Practice of Epidemiology The Impact of Different CD4 Cell-Count Monitoring and Switching Strategies on Mortality in HIV-Infected African Adults on Antiretroviral Therapy: An Application of Dynamic Marginal Structural Models

In Africa, antiretroviral therapy (ART) is delivered with limited laboratory monitoring, often none. In 2003–2004, investigators in the Development of Antiretroviral Therapy in Africa (DART) Trial randomized persons initiating ART in Uganda and Zimbabwe to either laboratory and clinical monitoring (LCM) or clinically driven monitoring (CDM). CD4 cell counts were measured every 12 weeks in both groups but were only returned to treating clinicians for man-agement in the LCM group. Follow-up continued through 2008. In observational analyses, dynamic marginal struc-tural models on pooled randomized groups were used to estimate survival under different monitoring-frequency and clinical/immunological switching strategies. Assumptions included no direct effect of randomized group onmortality or confounders and no unmeasured confounders which influenced treatment switch and mortality or treatment switch and time-dependent covariates. After 48 weeks of first-line ART, 2,946 individuals contributed 11,351 person-years of follow-up, 625 switches, and 179 deaths. The estimated survival probability after a further 240 weeks for post-48-week switch at the first CD4 cell count less than 100 cells/mm3 or non-Candida World Health Organi-zation stage 4 event (with CD4 count <250) was 0.96 (95 % confidence interval (CI): 0.94, 0.97) with 12-weekly CD4 testing, 0.96 (95 % CI: 0.95, 0.97) with 24-weekly CD4 testing, 0.95 (95 % CI: 0.93, 0.96) with a single CD4 test at 48 weeks (baseline), and 0.92 (95 % CI: 0.91, 0.94) with no CD4 testing. Comparing randomized groups b