centre (South Africa), using Poisson regression. Trends over time from up to 5 years prior to ART roll-out, to 4-6 years afterwards, are presented, overall and by age and sex. For Masaka and Kisesa, trends are analysed separately for HIV-negative and HIV-positive individuals. For Karonga and the Africa Centre, trends in AIDS and non-AIDS mortality are analysed using verbal autopsy data. Results For all-cause mortality, overall rate ratios (RRs) comparing the period 2-6 years following ART roll-out with the pre-ART period were 0.58 (5.9 vs. 10.2 deaths per 1000 person-years) in Karonga, 0.79 (7.2 vs. 9.1 deaths per 1000 person-years) in Kisesa, 0.61 (6.7 compared with 11.0 deaths per 1000 person-years) in Masaka and 0.79 (14.8 compared with 18.6 deaths per 1000 person-years) in the Africa Centre DSS. The mortality decline was seen only in HIV-positive individuals/AIDS mortality, with no decline in HIV-negative individuals/non-AIDS mortality. Less difference was seen in Kisesa where ART uptake was lower. Conclusions Falls in all-cause mortality are consistent with ART uptake. The largest falls occurred where ART provision has been decentralised or available locally, suggesting that this is important. [ABSTRACT FROM AUTHOR]

Objectives To present a simple method for estimating population-level anti-retroviral therapy (ART) need that does not rely on knowledge of past HIV incidence. Methods A new approach to estimating ART need is developed based on calculating age-specific proportions of HIV-infected adults expected to die within a fixed number of years in the absence of treatment. Mortality data for HIV-infected adults in the pre-treatment era from five African HIV cohort studies were combined to construct a life table, starting at age 15, smoothed with a Weibull model. Assuming that ART should be made available to anyone expected to die within 3 years, conditional 3-year survival probabilities were computed to represent proportions needing ART. The build-up of ART need in a successful programme continuously recruiting infected adults into treatment as they age to within 3 years of expected death was represented by annually extending the conditional survival range. Results The Weibull model: survival probability in the infected state from age 15 = exp(−0.0073 × (age − 15)1.69) fitted the pooled age-specific mortality data very closely. Initial treatment need for infected persons increased rapidly with age, from 15% at age 20-24 to 32% at age 40-44 and 42% at age 60-64. Overall need in the treatment of naïve population was 24%, doubling within 5 years in a programme continually recruiting patients entering the high-risk period for dying. Conclusion A reasonable projection of treatment need in an ART naive population can be made based on the age and gender profile of HIV-infected people. [ABSTRACT FROM AUTHOR]

Background: Many mathematical models have investigated the impact of expanding access to antiretroviral therapy (ART) on new HIV infections. Comparing results and conclusions across models is challenging because models have addressed slightly different questions and have reported different outcome metrics. This study compares the predictions of several mathematical models simulating the same ART intervention programmes to determine the extent to which models agree about the epidemiological impact of expanded ART. Methods and Findings: Twelve independent mathematical models evaluated a set of standardised ART intervention scenarios in South Africa and reported a common set of outputs. Intervention scenarios systematically varied the CD4 count threshold for treatment eligibility, access to treatment, and programme retention. For a scenario in which 80% of HIV-infected individuals start treatment on average 1 y after their CD4 count drops below 350 cells/ml and 85% remain on treatment after 3 y, the models projected that HIV incidence would be 35% to 54% lower 8 y after the introduction of ART, compared to a counterfactual scenario in which there is no ART. More variation existed in the estimated long-term (38 y) reductions in incidence. The impact of optimistic interventions including immediate ART initiation varied widely across models, maintaining substantial uncertainty about the theoretical prospect for elimination of HIV from the population using ART alone over the next four decades. The number of person-years of ART per infection averted over 8 y ranged between 5.8 and 18.7. Considering the actual scale-up of ART in South Africa, seven models estimated that current HIV incidence is 17% to 32% lower than it would have been in the absence of ART. Differences between model assumptions about CD4 decline and HIV transmissibility over the course of infection explained only a modest amount of the variation in model results. Conclusions: Mathematical models evaluating the impact of ART vary substantially in structure, complexity, and parameter choices, but all suggest that ART, at high levels of access and with high adherence, has the potential to substantially reduce new HIV infections. There was broad agreement regarding the short-term epidemiologic impact of ambitious treatment scale-up, but more variation in longer term projections and in the efficiency with which treatment can reduce new infections. Differences between model predictions could not be explained by differences in model structure or parameterization that were hypothesized to affect intervention impact. [ABSTRACT FROM AUTHOR]

