All-cause mortality in HIV-positive adults starting combination antiretroviral therapy

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 (IeDEA) 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 2 genders, 3 time periods after ART initiation, 4 age groups, and 7 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 to 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. Conclusions 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 modelers.

Global variations in mortality in adults after initiating antiretroviral treatment

“…In addition to incorporating more recent data and assessing time trends in ART mortality, this analysis adopts an innovative approach to correcting for unascertained mortality after LTFU, recognizing that the extent of the underascertainment of mortality is likely to differ substantially across settings. The previous analysis applied the same correction factors in all regions, leading to assumed mortality rates being roughly double those observed in IeDEA cohorts [6]. In the present analysis, no correction factors are applied in the North American, Latin American and Asia-Pacific datasets, with the result that mortality rates are substantially lower than estimated previously.…”

“…ART was defined as a combination of at least three antiretroviral drugs. Consistent with previous UNAIDS analyses [6,7], we defined baseline CD4 cell count as the CD4 cell count closest to the time of ART initiation and we defined patients as LTFU if their last visit date was more than six months prior to the database closure without any record of other outcomes (death or transfer). To estimate parameters in the Spectrum model, we used the same covariate categories as the Spectrum model: baseline CD4 cell count was categorized as 0-49, 50-99, 100-199, 200-249, 250-349, 350-499 or !500 cells/ml; time since ART initiation ('duration') was categorized as 0-5 months, 6-11 months or !12 months; and age was categorized as 15-24, 25-34, 35-44 or !45 years.…”

“…Consistent with previous UNAIDS analyses [6,7], we used Poisson regression models to estimate average mortality rates for each covariate category in Spectrum. We fitted separate regression models for the first 12 months after ART initiation and for durations more than 12 months after ART initiation, to account for nonproportional hazards.…”

“…AIDS mortality estimates produced by Spectrum and other mathematical models depend on assumptions about mortality rates after ART initiation. UNAIDS has previously relied on the International epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration to provide estimates of mortality of patients receiving ART in different regions to parameterize the Spectrum model [6,7]. Previous IeDEA analyses to estimate Spectrum parameters incorporated mortality data from patients starting ART in the pre-2011 [7] and 2009-2014 [6] periods.…”

“…UNAIDS has previously relied on the International epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration to provide estimates of mortality of patients receiving ART in different regions to parameterize the Spectrum model [6,7]. Previous IeDEA analyses to estimate Spectrum parameters incorporated mortality data from patients starting ART in the pre-2011 [7] and 2009-2014 [6] periods. These analyses were limited in their ability to estimate mortality of patients starting ART at higher CD4 cell counts, as such patients only became eligible for ART in low-income and middle-income countries after the WHO recommended universal ART eligibility in 2015 [8].…”