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

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.

Lopinavir Up-Regulates Expression of the Antiviral Protein Ribonuclease L in Human Papillomavirus-Positive Cervical Carcinoma Cells

“…This is highly significant when considered with the previously discussed findings that genital HPV infections can predispose to increased risk of HIV transmission in both men and women [29,30].…”

“…With current pricing strategies, anti-HPV vaccines are not an option in such settings, and as previously discussed, they will most likely have reduced efficacy in HIV-positive women. Furthermore, in view of the observation that infection with HPV can enhance the sexual transmission of HIV in both men and women [29,30], this clearly indicates that a simple, non-surgical treatment for HPV-related precancerous lesions may not only reduce the burden of cervical cancer but may also reduce the chances of HIV transmission.…”

Cervical Human Papillomavirus Infection and Shedding of Human Immunodeficiency Virus in Cervicovaginal Fluids

“…6,7,14,15 The lack of association between cervical HPV infection and HIV genital shedding observed in our study is consistent with the fact that HPV does not elicit a local inflammatory reaction. 1 In the study of Smith-McCune et al, 16 an increased risk of HIV acquisition associated with recent or concurrent HPV genital infection was described, particularly for some specific HPV types, considered to be a risk factor for HIV infection. Our data do not support this hypothesis because we did not observe any association between the 2 viruses at a genital level, where they seem to act independently.…”

Issues in cervical cancer incidence and treatment in HIV

“…Infection with multiple HPV types was shown to be an independent predictor of HIV seroconversion in a prospective cohort study of men who have sex with men [44]. Cervicovaginal HPV infection has been shown to be associated with an increased risk of HIV acquisition, particularly infection with high-risk HPV types [45]. Also, insulin-like growth factor (IGF) pathways are associated with both HIV and HPV progression [46], thus making this pathway a potential target for future treatment strategies.…”