Prevalence of hypertension and high-normal blood pressure among young adults in Zimbabwe: findings from a large, cross-sectional population-based survey.

BACKGROUND: Hypertension is the greatest driver of cardiovascular mortality and onset might be in youth. We aimed to investigate the prevalence of and risk factors for elevated blood pressure (hypertension ≥140 mm Hg systolic, ≥90 mm Hg diastolic, or both) and high-normal blood pressure (130-139 mm Hg systolic, 85-89 mm Hg diastolic, or both) among youth in Zimbabwe. METHODS: A population-based, cross-sectional survey of randomly sampled youth aged 18-24 years from 24 urban and peri-urban communities in three provinces (Harare, Bulawayo, and Mashonaland East) in Zimbabwe was conducted between Oct 4, 2021, and June 2, 2022. Standardised questionnaires were used by research assistants to collect sociodemographic, behavioural, and clinical data. Height, bodyweight, and blood pressure were recorded. Three seated blood pressure measurements were taken at standardised timepoints during participant interview using a digital sphygmomanometer and cuffs sized on mid-upper arm circumference. The association of potential risk factors with elevated blood pressure was examined using multivariable logistic regression. FINDINGS: 17 682 (94·4%) of 18 729 eligible participants were recruited, 17 637 (99·7%) of whom had complete data, and 16 883 (95·7%) of whom were included in the final study sample after excluding 754 (4·3%) pregnant women. The median age was 20 years (IQR 19-22), 9973 (59·1%) participants were female, and 6910 (40·9%) were male. The prevalence of hypertension was 7·4% (95% CI 7·0-7·8) and high-normal blood pressure was 12·2% (11·7-12·7). Overall, prevalence of hypertension was higher in men (8·7% [95% CI 8·2-9·6]) than in women (6·6% [6·0-6·9]), but with age increased to similar levels (at age 18 years 7·3% [6·2-8·6] and 4·3% [3·5-5·2]; at age 23-24 years 10·9% [9·3-12·6] and 9·5% [8·4-10·7] in men and women, respectively). After adjusting for factors associated with hypertension in the crude analysis, hypertension was associated with male sex (adjusted odds ratio 1·53 [95% CI 1·36-1·74]), increasing age (age 19-20 years 1·20 [1·00-1·44]; age 21-22 years 1·45 [1·20-1·75]; age 23-24 years 1·90 [1·57-2·30], vs age 18 years), and BMI of 30·0 kg/m2 or more (1·94 [1·53-2·47] vs 18·5-24·9 kg/m2). A BMI of 18·5 kg/m2 or less (0·79 [0·63-0·98] vs 18·5-24·9 kg/m2) and living with HIV (0·71 [0·55-0·92]) were associated with lower odds of hypertension. INTERPRETATION: Prevalence of elevated blood pressure is high among urban and peri-urban youth in Zimbabwe and increases rapidly with age. Further research is needed to understand drivers of blood pressure elevation and the extent of target organ damage in youth in Zimbabwe and similar sub-Saharan African settings, to guide implementation of prevention and management strategies. FUNDING: Wellcome Trust.

The impact of dual- versus single-dosing and fatty food co-administration on albendazole efficacy against hookworm among children in Mayuge district, Uganda: Results from a 2x2 factorial randomised controlled trial.

BACKGROUND: Mass Drug Administration (MDA) is the main strategy for control of soil-transmitted helminth (STH) infections, with single-dose benzimidazole (albendazole or mebendazole) the principal MDA option. In Mayuge district, Uganda, an MDA programme has been in place for over fifteen years but hookworm infection remains common and there is concern that the effectiveness of single-dose albendazole as currently used for MDA may be sub-optimal. This study aims to assess the efficacy of dual- versus single-dose albendazole, with and without fatty food co-administration against hookworm, the dominant form of STHs in Mayuge district, Uganda. METHODOLOGY: This was a 2x2 factorial randomised controlled trial to investigate two interventions simultaneously; 1) dual-dose versus single-dose albendazole, 2) taking albendazole with or without fatty food (200 grams of avocado eaten directly after medication). School children with hookworm infection were randomised in a 1:1:1:1 ratio to the four possible treatment groups. Three weeks after the treatment, stool samples were collected from trial participants to evaluate trial outcomes: cure rate and egg reduction rate (ERR). PRINCIPAL FINDINGS: A total of 225 participants were enrolled, and 222 (98.7%) seen at 3 weeks. The cure rate in the dual-dose group was 96.4% (95% CI: 90.9-99%), higher than 83.9% (95% CI: 75.7-90.2%) in the single-dose group (OR: 5.07, 95% CI:1.61-15.96, p = 0.002). The ERR was 97.6% and 94.5% in the dual-dose group and single-dose drug group, respectively (ERR difference 3.1%, 95% CI: -3.89-16.39%, p = 0.553). The cure rates among participants taking albendazole with and without avocado were 90.1% and 89.1%, respectively, with no statistical difference between the two groups (OR: 1.24, 95% CI: 0.51-3.03, p = 0.622). The ERR was 97.0% and 94.2% in the group receiving albendazole with and without avocado, respectively, and the difference in ERR between the two groups was 2.8% (95% CI -8.63-14.3%, p = 0.629). CONCLUSIONS/SIGNIFICANCE: In Ugandan school children, dual-dose albendazole improves the cure rate of hookworm compared to single-dose albendazole. However, there was no significant improvement in cure rate or egg reduction rate of hookworm with fatty-food co-administration. Dual-dose albendazole is a feasible alternative for improving drug effectiveness against hookworm infection and minimising drug resistance. TRIAL REGISTRATION: PACTR202202738940158.