Objectives National political commitment is likely to become particularly crucial to sustaining antiretroviral treatment programmes in the coming decade, as donor contributions to HIV funding decreases. The objective of this study is to synthesise information on existing indicators of political commitment to respond to national HIV epidemics. Methods The authors describe and critically evaluate the existing indicators and propose studies to validate them. Results Several indicators have been developed to measure governments' political commitment to respond to national HIV epidemics the AIDS Program Effort d Index, the United Nations General Assembly Special Session on HIV/AIDS Declaration of Commitment Indicators and the AIDS Policy Aggressiveness Indicators but the validity of these measures has not d been systematically assessed. The indicators differ in their intended use, collection methods, content categories, data coverage, and strengths and limitations. Several types of studies could be used to test indicator validity (based on indicator content, comparisons of the same indicator using different elicitation methods, relationship patterns between indicators, relations between indicators and other variables and the consequences of using the indicators). Conclusions The existing indicators of political commitment to respond to national HIV epidemics are useful for many purposes, including research, policymaking and advocacy. A range of studies could improve the understanding of indicator validity. New data collection and measurement approaches offer opportunities to improve how actors in the HIV community capture the complicated, multidimensional concept of political commitment. [ABSTRACT FROM AUTHOR]

Unlabelled: Background: Although access to life-saving treatment for patients infected with HIV in South Africa has improved substantially since 2004, treating all eligible patients (universal access) remains elusive. As the prices of antiretroviral drugs have dropped over the past years, availability of human resources may now be the most important barrier to achieving universal access to HIV treatment in Africa. We quantify the number of HIV health workers (HHWs) required to be added to the current HIV workforce to achieve universal access to HIV treatment in South Africa, under different eligibility criteria.Methods: We performed a time and motion study in three HIV clinics in a rural, primary care-based HIV treatment program in KwaZulu-Natal, South Africa, to estimate the average time per patient visit for doctors, nurses, and counselors. We estimated the additional number of HHWs needed to achieve universal access to HIV treatment within one year.Results: For universal access to HIV treatment for all patients with a CD4 cell count of ≤350 cells/μl, an additional 2,200 nurses, 3,800 counselors, and 300 doctors would be required, at additional annual salary cost of 929 million South African rand (ZAR), equivalent to US$ 141 million. For universal treatment ('treatment as prevention'), an additional 6,000 nurses, 11,000 counselors, and 800 doctors would be required, at an additional annual salary cost of ZAR 2.6 billion (US$ 400 million).Conclusions: Universal access to HIV treatment for patients with a CD4 cell count of ≤350 cells/μl in South Africa may be affordable, but the number of HHWs available for HIV treatment will need to be substantially increased. Treatment as prevention strategies will require considerable additional financial and human resources commitments. [ABSTRACT FROM AUTHOR]

Summary: The success of potent antiretroviral treatment for HIV infection is primarily determined by adherence. We systematically review the evidence of effectiveness of interventions to increase adherence to antiretroviral treatment in sub-Saharan Africa. We identified 27 relevant reports from 26 studies of behavioural, cognitive, biological, structural, and combination interventions done between 2003 and 2010. Despite study diversity and limitations, evidence suggests that treatment supporters, directly observed therapy, mobile-phone text messages, diary cards, and food rations can effectively increase adherence in sub-Saharan Africa. However, some interventions are unlikely to have large or lasting effects, and others are effective only in specific settings. These findings emphasise the need for more research, particularly for randomised controlled trials, to examine the effect of context and specific features of intervention content on effectiveness. Future work should assess intervention targeting and selection of interventions based on behavioural theories relevant to sub-Saharan Africa. [Copyright &y& Elsevier]

