Test and Treat (UTT) policy calls for first-line antiretroviral treatment (ART) initiation among all known HIV-positive patients, irrespective of CD4 cell count. We evaluate treatment outcomes of patients initiated on first-line ART directly before and after the implementation of UTT. Methods: We analysed prospectively collected clinical cohort data among ART-naïve adult patients within two HIV clinics in Johannesburg, South Africa. We compare two groups: 1) an unexposed pre-UTT group initiating treatment from 01 December 2014 to 31 May 2015; and 2) an exposed UTT group initiating treatment from 01 December 2016 to 31 May 2017. Primary treatment outcomes included lost to follow-up (LTFU) (>90 days late for the last scheduled visit with no subsequent clinical visit). Cox proportional hazards models were used to estimate the association between pre-UTT vs UTT initiation on LTFU by 12 months. Results: We included 2410 patients. A total of 1267 (52.6%) patients initiated ART before UTT implementation and 1143 (47.4%) after the change in policy. LTFU (adjusted Hazard Ratio (aHR): 1.51; 95% Confidence Interval (CI): 1.16-1.98) between groups and specifically among those initiating with a CD4 cell count ≤500 cells/mm 3 (aHR: 1.59; 95% CI: 1.21-2.10) was higher among patients initiating ART under UTT. Conclusion: LTFU under UTT proved higher than that of previous periods. Patients initiating first-line therapy under the treat-all policy may often start treatment in better health, subsequently not perceiving a direct benefit to treatment which may deter patients from consistent engagement in HIV treatment programmes.

Although third-line antiretroviral therapy (ART) is available in South Africa's public sector, its cost is substantially higher than first and second line. Identifying risk factors for failure on second-line treatment remains crucial to reduce the need for third-line drugs. We conducted a case–control study including 194 adult patients (≥18 years; 70 cases and 124 controls) who initiated second-line ART in Johannesburg, South Africa. Unconditional logistic regression was used to assess predictors of virologic failure (defined as 2 consecutive viral load measures ≥1000 copies/mL, ≥3 months after switching to second line). Variables included a social instability index, ART adherence, self-reported as well as diagnosed adverse drug reactions (ADRs), HIV disclosure, depression, and factors affecting access to HIV clinics. Overall 60.0% of cases and 54.0% of controls were female. Mean ages of cases and controls were 41.8 ± 9.6 and 43.3 ± 8.0, respectively. Virologic failure was predicted by ART adherence <90% [odds ratio (OR) 4.7; 95% confidence interval (95% CI): 2.1–10.5], younger age (<40 years of age; OR 0.6; 95% CI: 0.3–1.1), high social instability (OR 3.8; 95% CI: 1.30–11.5), self-reported ADR (OR 1.9; 95% CI: 1.0–3.5), disclosure to friends/colleagues rather than partner/relatives (OR 3.4; 95% CI: 1.3–9.1), and medium/high depression compared to low/no depression (OR 4.4; 95% CI: 1.5–13.4). Our results suggest complex socioeconomic factors contributing to risk of virologic failure, possibly by impacting ART adherence, among patients on second-line therapy in South Africa. Identifying patients with possible indicators of nonadherence could facilitate targeted interventions to reduce the risk of second-line treatment failure and mitigate the demand for third-line regimens.

BackgroundLong-term antiretroviral therapy (ART) adherence is critical for achieving optimal HIV treatment outcomes. Fixed-dose combination (FDC) single-pill regimens, introduced in South Africa in April 2013, has simplified pill taking. We evaluated treatment outcomes among patients initiated on a FDC compared to a similar multi-pill ART regimen in Johannesburg, South Africa.MethodsWe conducted a retrospective cohort study of ART-naïve HIV-positive non-pregnant adult (≥18 years) patients without tuberculosis who initiated first-line ART on tenofovir and emtricitabine or lamivudine with efavirenz at Themba Lethu Clinic in Johannesburg, South Africa. We compared those initiated on a multi-pill ART regimen (3–5 pills/day; September 1, 2011–August 31, 2012) to those initiated on a FDC ART regimen (one pill/day; September 1, 2013–August 31, 2014). Treatment outcomes included attrition (combination of lost to follow-up and mortality), missed medical visits, and virologic suppression (viral load <400 copies/mL) by 12 months post-ART initiation. Cox proportional hazards models and Poisson regression were used to estimate the association between FDCs vs multiple pills and treatment outcomes.ResultsWe included 3151 patients in our analysis; 2230 (70.8%) patients initiated multi-pill ART and 921 (29.2%) patients initiated on a FDC. By 12 months post-initiation, attrition (adjusted hazard ratio: 0.98; 95% CI: 0.77–1.24) was similar across regimen types (FDC vs multi-pill). Although not significant, patients on a FDC were marginally more likely to achieve viral suppression by 6 (adjusted relative rate [aRR]: 1.10; 95% CI: 0.99–1.23) and 12 months (aRR: 1.12; 95% CI: 0.92–1.36) on ART. Patients initiated on a FDC were significantly less likely to miss medical visits during the first 12 months of treatment (aRR: 0.66; 95% CI: 0.52–0.83).ConclusionOur results suggest FDCs may have a role to play in supporting patient adherence and medical monitoring through improved medical visit attendance. This may potentially improve treatment outcomes later on in treatment.

