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Genital Tract HIV RNA Levels and Their Associations With Human Papillomavirus Infection and Risk of Cervical Precancer

Ghartey, Jeny DO, MS*,†; Kovacs, Andrea MD; Burk, Robert D. MD§; Stewart Massad, L. MD; Minkoff, Howard MD; Xie, Xianhong PhD#; D'souza, Gypsyamber PhD**; Xue, Xiaonan PhD#; Heather Watts, D. MD††; Levine, Alexandra M. MD‡‡; Einstein, Mark H. MD, MS*,†; Colie, Christine MD§§; Anastos, Kathryn MD*,†; Eltoum, Isam-Eldin MD‖‖; Herold, Betsy C. MD§,†; Palefsky, Joel M. MD¶¶; Strickler, Howard D. MD, MPH#

JAIDS Journal of Acquired Immune Deficiency Syndromes: 1 July 2014 - Volume 66 - Issue 3 - p 316–323
doi: 10.1097/QAI.0000000000000157
Epidemiology and Prevention

Objective: Plasma HIV RNA levels have been associated with the risk of human papillomavirus (HPV) and cervical neoplasia in HIV-seropositive women. However, little is known regarding local genital tract HIV RNA levels and their relation with cervical HPV and neoplasia.

Design/Methods: In an HIV-seropositive women's cohort with semiannual follow-up, we conducted a nested case–control study of genital tract HIV RNA levels and their relation with incident high-grade squamous intraepithelial lesions (HSIL) subclassified as severe (severe HSIL), as provided for under the Bethesda 2001 classification system. Specifically, 66 incidents of severe HSIL were matched to 130 controls by age, CD4+ count, highly active antiretroviral therapy use, and other factors. We also studied HPV prevalence, incident detection, and persistence in a random sample of 250 subjects.

Results: Risk of severe HSIL was associated with genital tract HIV RNA levels (odds ratio comparing HIV RNA ≥ the median among women with detectable levels versus undetectable, 2.96; 95% confidence interval: 0.99 to 8.84; Ptrend = 0.03). However, this association became nonsignificant (Ptrend = 0.51) after adjustment for plasma HIV RNA levels. There was also no association between genital tract HIV RNA levels and the prevalence of any HPV or oncogenic HPV. However, the incident detection of any HPV (Ptrend = 0.02) and persistence of oncogenic HPV (Ptrend = 0.04) were associated with genital tract HIV RNA levels, after controlling plasma HIV RNA levels.

Conclusions: These prospective data suggest that genital tract HIV RNA levels are not a significant independent risk factor for cervical precancer in HIV-seropositive women, but they leave open the possibility that they may modestly influence HPV infection, an early stage of cervical tumorigenesis.

*Department of Obstetrics and Gynecology and Women's Health, Albert Einstein College of Medicine, Bronx, NY;

Department of Obstetrics and Gynecology and Women's Health, Montefiore Medical Center, Bronx, NY;

Department of Pediatrics, University of Southern California, Los Angeles, CA;

§Department of Pediatrics, Albert Einstein College of Medicine, Bronx, NY;

Department of Obstetrics and Gynecology, Washington University School of Medicine, St. Louis, MO;

Department of Obstetrics and Gynecology, Maimonides Medical Center, Brooklyn, NY;

#Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY;

**Department of Epidemiology, Johns Hopkins School of Public Health, Baltimore, MD;

††Department of Health and Human Services, National Institute of Child Health and Human Development, Bethesda, MD;

‡‡Department of Hematology, City of Hope National Medical Center, Duarte, CA;

§§Department of Obstetrics and Gynecology, Georgetown University Medical Center, Washington, DC;

‖‖Department of Pathology, University of Alabama, Birmingham, AL; and

¶¶Department of Medicine, University of California, San Francisco, CA.

Correspondence to: Jeny Ghartey, DO, MS, Albert Einstein College of Medicine/Montefiore Medical Center, 1300 Morris Park Avenue, Block 307, Bronx, NY 10461 (e-mail: jenyghartey@gmail.com).

Abstract presented at the Center For AIDS Research Joint Symposium on HIV Research in Women on September 19, 2012, Providence, RI.

The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993, and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is cofunded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI grant number UL1 RR024131). This project has also been funded in part with federal funds from the Frederick National Laboratory for Cancer Research, National Institutes of Health (HHSN261200800001E), the Einstein-Montefiore Center for AIDS Research (5P30AI051519-08), Einstein-Montefiore Clinical and Translational Science Award (1ULIRR025750 and KL2RR025749 to J.G.), and NIAID (R33AI079763 to B.C.H. and R01-CA-085178 to H.D.S.).

The authors have no conflicts of interest to disclose.

Author Contributions: Primary leaders of this study, involved in generation of the hypotheses and every aspect of data analysis and writing and review of the manuscript: J.G., X.X., B.C.H., J.M.P., and H.D.S. Writing and review of the manuscript: A.K., R.D.B., L.S.M, H.M., G.D., X.X., D.H.W., A.M.L., M.H.E., C.C., K.A., and I.E.E. Collection of the data: A.K., R.D.B., L.S.M, H.M., D.H.W., A.M.L., C.C., K.A., and I.E.E. The list of authors reflects the 6 sites that collected the data and the data analysis center in this multicenter cohort study, and the HPV Working Group members who headed this specific project. Clinical data and specimens used in this study were collected by the Women's Interagency HIV Study Collaborative Study Group with centers (principal investigators) at New York City/Bronx Consortium (Kathryn Anastos); Brooklyn, NY (H.M.); Washington, DC, Metropolitan Consortium (Mary Young.); The Connie Wofsy Study Consortium of Northern California (Ruth Greenblatt); Los Angeles County/Southern California Consortium (A.M.L.); Chicago Consortium (Mardge Cohen); and Data Coordinating Center (Stephen Gange).

Received March 19, 2014

Accepted March 25, 2014

© 2014 by Lippincott Williams & Wilkins