Infection with human papillomavirus (HPV) significantly increased the likelihood of HIV acquisition among men taking part in 2 African circumcision trials, according to presentations at the 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009) last month in Cape Town, South Africa.

By Liz Highleyman

A large body of research has linked the presence of several sexually transmitted disease (STDs), including genital herpes, to an increased risk of becoming infected with HIV. Few studies, however, have looked at the effect of HPV -- which causes genital warts and genital, anal, cervical, and oral cancers -- on HIV acquisition.

Two research teams presented data on the connection between HPV and HIV infection among men taking part in large trials of circumcision as a strategy for HIV prevention. In both studies, sexually active HIV negative men were randomly assigned to undergo circumcision immediately or after a waiting period; circumcision was associated with as much as a 60% reduction in the risk of becoming infected with HIV.

Kenyan Study

Jennifer Smith and colleagues performed an analysis of men aged 18-24 taking part in a circumcision trial in Kisumu, Kenya. The investigators examined cell specimens from the penis shaft and glans that were collected at the baseline study visit. The specimens were tested with a PCR assay to detect a range of high-risk (cancer-causing) and low-risk HPV DNA types.

Results

	Among 2168 men with available data, 50% were HPV DNA positive at baseline.
	35% were infected with high-risk HPV strain while 15% had low-risk strains.
	Men with detectable HPV in their penis glans specimens had a 5.8% risk of becoming infected with HIV during the study period, compared with 3.7% for men with HPV negative glans specimens, a statistically significant difference (P=0.01).
	After controlling for circumcision status, the adjusted hazard ratio for HPV positive glans specimens was 1.8, or nearly double the risk of HIV infection.
	The hazard ratio for HPV positive penis shaft samples was 1.1, but this did not reach statistical significance.
	The increased risk of HIV infection associated with HPV was similar in circumcised and uncircumcised men, and in those with high-risk and low-risk HPV strains.

University of North Carolina at Chapel Hill, Chapel Hill, NC; University of Manitoba, Winnipeg, Canada; Research Triangle Institute, Research Triangle Park, NC; UNIM Project, Kisumu, Kenya; University of Nairobi, Nairobi, Kenya; VU University Medical Center, Amsterdam, Netherlands; University of Illinois at Chicago, Chicago, IL.

South African Study

Bernard Auvert and colleagues looked at the effect of HPV infection on HIV acquisition in another circumcision trial, this one in Orange Farm, South Africa. At the end of the study (i.e., after circumcision), investigators collected urethral swab specimens from 1683 participants, which were tested for 13 high-risk and 24 low-risk types of HPV DNA.

Results

	17.5% of participants were infected with 1 or more low-risk HPV types, while 14.3% had 1 or more high-risk types.
	After adjusting for other factors, men with at least 1 type of HPV were 4.6 times more likely to become infected with HIV.
	The risk of HIV infection increased among men with multiple HPV types, reaching about 20% for those with 5 or more types.
	Further analysis revealed that the increased likelihood of HIV infection was attributable only to high-risk HPV strains, while low-risk types conferred no extra risk.

INSERM U687, Villejuif, France; University of Versailles, Versailles, France; NICD, Johannesburg, South Africa; Progressus, Johannesburg, South Africa.

Comment

As to the reasons why HPV increases HIV acquisition risk, Smith suggested that HPV infection might alter local cytokine (chemical messenger) levels or might bring more HIV-susceptible CD4 T-cells to the area.

Both Smith and Auvert noted that the presence of HPV infection could also be a marker for high-risk sexual behavior that increases the risk for HIV acquisition.

Taken together, these findings suggest that an intervention to reduce the rate of HPV -- for example, a vaccine such as Gardasil or Cervarix -- might have the added benefit of reducing new HIV infections.

8/11/09

References

JS Smith, S Moses, M Hudgens, and others. Risk of HIV acquisition among men with and without human papillomavirus infection in Kisumu, Kenya. 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract WELBC104.

B Auvert, P Lissouba, E Cutler, and others. Is genital human papillomavirus infection associated with HIV incidence? 5th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention (IAS 2009). July 19-22, 2009. Cape Town, South Africa. Abstract TUAC202.

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