The effect of interrupted/deferred antiretroviral therapy on disease risk: A SMART and START combined analysis. Journal of Infectious Disease
Borges et al. on behalf of the Strategies for Management of Antiretroviral Therapy (SMART) and Strategic Timing of AntiRetroviral Treatment (START) studies aimed to quantify the relative difference between deferred/intermittent antiretroviral therapy (ART) and immediate/continuous ART on risk of AIDS- and non-AIDS–defining events. Endpoints assessed were AIDS, serious non-AIDS (SNA), cardiovascular disease (CVD), cancer, and death.
Among 10’156 participants, there were 124 AIDS, 247 SNA, 117 cancers, 103 CVD, and 120 deaths. Interventions in each trial led to similar differences in CD4 count and viral suppression. Pooled HRs (95% confidence interval) of deferred/intermittent ART versus immediate/continuous ART were for AIDS 3.63 (2.37–5.56); SNA 1.62 (1.25–2.09); CVD 1.59 (1.07–2.37); cancer 1.93 (1.32– 2.83); and death 1.80 (1.24–2.61). Underlying risk was greater in SMART than START. Given the similar HRs for each trial, absolute risk differences between treatment groups were greater in SMART than START. Pooled HRs were similar across subgroups.
In conclusion, compared to a strategy of immediate/continuous ART, a strategy of deferred/intermittent ART, increased the risk of AIDS and SNA events among HIV-positive persons consistently in SMART and START. Interventions in SMART and START led to similar absolute differences in mean CD4+ cell count and percentage with viral suppression, which in turn led to similar relative risk estimates for AIDS and SNA in each study. Pooled treatment differences for the composite outcome of AIDS, SNA, or death were similar across a number of subgroups.