HIV programmatic outcomes following implementation of the 'Treat-All' policy in a public sector setting in Eswatini: a prospective cohort study.

INTRODUCTION: The Treat-All policy - antiretroviral therapy (ART) initiation irrespective of CD4 cell criteria - increases access to treatment. Many ART programmes, however, reported increasing attrition and viral failure during treatment expansion, questioning the programmatic feasibility of Treat-All in resource-limited settings. We aimed to describe and compare programmatic outcomes between Treat-All and standard of care (SOC) in the public sectors of Eswatini. METHODS: This is a prospective cohort study of ≥16-year-old HIV-positive patients initiated on first-line ART under Treat-All and SOC in 18 health facilities of the Shiselweni region, from October 2014 to March 2016. SOC followed the CD4 350 and 500 cells/mm3 treatment eligibility thresholds. Kaplan-Meier estimates were used to describe crude programmatic outcomes. Multivariate flexible parametric survival models were built to assess associations of time from ART initiation with the composite unfavourable outcome of all-cause attrition and viral failure. RESULTS: Of the 3170 patients, 1888 (59.6%) initiated ART under Treat-All at a median CD4 cell count of 329 (IQR 168 to 488) cells/mm3 compared with 292 (IQR 161 to 430) (p < 0.001) under SOC. Although crude programme retention at 36 months tended to be lower under Treat-All (71%) than SOC (75%) (p = 0.002), it was similar in covariate-adjusted analysis (adjusted hazard ratio [aHR] 1.06, 95% CI 0.91 to 1.23). The hazard of viral suppression was higher for Treat-All (aHR 1.12, 95% CI 1.01 to 1.23), while the hazard of viral failure was comparable (Treat-All: aHR 0.89, 95% CI 0.53 to 1.49). Among patients with advanced HIV disease (n = 1080), those under Treat-All (aHR 1.13, 95% CI 0.88 to 1.44) had a similar risk of an composite unfavourable outcome to SOC. Factors increasing the risk of the composite unfavourable outcome under both interventions were aged 16 to 24 years, being unmarried, anaemia, ART initiation on the same day as HIV care enrolment and CD4 ≤ 100 cells/mm3 . Under Treat-All only, the risk of the unfavourable outcome was higher for pregnant women, WHO III/IV clinical stage and elevated creatinine. CONCLUSIONS: Compared to SOC, Treat-All resulted in comparable retention, improved viral suppression and comparable composite outcomes of retention without viral failure.

Feasibility of antiretroviral therapy initiation under the treat-all policy under routine conditions: a prospective cohort study from Eswatini.

INTRODUCTION: The World Health Organization recommends the Treat-All policy of immediate antiretroviral therapy (ART) initiation, but questions persist about its feasibility in resource-poor settings. We assessed the feasibility of Treat-All compared with standard of care (SOC) under routine conditions. METHODS: This prospective cohort study from southern Eswatini followed adults from HIV care enrolment to ART initiation. Between October 2014 and March 2016, Treat-All was offered in one health zone and SOC according to the CD4 350 and 500 cells/mm3 treatment eligibility thresholds in the neighbouring health zone, each of which comprised one secondary and eight primary care facilities. We used Kaplan-Meier estimates, multivariate flexible parametric survival models and standardized survival curves to compare ART initiation between the two interventions. RESULTS: Of the 1726 (57.3%) patients enrolled under Treat-All and 1287 (42.7%) under SOC, cumulative three-month ART initiation was higher under Treat-All (91%) than SOC (74%; p < 0.001) with a median time to ART of 1 (IQR 0 to 14) and 10 (IQR 2 to 117) days respectively. Under Treat-All, ART initiation was higher in pregnant women (vs. non-pregnant women: adjusted hazard ratio (aHR) 1.96, 95% confidence interval (CI) 1.70 to 2.26), those with secondary education (vs. no formal education: aHR 1.48, 95% CI 1.12 to 1.95), and patients with an HIV-positive diagnosis before care enrolment (aHR 1.22, 95% CI 1.10 to 1.36). ART initiation was lower in patients attending secondary care facilities (aHR 0.64, 95% CI 0.58 to 0.72) and for CD4 351 to 500 when compared with CD4 201 to 350 cells/mm3 (aHR 0.84, 95% CI 0.72 to 1.00). ART initiation varied over time for TB cases, with lower hazard during the first two weeks after HIV care enrolment and higher hazards thereafter. Of patients with advanced HIV disease (n = 1085; 36.0%), crude 3-month ART initiation was similar in both interventions (91% to 92%) although Treat-All initiated patients more quickly during the first month after HIV care enrolment. CONCLUSIONS: ART initiation was high under Treat-All and without evidence of de-prioritization of patients with advanced HIV disease. Additional studies are needed to understand the long-term impact of Treat-All on patient outcomes.

