Type-Specific Cervico-Vaginal Human Papillomavirus Infection Increases Risk of HIV Acquisition Independent of Other Sexually Transmitted Infections

Karen K Smith-Mccune,Joel M Palefsky,Maria Da Costa,Mike Z Chirenje,Ariane Van Der Straten,George F Sawaya,Tsitsi Magure,Rudo Makunike-Mutasa,Yifei Ma,Tsungai Chipato,Stephen Shiboski,Jennifer Tuveson,Anna-Barbara Moscicki

doi:10.1371/journal.pone.0010094

Abstract

BackgroundSexually transmitted infections (STIs) such as herpes simplex virus (HSV)-2 are associated with an increased risk of HIV infection. Human papillomavirus (HPV) is a common STI, but little is know about its role in HIV transmission. The objective of this study was to determine whether cervico-vaginal HPV infection increases the risk of HIV acquisition in women independent of other common STIs.Methods and FindingsThis prospective cohort study followed 2040 HIV-negative Zimbabwean women (average age 27 years, range 18–49 years) for a median of 21 months. Participants were tested quarterly for 29 HPV types (with L1 PCR primers) and HIV (antibody testing on blood samples with DNA or RNA PCR confirmation). HIV incidence was 2.7 per 100 woman-years. Baseline HPV prevalence was 24.5%, and the most prevalent HPV types were 58 (5.0%), 16 (4.7%), 70 (2.4%), and 18 (2.3%). In separate regression models adjusting for baseline variables (including age, high risk partner, positive test for STIs, positive HSV-2 serology and condom use), HIV acquisition was associated with having baseline prevalent infection with HPV 58 (aHR 2.13; 95% CI 1.09–4.15) or HPV 70 (aHR 2.68; 95% CI 1.08–6.66). In separate regression models adjusting for both baseline variables and time-dependent variables (including HSV-2 status, incident STIs, new sexual partner and condom use), HIV acquisition was associated with concurrent infection with any non-oncogenic HPV type (aHR 1.70; 95% CI 1.02–2.85), any oncogenic HPV type (aHR 1.96; 95% CI 1.16–3.30), HPV 31 (aHR 4.25; 95% CI 1.81–9.97) or HPV 70 (aHR 3.30; 95% CI 1.50–7.20). Detection of any oncogenic HPV type within the previous 6 months was an independent predictor of HIV acquisition, regardless of whether HPV status at the HIV acquisition visit was included (aHR 1.95; 95% CI 1.19–3.21) or excluded (aHR 1.96; 95% CI 1.02–2.85) from the analysis.Conclusions/SignificanceCervico-vaginal HPV infection was associated with an increased risk of HIV acquisition in women, and specific HPV types were implicated in this association. The observational nature of our study precludes establishment of causation between HPV infection and HIV acquisition. However, given the high prevalence of HPV infection in women, further investigation of the role of HPV in HIV transmission is warranted.

Highlights

Human papillomavirus (HPV) is a common sexually transmitted infection (STI) and has been implicated as a causative agent of anogenital cancers including cervical, vaginal, vulvar, and anal cancer [1,2]
1Adjusted for Baseline variables: study arm, high risk behavior, high risk partner, positive test for N gonorrhoeae, C trachomatis, Trichomoniasis vaginalis or syphilis, cohabiting with sexual partner, age 25–34 years or .35 years, positive serology for herpes simplex virus (HSV)-2, no condom use within the prior 3 months, and regular partner not circumcised and Timedependent variables: condom non-use since last visit; new partner since last visit; circumcision status of new partner; incident infection since the last visit with HSV-2, N gonorrhoeae, C trachomatis, Trichomoniasis vaginalis. 2Non-oncogenic types defined as types 6, 11, 32, 40, 54, 55, 61, 69, 70, 83, 84, ‘‘mix’’, and untyped. 3Oncogenic types defined as 16, 18, 26, 31, 33, 35, 39, 45, 51, 52, 53, 56, 58, 59, 66, 68, 73 and 82v. doi:10.1371/journal.pone.0010094.t005. In this large cohort of Zimbabwean women, we found consistently increased risk of HIV acquisition associated with cervico-vaginal HPV infection, and specific HPV types (HPV 31, 58 and 70) were implicated in the association
Demographic information collected at enrollment and at each quarterly visit allowed us to control for time-dependent variables such as new sexual partners, HSV-2 serostatus, new STIs, or high-risk behavior by the participant or her regular partner

Summary

Introduction

Human papillomavirus (HPV) is a common sexually transmitted infection (STI) and has been implicated as a causative agent of anogenital cancers including cervical, vaginal, vulvar, and anal cancer [1,2]. About the converse relationship, i.e. the effect of HPV infection on risk of HIV acquisition. Having anal infection with 2 or more HPV types was recently shown to be an independent predictor of HIV seroconversion in a prospective cohort study of men who have sex with men [12]. The aim of this study was to determine the association between HPV infection and HIV acquisition in women in the setting of an effectiveness trial of the diaphragm and lubricant gel for HIV/STI prevention in Zimbabwe.

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Conclusion