AIDS 2012 Conference News: Quadrivalent HPV Vaccine Shows Strong Activity in HIV+ Women

A human papillomavirus (HPV) vaccine designed to protect against four high-risk HPV genotypes had strong activity in trials of young HIV-positive US women and young and middle-aged women in the United States, Brazil, and South Africa.

The quadrivalent vaccine and a bivalent vaccines are effective in preventing HPV infection in young women in the general population, but their activity in HIV-positive women was unknown until results of two studies presented at AIDS 2012. HIV-positive women and men run an increased risk of HPV infection and progression to HPV-related cancers, including invasive cervical cancer in women and anal cancer in men and women. A systematic review presented at AIDS 2012 determined that HPV infection doubles the risk of HIV acquisition in women and men.

The trial in young women involved 99 women from 16 to 23 years old in the Adolescent Medicine Trials Network (ATN). Women received the vaccine that protects against HPV types 6, 11, 16, and 18 on study day 1 and at weeks 8 and 24. Sixty-nine women had never taken antiretroviral therapy (ART) or had not taken ART in 6 month, while 30 women had taken ART for at least 6 months and had two viral loads below 400 copies/mL. ATN researchers compared vaccine responses in these women with responses in 276 HIV-negative women who received the same vaccine earlier in Brazil, Europe and the USA.

When comparing geometric mean antibody titers (GMTs) against the four HPV types in women on ART and the historical controls, the researchers found no significant differences. In women off ART, GMTs against HPV 16 and 18 were significantly lower than in historical controls but still relatively high. Seroconversion rates (defined as GMTs >20, 16, 20 and 24 mMu/mL against HPV-6, 11, 16 and 18) were 100% for all historical controls and all women on ART for all HPV types. Seroconversion rates for women off ART were 90% or higher for each HPV type. Side effects were mild and usually limited to injection sites.

The second HPV vaccine trial, ACTG A5240, enrolled 130 women with a CD4 count above 350 cells/mm3, 95 with 201 to 350 cells/mm3 and 94 with 200 cells/mm3 or fewer. The AIDS 2012 report involved women in the first two groups, 196 from the USA and 19 from Brazil or South Africa, who received the vaccine on the same schedule as in the just-described ATN trial.

Defining seroconversion as in the ATN trial, ACTG investigators recorded high seroconversion rates and GMTs in both study groups:

Women with CD4 count above 350 cells/mm3
• HPV-6: seroconversion rate 96%, GMT 425 mMu/mL
• HPV-11: seroconversion rate 97.6%, GMT 461 mMu/mL
• HPV-16: seroconversion rate 98.4%, GMT 1120 mMu/mL
• HPV-18: seroconversion rate 90.7%, GMT 164 mMu/mL

Women with CD4 count 201 to 350 cells/mm3
• HPV-6: seroconversion rate 100%, GMT 327 mMu/mL
• HPV-11: seroconversion rate 98.3%, GMT 388 mMu/mL
• HPV-16: seroconversion rate 98.2%, GMT 1077 mMu/mL
• HPV-18: seroconversion rate 84.3%, GMT 166 mMu/mL

No grade 3 or 4 adverse events were judged related to the HPV vaccine.

Most women in both trials were negative for HPV-6, 11, 16 or 18 when the studies began, and the GMT and seroconversion analyses involved only women negative for those types at baseline.

ATN investigators believe their results support vaccination of young HIV-positive women. The ACTG researchers think their data suggest that most HIV-positive women would benefit from HPV vaccination. The US Centers for Disease Control (CDC) recommends HPV vaccination for all teen girls and women through age 26 who did not get all three doses of the vaccine when they were younger.

Prior research in the general population found that the quadrivalent vaccine protects against most cervical cancers in women, and against cancers of the anus, vagina and vulva. These first two studies in HIV-positive women do not prove that the vaccine protects women with HIV from these cancers, only that the vaccine is active against four high-risk HPV types. But since the vaccine is recommended for all young women (and for all young HIV-positive men as well), the new findings strengthen that recommendation and show that the vaccine is generally safe in HIV-positive women.

Sources:
J. Kahn, J. Xu, B. Kapogiannis, et al. Immunogenicity of the HPV-6, -11, -16, -18 vaccine in HIV-positive young women. XIX International AIDS Conference. 22-27 July 2012. Abstract WEAB0202.

E.M. Kojic, M. Cespedes, T. Umbleja, et al. Safety and immunogenicity of the quadrivalent human papillomavirus vaccine in HIV-positive women. XIX International AIDS Conference. 22-27 July 2012. Abstract WEAB0203.

Houlihan CF, Larke NL, Watson-Jones D, et al. HPV infection and increased risk of HIV acquisition: a systematic review and meta-analysis. XIX International AIDS Conference. July 22-27, 2012, Washington, DC. Abstract WEPE258.

Centers for Disease Control and Prevention. HPV vaccines.

Click here for CDC advice on HPV vaccines

Written by Mark Mascolini on behalf of the International AIDS Society