Associations of HIV RNA Viral Load, CD4 Counts, HPV Detection, and Cytology Support Co-Testing for Cervical Cancer Screening Among Women Living with HIV

Carmen D Zorrilla,1,* Cecilia V Olmo-Lopez,2,* Adriana M Hernández Garayua,3,* Jessica Ibarra,1,* Hiram A Santiago-Rivera,1,* Ana M Mosquera,1,* Karen Martinez-Robles4,* 1Department of Obstetrics and Gynecology, Maternal-Infant Studies Center (CEMI-Spanish Acronym), UPR School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico; 2UCC School of Medicine, Bayamon, Puerto Rico; 3St. George’s University School of Medicine, Grenada, West Indies, Grenada; 4Lincoln Hospital Obstetrics and Gynecology Department, Bronx, NY, USA*These authors contributed equally to this workCorrespondence: Carmen D Zorrilla, Department of Obstetrics and Gynecology, Maternal-Infant Studies Center (CEMI-Spanish Acronym), UPR School of Medicine, Medical Sciences Campus, University of Puerto Rico, San Juan, PO Box 365067, Puerto Rico, Tel +1-787-771-4740, Fax +1-787-771-4739, Email [email protected]: This study addresses a research gap in cervical cancer screening for Women Living with HIV (WLHIV) in Puerto Rico, evaluating the associations between viral load (VL) thresholds, CD4 count, HPV detection, and the benefits of co-testing with cytology.Methods: We analyzed the HIV viral load (VL), HPV infection, CD4 counts, and cervical cytology in 354 WLHIV receiving consecutive comprehensive care, including Highly Active Antiretroviral Therapy (HAART). Retrospective data were obtained from visits from 2018 to 2023. Consecutive visits with ThinPrep co-testing for cytology and HPV were evaluated. Only one observation per woman was included to maintain a cross-sectional dataset. HPV was detected using Hologic ThinPrep Pap Test and PCR-based genotyping.Results: The prevalence of any HPV was 27% which correlated inversely with CD4 counts: 42.9% (≤ 200 cells/mm3), 35.5% (201– 499 cells/mm3), and 23.2% (> 500 cells/mm3) (p=0.017). Multivariate analysis demonstrated that HPV positivity was significantly associated with the likelihood of having an abnormal Pap result (OR = 6.35; 95% CI: 3.22– 12.52; p < 0.001). Cytologic abnormalities were more frequent with lower CD4 counts: 32.1% (≤ 200 cells/mm3), 11.8% (201– 499 cells/mm3), and 11.2% (> 500cells/mm3) (p=0.007). HPV was detected more frequently among women with detectable VL > 201 copies/mL (35.4% vs 26.1%). Abnormal cytology occurred in 22.9% of women with VL > 201 copies/mL versus 11.4% with VL ≤ 200 copies/mL (p=0.028) and among 34.8% of women with negative HPV tests, underscoring the value of co-testing.Conclusion: WLHIV demonstrate higher HPV prevalence and abnormal cytology rates, with persistence inversely related to CD4 counts. Viral suppression correlates with lower HPV prevalence and fewer cytologic abnormalities. Co-testing identified 34.8% of WLHIV with abnormal cytology and HPV-negative results. This study supports consideration of co-testing for cervical cancer screening in WLHIV, even among those with high ART uptake. Further prospective and multi-site studies are warranted to confirm these observations and inform policy or guideline changes.Keywords: human immunodeficiency virus-HIV, human papilloma virus-HPV, CD4 count, viral load, cervical cancer, immunization, co-testing