CD4 Trajectory Models and Onset of Non-AIDS-Defining Anal Genital Warts, Precancer, and Cancer in People Living with HIV Infection-1

Abstract

Background It is unclear how the characteristics of CD4 counts predict non-AIDS-defining human papillomavirus-related anogenital warts (AGWs) and anal high-grade squamous intraepithelial lesions/cancer (HSIL+) in people living with HIV infection-1 (PLWH). We compared the associations between 3 CD4 counts measures and these disease outcomes in the study. Methods Retrospective sociobehavioral and clinical data from electronic health records of 4803 PLWH from 2006 to 2018 were included. Three different measurements of CD4 counts-(a) nadir, (b) median, and (c) trajectory-were estimated. Six CD4 trajectory groups were constructed using the group-based trajectory modeling from all patients older than 18 years with ≥3 clinical visits. Univariate and multivariable logistic regression models were used to assess the associations with AGW and HSIL+, separately. Results A total of 408 AGW, 102 anal HSIL+ (43 HSIL, 59 cancer), 4 penile cancer, and 15 vaginal cancer cases were observed. Median CD4 (<200 cell/μL) was associated with AGW (odds ratio [OR], 2.2 [95% confidence interval {CI}, 1.6-3.0]), and anal HSIL+ (OR, 2.7 [95% CI, 1.5-5.0]; each, P < 0.001). Low nadir CD4 (<200 cell/μL) was associated with AGW (OR, 1.8 [95% CI, 1.3-2.6]) and anal HSIL+ (OR, 2.4 [95% CI, 1.2-4.7]; each, P ≤ 0.001). Different patterns (declining and sustained low CD4 counts) of CD4 trajectories showed the strongest associations with onset of both AGW (OR, 1.8-3.1) and HSIL+ (OR, 2.7-6.7). Conclusions People living with HIV infection-1 with the same median CD4 could have very different CD4 trajectories, implying different dynamics of immune status. CD4 trajectory could be a better predictor of incident AGW and HSIL+ among PLWH.