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Background: Despite the significant progress made in South Africa in getting millions of individuals living with HIV into care, many patients still present or re-enter care with Advanced HIV Disease (AHD). We aimed to estimate the prevalence of AHD among ART-naive and ART-experienced patients in South Africa using studies published between January 2010 and May 2022., Methods: We searched for relevant data on PubMed, CINAHL, Scopus and other sources, with a geographical filters limited to South Africa, up to May 31, 2022. Two reviewers conducted all screening, eligibility assessment, data extraction, and critical appraisal. We synthesized the data using the inverse-variance heterogeneity model and Freeman-Tukey transformation. We assessed heterogeneity using the I 2 statistic and publication bias using the Egger and Begg's test., Results: We identified 2,496 records, of which 53 met the eligibility criteria, involving 11,545,460 individuals. The pooled prevalence of AHD among ART-naive and ART-experienced patients was 43.45% (95% CI 40.1-46.8%, n = 53 studies) and 58.6% (95% CI 55.7 to 61.5%, n = 2) respectively. The time trend analysis showed a decline of 2% in the prevalence of AHD among ART-naive patients per year. However, given the high heterogeneity between studies, the pooled prevalence should be interpreted with caution., Conclusion: Despite HIV's evolution to a chronic disease, our findings show that the burden of AHD remains high among both ART-naive and ART-experienced patients in South Africa. This emphasizes the importance of regular measurement of CD4 cell count as an essential component of HIV care. In addition, providing innovative adherence support and interventions to retain ART patients in effective care is a crucial priority for those on ART., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: As adolescents and young people living with HIV (AYLH) age, they face a 'transition cascade,' a series of steps associated with transitions in their care as they become responsible for their own healthcare. In high-income countries, this usually includes transfer from predominantly paediatric/adolescent to adult clinics. In sub-Saharan Africa, paediatric HIV care is mostly provided in decentralized, non-specialist primary care clinics, where 'transition' may not necessarily include transfer of care but entails becoming more autonomous for one's HIV care. Using different age thresholds as proxies for when 'transition' to autonomy might occur, we evaluated pre- and post-transition outcomes among AYLH. Methods: We included AYLH aged Results: A total of 5516 AYLH from 16 sites were included at 'transition' age 16 (transition-16y), 3864 at 18 (transition-18y), 1463 at 20 (transition-20y) and 440 at 22 years (transition-22y). At transition-18y in the 12 months pre- and post-transition, 83% versus 74% of AYLH had no gap in care (difference 9.3 (95% confidence interval (CI) 7.8 to 10.9)); while 65% versus 62% were virally suppressed (difference 2.7 (-1.0 to 6.5%)). The strongest predictor of being retained post-transition was having no gap in the preceding year, across all transition age thresholds (transition-16y adjusted risk ratio (aRR) 1.72; 95% CI (1.60 to 1.86); transition-18y: aRR 1.76 (1.61 to 1.92); transition-20y: aRR 1.75 (1.53 to 2.01); transition-22y: aRR 1.47; (1.21 to 1.78)). Conclusions: AYLH with gaps in care need targeted support to prevent non-retention as they take on greater responsibility for their healthcare. Interventions to increase virologic suppression rates are necessary for all AYLH ageing to adulthood. Keywords: HIV; adolescents; youth; healthcare transition; retention; viral suppression; cascade of care, 1 | INTRODUCTION There is a growing cohort of adolescents and young adults living with HIV (AYLH), largely due to the increasing number of children with perinatally acquired HIV surviving [...]

Sub‐Saharan Africa carries the highest burden of HIV, with approximately 70% of all people living with HIV (PLWH) globally living in this region. The provision of antiretroviral treatment (ART) significantly affects already overburdened health systems, which need to accommodate large volumes of ART patients while facing a shortage of professional health workers, infrastructure challenges and medical resources. Finding alternative ways to provide routine services to PLWH has become significantly more urgent. Multi‐month dispensing (MMD) of ART aims to improve access to treatment for PLWH, while also improving the efficiency of the health system. This study explores the experienced benefits and challenges of community‐based MMD in order to make recommendations for future implementation efforts. Twenty focus group discussions were conducted with members of community ART refill groups (CARGs) who received 3‐monthly or 6‐monthy MMD. Individual interviews were also conducted with health providers. All interviews and focus group discussions took place between April and June 2019 conducted by research nurses in English, Shona or Ndebele. Multiple benefits of community‐based MMD were reported, including decreased congestion in health facilities, improved service delivery, decline in staff burnout and increased time availability for CARG members due to less time spent at clinics, improved ART adherence and social support experienced amongst members of CARGs. Identified challenges included the possibility of being exposed to HIV‐related stigma when belonging to a CARG, and low levels of medical supplies and ART stock at clinics. Recommendations were made by CARG members and health care workers on how CARGs could be improved and sustained in the future. Results from this study show that the implementation of community‐based MMD holds multiple benefits at an individual and health facility level. Future recommendations include evaluating the feasibility of MMD among other vulnerable populations. [ABSTRACT FROM AUTHOR]

