Impact of age and sex on CD4+ cell count trajectories following treatment initiation: An analysis of the Tanzanian HIV treatment database

Objective: New guidelines recommend that all HIV-infected individuals initiate antiretroviral treatment (ART) immediately following diagnosis. This study describes how immune reconstitution varies by gender and age to help identify poorly reconstituting subgroups and inform targeted testing initiatives. Design: Longitudinal data from the outpatient monitoring system of the National AIDS Control Program in Tanzania. Methods: An asymptotic nonlinear mixed effects model was fit to post-treatment CD4+ cell count trajectories, allowing for fixed effects of age and sex, and an age by sex interaction. Results: Across 220,544 clinic visits from 32,069 HIV-infected patients, age- and sex-specific average CD4+ cell count at ART initiation ranged from 83-136 cells/mm³, long term asymptotic CD4+ cell count ranged from 301-389 cells/mm³, and time to half of maximal CD4+ reconstitution ranged from 3.57-5.68 months. CD4+ cell count at ART initiation and asymptotic CD4+ cell count were 1.28 (95% CI: 1.18-1.40) and 1.25 (95% CI: 1.20-1.31) times higher, respectively, for females compared to males in the youngest age group (19-29 years). Older patients started treatment at higher CD4+ counts but experienced slower CD4+ recovery than younger adults. Treatment initiation at greater CD4+ cell counts was correlated with greater asymptotic CD4+ cell counts within all sex and age groups. Conclusion: Older adults should initiate care early in disease progression because total immune reconstitution potential and rate of reconstitution appears to decrease with age. Targeted HIV testing and care linkage remains crucial for patient populations who tend to initiate treatment at lower CD4+ cell counts, including males and younger adults.