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

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.

Effectiveness of four antiretroviral regimens for treating people living with HIV

“…Living with a partner or family member was associated with a better virologic response, probably because social bonding has a strong influence over not feeling lonely or depressed, and adhering and responding better to medication [17]. Onoya et al in South Africa [18] observed that the risk of virologic failure was up to 5 times higher in non-adherence cases. Lee, et al, 2017 [19] reported that virologic failure after 6 months of ART is associated with a substantial risk of death.…”

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

“…These relatively healthy patients may be less tolerant of ART-associated ADRs, which may reverse the recent gains made in retention in HIV treatment. Although access to ART has significantly improved, patients in resource-limited settings (including South Africa) still have few HIV treatment options beyond second-line ART, hence the need to closely monitor ART-related ADRs among patients receiving second-line ART [ 13 , 14 ]. However, the growth of the South African ART programmes was not followed by an equivalent growth in adverse event (AE) monitoring systems, and routine clinical data on ART AEs offers, at best, indicators of ART-associated ADRs.…”

Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa

“…Second-line ART only concerned a minority of patients, estimated at approximately 5.3% of all patients on ART in low-and middle-income countries (LMIC) in 2014 [2]. However, the need for second-line ART is forecast to grow in the coming years because of high firstline treatment failure rates, estimated at between 8 and 23% after 5 years [3]. This trend is expected to be reinforced by the growing demand for first-line ART following recent international guidelines recommending ART initiation irrespective of CD4 count [4].…”