Introduction: Older adolescents aged 15–19 years continue to have high rates of loss to follow up (LTFU), and high rates of virologic non‐suppression (VNS) compared to younger adolescents and adults. Adolescent females are at risk of pregnancy, which puts those living with HIV at a dual vulnerability. Our study assessed the factors associated with VNS and LTFU in older adolescents (including pregnant females) who initiated antiretroviral therapy (ART) in South Africa. Methods: We included adolescents aged 15–19 years initiating ART between 2004 and 2019, with ≥ one viral load (VL) measurement between 4 and 24.5 months, and ≥ 6 months follow‐up, from six South African cohorts of the International epidemiology Databases to Evaluate AIDS‐Southern Africa (IeDEA‐SA). We defined VNS as VL ≥400 copies/ml and LTFU as not being in care for ≥180 days from ART start and not known as transferred out of the clinic or dead in the first 24 months on ART. We examined factors associated with VNS and LTFU using Fine&Gray competing risk models. Results: We included a total of 2733 adolescents, 415 (15.2%) males, median (IQR) age at ART start of 18.6 (17.3, 19.4) years. Among females, 585/2318 (25.2%) were pregnant. Over the 24‐month follow‐up, 424 (15.5%) of all adolescents experienced VNS: range (11.1% pregnant females and 20.5% males). Over half of all adolescents were LTFU before any other event could occur. The hazard of VNS reduced with increasing age and CD4 count above 200 cells/μl at ART initiation among all adolescents having adjusted for all measured patient characteristics [adjusted sub‐distribution hazard ratio (aSHR) 19 vs. 15 years: 0.50 (95% CI: 0.36, 0.68), aSHR: >500 vs. ≤200 cells/μl: 0.22 (95% CI: 0.16, 0.31)]. The effect of CD4 count persisted in pregnant females. Increasing age and CD4 count >200 cells/μl were risk factors for LTFU among all adolescents. Conclusions: Older adolescents had a high risk of LTFU shortly after ART start and a low risk of VNS, especially those initiating treatment during pregnancy. Interventions addressing adherence and retention should be incorporated into adolescent‐friendly services to prevent VNS and LTFU and endeavour to trace lost adolescents as soon as they are identified. [ABSTRACT FROM AUTHOR]

Introduction: Lesotho, the country with the second‐highest HIV/AIDS prevalence (23.6%) in the world, has made considerable progress towards achieving the "95‐95‐95" UNAIDS targets, but recent success in improving treatment access to all known HIV positive individuals has severely strained existing healthcare infrastructure, financial and human resources. Lesotho also faces the challenge of a largely rural population who incur a significant time and financial burden to visit healthcare facilities. Using data from a cluster‐randomized non‐inferiority trial conducted between August 2017 and July 2019, we evaluated costs to providers and costs to patients of community‐based differentiated models of multi‐month delivery of antiretroviral therapy (ART) in Lesotho. Methods: The trial of multi‐month dispensing compared 12‐month retention in care among three arms: conventional care, which required quarterly facility visits and ART dispensation (3MF); three‐month community adherence groups (CAGs) (3MC) and six‐month community ART distribution (6MCD). We first estimated the average total annual cost of providing HIV care and treatment followed by the total cost per patient retained 12 months after entry for each arm, using resource utilization data from the trial and local unit costs. We then estimated the average annual cost to patients in each arm with self‐reported questionnaire data. Results: The average total annual cost of providing HIV care and treatment per patient was the highest in the 3MF arm ($122.28, standard deviation [SD] $23.91), followed by 3MC ($114.20, SD $23.03) and the 6MCD arm ($112.58, SD $21.44). Per patient retained in care, the average provider cost was $125.99 (SD $24.64) in the 3MF arm and 6% to 8% less for the other two arms ($118.38, SD $23.87 and $118.83, SD $22.63 for the 3MC and 6MCD respectively). There was a large reduction in patient costs for both differentiated service delivery arms: from $44.42 (SD $12.06) annually in the 3MF arm to $16.34 (SD $5.11) annually in the 3MC (63% reduction) and $18.77 (SD $8.31) annually in 6MCD arm (58% reduction). Conclusions: Community‐based, multi‐month models of ART in Lesotho are likely to produce small cost savings to treatment providers and large savings to patients in Lesotho. Patient cost savings may support long‐term adherence and retention in care. [ABSTRACT FROM AUTHOR]