Retention on ART and predictors of disengagement from care in several alternative community-centred ART refill models in rural Swaziland.

INTRODUCTION: A broad range of community-centred care models for patients stable on anti-retroviral therapy (ART) have been proposed by the World Health Organization to better respond to patient needs and alleviate pressure on health systems caused by rapidly growing patient numbers. Where available, often a single alternative care model is offered in addition to routine clinical care. We operationalized several community-centred ART delivery care models in one public sector setting. Here, we compare retention in care and on ART and identify predictors of disengagement with care. METHODS: Patients on ART were enrolled into three community-centred ART delivery care models in the rural Shiselweni region (Swaziland), from 02/2015 to 09/2016: Community ART Groups (CAGs), comprehensive outreach care and treatment clubs. We used Kaplan-Meier estimates to describe crude retention in care model and retention on ART (including patients who returned to clinical care). Multivariate Cox proportional hazard models were used to determine factors associated with all-cause attrition from care model and disengagement with ART. RESULTS: A total of 918 patients were enrolled. CAGs had the most participants with 531 (57.8%). Median age was 44.7 years (IQR 36.3 to 54.4), 71.8% of patients were female, and 62.6% fulfilled eligibility criteria for community ART. The 12-month retention in ART was 93.7% overall; it was similar between model types (p = 0.52). A considerable proportion of patients returned from community ART to clinical care, resulting in lower 12 months retention in care model (82.2% overall); retention in care model was lowest in CAGs at 70.4%, compared with 86.3% in outreach and 90.4% in treatment clubs (p < 0.001). In multivariate Cox regression models, patients in CAGs had a higher risk of disengaging from care model (aHR 3.15, 95% CI 2.01 to 4.95, p < 0.001) compared with treatment clubs. We found, however, no difference in attrition in ART between alternative model types. CONCLUSIONS: Concurrent implementation of three alternative community-centred ART models in the same region was feasible. Although a considerable proportion of patients returned back to clinical care, overall ART retention was high and should encourage programme managers to offer community-centred care models adapted to their specific setting.

Successes and challenges in optimizing the viral load cascade to improve antiretroviral therapy adherence and rationalize second-line switches in Swaziland.

INTRODUCTION: As antiretroviral therapy (ART) is scaled up, more patients become eligible for routine viral load (VL) monitoring, the most important tool for monitoring ART efficacy. For HIV programmes to become effective, leakages along the VL cascade need to be minimized and treatment switching needs to be optimized. However, many HIV programmes in resource-constrained settings report significant shortfalls. METHODS: From a public sector HIV programme in rural Swaziland, we evaluated the VL cascade of adults (≥18 years) on ART from the time of the first elevated VL (>1000 copies/mL) between January 2013 and June 2014 to treatment switching by December 2015. We additionally described HIV drug resistance for patients with virological failure. We used descriptive statistics and Kaplan-Meier estimates to describe the different steps along the cascade and regression models to determine factors associated with outcomes. RESULTS AND DISCUSSION: Of 828 patients with a first elevated VL, 252 (30.4%) did not receive any enhanced adherence counselling (EAC). Six hundred and ninety-six (84.1%) patients had a follow-up VL measurement, and the predictors of receiving a follow-up VL were being a second-line patient (adjusted hazard ratio (aHR): 0.72; p = 0.051), Hlathikhulu health zone (aHR: 0.79; p = 0.013) and having received two EAC sessions (aHR: 1.31; p = 0.023). Four hundred and ten patients (58.9%) achieved VL re-suppression. Predictors of re-suppression were age 50 to 64 (adjusted odds ratio (aOR): 2.02; p = 0.015) compared with age 18 to 34 years, being on second-line treatment (aOR: 3.29; p = 0.003) and two (aOR: 1.66; p = 0.045) or three (aOR: 1.86; p = 0.003) EAC sessions. Of 278 patients eligible to switch to second-line therapy, 120 (43.2%) had switched by the end of the study. Finally, of 155 successfully sequenced dried blood spots, 144 (92.9%) were from first-line patients. Of these, 133 (positive predictive value: 92.4%) had resistance patterns that necessitated treatment switching. CONCLUSIONS: Patients on ART with high VLs were more likely to re-suppress if they received EAC. Failure to re-suppress after counselling was predictive of genotypically confirmed resistance patterns requiring treatment switching. Delays in switching were significant despite the ability of the WHO algorithm to predict treatment failure. Despite significant progress in recent years, enhanced focus on quality care along the VL cascade in resource-limited settings is crucial.