The role of CPAP as a potential bridge to invasive ventilation and as a ceiling-of-care for patients hospitalized with Covid-19-An observational study.

BACKGROUND: Continuous positive airway pressure (CPAP) ventilation may be used as a potential bridge to invasive mechanical ventilation (IMV), or as a ceiling-of-care for persistent hypoxaemia despite standard oxygen therapy, according to UK guidelines. We examined the association of mode of respiratory support and ceiling-of-care on mortality. METHODS: We conducted a retrospective cohort analysis of routinely collected de-identified data of adults with nasal/throat SARs-CoV-2 swab-positive results, at the Calderdale and Huddersfield NHS Foundation Trust between 10th March-19th April 2020 (outcomes determined on 22nd May). FINDINGS: Of 347 patients with SARs-CoV-2 swab-positive results, 294 (84.7%) patients admitted for Covid-19 were included in the study. Sixty-nine patients were trialled on CPAP, mostly delivered by face mask, either as an early ceiling of care instituted within 24 hours of admission (N = 19), or as a potential bridge to IMV (N = 44). Patients receiving a ceiling of care more than 24 hours after admission (N = 6) were excluded from the analysis. Two hundred and fifteen patients (73.1%) maximally received air/standard oxygen therapy, and 45 (15.3%) patients maximally received CPAP. Thirty-four patients (11.6%) required IMV, of which 24 had received prior CPAP. There were 138 patients with an early ceiling-of-care plan (pre-admission/within 24h). Overall, 103(35.0%) patients died and 191(65.0%) were alive at study end. Among all patients trialled on CPAP either as a potential bridge to IMV (N = 44) or as a ceiling-of-care (N = 19) mortality was 25% and 84%, respectively. Overall, there was strong evidence for higher mortality among patients who required CPAP or IMV, compared to those who required only air/oxygen (aOR 5.24 95%CI: 1.38, 19.81 and aOR 46.47 95%CI: 7.52, 287.08, respectively; p<0.001), and among patients with early ceiling-of-care compared to those without a ceiling (aOR 41.81 95%CI: 8.28, 211.17; p<0.001). Among patients without a ceiling of care (N = 137), 10 patients required prompt intubation following failed oxygen therapy, but 44 patients received CPAP. CPAP failure, defined as death (N = 1) or intubation (N = 24), occurred in 57% (N = 25) of patients. But in total, 75% (N = 33) of those started on CPAP with no ceiling of care recovered to discharge-19 without the need for IMV, and 14 following IMV. CONCLUSION: Our data suggest that among patients with no ceiling-of-care, an initial trial of CPAP as a potential bridge to IMV offers a favourable therapeutic alternative to early intubation. In contrast, among patients with a ceiling-of care, CPAP seems to offer little additional survival benefit beyond oxygen therapy alone. Information on ceilings of respiratory support is vital to interpreting mortality from Covid-19. STRENGTHS AND LIMITATIONS OF THIS STUDY: Sample size relatively small.Study sample representative of hospitalised Covid-19 patients in UK.Previously unreported data on role of ceilings-of-care in hospitalised Covid-19 patients.Novel data on use of CPAP separated by indication.

HIV testing and treatment coverage achieved after 4 years across 14 urban and peri-urban communities in Zambia and South Africa: An analysis of findings from the HPTN 071 (PopART) trial.

