HPV vaccine shows promise for HIV-positive patients with AIN

A vaccine made from a fragment of the human papilloma virus (HPV) is safe for use in HIV-positive patients with high-grade anal intraepithelial neoplasia (AIN), according to the results of a clinical trial published in the 12^th May edition of AIDS. The study also provided preliminary evidence that the vaccine may be useful in treating the condition.

AIN is a pre-cancerous condition caused by infection of the cells in the anus being infected with ‘high risk’ forms of HPV, the virus that causes warts. AIN can progress to anal cancer if left untreated and is more common in gay men than in men in general. It is also common among HIV-positive men and women, and does not usually resolve after patients start taking antiretroviral therapy.

Currently available treatments for AIN include surgical removal, use of infra-red radiation and treatment with trichloroacetic acid. However, these are often not completely successful in treating the condition, particularly where it is widespread or found in many different places in or around the anus.

Investigators from the University of California, San Francisco, wished to assess the safety of a new vaccine in HIV-positive patients with high-grade AIN, following success with a similar vaccine in a group of HIV-negative patients. They used SGN-00101, which is also called HspE7, a vaccine made from the E7 protein of HPV type 16 fused to a protein from a bacterium.

Thirteen men and two women with high-grade AIN received three injections of the vaccine into the thigh at four-weekly intervals. Five patients each received 100, 500 and 1000µg with each injection. All of the patients were over 18 years old and were taking anti-HIV treatment, with CD4 cell counts above 200 cells/mm³ and viral loads below 500 copies/ml.

The injections were well tolerated, with no serious side-effects related to the vaccine. All of the participants experienced injection site reactions, although only one of these was severe. Patients given higher doses tended to have worse reactions.

The injections did not affect the patients’ HIV viral loads. Although they did cause the patient’s CD4 and CD8 cell counts to fall in the 24 weeks after the first injection, these changes were small and the vaccine did not alter the ratio of CD4 to CD8 T-cells.

Four patients showed a partial regression of AIN from grades two or three to grade one after 48 weeks: two of these received 100µg and two received 200µg injections.

One patient, who received injections containing 1000µg SGN-00101 showed complete regression of AIN from grade three. This patient, along with two of the partial responders, also showed a clearance of HPV in anal samples. In contrast, none of the ten patients who did not show regression of AIN had cleared HPV infection.

“This is the first reported study of a therapeutic vaccine directed against HPV antigens to treat high grade AIN in HIV-positive individuals,” write the investigators. “Our results show that the vaccine is safe and well tolerated in these individuals.”

The investigators point out that their study could not demonstrate whether the vaccine is effective in treating AIN, as it was too small and did not contain a control group. “However, [our data] support further studies of SGN-00101 to treat high grade AIN in HIV-positive individuals”, they write. “The one complete response was in the 1000µg cohort and we recommend that future studies be performed using this dose.”

Prevalence of HPV

In a second study published in the same edition of AIDS, doctors from Barcelona report on the prevalence of HPV infection in a cohort of 74 HIV-positive men from their clinic.

They found high levels of HPV infection in the anuses, penises and mouths of the men. HPV can lead to cancer in any of these areas of the body, but many of the men had no signs of disease despite being infected with the virus.

Overall, 78% of the men had anal HPV infection, with 43% having abnormal anal cells, including AIN. Alcohol use was the only factor linked to HPV infection in the anus, although having a viral load above 400 copies/ml and having had receptive anal sex more than five times was linked to anal abnormalities.

HPV infection in the penis was found in 36% of the men and in the mouths of 30%. Simultaneous infection in two or more sites of the body was found in 46% of the men.

The cohort included 40 gay, 12 bisexual and 22 heterosexual men, but there were no significant differences in the rates of infection between the gay or bisexual and the heterosexual men.

“Our findings support the need for a close follow up in all HIV / HPV co-infected patients in order to detect early cancer changes in the anus, penis and mouth,” the researchers write.

They claim that their discovery of HPV infection of the penis may be important in the spread of the virus: “The rate of high-risk penile HPV infection may account for the spread of the disease and forces all co-infected patients to use condoms, even for oral sex,” they write. However, further studies are needed to establish whether condom use reduces the transmission of HPV virus in men with HIV.