Abstract 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.

In resource-limited settings, early mortality on antiretroviral therapy (ART) is approximately 10%; yet, it is unclear how much of that mortality occurs in care or after lost to follow-up. We assessed mortality rates and predictors of death among 12,222 nonpregnant ART-naive adults initiating first-line ART between April 2004 and May 2012 in South Africa, stratified by person-years in care and lost. We found 14.6% of patients died and being lost accounted for a minority of deaths across multiple definitions of loss (population attributable-risk percent ranged from 10.4% to 42.5%). Although mortality rates in patients lost were much higher than in care, most ART-related mortality occurred on treatment.

In resource-limited settings, early mortality on antiretroviral therapy (ART) is approximately 10%; yet, it is unclear how much of that mortality occurs in care or after lost to follow-up.We assessed mortality rates and predictors of death among 12,222 nonpregnant ART-naive adults initiating first-line ART between April 2004 and May 2012 in South Africa, stratified by person-years in care and lost.We found 14.6% of patients died and being lost accounted for a minority of deaths across multiple definitions of loss (population attributable-risk percent ranged from 10.4% to 42.5%).Although mortality rates in patients lost were much higher than in care, most ART-related mortality occurred on treatment.