BACKGROUND: In 2014, the Joint United Nations Programme on HIV/AIDS (UNAIDS) set the 90-90-90 targets: that 90% of people living with HIV know their HIV status, that 90% of those who know their HIV-positive status are on antiretroviral therapy (ART), and that 90% of those on treatment are virally suppressed. The aim was to reach these targets by 2020. We assessed the feasibility of achieving the first two targets, and the corresponding 81% ART coverage target, as part of the HIV Prevention Trials Network (HPTN) 071 Population Effects of Antiretroviral Therapy to Reduce HIV Transmission (PopART) community-randomized trial. METHODS AND FINDINGS: The study population was individuals aged ≥15 years living in 14 urban and peri-urban "PopART intervention" communities in Zambia and South Africa (SA), with a total population of approximately 600,000 and approximately 15% adult HIV prevalence. Community HIV care providers (CHiPs) delivered the PopART intervention during 2014-2017. This was a combination HIV prevention package including universal home-based HIV testing, referral of HIV-positive individuals to government HIV clinic services that offered universal ART (Arm A) or ART according to national guidelines (Arm B), and revisits to HIV-positive individuals to support linkage to HIV care and retention on ART. The intervention was delivered in 3 "rounds," each about 15 months long, during which CHiPs visited all households and aimed to contact all individuals aged ≥15 years at least once. In Arm A in Round 3 (R3), 67% (41,332/61,402) of men and 86% (56,345/65,896) of women in Zambia and 56% (17,813/32,095) of men and 71% (24,461/34,514) of women in SA participated in the intervention, among 193,907 residents aged ≥15 years. Following participation, HIV status was known by 90% of men and women in Zambia and by 78% of men and 85% of women in SA. The median time from CHiP referral of HIV-positive individuals to ART initiation was approximately 3 months. By the end of R3, an estimated 95% of HIV-positive women and 85% of HIV-positive men knew their HIV status, and among these individuals, approximately 90% of women and approximately 85% of men were on ART. ART coverage among all HIV-positive individuals was approximately 85% in women and approximately 75% in men, up from about 45% at the start of the study. ART coverage was lowest among men aged 18 to 34 and women aged 15 to 24 years, and among mobile individuals/in-migrants. Findings from Arm B were similar. The main limitations to our study were that estimates of testing and treatment coverage among men relied on considerable extrapolation because, in each round, approximately one-third of men did not participate in the PopART intervention; that our findings are for a service delivery model that was relatively intensive; and that we did not have comparable data from the 7 "standard-of-care" (Arm C) communities. CONCLUSIONS: Our study showed that very high HIV testing and treatment coverage can be achieved through persistent delivery of universal testing, facilitated linkage to HIV care, and universal treatment services. The ART coverage target of 81% was achieved overall, after 4 years of delivery of the PopART intervention, though important gaps remained among men and young people. Our findings are consistent with previously reported findings from southern and east Africa, extending their generalisability to urban settings with high rates of in-migration and mobility and to Zambia and SA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01900977.

Effect of Universal Testing and Treatment on HIV Incidence - HPTN 071 (PopART).

BACKGROUND: A universal testing and treatment strategy is a potential approach to reduce the incidence of human immunodeficiency virus (HIV) infection, yet previous trial results are inconsistent. METHODS: In the HPTN 071 (PopART) community-randomized trial conducted from 2013 through 2018, we randomly assigned 21 communities in Zambia and South Africa (total population, approximately 1 million) to group A (combination prevention intervention with universal antiretroviral therapy [ART]), group B (the prevention intervention with ART provided according to local guidelines [universal since 2016]), or group C (standard care). The prevention intervention included home-based HIV testing delivered by community workers, who also supported linkage to HIV care and ART adherence. The primary outcome, HIV incidence between months 12 and 36, was measured in a population cohort of approximately 2000 randomly sampled adults (18 to 44 years of age) per community. Viral suppression (<400 copies of HIV RNA per milliliter) was assessed in all HIV-positive participants at 24 months. RESULTS: The population cohort included 48,301 participants. Baseline HIV prevalence was 21% or 22% in each group. Between months 12 and 36, a total of 553 new HIV infections were observed during 39,702 person-years (1.4 per 100 person-years; women, 1.7; men, 0.8). The adjusted rate ratio for group A as compared with group C was 0.93 (95% confidence interval [CI], 0.74 to 1.18; P = 0.51) and for group B as compared with group C was 0.70 (95% CI, 0.55 to 0.88; P = 0.006). The percentage of HIV-positive participants with viral suppression at 24 months was 71.9% in group A, 67.5% in group B, and 60.2% in group C. The estimated percentage of HIV-positive adults in the community who were receiving ART at 36 months was 81% in group A and 80% in group B. CONCLUSIONS: A combination prevention intervention with ART provided according to local guidelines resulted in a 30% lower incidence of HIV infection than standard care. The lack of effect with universal ART was unanticipated and not consistent with the data on viral suppression. In this trial setting, universal testing and treatment reduced the population-level incidence of HIV infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; HPTN 071 [PopArt] ClinicalTrials.gov number, NCT01900977.).

Understanding the Time Needed to Link to Care and Start ART in Seven HPTN 071 (PopART) Study Communities in Zambia and South Africa.

To achieve UNAIDS 90:90:90 targets at population-level, knowledge of HIV status must be followed by timely linkage to care, initiation and maintenance of antiretroviral therapy (ART) for all people living with HIV (PLHIV). Interpreting quantitative patterns using qualitative data, we investigate time taken to link to care and initiate ART amongst individuals aware of their HIV-status in high HIV-prevalence urban communities in the HPTN 071 (PopART) study, a community-randomised trial of a combination HIV prevention package, including universal testing and treatment, in 21 communities in Zambia and South Africa. Data are drawn from the seven intervention communities where immediate ART irrespective if CD4 count was offered from the trial-start in 2014. Median time from HIV-diagnosis to ART initiation reduced after 2 years of delivering the intervention from 10 to 6 months in both countries but varied by gender and community of residence. Social and health system realities impact decisions made by PLHIV about ART initiation.

The cascade of care following community-based detection of HIV in sub-Saharan Africa - A systematic review with 90-90-90 targets in sight.