Background: Lesotho adopted the test-and-treat approach for HIV treatment in June 2016, which increased antiretroviral treatment (ART) clinic volume. We evaluated community-based vs. facilitybased differentiated models of multimonth dispensing of ART among stable HIV-infected adults in Lesotho. Methods: Thirty facilities were randomized to 3 arms, facility 3-monthly ART (3MF) (control), community ART groups (3MC), and 6-monthly community distribution points (6MCD). We estimated risk differences (RDs) between arms using population-averaged generalized estimating equations, controlling for baseline imbalances and specifying for clustering. The primary outcome was retention in ART care by intention-to-treat and virologic suppression as a secondary outcome (ClinicalTrials.gov: NCT03438370). Results: A total of 5,336 participants were enrolled, with 1898, 1558, and 1880 in 3MF, 3MC, and 6MCD, respectively. Retention in ART care was not different across arms and achieved the prespecified noninferiority limit (23.25%) between 3MC vs. 3MF (control); 6MCD vs. 3MF; and 6MCD vs. 3MC, adjusted RD = 20.1% [95% confidence interval (CI): 21.6% to 1.5%], adjusted RD = 21.3% (95% CI: 23.0% to 0.5%), and adjusted RD = 21.2% (95% CI: 22.9% to 0.5%), respectively. After 12 months, 98.6% (n = 1503), 98.1% (n = 1126), and 98.3% (n = 1285) were virally load (VL) suppressed in 3MF, 3MC, and 6MCD, respectively. There were no differences in VL between 3MC vs. control and 6MCD vs. control, risk ratio (RR) = 1.00 (95% CI: 0.98 to 1.01) and RR = 1.00 (95% CI: 0.98 to 1.01), respectively. Conclusions: There were no differences in retention and VL suppression for stable HIV-infected participants receiving multimonth dispensing of ART within community-based differentiated models when compared with the facility-based standard-ofcare model. [ABSTRACT FROM AUTHOR]

Introduction: Multimonth dispensing (MMD) of antiretroviral treatment (ART) aims to reduce patient-related barriers to access long-term treatment and improve health system efficiency. However, randomized evidence of its clinical effectiveness is lacking. We compared MMD within community ART refill groups (CARGs) vs. standard-of-care facility-based ART delivery in Zimbabwe. Methods: A three-arm, cluster-randomized, pragmatic noninferiority trial was performed. Thirty health care facilities and associated CARGs were allocated to either ART collected three-monthly at facility (3MF, control); ART delivered three-monthly in CARGs (3MC); or ART delivered six-monthly in CARGs (6MC). Stable adults receiving ART $six months with baseline viral load (VL),1000 copies/ml were eligible. Retention in ART care (primary outcome) and viral suppression (VS) 12 months after enrollment were compared, using regression models specified for clustering (ClinicalTrials.gov: NCT03238846). Results: 4800 participants were recruited, 1919, 1335, and 1546 in arms 3MF, 3MC, and 6MC, respectively. For retention, the prespecified noninferiority limit (-3.25%, risk difference [RD]) was met for comparisons between all arms, 3MC (94.8%) vs. 3MF (93.0%), adjusted RD = 1.1% (95% CI: -0.5% to 2.8%); 6MC (95.5%) vs. 3MF: aRD = 1.2% (95% CI: -1.0% to 3.6%); and 6MC vs. 3MC: aRD = 0.1% (95% CI: -2.4% to 2.6%). VL completion at 12 months was 49%, 45%, and 8% in 3MF, 3MC, and 6MC, respectively. VS in 3MC (99.7%) was high and not different to 3MF (99.1%), relative risk = 1.0 (95% CI: 1.0-1.0). VS was marginally reduced in 6MC (92.9%) vs. 3MF, relative risk = 0.9 (95% CI: 0.9-1.0). Conclusion: Retention in CARGs receiving three- and six-monthly MMD was noninferior versus standard-of-care facility-based ART delivery. VS in 3MC was high. VS in six-monthly CARGs requires further evaluation. [ABSTRACT FROM AUTHOR]

