Therapeutic Human Papillomavirus Vaccine Safe and Immunogenic in Men Who Have Sex with Men

By Liz Highleyman

Two vaccines were recently approved for the prevention of human papillomavirus (HPV) infection, which can lead to cervical, anal, and other similar cancers. However, these vaccines are only effective in people who have not yet been infected, and do not prevent progression to cancer in people who already have "high-risk" (cancer-causing) HPV types.

Cervical cancer is an AIDS-defining illness, and anal cancer is a growing concern in HIV positive men, despite the use of HAART. To address this issue, Australian researchers are developing a therapeutic vaccine designed to prevent the development of anogenital cancer in people who are already infected with HPV

As reported at the recent 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention in Sydney, Australia (July 22-25), the investigators tested the candidate HPV-16 E6E7 vaccine in a study of 35 HIV-positive men who have sex with men in Melbourne and Sydney.

Most of the men (94%) were on HAART, and they had a current CD4 count of 627 cells/mm3 and a nadir (lowest-ever) CD4 count of 154 cells/mm3. The researchers tested the vaccine in people with HIV to see if it would stimulate an immune response in people with moderate immunosuppression.

All of the men were infected with high-risk HPV types, including HPV-16 (59%), HPV-18 (32%), and 9 other types (17%-41%); many had more than 1 type. Pap smears showed that most (80%) had some degree of abnormal anal cells at baseline, including low-grade anal intraepithelial neoplasia (AIN) (31%) and high-grade AIN (14%).

Participants were randomly assigned to receive either the HPV-16 E6E7 vaccine plus an adjuvant known as Iscomatrix at doses of 25 mg, 70 mg, or 240 mg, or else placebo injections. Three groups received injections on days 0, 28, and 84, while a fourth group received injections on days 0, 14, and 70.

Results

• 33 of the participants (94%) completed the study.

• After 36 weeks of follow-up, the vaccine was generally well tolerated.

• Most recipients reported moderate-to-severe short-term injection site reactions, as well as systemic reactions including headache, myalgia, and fatigue.

• All participants maintained stable CD4 cell counts throughout the study.

• 5 participants had transient episodes of detectable viral load ("blips"), 3 of which returned below the limit of detection by the next test, and 2 of which occurred near the end of the study.

• 96% of vaccine recipients had at least a 4-fold increase in HPV-16 IgG antibodies from pre-vaccination levels.

• 71% had at least a 3-fold increase in interferon-gamma responses to the E6E7 peptides in the vaccine, but this did not appear to have a dose-response relationship.

• There were no clear trends with regard to HPV detectability or anal disease progression.

• 2 vaccine recipients cleared HPV-16 (compared with zero in the placebo arm), but 3 others newly acquired HPV-16.

• 4 of 6 participants who started with high-grade AIN experienced resolution, but others developed new high-grade AIN during follow-up.

Conclusion

"The novel therapeutic HPV-16 E6E7 Iscomatrix vaccine appears safe and reasonably well tolerated" in HIV-positive people, the investigators concluded. "Antibody and cell-mediated immune responses were strong despite previous severe immunosuppression."

Given the promising results from this study, the researchers plan to conduct further clinical trials.

Carlton Clinic, Carlton, Australia; Alfred Hospital, Melbourne, Australia; STI Research Centre, University of Sydney, Australia; CSL Ltd, Melbourne, Australia; Prahran Market Clinic, South Yarra, Australia

08/31/07

Reference
J Anderson, J Hoy, R Hillman, and others. A randomised, placebo-controlled, dose escalation study to determine the safety, tolerability and immunogenicity of an HPV therapeutic vaccine in HIV-positive participants with oncogenic HPV infection of the anus. 4th International AIDS Society Conference on HIV Pathogenesis, Treatment, and Prevention. Sydney, Australia, July 22-25, 2007. Abstract MOPEB089.