Infection with one or more of the cancer-causing subtypes of the human papilloma virus (HPV) multiplied the risk of acquiring HIV among young men in by 4.5-fold in a randomised controlled study of circumcision in South Africa.
Bertran Auvert, the principal investigator of the ANRS1265 circumcision trial in Orange Farm, South Africa, hinted that he was proposing a trial of one of the HPV vaccines as a method of reducing HIV infection.
The substudy of HPV infection collected swabs for DNA analysis from 1683 men and tested them for the presence of 13 of the high-risk, cancer-causing subtypes of HPV and 24 of the low-risk wart-forming ones. HPV samples were collected when the study terminated, 21 months after participants were circumcised.
Observed HPV prevalence was related to the risk of seroconversion during the study and the researchers also related it for the purposes of multivariate analysis to the participants’ age, education level, number of sexual partners, condom use, and whether they had TB or other sexually transmitted infections including herpes, gonorrhoea and chlamydia.
During the trial, two per cent of trial participants became infected with HIV, and 17.5% and 14.3% when tested were infected with at least one low-risk or high-risk strain of HPV respectively. The most common types of high-risk HPV were type 16 (3.5%) and 18 (3.1%).
Participants with at least one strain of HPV were 5.5 times more likely to acquire HIV than participants without high-risk HPV and were still 4.6 times more likely when this was adjusted by taking into account other factors influencing HIV infection.
This was associated exclusively with high-risk HPV infection. Participants with low-risk types of HPV were no more likely to acquire HIV than HPV-uninfected men (adjusted risk ratio 0.92) whereas men with high-risk HPV were four times more likely (adjusted risk ratio 3.8).
The likelihood of acquiring HIV increased dramatically in men with multiple subtypes of HPV. Auvert calculated that annual HIV incidence in men without HPV was less than one per cent, 3-4% in men with one or two types, 10% in men with three types and 21% in men with five types. Each infection with an additional high-risk type of HPV increased the likelihood of HIV acquisition by two-thirds.
Auvert commented that one possible limitation of his study was that because HPV infection was determined at the end of the study, HIV infection might predate HPV infection: however he commented that because HIV infections were by definition recent in this study, the men who caught HIV would not have suffered a significant amount of immune damage and should be no more vulnerable to HPV than average.
He quoted several other studies that found that high-risk HPV infection was associated with increased risk of HI infection (relative risk ranging from 1.7 to 3.5). Auvert also presented another study in a poster at the conference which showed that there was a 3.4-fold higher risk of HIV infection in female sex workers with high-risk HPV infection.
An audience member suggested that it might be worth funding a trial of one of the HPV vaccines as an HIV prevention measure and Auvert hinted that he was in talks with possible funders.
Auvert B et al. High risk HPV infection is associated with HIV acquisition among South African female sex workers. 5th IAS Conference on HIV Pathogenesis, Treatment and Prevention, Cape Town, abstract TUPEC073, 2009.