Background: Periods of droughts can lead to decreased food security, and altered behaviours, potentially affecting outcomes on antiretroviral therapy (ART) among persons with HIV (PWH). We investigated whether decreased rainfall is associated with adverse outcomes among PWH on ART in Southern Africa. Methods: Data were combined from 11 clinical cohorts of PWH in Lesotho, Malawi, Mozambique, South Africa, Zambia, and Zimbabwe, participating in the International epidemiology Databases to Evaluate AIDS Southern Africa (IeDEA-SA) collaboration. Adult PWH who had started ART prior to 01/06/2016 and were in follow-up in the year prior to 01/06/2016 were included. Two-year rainfall from June 2014 to May 2016 at the location of each HIV centre was summed and ranked against historical 2-year rainfall amounts (1981–2016) to give an empirical relative percentile rainfall estimate. The IeDEA-SA and rainfall data were combined using each HIV centre's latitude/longitude. In individual-level analyses, multivariable Cox or generalized estimating equation regression models (GEEs) assessed associations between decreased rainfall versus historical levels and four separate outcomes (mortality, CD4 counts < 200 cells/mm3, viral loads > 400 copies/mL, and > 12-month gaps in follow-up) in the two years following the rainfall period. GEEs were used to investigate the association between relative rainfall and monthly numbers of unique visitors per HIV centre. Results: Among 270,708 PWH across 386 HIV centres (67% female, median age 39 [IQR: 32–46]), lower rainfall than usual was associated with higher mortality (adjusted Hazard Ratio: 1.18 [95%CI: 1.07–1.32] per 10 percentile rainfall rank decrease) and unsuppressed viral loads (adjusted Odds Ratio: 1.05 [1.01–1.09]). Levels of rainfall were not strongly associated with CD4 counts < 200 cell/mm3 or > 12-month gaps in care. HIV centres in areas with less rainfall than usual had lower numbers of PWH visiting them (adjusted Rate Ratio: 0.80 [0.66–0.98] per 10 percentile rainfall rank decrease). Conclusions: Decreased rainfall could negatively impact on HIV treatment behaviours and outcomes. Further research is needed to explore the reasons for these effects. Interventions to mitigate the health impact of severe weather events are required. [ABSTRACT FROM AUTHOR]

Background Co-trimoxazole is recommended for all children with human immunodeficiency virus. In this analysis, we evaluate trends in pediatric co-trimoxazole use and survival on co-trimoxazole in children using antiretroviral therapy (ART). Methods We used data collected between January 1, 2006, and March 31, 2016, from the International Epidemiology Databases to Evaluate AIDS. Logistic regression was used to evaluate factors associated with using co-trimoxazole at ART initiation. Competing risk regression was used to assess factors associated with death. Results A total of 54113 children were included in this study. The prevalence of co-trimoxazole use at ART initiation increased from 66.5% in 2006 to a peak of 85.6% in 2010 and then declined to 48.5% in 2015–2016. A similar trend was observed among children who started ART with severe immunodeficiency. After adjusting for year of ART initiation, younger age (odds ratio [OR], 1.18 for <1 vs 1 to <5 years of age [95% confidence interval (CI), 1.09–1.28]), lower height-for-age z score (OR, 1.15 for less than −3 vs greater than −2 [95% CI, 1.08–1.22]), anemia (OR, 1.08 [95% CI, 1.02–1.15]), severe immunodeficiency (OR, 1.25 [95% CI, 1.18–1.32]), and receiving care in East Africa (OR, 8.97 vs Southern Africa [95% CI, 8.17–9.85]) were associated with a high prevalence of co-trimoxazole use. Survival did not differ according to co-trimoxazole use in children without severe immunodeficiency (hazard ratio, 1.01 for nonusers versus users [95% CI, 0.77–1.34]). Conclusions Recent declines in co-trimoxazole use may not be linked to the current shift toward early ART initiation. Randomized trial data might be needed to establish the survival benefit of co-trimoxazole in children without severe immunodeficiency. [ABSTRACT FROM AUTHOR]

