 |
|
|
| |
Robust Response to Quadrivalent HPV Vaccine in Young HIV-Positive Women
|
| |
| |
XIX International AIDS Conference, July 22-27, 2012, Washington, DC
Mark Mascolini
Sixteen- to 23-year-old HIV-positive women had robust responses to a vaccine directed against human papillomavirus (HPV) genotypes 6, 11, 16, and 18, according to results of a US Adolescent Trials Network study [1]. Vaccine responses were greater in women taking combination antiretroviral therapy (ART) than in those naive to ART or off treatment for at least 6 months.
HPV, the most commonly sexually transmitted infection in the United States, can lead to cervical cancer, anal cancer, and other cancers [2]. Two vaccines, Cervarix and Gardasil, protect against most cervical cancers in women, and Gardasil protects against genital warts and cancers of the anus, vagina, and vulva. Cervarix is active against HPV types 16 and 18 and Gardasil against types 6, 11, 16, and 18. Two studies presented at the International AIDS Conference are the first to test the immunogenicity of Gardasil in HIV-positive women. (NATAP reports the other study separately.) People with HIV have a higher risk of HPV infection and progression of HPV-related malignancies.
A phase 2, open-label, 14-site trial mounted by the Adolescent Trials Network for HIV/AIDS Interventions (ATN) enrolled 16- to 23-year-old women behaviorally infected with HIV (after age 9). Of the 99 study participants, 69 (70%) had never taken antiretrovirals or had not taken ART for at least 6 months, and 30 had taken ART for at least 6 months and had two HIV loads below 400 copies. The trial excluded women with recent anogenital warts of a history of cervical intraepithelial neoplasia 2 or 3.
Study participants got three vaccine doses, one at baseline and one at weeks 8 and 24. ATN investigators tested enrollees for immunogenicity before the first dose, before and 4 weeks after the third dose, and 24 weeks after the third dose. They determined immunogenicity by (1) measuring geometric mean titers to HPV-6, 11, 16, and 18 four weeks after the third dose, and (2) at the same time measuring seroconversion rates for HPV-6, 11, 16, and 18 among participants seronegative and HPV DNA-negative for those types at baseline. A comparison control group included 276 healthy HIV-negative women from Brazil, Europe, and the United who received the same vaccine [3].
Study participants averaged 21 years in age, and 79% were non-Hispanic black. When these women got their first vaccine dose, 85% had a CD4 count at or above 350, while 40% had an HIV load below 400 copies. Whereas 56% of participants were seronegative and HPV DNA-negative for HPV-16, 74% were seronegative and HPV-DNA negative for HPV-18, 42% were double-negative for HPV-6, and 68% were double-negative for HPV-11.
When comparing women on ART with historical controls, researchers found no differences in average geometric mean titers for any of the HPV genotypes:
Average geometric mean titers with HIV and on ART versus without HIV:
-- HPV-6: 1139 versus 582
-- HPV-11: 1454 versus 697
-- HPV-16: 5037 versus 3892
-- HPV-18: 963 versus 801
When comparing HIV-positive women off ART with historical controls, researchers found two significant differences in average geometric mean titers for any of the HPV genotypes:
Average geometric mean titers with HIV and off ART versus without HIV:
-- HPV-6: 547 versus 582
-- HPV-11: 665 versus 697
-- HPV-16: 2176 versus 3892 (P = 0.0003)
-- HPV-18: 445 versus 801 (P = 0.0002)
Seroconversion rates were 100% for all controls and all antiretroviral-treated women for all four HPV types. Seroconversion rates for untreated HIV-positive women were 96.3% for HPV-6 (not significant versus controls), 95.5% for HPV-11 (P = 0.03 versus controls), 94.6% for HPV-16 (P = 0.03 versus controls), and 90.0% for HPV-18 (P = 0.0002 versus controls).
Seroconversion rates for HPV-18 at 48 weeks dropped to 73.9% in HIV-positive untreated women and to 87.5% in HIV-positive treated women.
One quarter of women (26.3%) reported local pain (highest grade 2), and 2% reported induration at the injection site (highest grade 2). No grade 3 or 4 adverse events were possibly, probably, or definitely attributed to the vaccine. No concerning changes in CD4 count or HIV load emerged.
"Among HIV-infected young women who were HPV DNA and HPV seronegative at the time of vaccination," the ATN researchers concluded, "HPV type-specific immune responses to vaccination were generally robust." This study does not establish whether the quadrivalent vaccine protects HIV-positive women from genital warts, cervical cancer, or other cancers.
The researchers believe the findings support recommendations (1) to vaccinate young HIV-positive women and (2) to target vaccination to 11- and 12-year-olds, who are less likely to have acquired HIV behaviorally.
The CDC recommends HPV vaccination for (1) all teen girls and women through age 26 who did not get all three doses of the vaccine when they were younger, (2) all teen boys and men through age 21 who did not get all three doses of the vaccine when they were younger, and (3) any man who has sex with men and men with compromised immune systems (including HIV-positive men) through age 26 if they did not get fully vaccinated when they were younger [4].
References
1. Kahn J, Xu J, Kapogiannis B, et al. Immunogenicity of the HPV-6, -11, -16, -18 vaccine in HIV-positive young women. XIX International AIDS Conference. July 22-27, 2012. Abstract WEAB0202.
2. Centers for Disease Control and Prevention. Human papillomavirus (HPV). http://www.cdc.gov/hpv/.
3. Villa LL, Costa RL, Petta CA, et al. High sustained efficacy of a prophylactic quadrivalent human papillomavirus types 6/11/16/18 L1 virus-like particle vaccine through 5 years of follow-up. Br J Cancer. 2006;95:1459-1466.
4. Centers for Disease Control and Prevention. HPV vaccines. http://www.cdc.gov/hpv/vaccine.html.
|
| |
|
|
|
|
|
