Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis

Abstract

Background HIV-1 viral load (VL) testing is recommended to monitor antiretroviral therapy (ART) but not universally available. We examined monitoring of first-line and switching to second-line ART in sub-Saharan Africa, 2004–2013. Methods Adult HIV-1 infected patients starting combination ART in 16 countries were included. Switching was defined as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to a protease inhibitor (PI)-based regimen, with a change of ≥1 NRTI. Virological and immunological failures were defined per World Health Organization criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% confidence intervals (CI) comparing routine VL monitoring, targeted VL monitoring, CD4 cell monitoring and clinical monitoring, adjusted for programme and individual characteristics. Findings Of 297,825 eligible patients, 10,352 patients (3·5%) switched during 782,412 person-years of follow-up. Compared to CD4 monitoring hazard ratios for switching were 3·15 (95% CI 2·92–3·40) for routine VL, 1·21 (1·13–1·30) for targeted VL and 0·49 (0·43–0·56) for clinical monitoring. Overall 58.0% of patients with confirmed virological and 19·3% of patients with confirmed immunological failure switched within 2 years. Among patients who switched the percentage with evidence of treatment failure based on a single CD4 or VL measurement ranged from 32·1% with clinical to 84.3% with targeted VL monitoring. Median CD4 counts at switching were 215 cells/µl under routine VL monitoring but lower with other monitoring (114–133 cells/µl). Interpretation Overall few patients switched to second-line ART and switching occurred late in the absence of routine viral load monitoring. Switching was more common and occurred earlier with targeted or routine viral load testing.

Alarming rates of virological failure and drug resistance in patients on long-term antiretroviral treatment in routine HIV clinics in Togo

“…Here, we show low efficacy of long-term ART in Togo. As observed in many other subSaharan countries, a similar proportion (10.3%) of patients on ART for more than 4 years switched to second-line ART [7]. Importantly, among those still on first-line ART, 42% had viral load greater than 1000 copies/ml and either were on a completely ineffective ART regime or were with only a single drug still active.…”

Early antiretroviral therapy initiation: access and equity of viral load testing for HIV treatment monitoring

“…Viral load test access has increased modestly between 2013 and 2015, despite the target of 90% access by 2020. 15–18 Previous large scale-up test implementation programmes provide perspective. For example, after nearly 10 years of CD4 test scale-up, an estimated 60% of patients in low-resource settings had access to WHO-recommended levels of CD4 testing in 2012.…”

Development of an algorithm for determination of the likelihood of virological failure in HIV-positive adults receiving antiretroviral therapy in decentralized care

“…VL monitoring allows for early detection of virological failure (VF) before clinical disease progression and accumulation of resistance mutations has occurred [3–5]. Viral load results can also be used for adherence counselling, and may save costs by preventing unnecessary switches to 2nd line ART [6,7].…”