INTRODUCTION: We aimed to establish how effective community-based HIV testing services (HTS), including home and community location based (non-health facility) HIV testing services (HB-/CLB-HTS), are in improving care in sub-Saharan Africa (SSA), with a view to achieving the 90-90-90 targets. METHODS: We conducted a systematic review of published literature from 2007-17 which reported on the proportion of individuals who link-to-care and/or initiate ART after detection with HIV through community-based testing. A meta-analysis was deemed inappropriate due to heterogeneity in reporting. RESULTS AND DISCUSSION: Twenty-five care cascades from 6 SSA countries were examined in the final review- 15 HB-HTS, 8 CLB-HTS, 2 combined HB-/CLB-HTS. Proportions linked-to-care over 1-12 months ranged from 14-96% for HB-HTS and 10-79% for CLB-HTS, with most studies reporting outcomes over short periods (3 months). Fewer studies reported ART-related outcomes following community-based testing and most of these studies included <50 HIV-positive individuals. Proportions initiating ART ranged from 23-93%. One study reported retention on ART (76% 6 months after initiation). Viral suppression 3-12 months following ART initiation was 77-85% in three studies which reported this. There was variability in definitions of outcomes, numerators/denominators and observation periods. Outcomes varied between studies even for similar time-points since HTS. The methodological inconsistencies hamper comparisons. Previously diagnosed individuals appear more likely to link-to-care than those who reported being newly-diagnosed. It appears that individuals diagnosed in the community need time before they are ready to link-to-care/initiate ART. Point-of-care (POC) CD4-counts at the time of HTS did not achieve higher proportions linking-to-care or initiating ART. Similarly, follow-up visits to HIV-positive individuals did not appear to enhance linkage to care overall. CONCLUSION: This systematic review summarises the available data on linkage to care/ART initiation following community-based detection of HIV, to help researchers and policy makers evaluate findings. The available evidence suggests that different approaches to community-based HTS including HB-HTS and CLB-HTS, are equally effective in achieving linkage to care and ART initiation among those detected. Engagement and support for newly diagnosed individuals may be key to achieving all three UNAIDS 90-90-90 targets. We also recommend that standardised measures of reporting of steps on the cascade of care are needed, to measure progress against targets and compare across settings.

Comparative assessment of five trials of universal HIV testing and treatment in sub-Saharan Africa.

DESIGN: Universal voluntary HIV counselling and testing followed by prompt initiation of antiretroviral therapy (ART) for all those diagnosed HIV-infected (universal test and treat, UTT) is now a global health standard. However, its population-level impact, feasibility and cost remain unknown. Five community-based trials have been implemented in sub-Saharan Africa to measure the effects of various UTT strategies at population level: BCPP/YaTsie in Botswana, MaxART in Swaziland, HPTN 071 (PopART) in South Africa and Zambia, SEARCH in Uganda and Kenya and ANRS 12249 TasP in South Africa. This report describes and contrasts the contexts, research methodologies, intervention packages, themes explored, evolution of study designs and interventions related to each of these five UTT trials. METHODS: We conducted a comparative assessment of the five trials using data extracted from study protocols and collected during baseline studies, with additional input from study investigators. We organized differences and commonalities across the trials in five categories: trial contexts, research designs, intervention packages, trial themes and adaptations. RESULTS: All performed in the context of generalized HIV epidemics, the trials highly differ in their social, demographic, economic, political and health systems settings. They share the common aim of assessing the impact of UTT on the HIV epidemic but differ in methodological aspects such as study design and eligibility criteria for trial populations. In addition to universal ART initiation, the trials deliver a wide range of biomedical, behavioural and structural interventions as part of their UTT strategies. The five studies explore common issues, including the uptake rates of the trial services and individual health outcomes. All trials have adapted since their initiation to the evolving political, economic and public health contexts, including adopting the successive national recommendations for ART initiation. CONCLUSIONS: We found substantial commonalities but also differences between the five UTT trials in their design, conduct and multidisciplinary outputs. As empirical literature on how UTT may improve efficiency and quality of HIV care at population level is still scarce, this article provides a foundation for more collaborative research on UTT and supports evidence-based decision making for HIV care in country and internationally.

Predictors of timely linkage-to-ART within universal test and treat in the HPTN 071 (PopART) trial in Zambia and South Africa: findings from a nested case-control study.

