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

Abstract

Background: HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa.

Methods: We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.

Findings: Of 297,825 eligible patients, 10,352 (3%) switched to second-line ART during 782 ,412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine viral load monitoring, 1·21 (1·13-1·30) for targeted viral load monitoring, and 0·49 (0·43-0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5-59·6) switched by 2 years, and of 15,892 patients with confirmed immunological failure, 19·3% (18·5-20·0) switched by 2 years. Of 10,352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117-335) with routine viral load monitoring, but were lower with other types of monitoring (range 114-133 cells per μL).

Interpretation: Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.

Funding: National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation.

Figure 1. Cumulative probability of confirmed virological failure during routine viral load monitoring and switching to second-line antiretroviral therapy according to monitoring strategy

Confirmed virological failure was defined as two values above 1,000 copies/ml within one year. Routine VL monitoring was assumed if at least 75 VL tests had been done per 100 person-years. CD4 monitoring was assumed if at least 75 CD4 counts had been done per 100 person-years. Targeted VL monitoring was assumed if in addition to CD4 monitoring at least 5 but less than 75 VL measurements were done per 100 person-years. A site was considered to use clinical monitoring if it did not meet the criteria for any other monitoring strategy.

Figure 2. Viral load testing and switching to second-line antiretroviral therapy

Bubble plot of rates of viral load testing and switching to second-line ART according to monitoring strategy. Each bubble represents the estimate for one treatment programme and calendar year. The size of the circles is proportional to the number of person-years in the respective year and programme. The black line shows the fit from regression model. Routine VL monitoring was assumed if at least 75 VL tests had been done per 100 person-years. CD4 monitoring was assumed if at least 75 CD4 counts had been done per 100 person-years. Targeted VL monitoring was assumed if in addition to CD4 monitoring at least 5 but less than 75 VL measurements were done per 100 person-years. A site was considered to use clinical monitoring if it did not meet the criteria for any other monitoring strategy.