Relationship between CD4 ⁺ T-cell counts/HIV-1 RNA plasma viral load and AIDS-defining events among persons followed in the ACTG longitudinal linked randomized trials study

Background: AIDS-defining events (ADEs) decreased in the era of highly active antiretroviral therapy but still lead to hospitalizations and deaths. Understanding factors related to ADEs is important to mitigate events. Methods: We examined the relationship between demographics, behaviors, comorbidities, laboratory, clinical measurements, and ADEs diagnosed among subjects randomized to antiretroviral treatments (ART)/strategies and followed prospectively. Logistic regression models using generalized estimating equations generated odds ratios (ORs) focusing on the relationship between current CD4 ⁺ T-cell count (CD4)/HIV-1 RNA viral load (VL) and ADEs in the subsequent 16-week study period. Results: Among the 2948 subjects in the analysis, overall incidence of ADEs was 1.53 per 100 person-years. Multivariate regression models adjusted for demographics, body mass index, and ADE history. A 6-level time-varying variable examined VL (>100,000 copies/mL, ≤100,000) at CD4 levels (0-50, 51-200, >200 cells/μL); reference level was CD4 >200/VL ≤100,000. Among ART naives, odds of having an ADE in the subsequent 16-week interval were greater among subjects with lower CD4 counts; this relationship was modified by VL level (CD4 ≤50/VL >100,000: OR 37.2; CD4 ≤50/VL ≤100,000: OR 30.5; CD4 51-200/VL >100,000: OR 13.0; CD4 51-200/VL ≤100,000: OR 4.5; all P values >0.001). Similar results were seen among ART-experienced subjects. Conclusions: Recent CD4 and VL values are closely associated with development of ADEs even after examining a multitude of potential factors.