Summary [ABSTRACT FROM AUTHOR]

Background: Since November 2009, WHO recommends that adults infected with HIV should initiate antiretroviral therapy (ART) at CD4+ cell counts of ≤350 cells/µl rather than ≤200 cells/µl. South Africa decided to adopt this strategy for pregnant and TB co-infected patients only. We estimated the impact of fully adopting the new WHO guidelines on HIV epidemic dynamics and associated costs. Methods and Finding: We used an established model of the transmission and control of HIV in specified sexual networks and healthcare settings. We quantified the model to represent Hlabisa subdistrict, KwaZulu-Natal, South Africa. We predicted the HIV epidemic dynamics, number on ART and program costs under the new guidelines relative to treating patients at ≤200 cells/µl for the next 30 years. During the first five years, the new WHO treatment guidelines require about 7% extra annual investments, whereas 28% more patients receive treatment. Furthermore, there will be a more profound impact on HIV incidence, leading to relatively less annual costs after seven years. The resulting cumulative net costs reach a break-even point after on average 16 years. Conclusions: Our study strengthens the WHO recommendation of starting ART at ≤350 cells/µl for all HIV-infected patients. Apart from the benefits associated with many life-years saved, a modest frontloading appears to lead to net savings within a limited time-horizon. This finding is robust to alternative assumptions and foreseeable changes in ART prices and effectiveness. Therefore, South Africa should aim at rapidly expanding its healthcare infrastructure to fully embrace the new WHO guidelines. [ABSTRACT FROM AUTHOR]

Background: Important advances in the development and production of quality-certified pediatric antiretroviral (ARV) formulations have recently been made despite significant market disincentives for manufacturers. This progress resulted from lobbying and innovative interventions from HIV/AIDS activists, civil society organizations, and international organizations. Research on uptake and dispersion of these improved products across countries and international organizations has not been conducted but is needed to inform next steps towards improving child health. Methods: We used information from the World Health Organization Prequalification Programme and the United States Food and Drug Administration to describe trends in quality-certification of pediatric formulations and used 7,989 donor-funded, pediatric ARV purchase transactions from 2002-2009 to measure uptake and dispersion of new pediatric ARV formulations across countries and programs. Prices for new pediatric ARV formulations were compared to alternative dosage forms. Results: Fewer ARV options exist for HIV/AIDS treatment in children than adults. Before 2005, most pediatric ARVs were produced by innovator companies in single-component solid and liquid forms. Five 2-in1 and four 3-in-1 generic pediatric fixed-dose combinations (FDCs) in solid and dispersible forms have been quality-certified since 2005. Most (67%) of these were produced by one quality-certified manufacturer. Uptake of new pediatric FDCs outside of UNITAID is low. UNITAID accounted for 97-100% of 2008-2009 market volume. In total, 33 and 34 countries reported solid or dispersible FDC purchases in 2008 and 2009, respectively, but most purchases were made through UNITAID. Only three Global Fund country recipients reported purchase of these FDCs in 2008. Prices for pediatric FDCs were considerably lower than liquids but typically higher than half of an adult FDC. Conclusion: Pediatric ARV markets are more fragile than adult markets. Ensuring a long-term supply of quality, well-adapted ARVs for children requires ongoing monitoring and improved understanding of global pediatric markets, including country-based research to explain and address low uptake of new, improved formulations. Continued innovation in pediatric ARV development may be threatened by outdated procurement practices failing to connect clinicians making prescribing decisions, supply chain staff dealing with logistics, donors, international organizations, and pharmaceutical manufacturers. Perceptions of global demand must be better informed by accurate estimates of actual country-level demand. [ABSTRACT FROM AUTHOR]