INTRODUCTION: HPTN 071 (PopART) is a three-arm community randomized trial in Zambia and South Africa evaluating the impact of a combination HIV prevention package, including universal test and treat (UTT), on HIV incidence. This nested study examined factors associated with timely linkage-to-care and ART initiation (TLA) (i.e. within six-months of referral) in the context of UTT within the intervention communities of the HPTN 071 (PopART) trial. METHODS: Of the 7572 individuals identified as persons living with HIV (PLWH) (and not on antiretroviral treatment (ART)) during the first year of the PopART intervention provided by Community HIV-care Providers (CHiPs) through door-to-door household visits, individuals who achieved TLA (controls) and those who did not (cases), stratified by gender and community, were randomly selected to be re-contacted for interview. Standardized questionnaires were administered to explore factors potentially associated with TLA, including demographic and behavioural characteristics, and participants' opinions on HIV and related services. Odds ratios comparing cases and controls were estimated using a multi-variable logistic regression. RESULTS: Data from 705 participants (333 cases/372 controls) were analysed. There were negligible differences between cases and controls by demographic characteristics including age, marital or socio-economic position. Prior familiarity with the CHiPs encouraged TLA (aOR of being a case: 0.58, 95% CI: 0.39 to 0.86, p = 0.006). Participants who found clinics overcrowded (aOR: 1.51, 95% CI: 1.08 to 2.12, p = 0.006) or opening hours inconvenient (aOR: 1.63, 95% CI: 1.06 to 2.51, p = 0.02) were less likely to achieve TLA, as were those expressing stronger feelings of shame about having HIV (ptrend  = 0.007). Expressing "not feeling ready" (aOR: 2.75, 95% CI: 1.89 to 4.01, p < 0.001) and preferring to wait until they felt sick (aOR: 2.00, 95% CI: 1.27 to 3.14, p = 0.02) were similarly indicative of being a case. Worrying about being seen in the clinic or about how staff treated patients was not associated with TLA. While the association was not strong, we found that the greater the number of self-reported lifetime sexual partners the more likely participants were to achieve TLA (ptrend  = 0.06). There was some evidence that participants with HIV-positive partners on ART were less likely to be cases (aOR: 0.75, 95% CI: 0.53 to 1.06, p = 0.07). DISCUSSION: The lack of socio-demographic differences between cases and controls is encouraging for a "universal" intervention that seeks to ensure high coverage across whole communities. Making clinics more "patient-friendly" could enhance treatment uptake further. The finding that those with higher risk behaviour are more actively engaging with UTT holds promise for treatment-as-prevention.

A universal testing and treatment intervention to improve HIV control: One-year results from intervention communities in Zambia in the HPTN 071 (PopART) cluster-randomised trial.

BACKGROUND: The Joint United Nations Programme on HIV/AIDS (UNAIDS) 90-90-90 targets require that, by 2020, 90% of those living with HIV know their status, 90% of known HIV-positive individuals receive sustained antiretroviral therapy (ART), and 90% of individuals on ART have durable viral suppression. The HPTN 071 (PopART) trial is measuring the impact of a universal testing and treatment intervention on population-level HIV incidence in 21 urban communities in Zambia and South Africa. We report observational data from four communities in Zambia to assess progress towards the UNAIDS targets after 1 y of the PopART intervention. METHODS AND FINDINGS: The PopART intervention comprises annual rounds of home-based HIV testing delivered by community HIV-care providers (CHiPs) who also support linkage to care, ART retention, and other services. Data from four communities in Zambia receiving the full intervention (including immediate ART for all individuals with HIV) were used to determine proportions of participants who knew their HIV status after the CHiP visit; proportions linking to care and initiating ART following referral; and overall proportions of HIV-infected individuals who knew their status (first 90 target) and the proportion of these on ART (second 90 target), pre- and post-intervention. We are not able to assess progress towards the third 90 target at this stage of the study. Overall, 121,130 adults (59,283 men and 61,847 women) were enumerated in 46,714 households during the first annual round (December 2013 to June 2015). Of the 45,399 (77%) men and 55,703 (90%) women consenting to the intervention, 80% of men and 85% of women knew their HIV status after the CHiP visit. Of 6,197 HIV-positive adults referred by CHiPs, 42% (95% CI: 40%-43%) initiated ART within 6 mo and 53% (95% CI: 52%-55%) within 12 mo. In the entire population, the estimated proportion of HIV-positive adults who knew their status increased from 52% to 78% for men and from 56% to 87% for women. The estimated proportion of known HIV-positive individuals on ART increased overall from 54% after the CHiP visit to 74% by the end of the round for men and from 53% to 73% for women. The estimated overall proportion of HIV-positive adults on ART, irrespective of whether they knew their status, increased from 44% to 61%, compared with the 81% target (the product of the first two 90 targets). Coverage was lower among young men and women than in older age groups. The main limitation of the study was the need for assumptions concerning knowledge of HIV status and ART coverage among adults not consenting to the intervention or HIV testing, although our conclusions were robust in sensitivity analyses. CONCLUSIONS: In this analysis, acceptance of HIV testing among those consenting to the intervention was high, although linkage to care and ART initiation took longer than expected. Knowledge of HIV-positive status increased steeply after 1 y, almost attaining the first 90 target in women and approaching it in men. The second 90 target was more challenging, with approximately three-quarters of known HIV-positive individuals on ART by the end of the annual round. Achieving higher test uptake in men and more rapid linkage to care will be key objectives during the second annual round of the intervention. TRIAL REGISTRATION: ClinicalTrials.gov NCT01900977.

Baseline CD4 Count and Adherence to Antiretroviral Therapy: A Systematic Review and Meta-Analysis.

