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  5th IAS Conference on HIV Pathogenesis, Treatment and Prevention
July 19th-22nd 2009
Capetown, South Africa
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Preliminary analyses suggest a higher rate of
HIV seroconversion among men who were HPV positive at baseline

  Preliminary analyses suggest a higher rate of HIV seroconversion among men who were HPV positive at baseline. Further analyses and additional studies are required to confirm whether HPV infection increases risk for HIV.
Risk of HIV acquisition among men with and without human papillomavirus infection in Kisumu, Kenya

Presented by Jennifer S. Smith (United States).
J.S. Smith1, S. Moses2, M. Hudgens1, C.B. Parker3, K. Agot4, I. Maclean2, J.O. Ndinya-Achola5, P.J.F. Snijders6, C.J.L.M. Meijer6, R.C. Bailey7
1University of North Carolina, Chapel Hill, United States, 2University of Manitoba, Winnipeg, Canada,3Research Triangle Institute, Research Triangle Park, United States, 4UNIM Project, Kisumu, Kenya,5University of Nairobi, Nairobi, Kenya, 6VU University Medical Center, Amsterdam, Netherlands, 7University of Illinois at Chicago, Chicago, United States
Background: Although several sexually transmitted infections (STIs) have been associated with an increased risk of HIV infection, there are few data concerning the potential effect of human papillomavirus (HPV) infection on HIV acquisition.
Methods: HIV-seronegative, sexually active 18-24 year-old men within a randomized trial of male circumcision provided penile exfoliated cell specimens from two anatomical sites (the shaft, and glans/coronal sulcus) at the baseline study visit. Specimens were tested with the GP5+/6+ PCR assay to detect a wide-range of HPV DNA types. HIV incidence [95% confidence interval (CI)] was calculated using Kaplan-Meier methods, and relative risk (RR) [95% CI] was estimated from proportional hazards models.
Results: Among 2,168 men with data on baseline HPV classified strictly as circumcised or uncircumcised over follow-up, 1,089 (50%) were HPV DNA positive at baseline. 754 (35%) were high-risk HPV positive and 335 (15%) were low-risk positive.
In 1,101 uncircumcised men, the 42-month HIV incidence was 9.5 [4.7, 14.1] in high-risk baseline HPV positive men vs 8.1 [2.9, 13.0] in low-risk HPV positive men vs 4.9 [2.3, 7.3] in HPV-negative men (p=0.15, log-rank test).
In 1,067 circumcised men, the 42-month HIV incidence was 3.0 [1.1, 4.8] in high-risk- vs 3.0 [0.0, 6.4] in low-risk- vs 2.1 [0.0, 4.5] in HPV-negative men (p=0.08, log-rank test).
The RR of HIV infection in men positive for any HPV type at baseline was 1.4 [0.8-2.5](p=0.25) in uncircumcised men; and 3.2 [1.0-9.6] (p=0.05) in circumcised men. Controlling for circumcision status, the RR of HIV infection in men positive for HPV was 1.7 [1.0, 2.9](p=0.04).
Conclusions: Preliminary analyses suggest a higher rate of HIV seroconversion among men who were HPV positive at baseline. Further analyses and additional studies are required to confirm whether HPV infection increases risk for HIV.

HPV in Men Linked to Increased HIV Risk
MedPage Today
Published: July 24, 2009
CAPE TOWN, South Africa, July 24 -- Men infected with human papillomavirus have an 80% increase in the risk of getting HIV, a researcher said here.
Action Points
* Explain to interested patients that many sexually transmitted diseases are known to increase the risk of getting HIV.
* Note that this study found that infection with human papillomavirus, responsible for cervical cancer in women, is associated with and increased risk of getting HIV in men.
* Note that this study was published as an abstract and presented orally at a conference. These data and conclusions should be considered to be preliminary until published in a peer-reviewed journal.
The finding comes from analysis of data collected during the landmark trial of male circumcision in Kisumu, Kenya, according to Jennifer Smith, PhD, of the University of North Carolina Chapel Hill.
That study showed that circumcision reduced the risk of getting HIV by more than 50%, Dr. Smith noted at the 2009 International AIDS Society conference.
But as part of the study, researchers also collected data regarding other sexually transmitted diseases, including human papillomavirus (HPV), she said in a late-breaker session in the final day of the conference.
"Many (sexually transmitted infections) have been previously found to be associated with increased risk of HIV infection," Dr. Smith said. "However, surprisingly few data are available currently on any potential effect of HPV on HIV acquisition risk."
To help fill the gap, she and colleagues studied participants in the Kisumu trial, looking at the 42-month risk of HIV seroconversion among men positive for HPV at the start of the study, compared with those who were not.
The study had data on HPV status for 2,168 men, including 1,089 who had the virus at baseline. Of those, 754 had high-risk strains of HPV (those that cause cancer in women) and 335 had low-risk strains.
Samples were taken from the penile shaft and foreskin, and from the glans and coronal sulcus, Dr. Smith said. The researchers controlled for the effect of circumcision, the main intervention in the study.
It turned that that only positive samples from the glans were associated with increased risk of HIV, she said.
For those men, the risk of getting HIV over the study period was 5.8%, compared with 3.7% for men whose glans samples were negative at baseline. The difference was significant at P=0.01.
The acquisition rates translated into a hazard ratio of 1.8 (95% CI 1.1 to 2.9), Dr. Smith said. (In contrast, the hazard ratio for positive samples collected from the shaft was 1.1, but the confidence interval crossed unity.)
The type of HPV isolated (high- or low-risk) was not associated with any difference in the chance of getting HIV.
Dr. Smith said more research is needed to explain the increase in risk. Possible explanations, she said, include residual confounding because of sexual behavior, or some sort of biological mechanism.
For instance, she said, the HPV virus might induce local cytokines, such as macrophage inflammatory protein-3 and interleukin-8, which play a role in susceptibility to HIV.
Or, the immunological process of clearing an HPV infection might bring increased numbers of CD4-positive T cells -- the targets of HIV -- to sites where they could be infected, she said.
The association "could be a marker for (risky) sexual behavior," said Timothy Farley, PhD, of the World Health Organization's reproductive health department, who chaired the session at which the research was presented.
Whatever the case, he said, it's interesting to theorize that the process of clearing the papillomavirus -- which can occur repeatedly -- may have immunological consequences that increase susceptibility to HIV.
"It's speculation as to what the mechanism might be, but it's an intriguing one," he said.
Whether a vaccine approach might affect the risk is also up in the air, he said, noting that current vaccines target the high-risk, cancer-causing strains of HPV, while Dr. Smith's study showed no difference in HIV risk based on the HPV strain involved.
Dr. Farley noted that another circumcision trial, conducted in South Africa, had also showed an increased HIV risk for men infected with HPV.