Treatment outcomes of over 1000 patients on second-line, protease inhibitor-based antiretroviral therapy from four public-sector HIV treatment facilities across Johannesburg, South Africa.

OBJECTIVES: To report predictors of outcomes of second-line ART for HIV treatment in a resource-limited setting. METHODS: All adult ART-naïve patients who initiated standard first-line treatment between April 2004 and February 2012 at four public-sector health facilities in Johannesburg, South Africa, experienced virologic failure and initiated standard second-line therapy were included. We assessed predictors of attrition (death and loss to follow-up [≥3 months late for a scheduled visit]) using Cox proportional hazards regression and predictors of virologic suppression (viral load <400 copies/ml ≥3 months after switch) using modified Poisson regression with robust error estimation at 1 year and ever after second-line ART initiation. RESULTS: A total of 1236 patients switched to second-line treatment in a median (IQR) of 1.9 (0.9-4.6) months after first-line virologic failure. Approximately 13% and 45% of patients were no longer in care at 1 year and at the end of follow-up, respectively. Patients with low CD4 counts (<50 vs. ≥200, aHR: 1.85; 95% CI: 1.03-3.32) at second-line switch were at greater risk for attrition by the end of follow-up. About 75% of patients suppressed by 1 year, and 85% had ever suppressed by the end of follow-up. CONCLUSIONS: Patients with poor immune status at switch to second-line ART were at greater risk of attrition and were less likely to suppress. Additional adherence support after switch may improve outcomes.

Adverse Drug Reactions Among Patients Initiating Second-Line Antiretroviral Therapy in South Africa.

INTRODUCTION: Understanding 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. OBJECTIVE: This 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. METHODS: This 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. RESULTS: A 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). CONCLUSIONS: The 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.

Predicting the Need for Third-Line Antiretroviral Therapy by Identifying Patients at High Risk for Failing Second-Line Antiretroviral Therapy in South Africa.

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.