Incidence and Predictors of Pregnancy in Women Enrolled in Large Multinational HIV Treatment Trials of the AIDS Clinical Trials Group.

OBJECTIVES: Women are under-represented in clinical trials and must often commit to using contraception to enroll. We sought to determine the incidence and predictors of pregnancy in women participating in HIV treatment trials. DESIGN: Individual participant data meta-analysis. METHODS: We included data from multicountry HIV treatment trials conducted during the period 2005-2019 by the AIDS Clinical Trials Group that included females with HIV who were of reproductive potential, did not intend to become pregnant, and agreed to use effective contraception during study treatment. We extracted data from all female participants of age 18-55 years, including occurrence and dates of pregnancy on-study; however, only a few incident pregnancy predictor variables were available for analysis. RESULTS: One thousand six hundred twenty-six women from 4 trials were included. Over a median of 28 months (6461 person-years) of follow-up, 143 (9%) women became pregnant, for an overall incidence of 2.2 pregnancies/100 person-years (range 0.5-3/100 person-years, by study). In multivariable analysis including baseline age, type of regimen, and country as predictor variables, younger age remained the strongest predictor of incident pregnancy ( P < 0.0001 adjusted for country and antiretroviral treatment regimen). CD4 and HIV-1 RNA were not associated with pregnancy incidence. CONCLUSIONS: Pregnancy incidence was 2.2/100 person-years in female participants of HIV treatment trials. Rather than leading to exclusion of young women from trials, this finding should prompt appropriate adaptations in study design and analysis for earlier generation of pregnancy safety information for drugs.

A Randomized Clinical Trial of Human Papillomavirus Test-and-Treat as Compared to Cytology-Based Screening for Prevention of Cervical Cancer Among Women With Human Immunodeficiency Virus: AIDS Clinical Trials Group Protocol A5282.

BACKGROUND: Cytology-based cervical cancer screening followed by confirmation and treatment of biopsy-proven high-grade squamous intraepithelial lesions (bHSIL) is difficult to implement in resource-constrained settings. We hypothesized that high-risk human papillomavirus (hrHPV) testing followed by immediate cryotherapy of women with hrHPV (HPV screen-and-treat) may improve outcomes. METHODS: Randomized, open-label, phase 2, multinational clinical trial enrolling women with human immunodeficiency virus (HIV) age 18 or older with cervical hrHPV and having no cervical lesions or lesions appropriate for cryotherapy. Women were randomized to immediate cryotherapy (Arm A) or cytology-based screening (Arm B). For Arm A, cervical biopsies were obtained followed by cervical cryotherapy, and in Arm B, women with abnormal cytology underwent colposcopy followed by loop electroexcision procedure (LEEP) if bHSIL was detected. Women were followed through 30 months. The primary outcome was time to bHSIL detected from Month 6 through study completion. RESULTS: In total, 288 women (145 in Arm A, 143 in Arm B) were randomized: median age 35 years, 84% on antiretroviral therapy, median CD4 501 cells/mm3. In Arm A, 39 (27%) of women had bHSIL at entry, and in Arm B, 88 (62%) had abnormal cytology, 22 (15%) were diagnosed with bHSIL, 12 (8%) underwent LEEP. In follow-up, 30 (21%) and 31 (22%) developed bHSIL; time to bHSIL was similar between arms (P=.94). The prevalence of hrHPV at Month 6 was similar between arms (61% and 70%, P=.13). CONCLUSIONS: HPV test-and-treat was not associated with improved bHSIL outcomes as compared to cytology-based screening. More effective treatment options are required to improve outcomes from screen-and-treat programs. CLINICAL TRIALS REGISTRATION: NCT01315363.