All-cause mortality in HIV-positive adults starting combination antiretroviral therapy: correcting for loss to follow-up

Abstract

Objective: To estimate mortality in HIV-positive patients starting combination antiretroviral therapy (ART) and to discuss different approaches to calculating correction factors to account for loss to follow-up.

Methods: A total of 222 096 adult HIV-positive patients who started ART 2009-2014 in clinics participating in the International epidemiology Databases to Evaluate AIDS collaboration in 43 countries in sub-Saharan Africa, Asia Pacific, Latin America, and North America were included. To allow for underascertainment of deaths due to loss to follow-up, two correction factors (one for the period 0-6 months on ART and one for later periods) or 168 correction factors (combinations of two sexes, three time periods after ART initiation, four age groups, and seven CD4 groups) based on tracing patients lost in Kenya and data linkages in South Africa were applied. Corrected mortality rates were compared with a worst case scenario assuming all patients lost to follow-up had died.

Results: Loss to follow-up differed between regions; rates were lowest in central Africa and highest in east Africa. Compared with using two correction factors (1.64 for the initial ART period and 2.19 for later), applying 168 correction factors (range 1.03-4.75) more often resulted in implausible mortality rates that exceeded the worst case scenario. Corrected mortality rates varied widely, ranging from 0.2 per 100 person-years to 54 per 100 person-years depending on region and covariates.

Conclusion: Implausible rates were less common with the simpler approach based on two correction factors. The corrected mortality rates will be useful to international agencies, national programmes, and modellers.

Figure 1

Correction factors. The South African set of two correction factors is shown in black, the two sets of 168 correction factors derived from the South African and Kenyan data are shown in colour.

Figure 2

Examples of sensitivity analyses for Asia Pacific (A), Southern Africa (B), Central Africa (C), Latin America (D), West Africa (E), East Africa (F) and North America (G). The different corrected mortality estimates are compared with worst-case scenario estimates (upper black dashed line) and best-case scenario estimates (lower black dashed line) and crude mortality (black dotted line). Crude mortality and mortality from best-case scenario are closely similar.