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In high-income countries, viral load is routinely measured to detect failure of antiretroviral therapy (ART) and guide switching to second-line ART. Viral load monitoring is not generally available in resource-limited settings. We examined switching from nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line regimens to protease inhibitor-based regimens in Africa, South America and Asia.Multicohort study of 17 ART programmes. All sites monitored CD4 cell count and had access to second-line ART and 10 sites monitored viral load. We compared times to switching, CD4 cell counts at switching and obtained adjusted hazard ratios for switching (aHRs) with 95% confidence intervals (CIs) from random-effects Weibull models.A total of 20 113 patients, including 6369 (31.7%) patients from 10 programmes with access to viral load monitoring, were analysed; 576 patients (2.9%) switched. Low CD4 cell counts at ART initiation were associated with switching in all programmes. Median time to switching was 16.3 months [interquartile range (IQR) 10.1–26.6] in programmes with viral load monitoring and 21.8 months (IQR 14.0–21.8) in programmes without viral load monitoring (P < 0.001). Median CD4 cell counts at switching were 161 cells/μl (IQR 77–265) in programmes with viral load monitoring and 102 cells/μl (44–181) in programmes without viral load monitoring (P < 0.001). Switching was more common in programmes with viral load monitoring during months 7–18 after starting ART (aHR 1.38; 95% CI 0.97–1.98), similar during months 19–30 (aHR 0.97; 95% CI 0.58–1.60) and less common during months 31–42 (aHR 0.29; 95% CI 0.11–0.79).In resource-limited settings, switching to second-line regimens tends to occur earlier and at higher CD4 cell counts in ART programmes with viral load monitoring compared with programmes without viral load monitoring.