IntroductionUnderstanding the occurrence of antiretroviral (ARV)-related adverse events (AEs) among patients receiving second-line antiretroviral therapy (ART) is important in preventing switches to more limited and expensive third-line regimens.ObjectiveThis study aimed to estimate the rates and examine predictors of AEs among adult HIV-1-infected patients receiving second-line ART in the Right to Care (RTC) clinical cohort in South Africa.MethodsThis was a cohort study of HIV-1-infected adult patients (≥ 18 years of age) initiating standard second-line ART in South Africa from 1 April 2004 to 10 January 2016. Our primary outcome was the development of an AE within 24 months of initiating second-line therapy. We used Kaplan–Meier survival analysis to determine AE incidence in the first 24 months of second-line ART. Predictors of AEs were modelled using a Cox proportional hazards model.ResultsA total of 7708 patients initiated second-line ART, with 44.5% developing at least one AE over the first 24 months of second-line treatment. The highest AE incidence was observed among patients receiving abacavir (ABC) + lamivudine (3TC) + ritonavir-boosted lopinavir/atazanavir (LPVr/ATVr) (52.7/100 person-years (PYs), 95% confidence interval (CI): 42.9–64.8), while patients initiated on a tenofovir (TDF) + emtricitabine (FTC)/3TC + LPVr regimen had the lowest rate of AEs (26.4/100 PYs, 95% CI: 24.9–28.3). Clinical predictors of AEs included experiencing AEs when receiving first-line ART (adjusted hazard ratio (aHR) 2.3, 95% CI: 1.9–2.8), lower CD4 cell count (0–199 vs. ≥ 350 cells/mm3; aHR 1.4, 95% CI: 1.4–1.8), and switching to second-line therapy from an ABC-base first-line regimen (ABC + 3TC + efavirenz/nevirapine [EFV/NVP] vs. TDF + 3TC/FTC + EFV/NVP; aHR 3.4, 95% CI: 1.1–11.1).ConclusionsThe rates of AEs were lowest among patients receiving a TDF-based second-line regimen. Patients with poorer health at the time of switch were at higher risk of AEs when receiving second-line ART and may require closer monitoring to improve the durability of second-line therapy.

BackgroundWhile efficacy data exist, there are limited data on the outcomes of patients on third-line antiretroviral therapy (ART) in sub-Saharan Africa in actual practice. Being able to identify predictors of switch to third-line ART will be essential for planning for future need. We identify predictors of switch to third-line ART among patients with significant viraemia on a protease inhibitor (PI)-based second-line ART regimen. Additionally, we describe characteristics of all patients on third-line at a large public sector HIV clinic and present their early outcomes.MethodsRetrospective analysis of adults (≥ 18 years) on a PI-based second-line ART regimen at Themba Lethu Clinic, Johannesburg, South Africa as of 01 August 2012, when third-line treatment became available in South Africa, with significant viraemia on second-line ART (defined as at least one viral load ≥ 1000 copies/mL on second-line ART after 01 August 2012) to identify predictors of switch to third-line (determined by genotype resistance testing). Third-line ART was defined as a regimen containing etravirine, raltegravir or ritonavir boosted darunavir, between August 2012 and January 2016. To assess predictors of switch to third-line ART we used Cox proportional hazards regression among those with significant viraemia on second-line ART after 01 August 2012. Then among all patients on third-line ART we describe viral load suppression, defined as a viral load < 400 copies/mL, after starting third-line ART.ResultsAmong 719 patients in care and on second-line ART as of August 2012 (with at least one viral load ≥ 1000 copies/mL after 01 August 2012), 36 (5.0% over a median time of 54 months) switched to third-line. Time on second-line therapy (≥ 96 vs. < 96 weeks) (adjusted Hazard Ratio (aHR): 2.53 95% CI 1.03–6.22) and never reaching virologic suppression while on second-line ART (aHR: 3.37 95% CI 1.47–7.73) were identified as predictors of switch. In a separate cohort of patients on third-line ART, 78.3% (47/60) and 83.3% (35/42) of those in care and with a viral load suppressed their viral load at 6 and 12 months, respectively.ConclusionsOur results show that the need for third-line is low (5%), but that patients’ who switch to third-line ART have good early treatment outcomes and are able to suppress their viral load. Adherence counselling and resistance testing should be prioritized for patients that are at risk of failure, in particular those who never suppress on second-line and those who have been on PI-based regimen for extended periods.Electronic supplementary materialThe online version of this article (10.1186/s12981-018-0196-9) contains supplementary material, which is available to authorized users.