Introduction: Differentiated models of care that include referral of antiretroviral treatment (ART) clients to adherence clubs are an important strategy to help clinics manage increased number of clients living with HIV in resource-constrained settings. This study reported on (i) clinical outcomes among ART clients attending community-based adherence clubs and (ii) experiences of adherence clubs and perceptions of factors key to successful adherence club implementation among clients and healthcare workers. Methods: A retrospective cohort analysis of routine data and a descriptive analysis of data collected through self-administered surveys completed by clients and healthcare workers were completed. Clients starting ART at the study clinic, between January 2014 and December 2015, were included in the cohort analysis and followed up until December 2016. The survey data were collected from August to September 2017. The primary outcome for the cohort analysis was a comparison of loss to follow-up (LTFU) between clients staying in clinic care and those referred to adherence clubs. Survey data reported on client experiences of and healthcare worker perceptions of adherence club care. Results: Cohort analysis reported on 465 participants, median baseline CD4 count 374 (IQR: 234 to 532) cells/μl and median follow-up time 20.7 (IQR 14.1 to 27.7) months. Overall, 202 (43.4%) participants were referred to an adherence club. LTFU was lower in those attending an adherence club (aHR =0.25, 95% CI: 0.11 to 0.56). This finding was confirmed on analysis restricted to those eligible for adherence club referral (aHR =0.28, 95% CI: 0.12 to 0.65). Factors highlighted as associated with successful adherence club implementation included: (i) referral of stable clients to the club, (ii) an ideal club size of ≥20 members, (iii) club services led by a counsellor (iv) using churches or community halls as venues (v) effective communication between all parties, and (vi) timely delivery of prepacked medication. Conclusions: This study showed good clinical outcomes, positive patient experiences and healthcare worker perceptions of the adherence club model. Factors associated with successful adherence club implementation, highlighted in this study, can be used to guide implementers in the scale-up of adherence club services across varied high-burden settings. [ABSTRACT FROM AUTHOR]

Introduction: WHO recommends antiretroviral treatment (ART) for all HIV-positive individuals. This study evaluated the association between baseline CD4 count and attrition in a cohort of HIV positive adults initiating ART at three department of health (DOH) clinics routinely providing ART at baseline CD4 counts >500cells/μL for the HPTN 071 (PopART) trial. Methods: All clients attending the DOH clinics were managed according to standard care guidelines with the exception that those starting ART outside of pertinent local guidelines signed research informed consent. DOH data on all HIV-positive adult clients recorded as having initiated ART between January 2014 and November 2015 at the three study clinics was analysed. Attrition, included clients lost to follow up or died, and was defined as ‘being three or more months late for an antiretroviral pharmacy pick-up appointment’. All clients were followed until attrition, transfer out or end May 2016. Results: A total of 2423 clients with a median baseline CD4 count of 328 cells/μL (IQR 195–468) were included of whom 631 (26.0%) experienced attrition and 140 (5.8%) were TFO. Attrition was highest during the first six months of ART (IR 38.3/100 PY; 95% CI 34.8–42.1). Higher attrition was found amongst those with baseline CD4 counts > 500 cells/μL compared to those with baseline CD4 counts of 0–500 cells/μL (aHR 1.26, 95%CI 1.05 to 1.52) This finding was confirmed on subset analyses when restricted to individuals non-pregnant at baseline and when restricted to individuals with follow up of > 12months. Conclusions: Attrition in this study was high, particularly during the first six months of treatment. Attrition was highest amongst clients starting ART at baseline CD4 counts > 500 cells/μL. Strategies to improve retention amongst ART clients, particularly those starting ART at baseline CD4 counts >500cells/μL, need strengthening. Improved monitoring of clients moving in and out of ART care and between clinics will assist in better understanding attrition and ART coverage in high burden countries. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Adolescents and youth receiving antiretroviral treatment (ART) in sub‐Saharan Africa have high attrition and inadequate ART outcomes, and evaluations of interventions improving ART outcomes amongst adolescents are very limited. Sustainable Development Goal (SDG) target 3c is to substantially increase the health workforce in developing countries. We measured the effectiveness and cost‐effectiveness of community‐based support (CBS) provided by lay health workers for adolescents and youth receiving ART in South Africa. Methods: A retrospective cohort study including adolescents and youth who initiated ART at 47 facilities. Previously unemployed CBS‐workers provided home‐based ART‐related education, psychosocial support, symptom screening for opportunistic infections and support to access government grants. Outcomes were compared between participants who received CBS plus standard clinic‐based care versus participants who received standard care only. Cumulative incidences of all‐cause mortality and loss to follow‐up (LTFU), adherence measured using medication possession ratios (MPRs), CD4 count slope, and virological suppression were analysed using multivariable Cox, competing‐risks regression, generalized estimating equations and mixed‐effects models over five years of ART. An expenditure approach was used to determine the incremental cost of CBS to usual care from a provider perspective. Incremental cost‐effectiveness ratios were calculated as annual cost per patient‐loss (through death or LTFU) averted. Results: Amongst 6706 participants included, 2100 (31.3%) received CBS. Participants who received CBS had reduced mortality, adjusted hazard ratio (aHR) = 0.52 (95% CI: 0.37 to 0.73; p < 0.0001). Cumulative LTFU was 40% lower amongst participants receiving CBS (29.9%) compared to participants without CBS (38.9%), aHR = 0.60 (95% CI: 0.51 to 0.71); p < 0.0001). The effectiveness of CBS in reducing attrition ranged from 42.2% after one year to 35.9% after five years. Virological suppression was similar after three years, but after five years 18.8% CBS participants versus 37.2% non‐CBS participants failed to achieve viral suppression, adjusted odds ratio = 0.24 (95% CI: 0.06 to 1.03). There were no significant differences in MPR or CD4 slope. The cost of CBS was US$49.5/patient/year. The incremental cost per patient‐loss averted was US$600 and US$776 after one and two years, respectively. Conclusions: CBS for adolescents and youth receiving ART was associated with substantially reduced patient attrition, and is a low‐cost intervention with reasonable cost‐effectiveness that can aid progress towards several health, economic and equality‐related SDG targets. [ABSTRACT FROM AUTHOR]