Background: Universal access to antiretroviral therapy (ART) in low- and middle-income countries faces numerous challenges: increasing numbers of people needing ART, new guidelines recommending more expensive antiretroviral (ARV) medicines, limited financing, and few fixed-dose combination (FDC) products. Global initiatives aim to promote efficient global ARV markets, yet little is known about market dynamics and the impact of global policy interventions.Methods: We utilize several data sources, including 12,958 donor-funded, adult first-line ARV purchase transactions, to describe the market from 2002-2008. We examine relationships between market trends and: World Health Organization (WHO) HIV/AIDS treatment guidelines; WHO Prequalification Programme (WHO Prequal) and United States (US) Food and Drug Administration (FDA) approvals; and procurement policies of the Global Fund to Fight AIDS, Tuberculosis, and Malaria (GFATM), US President's Emergency Plan for AIDS Relief (PEPFAR) and UNITAID.Results: WHO recommended 7, 4, 24, and 6 first-line regimens in 2002, 2003, 2006 and 2009 guidelines, respectively. 2009 guidelines replaced a stavudine-based regimen ($88/person/year) with more expensive zidovudine- ($154-260/person/year) or tenofovir-based ($244-465/person/year) regimens. Purchase volumes for ARVs newly-recommended in 2006 (emtricitabine, tenofovir) increased >15-fold from 2006 to 2008. Twenty-four generic FDCs were quality-approved for older regimens but only four for newer regimens. Generic FDCs were available to GFATM recipients in 2004 but to PEPFAR recipients only after FDA approval in 2006. Price trends for single-component generic medicines mirrored generic FDC prices. Two large-scale purchasers, PEPFAR and UNITAID, together accounted for 53%, 84%, and 77% of market volume for abacavir, emtricitabine, and tenofovir, respectively, in 2008. PEPFAR and UNITAID purchases were often split across two manufacturers.Conclusions: Global initiatives facilitated the creation of fairly efficient markets for older ARVs, but markets for newer ARVs are less competitive and slower to evolve. WHO guidelines shape demand, and their complexity may help or hinder achievement of economies of scale in pharmaceutical manufacturing. Certification programs assure ARV quality but can delay uptake of new formulations. Large-scale procurement policies may decrease the numbers of buyers and sellers, rendering the market less competitive in the longer-term. Global policies must be developed with consideration for their short- and long-term impact on market dynamics. [ABSTRACT FROM AUTHOR]

Background: KwaZulu-Natal is the South African province worst affected by HIV and the focus of early modeling studies investigating strategies of antiretroviral treatment (ART) delivery. The reality of antiretroviral roll-out through primary care has differed from that anticipated and real world data are needed to inform the planning of further scaling up of services. We investigated the factors associated with uptake of antiretroviral treatment through a primary healthcare system in rural South Africa. Methods: Detailed demographic, HIV surveillance and geographic information system (GIS) data were used to estimate the proportion of HIV positive adults accessing antiretroviral treatment within northern KwaZulu-Natal, South Africa in the period from initiation of antiretroviral roll-out until the end of 2008. Demographic, spatial and socioeconomic factors influencing the likelihood of individuals accessing antiretroviral treatment were explored using multivariable analysis. Results: Mean uptake of ART among HIV positive resident adults was 21.0% (95%CI 20.1-21.9). Uptake among HIV positive men (19.2%) was slightly lower than women (21.8%, P = 0.011). An individual's likelihood of accessing ART was not associated with level of education, household assets or urban/rural locale. ART uptake was strongly negatively associated with distance from the nearest primary healthcare facility (aOR = 0.728 per square-root transformed km, 95%CI 0.658-0.963, P = 0.002). Conclusions: Despite concerns about the equitable nature of antiretroviral treatment rollout, we find very few differences in ART uptake across a range of socio-demographic variables in a rural South African population. However, even when socio-demographic factors were taken into account, individuals living further away from primary healthcare clinics were still significantly less likely to be accessing ART [ABSTRACT FROM AUTHOR]