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The causal effect of switching to second-line ART in programmes without access to routine viral load monitoring

Objectives:We examined the effect of switching to second-line antiretroviral therapy (ART) on mortality in patients who experienced immunological failure in ART programmes without access to routine viral load monitoring in sub-Saharan Africa. Design and setting:Collaborative analysis of two ART programmes in Lusaka, Zambia and Lilongwe, Malawi. Methods:We included all adult patients experiencing immunological failure based on WHO criteria. We used Cox proportional hazards models weighted by the inverse probability of switching to compare mortality between patients who switched and patients who did not; and between patients who switched immediately and patients who switched later. Results are expressed as hazard ratios with 95% credible intervals (95% CI). Results:Among 2411 patients with immunological failure 324 patients (13.4%) switched to second-line ART during 3932 person-years of follow-up. The median CD4 cell count at start of ART and failure was lower in patients who switched compared to patients who did not: 80 versus 155 cells/&mgr;l (P < 0.001) and 77 versus 146 cells/&mgr;l (P < 0.001), respectively. Adjusting for baseline and time-dependent confounders, mortality was lower among patients who switched compared to patients remaining on failing first-line ART: hazard ratio 0.25 (95% CI 0.09–0.72). Mortality was also lower among patients who remained on failing first-line ART for shorter periods: hazard ratio 0.70 (95% CI 0.44–1.09) per 6 months shorter exposure. Conclusion:In ART programmes switching patients to second-line regimens based on WHO immunological failure criteria appears to reduce mortality, with the greatest benefit in patients switching immediately after immunological failure is diagnosed.