Background: Sub-Saharan Africa is the world region with the greatest number of people eligible to receive antiretroviral treatment (ART). Less frequent dispensing of ART and community-based ART-delivery models are potential strategies to reduce the load on overburdened healthcare facilities and reduce the barriers for patients to access treatment. However, no large-scale trials have been conducted investigating patient outcomes or evaluating the cost-effectiveness of extended ART-dispensing intervals within community ART-delivery models. This trial will assess the clinical effectiveness, cost-effectiveness and acceptability of providing ART refills on a 3 vs. a 6-monthly basis within community ART-refill groups (CARGs) for stable patients in Zimbabwe.Methods: In this pragmatic, three-arm, parallel, unblinded, cluster-randomized non-inferiority trial, 30 clusters (healthcare facilities and associated CARGs) are allocated using stratified randomization in a 1:1:1 ratio to either (1) ART refills supplied 3-monthly from the health facility (control arm), (2) ART refills supplied 3-monthly within CARGs, or (3) ART refills supplied 6-monthly within CARGs. A CARG consists of 6-12 stable patients who meet in the community to receive ART refills and who provide support to one another. Stable adult ART patients with a baseline viral load < 1000 copies/ml will be invited to participate (1920 participants per arm). The primary outcome is the proportion of participants alive and retained in care 12 months after enrollment. Secondary outcomes (measured at 12 and 24 months) are the proportions achieving virological suppression, average provider cost per participant, provider cost per participant retained, cost per participant retained with virological suppression, and average patient-level costs to access treatment. Qualitative research will assess the acceptability of extended ART-dispensing intervals within CARGs to both providers and patients, and indicators of potential facility-level decongestion due to the interventions will be assessed.Discussion: Cost-effective health system models that sustain high levels of patient retention are urgently needed to accommodate the large numbers of stable ART patients in sub-Saharan Africa. This will be the first trial to evaluate extended ART-dispensing intervals within a community-based ART distribution model, and results are intended to inform national and regional policy regarding their potential benefits to both the healthcare system and patients.Trial Registration: ClinicalTrials.gov, ID: NCT03238846 . Registered on 27 July 2017. [ABSTRACT FROM AUTHOR]

Background: Young Southern African women have the highest HIV incidence globally. Pregnancy doubles the risk of HIV acquisition further, and maternal HIV acquisition contributes significantly to the paediatric HIV burden. Little data on combination HIV prevention interventions during pregnancy and lactation are available. We measured HIV incidence amongst pregnant and postpartum women receiving a community-based combination HIV prevention intervention in a high HIV incidence setting in South Africa. Methods: A cohort study that included HIV-uninfected pregnant women was performed. Lay community-based workers provided individualized HIV prevention counselling and performed three-monthly home and clinic-based individual and couples HIV testing. Male partners were referred for circumcision, sexually transmitted infections or HIV treatment as appropriate. Kaplan-Meier analyses and Cox’s regression were used to estimate HIV incidence and factors associated with HIV acquisition. Results: The 1356 women included (median age 22.5 years) received 5289 HIV tests. Eleven new HIV infections were detected over 828.3 person-years (PY) of follow-up, with an HIV incidence rate of 1.33 infections/100 PY (95% CI: 0.74–2.40). Antenatally, the HIV incidence rate was 1.49 infections/100 PY (95% CI: 0.64–2.93) and postnatally the HIV incidence rate was 1.03 infections/100 PY (95% CI: 0.33–3.19). 53% of male partners received HIV testing and 66% of eligible partners received referral for circumcision. Women within known serodiscordant couples, and women with newly diagnosed HIV-infected partners, adjusted hazard ratio (aHR) = 32.7 (95% CI: 3.8–282.2) and aHR = 126.4 (95% CI: 33.8–472.2) had substantially increased HIV acquisition, respectively. Women with circumcised partners had a reduced risk of incident HIV infection, aHR = 0.22 (95% CI: 0.03–1.86). Conclusions: Maternal HIV incidence was substantially lower than previous regional studies. Community-based combination HIV prevention interventions may reduce high maternal HIV incidence in resource-poor settings. Expanded roll-out of home-based couples HIV testing and initiating pre-exposure prophylaxis for pregnant women within serodiscordant couples is needed in Southern Africa. [ABSTRACT FROM AUTHOR]