BACKGROUND: In light of recent changes to antiretroviral treatment (ART) guidelines of the World Health Organization and ongoing concerns about adherence with earlier initiation of ART, we conducted a systematic review of published literature to review the association between baseline (pre-ART initiation) CD4 count and ART adherence among adults enrolled in ART programs worldwide. METHODS: We performed a systematic search of English language original studies published between January 1, 2004 and September 30, 2015 using Medline, Web of Science, LILACS, AIM, IMEMR, and WPIMR databases. We calculated the odds of being adherent at higher CD4 count compared with lower CD4 count according to study definitions and pooled data using random effects models. RESULTS: Twenty-eight articles were included in the review and 18 in the meta-analysis. The odds of being adherent was marginally lower for patients in the higher CD4 count group (pooled odds ratio, 0.90; 95% confidence interval, 0.84 to 0.96); however, the majority of studies found no difference in the odds of adherence when comparing CD4 count strata. In analyses restricted to comparisons above and below a CD4 count of 500 cells per microliter, there was no difference in adherence (pooled odds ratio, 1.01; 95% confidence interval: 0.97 to 1.05). CONCLUSIONS: This review was unable to find consistent evidence of differences in adherence according to baseline CD4 count. Although this is encouraging for the new recommendations to treat all HIV-positive individuals irrespective of CD4 count, there is a need for additional high-quality studies, particularly among adults initiating ART at higher CD4 cell counts.

HIV-related stigma and universal testing and treatment for HIV prevention and care: design of an implementation science evaluation nested in the HPTN 071 (PopART) cluster-randomized trial in Zambia and South Africa.

BACKGROUND: Stigma and discrimination related to HIV and key populations at high risk of HIV have the potential to impede the implementation of effective HIV prevention and treatment programmes at scale. Studies measuring the impact of stigma on these programmes are rare. We are conducting an implementation science study of HIV-related stigma in communities and health settings within a large, pragmatic cluster-randomized trial of a universal testing and treatment intervention for HIV prevention in Zambia and South Africa and will assess how stigma affects, and is affected by, implementation of this intervention. METHODS/DESIGN: A mixed-method evaluation will be nested within HIV prevention trials network (HPTN) 071/PopART (Clinical Trials registration number NCT01900977), a three-arm trial comparing universal door-to-door delivery of HIV testing and referral to prevention and treatment services, accompanied by either an immediate offer of anti-retroviral treatment to people living with HIV regardless of clinical status, or an offer of treatment in-line with national guidelines, with a standard-of-care control arm. The primary outcome of HPTN 071/PopART is HIV incidence measured among a cohort of 52 500 individuals in 21 study clusters. Our evaluation will include integrated quantitative and qualitative data collection and analysis in all trial sites. We will collect quantitative data on indicators of HIV-related stigma over 3 years from large probability samples of community members, health workers and people living with HIV. We will collect qualitative data, including in-depth interviews and observations from members of these same groups sampled purposively. In analysis, we will: (1) compare HIV-related stigma measures between study arms, (2) link data on stigma to measures of the success of implementation of the PopART intervention and (3) explore changes in the dominant drivers and manifestations of stigma in study communities and the health system. DISCUSSION: HIV-related stigma may impede the successful implementation of HIV prevention and treatment programmes. Using a novel study-design nested within a large, community randomized trial we will evaluate the extent to which HIV-related stigma affects and is affected by the implementation of a comprehensive combination HIV prevention intervention including a universal test and treatment approach.

HPTN 071 (PopART): rationale and design of a cluster-randomised trial of the population impact of an HIV combination prevention intervention including universal testing and treatment - a study protocol for a cluster randomised trial.

BACKGROUND: Effective interventions to reduce HIV incidence in sub-Saharan Africa are urgently needed. Mathematical modelling and the HIV Prevention Trials Network (HPTN) 052 trial results suggest that universal HIV testing combined with immediate antiretroviral treatment (ART) should substantially reduce incidence and may eliminate HIV as a public health problem. We describe the rationale and design of a trial to evaluate this hypothesis. METHODS/DESIGN: A rigorously-designed trial of universal testing and treatment (UTT) interventions is needed because: i) it is unknown whether these interventions can be delivered to scale with adequate uptake; ii) there are many uncertainties in the models such that the population-level impact of these interventions is unknown; and ii) there are potential adverse effects including sexual risk disinhibition, HIV-related stigma, over-burdening of health systems, poor adherence, toxicity, and drug resistance.In the HPTN 071 (PopART) trial, 21 communities in Zambia and South Africa (total population 1.2 m) will be randomly allocated to three arms. Arm A will receive the full PopART combination HIV prevention package including annual home-based HIV testing, promotion of medical male circumcision for HIV-negative men, and offer of immediate ART for those testing HIV-positive; Arm B will receive the full package except that ART initiation will follow current national guidelines; Arm C will receive standard of care. A Population Cohort of 2,500 adults will be randomly selected in each community and followed for 3 years to measure the primary outcome of HIV incidence. Based on model projections, the trial will be well-powered to detect predicted effects on HIV incidence and secondary outcomes. DISCUSSION: Trial results, combined with modelling and cost data, will provide short-term and long-term estimates of cost-effectiveness of UTT interventions. Importantly, the three-arm design will enable assessment of how much could be achieved by optimal delivery of current policies and the costs and benefits of extending this to UTT. TRIAL REGISTRATION: ClinicalTrials.gov NCT01900977.

HPTN 071 (PopART): a cluster-randomized trial of the population impact of an HIV combination prevention intervention including universal testing and treatment: mathematical model.

