Objective To describe province-wide outcomes and temporal trends of the Western Cape Province antiretroviral treatment (ART) programme 5 years since inception, and to demonstrate the utility of the WHO monitoring system for ART. Methods The treatment programme started in 2001 through innovator sites. Rapid scaling-up of ART provision began early in 2004, located predominantly in primary-care facilities. Data on patients starting ART were prospectively captured into facility-based registers, from which monthly cross-sectional activity and quarterly cohort reports were aggregated. Retention in care, mortality, loss to follow-up and laboratory outcomes were calculated at 6-monthly durations on ART.Findings By the end of March 2006, 16 234 patients were in care. The cohort analysis included 12 587 adults and 1709 children. Women accounted for 70% of adults enrolled. After 4 and 3 years on ART respectively, 72.0% of adults (95% confidence interval, CI: 68.0-75.6) and 81.5% (95% CI: 75.7-86.1) of children remained in care. The percentage of adults starting ART with CD4 counts less than 50 cells/µl fell from 51.3% in 2001 to 21.5% in 2005, while mortality at 6 months fell from 12.7% to 6.6%, offset in part by an increase in loss to follow-up (reaching 4.7% at 6 months in 2005). Over 85% of adults tested had viral loads below 400 copies/ml at 6-monthly durations until 4 years on ART. Conclusion The location of care in primary-care sites in this programme was associated with good retention in care, while the scaling-up of ART provision was associated with reduced early mortality.Bulletin of the World Health Organization 2008;86:678-687.Une traduction en français de ce résumé figure à la fin de l'article. Al final del artículo se facilita una traducción al español. ‫املقالة.‬ ‫لهذه‬ ‫الكامل‬ ‫النص‬ ‫نهاية‬ ‫يف‬ ‫الخالصة‬ ‫لهذه‬ ‫العربية‬ ‫الرتجمة‬

BackgroundHIV-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.MethodsA 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.ResultsThree 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.ConclusionCommunity-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.

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.

IntroductionIncreasing numbers of patients are starting antiretroviral treatment (ART) at advanced age or reaching advanced age while on ART. We compared baseline characteristics and ART outcomes of older adults (aged ≥55 years) vs. younger adults (aged 25–54 years) in routine care settings in South Africa.MethodsA multicentre cohort study of ART-naïve adults starting ART at 89 public sector facilities was conducted. Mortality, loss to follow-up (LTFU), immunological and virological outcomes until five years of ART were compared using competing-risks regression, generalised estimating equations and mixed-effects models.Results4065 older adults and 86,006 younger adults were included. There were more men amongst older adults; 44.7% vs. 33.4%; RR = 1.34 (95% CI: 1.29–1.39). Mortality after starting ART was substantially higher amongst older adults, adjusted sub-hazard ratio (asHR) = 1.44 over 5 years (95% CI: 1.26–1.64), particularly for the period 7–60 months of treatment, asHR = 1.73 (95% CI: 1.44–2.10). LTFU was lower in older adults, asHR = 0.87 (95% CI: 0.78–0.97). Achievement of virological suppression was greater in older adults, adjusted odds ratio = 1.42 (95% CI: 1.23–1.64). The probabilities of viral rebound and confirmed virological failure were both lower in older adults, adjusted hazard ratios = 0.69 (95% CI: 0.56–0.85) and 0.64 (95% CI: 0.47–0.89), respectively. The rate of CD4 cell recovery (amongst patients with continuous viral suppression) was 25 cells/6 months of ART (95% CI: 17.3–33.2) lower in older adults.ConclusionsAlthough older adults had better virological outcomes and reduced LTFU, their higher mortality and slower immunological recovery warrant consideration of age-specific ART initiation criteria and management strategies.

Childrens' baseline condition when starting ART has improved considerably. Improving immunological treatment outcomes, the high medium-term patient retention with lack of temporal deterioration despite rapid patient number increases, provide evidence that pediatric ART programs are increasingly effective for those accessing them. However, children must start treatment when younger, following current international guidelines.