Retaining high levels of patients in care who are virally suppressed over long treatment periods has been an important challenge for antiretroviral treatment (ART) programmes in sub-Saharan Africa, the region having the highest HIV burden globally. Clinic-linked community-based adherence support (CBAS) programmes provide home-based adherence and psychosocial support for ART patients. However, there is little evidence of their longer-term impact. This study assessed the effectiveness of CBAS after eight years of ART. CBAS workers are lay healthcare personnel providing regular adherence and psychosocial support for ART patients and their households through home visits addressing household challenges affecting adherence. A multicentre cohort study using routinely collected data was undertaken at six public ART sites in a high HIV-prevalence South African district. Patient retention, loss to follow-up (LTFU), viral suppression and CD4 cell restoration were compared between patients with and without CBAS, using competing-risks regression, linear mixed models and log-binomial regression. 3861 patients were included, of whom 1616 (41.9%) received CBAS. Over 14,792 patient-years of observation, the cumulative incidence of LTFU was 37.3% and 46.2% amongst patients with and without CBAS, respectively, following 8 years of ART; adjusted subhazard ratio (CBAS vs. no CBAS) = 0.74 (95% CI: 0.66–0.84;P < .0001). Amongst patients on ART for 6.5–8 years, proportions not achieving viral suppression were 11.4% and 19.4% in patients with and without CBAS, respectively; adjusted risk ratio = 0.47 (95% CI: 0.26–0.86;P = .015). Annual CD4 cell increases from baseline were 62.8 cells/µL/year and 51.5 cells/µL/year amongst patients with and without CBAS, respectively, after 6.5 years or more (P = .034). After adjustment, annual CD4 cell recovery was 15.1 cells/µL/year (95% CI: 2.7–27.6) greater in CBAS patients (P = .017). ART patients who received CBAS had improved long-term patient retention, viral suppression and immunological restoration. CBAS is an intervention that can improve longer-term ART programme outcomes in resource-limited settings. [ABSTRACT FROM AUTHOR]

Adherence to antiretroviral treatment (ART) is a challenge in childhood, and children on ART have reduced virological suppression compared to adults. This study evaluated the effect of community-based adherence support (CBAS) on virological outcomes amongst children receiving ART in four South African provinces. Patient Advocates are lay CBAS workers who provide adherence and psychosocial support for patients, undertaking home visits to address household challenges affecting adherence. Patient Advocates provide counselling for children's carers regarding adherence and psychosocial problems. A multicentre cohort study using routinely collected data was conducted at 57 public ART sites including ART-naive children (<16 years) starting ART. Virological suppression until four years of ART was compared between children who received and did not receive CBAS. Analyses were by intention-to-treat, controlling for confounding using multivariable generalised estimating equations. A total of 4853 children were included, of whom 982 (20.2%) received CBAS. The median baseline age was 6.3 years and the baseline CD4 cell percentage was 12.0%; both were equivalent between the two groups. CBAS children had more advanced baseline clinical disease (62.1% vs. 52.6% World Health Organisation stages III or IV;P< 0.0001). A total of 5908 viral load results were analysed. Virological suppression was 65.6% (95% confidence interval [CI]: 62.7–68.4%) vs. 55.5% (95% CI: 54.1–57.0%) in CBAS and non-CBAS children, respectively, at any time-point on treatment (P< 0.0001). In analyses controlling for baseline clinical, demographic, site-related variables and time on ART, children receiving CBAS were more likely to achieve virological suppression, adjusted odds ratio (aOR) 1.60 (95% CI: 1.35–1.89;P< 0.0001). The effect of CBAS increased in magnitude with increasing durations of ART, and CBAS particularly improved virological suppression in a higher-risk subgroup (children younger than two years, aOR 2.47 [95% CI: 1.59–3.84]). CBAS was associated with improved virological suppression in children receiving ART. Expanded implementation of this low-cost intervention should be considered in resource-poor settings. [ABSTRACT FROM AUTHOR]

