Joint estimation of CD4(+) cell progression and survival in untreated individuals with HIV-1 infection

OBJECTIVE: We compiled the largest dataset of seroconverter cohorts to date from 25 countries across Africa, North America, Europe, and Southeast/East (SE/E) Asia to simultaneously estimate transition rates between CD4(+) cell stages and death, in antiretroviral therapy (ART)-naive HIV-1-infected individuals. DESIGN: A hidden Markov model incorporating a misclassification matrix was used to represent natural short-term fluctuations and measurement errors in CD4(+) cell counts. Covariates were included to estimate the transition rates and survival probabilities for each subgroup. RESULTS: The median follow-up time for 16 373 eligible individuals was 4.1 years (interquartile range 1.7–7.1), and the mean age at seroconversion was 31.1 years (SD 8.8). A total of 14 525 individuals had recorded CD4(+) cell counts pre-ART, 1885 died, and 6947 initiated ART. Median (interquartile range) survival for men aged 20 years at seroconversion was 13.0 (12.4–13.4), 11.6 (10.9–12.3), and 8.3 years (7.9–8.9) in Europe/North America, Africa, and SE/E Asia, respectively. Mortality rates increase with age (hazard ratio 2.22, 95% confidence interval 1.84–2.67 for >45 years compared with <25 years) and vary by region (hazard ratio 2.68, 1.75–4.12 for Africa and 1.88, 1.50–2.35 for Asia compared with Europe/North America). CD4(+) cell decline was significantly faster in Asian cohorts compared with Europe/North America (hazard ratio 1.45, 1.36–1.54). CONCLUSION: Mortality and CD4(+) cell progression rates exhibited regional and age-specific differences, with decreased survival in African and SE/E Asian cohorts compared with Europe/North America and in older age groups. This extensive dataset reveals heterogeneities between regions and ages, which should be incorporated into future HIV models.