BACKGROUND: The HPTN 052 trial confirmed that antiretroviral therapy (ART) can nearly eliminate HIV transmission from successfully treated HIV-infected individuals within couples. Here, we present the mathematical modeling used to inform the design and monitoring of a new trial aiming to test whether widespread provision of ART is feasible and can substantially reduce population-level HIV incidence. METHODS AND FINDINGS: The HPTN 071 (PopART) trial is a three-arm cluster-randomized trial of 21 large population clusters in Zambia and South Africa, starting in 2013. A combination prevention package including home-based voluntary testing and counseling, and ART for HIV positive individuals, will be delivered in arms A and B, with ART offered universally in arm A and according to national guidelines in arm B. Arm C will be the control arm. The primary endpoint is the cumulative three-year HIV incidence. We developed a mathematical model of heterosexual HIV transmission, informed by recent data on HIV-1 natural history. We focused on realistically modeling the intervention package. Parameters were calibrated to data previously collected in these communities and national surveillance data. We predict that, if targets are reached, HIV incidence over three years will drop by >60% in arm A and >25% in arm B, relative to arm C. The considerable uncertainty in the predicted reduction in incidence justifies the need for a trial. The main drivers of this uncertainty are possible community-level behavioral changes associated with the intervention, uptake of testing and treatment, as well as ART retention and adherence. CONCLUSIONS: The HPTN 071 (PopART) trial intervention could reduce HIV population-level incidence by >60% over three years. This intervention could serve as a paradigm for national or supra-national implementation. Our analysis highlights the role mathematical modeling can play in trial development and monitoring, and more widely in evaluating the impact of treatment as prevention.

Uptake of home-based voluntary HIV testing in sub-Saharan Africa: a systematic review and meta-analysis.

INTRODUCTION: Improving access to HIV testing is a key priority in scaling up HIV treatment and prevention services. Home-based voluntary counselling and testing (HBT) as an approach to delivering wide-scale HIV testing is explored here. METHODS AND FINDINGS: We conducted a systematic review and random-effects meta-analysis of studies published between 1 January 2000 and 24 September 2012 that reported on uptake of HBT in sub-Saharan Africa, to assess the proportion of individuals accepting HBT and receiving their test result. Our initial search yielded 1,199 articles; 114 were reviewed as full-text articles, and 19 publications involving 21 studies (n = 524,867 individuals offered HBT) were included for final review and meta-analysis. The studies came from five countries: Uganda, Malawi, Kenya, South Africa, and Zambia. The proportion of people who accepted HBT (n = 474,377) ranged from 58.1% to 99.8%, with a pooled proportion of 83.3% (95% CI: 80.4%-86.1%). Heterogeneity was high (τ(2) = 0.11). Sixteen studies reported on the number of people who received the result of HBT (n = 432,835). The proportion of individuals receiving their results out of all those offered testing ranged from 24.9% to 99.7%, with a pooled proportion of 76.7% (95% CI: 73.4%-80.0%) (τ(2) = 0.12). HIV prevalence ranged from 2.9% to 36.5%. New diagnosis of HIV following HBT ranged from 40% to 79% of those testing positive. Forty-eight percent of the individuals offered testing were men, and they were just as likely to accept HBT as women (pooled odds ratio = 0.84; 95% CI: 0.56-1.26) (τ(2) = 0.33). The proportion of individuals previously tested for HIV among those offered a test ranged from 5% to 66%. Studies in which <30% of individuals had been previously tested, local HIV prevalence was <10%, incentives were provided, or HBT was offered to household members of HIV-positive individuals showed higher uptake of testing. No evidence was reported of negative consequences of HBT. CONCLUSIONS: HBT could substantially increase awareness of HIV status in previously undiagnosed individuals in sub-Saharan Africa, with over three-quarters of the studies in this review reporting >70% uptake. It could be a valuable tool for treatment and prevention efforts.

Treatment outcomes from the largest antiretroviral treatment program in Myanmar (Burma): a cohort analysis of retention after scale-up.

BACKGROUND: Antiretroviral treatment (ART) coverage in Myanmar is well below average. This study describes retention and baseline predictors of prognosis from the largest ART program in the country. METHODS: A cohort analysis of adult patients who initiated ART during 2003-2007 was conducted, with follow-up until the end of 2009. The primary outcome was attrition [death plus losses to follow-up (LTF)]. Baseline variables were assessed as potential risk factors. The cumulative probabilities of death, LTF, and attrition up to 5 years were described using Kaplan-Meier estimates. Cox regression was used to calculate hazard ratios of attrition, overall and separately for 2 time periods on ART: 1-6 and 7-36 months. RESULTS: A total of 5963 adults enrolled in the program, providing 17,581 person-years of follow-up. Median age at baseline was 33 years [interquartile range (IQR): 28-38], 61% were men, 45% were in World Health Organization stage IV, and the median CD4 count was 71 cells per cubic millimeter (IQR: 29-164). There were 821 (13.8%) deaths and 389 (6.5%) LTF over the study period, with a 72% probability of being retained in care in the 5-year cohort. Double the rate of loss was contributed by death compared with LTF, and attrition was almost 4 times higher in the period 1-6 months compared with 7-36 months. In the multivariable analyses of the program overall, older age [adjusted hazard ratio (aHR): 1.56, 95% confidence interval (CI): 1.25 to 1.94], being male (aHR: 1.52, 95% CI: 1.25 to 1.85), World Health Organization stage IV (aHR: 1.44, 95% CI: 1.19 to 1.74), and body mass index <16 kg/m² (aHR: 2.13, 95% CI: 1.71 to 2.66) were independently predictive of attrition. CONCLUSIONS: The excellent retention over >6 years in this large cohort demonstrates that ART delivery at the primary care level in Myanmar is feasible and should encourage support for further ART expansion in the country.

