Background:  Studies reporting 1-year mortality of patients starting ART often report mortality by CD4 intervals without adjusting for loss to follow up (LTFU). This prevents incorporation into models projecting multi-year, population-level impacts of policies on what CD4 count to begin ART. We propose a new meta-analysis approach of grouped mortality data to estimate a smooth parametric relationship to predict 1-year mortality among all starting ART, including the LTFU, at any CD4 count 10 to 400.

Methods:  We searched public databases for reports of mortality on ART by initiating CD4 count. For each reported CD4 strata we recorded the 1-year mortality and LTFU rate and N. We used multiple imputation to overcome patient grouping by CD4 intervals and a 2-stage maximum likelihood (ML) approach to estimate unobserved mortality among those LTFU. We regressed logged mortality (adjusted for LTFU) on logged initiating CD4 count weighted by sample size. We varied the value of mortality among those lost from 0 to 100% and identified the ML estimate as our point estimate of 1-year mortality among the LTFU.

Results:  We included 21 reports of data on 58,058 patients from 14 countries and 57 CD4 count observations. One-year mortality ranged 1.3 to 40% and 1-year LTFU from 0.3 to 24%. Without adjusting for LTFU, we estimate those initiating ART at a CD4 of 200 have a predicted 1-year mortality of 5% and that prediction increases sharply with lower CD4 count. After searching values of unobserved mortality (range 0 to 100%), the best fit occurs when mortality among those lost is 40% (F stat 20.8). Adjusting for LTFU, predicted mortality was higher at all CD4 counts, while the slope of mortality with respect to initiation CD4 is flatter. Incorporating this adjustment, predicted 1-year mortality among those with a CD4 <200 cells/mm³ and >500 was 7.5% to 12.1% and 5.5%, respectively. Comparing those starting ART <500 to those at 50 cells/mm³, 1-year ART mortality was halved (12.13% vs 5.5). Comparison of our curve with survival data from HIV⁺ not on ART reveals our approach may overestimate 1-year mortality at the highest CD4 counts.

Conclusions:  Our findings confirm patients initiated at lower CD4 counts are at significantly greater risk of death during the first year on ART, but suggest the benefit to earlier initiation is not as great as would appear in data not adjusted for LTFU.