Background HIV-positive children in low-income settings face many challenges to adherence to antiretroviral treatment (ART) and have increased mortality on treatment compared to children in developed countries. Adult ART programmes have demonstrated benefit from community support to improve treatment outcomes; however, there are no empirical data on the effectiveness of this intervention in children. This study compared clinical, virological and immunological outcomes between children who received and who did not receive community-based adherence support from patient advocates (PAs) in four South African provinces. Methods A multicentre cohort study of ART-naïve children was conducted at 47 public ART facilities. Outcome measures were mortality, patient retention, virological suppression and CD4 percentage changes on ART. PAs are lay community health workers who provide adherence and psychosocial support for children's caregivers, and they undertake home visits to ascertain household challenges potentially impacting on adherence in the child. Corrected mortality estimates were calculated, correcting for deaths amongst those lost to follow-up (LTFU) using probability-weighted Kaplan-Meier and Cox functions. Results Three thousand five hundred and sixty three children were included with a median baseline age of 6.3 years and a median baseline CD4 cell percentage of 12.0%. PA-supported children numbered 323 (9.1%). Baseline clinical status variables were equivalent between the two groups. Amongst children LTFU, 38.7% were known to have died. Patient retention after 3 years of ART was 91.5% (95% CI: 86.8% to 94.7%) vs. 85.6% (95% CI: 83.3% to 87.6%) amongst children with and without PAs, respectively ( p =0.027). Amongst children aged below 2 years at baseline, retention after 3 years was 92.2% (95% CI: 76.7% to 97.6%) vs. 74.2% (95% CI: 65.4% to 81.0%) in children with and without PAs, respectively ( p=0.053). Corrected mortality after 3 years of ART was 3.7% (95% CI: 1.9% to 7.4%) vs. 8.0% (95% CI: 6.5% to 9.8%) amongst children with and without PAs, respectively ( p=0.060). In multivariable analyses, children with PAs had reduced probabilities of both attrition and mortality, adjusted hazard ratio (AHR) 0.57 (95% CI: 0.35 to 0.94) and 0.39 (95% CI: 0.15 to 1.04), respectively. Conclusion Community-based adherence support is an effective way to improve patient retention amongst children on ART. Expanded implementation of this intervention should be considered in order to reach ART programmatic goals in low-income settings as more children access treatment. [ABSTRACT FROM AUTHOR]

Introduction: Antiretroviral treatment (ART) guidelines recommend life-long ART for all HIV-positive individuals. This study evaluated tuberculosis (TB) incidence on ART in a cohort of HIVpositive individuals starting ART regardless of CD4 count in a programmatic setting at 3 clinics included in the HPTN 071 (PopART) trial in South Africa. Methods: A retrospective cohort analysis of HIV-positive individuals aged ≥18 years starting ART, between January 2014 and November 2015, was conducted. Follow-up was continued until 30 May 2016 or censored on the date of (1) incident TB, (2) loss to follow-up from HIV care or death, or (3) elective transfer out; whichever occurred first. Results: The study included 2423 individuals. Median baseline CD4 count was 328 cells/mL (interquartile range 195-468); TB incidence rate was 4.41/100 person-years (95% confidence interval [CI]: 3.62 to 5.39). The adjusted hazard ratio of incident TB was 0.27 (95% CI: 0.12 to 0.62) when comparing individuals with baseline CD4 .500 and ≤500 cells/mL. Among individuals with baseline CD4 count .500 cells/mL, there were no incident TB cases in the first 3 months of follow-up. Adjusted hazard of incident TB was also higher among men (adjusted hazard ratio 2.16; 95% CI: 1.41 to 3.30). Conclusions: TB incidence after ART initiation was significantly lower among individuals starting ART at CD4 counts above 500 cells/mL. Scale-up of ART, regardless of CD4 count, has the potential to significantly reduce TB incidence among HIV-positive individuals. However, this needs to be combined with strengthening of other TB prevention strategies that target both HIV-positive and HIV-negative individuals. [ABSTRACT FROM AUTHOR]