Similar mortality and reduced loss to follow-up in integrated compared with vertical programs providing antiretroviral treatment in sub-saharan Africa.

BACKGROUND: Vertical HIV programs have achieved good results but may not be feasible or appropriate in many resource-limited settings. Médecins sans Frontières has treated HIV in vertical programs since 2000 and over time integrated HIV treatment into general health care services using simplified protocols. We analyzed the survival probability among patients receiving antiretroviral therapy (ART) from 2003 to 2010 in integrated versus vertical programs in 9 countries in sub-Saharan Africa. METHODS AND FINDINGS: Cox regression assessed mortality and program design association, adjusting for baseline age, body mass index, clinical WHO stage, tuberculosis, program age and setting. The analysis included 15,403 HIV-positive adults on ART in 7 vertical (14,124 patients) and 10 integrated (1279 patients) programs. Cox regression including 14,523 patients followed for up to 30 months ART showed similar outcomes for mortality (adjusted hazard ratio (aHR) 1.02; 95% confidence interval (CI): 0.83 to 1.24) and lower risk of loss to follow-up (aHR: 0.71; 95% CI: 0.61 to 0.83) in integrated compared with vertical programs. The greatest risk of death was from initiating ART at WHO stage 4 (aHR 1.99, 95% CI: 1.74 to 2.29), although greater program experience was protective (aHR: 0.77, 95% CI: 0.66 to 0.89). Risk of loss to follow-up was greater in experienced programs (aHR: 3.33; 95% CI: 2.92 to 3.79) and rural settings (aHR: 3.82; 95% CI: 3.49 to 4.20). CONCLUSIONS: ART delivery in integrated general health care programs results in good outcomes. Compared with vertical HIV programs, patients initiated ART in integrated programs at more advanced stages of clinical immunosuppression yet had similar risk of death and lower risk of loss to follow-up.

Universal testing and treatment as an HIV prevention strategy: research questions and methods.

Achieving high coverage of antiretroviral treatment (ART) in resource-poor settings will become increasingly difficult unless HIV incidence can be reduced substantially. Universal voluntary counselling and testing followed by immediate initiation of ART for all those diagnosed HIV-positive (universal testing and treatment, UTT) has the potential to reduce HIV incidence dramatically but would be very challenging and costly to deliver in the short term. Early modelling work in this field has been criticised for making unduly optimistic assumptions about the uptake and coverage of interventions. In future work, it is important that model parameters are realistic and based where possible on empirical data. Rigorous research evidence is needed before the UTT approach could be considered for wide-scale implementation. This paper reviews the main areas that need to be explored. We consider in turn research questions related to the provision of services for universal testing, services for immediate treatment of HIV-positives and the population-level impact of UTT, and the research methods that could be used to address these questions. Ideally, initial feasibility studies should be carried out to investigate the acceptability, feasibility and uptake of UTT services. If these studies produce promising results, there would be a strong case for a cluster-randomised trial to measure the impact of a UTT intervention on HIV incidence, and we consider the main design features of such a trial.

Incidence of tuberculosis in HIV-infected patients before and after starting combined antiretroviral therapy in 8 sub-Saharan African HIV programs.

SETTING: Eight HIV programs in sub-Saharan Africa. OBJECTIVE: To describe the incidence of pulmonary and extrapulmonary tuberculosis before and after the start of combined antiretroviral therapy (ART) and investigate associated risk factors. DESIGN: Multicohort study. Adults enrolled between January 2006 and September 2008. RESULTS: A total of 30,134 patients contributed 25,916 person-years of follow-up. The incidence of tuberculosis was 10.5 per 100 person-years during the pre-ART and 5.4 during the ART period. For all types of tuberculosis, incidence was similar in the pre-ART period and initial 3 months of ART but declined over time receiving ART (from 13 per 100 person-years in the first 3 months to 1.5 per 100 person-years after 12 months of therapy). Throughout follow-up, rates of pulmonary tuberculosis remained 2-fold to 3-fold higher than extrapulmonary tuberculosis rates. Smear-negative pulmonary tuberculosis was higher than smear-positive incidence and varied greatly across sites during the pre-ART period. Incidence was lower in rural sites, women, patients without prior history of tuberculosis, body mass index ≥18.5 kg/m², and ≥200 nadir CD4 cells per microliter. Recurrence rate was 1.7 per 100 person-years (95% confidence interval: 1.0 to 2.8). CONCLUSIONS: Our findings show the high burden that tuberculosis represents for HIV programs and highlight the importance of earlier ART start and the need to implement intensified tuberculosis finding, isoniazide prophylaxis, and infection control.