- Category: HPV Vaccines
- Published on Tuesday, 29 July 2014 00:00
- Written by Liz Highleyman
The quadrivalent human papillomavirus (HPV) vaccine worked as well for teens and young adults with HIV as it did for their HIV negative counterparts, according to study findings presented the 20thInternational AIDS Conference last week in Melbourne.
Human papillomavirus is a common sexually transmitted infection that causes abnormal cell growth. High-risk strains, including type 16 and 18, can cause cervical and anal cancer. People typically become infected with HPV shortly after they become sexually active, regardless of HIV status. But HIV positive people tend to harbor more HPV types, are less likely to spontaneously clear HPV, and may experience faster disease progression from dysplasia (abnormal cell changes) to cancer.
An effective quadrivalent vaccine (Gardasil) protects against infection with HPV types 6, 11, 16, and 18; a bivalent vaccine (Cervarix) is effective only against HPV 16 and 18. Studies have shown that the quadrivalent vaccine prevents genital and anal lesions that could progress to cancer. In many countries, HPV vaccination is recommended for girls and boys from pre-adolescence through young adults in their mid-twenties. Beyond that age, most people will already be infected with HPV, but the vaccine may still be beneficial for those who do not carry all the covered types.
Veronica Rainone of the University of Milan and colleagues evaluated the safety and efficacy of a quadrivalent HPV vaccine for HIV positive young people who did not have evidence of infection with the covered HPV types at study entry.
The researchers looked at both humoral immunity, or antibody production, and HPV-specific cell-mediated immune responses carried out by CD4 T-cells and other immune cells. The latter type of immunity may be compromised in people with HIV, especially those who are not on effective antiretroviral therapy (ART).
This prospective, open-label study included 46 HIV positive young women and men (age 13-27 years) and 47 HIV negative control subjects (age 14-27). Participants had well-controlled HIV disease: they had been on ART for at least 10 years, had 2 or more undetectable HIV viral load measurements (<37 copies/mL) during the previous 6 months, and had CD4 counts above 350 cells/mm3. Those with a history of prior HPV vaccination or who had anal or genital warts or other HPV-related lesions were excluded.
All participants received a standard regimen of 3 doses of the Gardasil vaccine at baseline and at 2 and 6 months later.
Blood samples were collected at enrollment and 1 month after each vaccine dose, with follow-up continuing through 18 months. The researchers evaluated humoral immunity as indicated by IgG antibody titers against HPV types 6, 8, 11, and 18. Cell-mediated immunity was determined by T-cell patterns, immune activation, and cytokines production. Participants were monitored for adverse events after each vaccine dose.
- Overall, participants demonstrated good antibody responses.
- Anti-HPV IgG levels rose in both HIV positive and HIV negative participants by month 3, peaked at month 7, decreased somewhat by month 12, and stabilized by the end of follow-up at 18 months.
- HIV positive participants responded a bit more slowly on average, with 45% showing protective antibody levels by month 1, compared with 57% of HIV negative participants; however, everyone in both groups had adequate antibody protection by month 7.
- Antibody levels were slightly lower in the HIV positive group, but the difference was not statistically significant.
- Both HIV positive and negative participantsdemonstrated strong HPV-specific cell-mediated immunity.
- Both groups showed expansion of naive and central memory T-cells, with subsequent differentiation into effector memory cells, with no significant differences between groups.
- T-cell activation markers on CD4 and CD8 cells increased significantly by month 3 and month 7 in both HIV positive and negative participants, though people with HIV reached a higher percentage of activated CD4 cells.
- Likewise, both groups showed significant increases in HPV-specific CD4 cells producing interleukin 2 and interferon-gamma, and HPV-specific CD8 cells producing interferon-gamma and tumor necrosis factor-alfa.
- Levels of the cytokines perforin and granzyme B also increased in both groups, again with no significant differences.
- The most common side effects were injection site reactions and mild systemic reactions; no severe or life-threatening adverse events were reported.
- HIV positive participants were somewhat more likely than negative people to report localized pain (33% vs 19%), headaches (14% vs 2%), and malaise (7% vs 1%).
- HIV positive participants experienced a slight increase in CD4 percentage and most maintained undetectable HIV viral load.
The standard three-dose quadrivalent HPV vaccination regimen "generated antibody responses against HPV vaccine types that lasted for at least 18 months among HIV-infected adolescents and young adults and age- and sex-matched HIV-uninfected individuals," the researchers summarized
In addition, vaccination "induced functional activation of the T-cell compartment and primed a robust cell-mediated immunity characterized by Th1-type cytokines and cytotoxic CD8+ T-cell responses up to 7 months after the first vaccine dose," they added. "No adverse effects on markers of HIV-associated loss of immune competence were reported during the study period."
Vaccine-induced cell-mediated immunity did not differ significantly between HIV positive and negative participants, suggesting that "this arm of the immune system is not impaired in HIV-infected adolescents and young adults, thus supporting current recommendations to vaccinate HIV-infected individuals," the investigators concluded.
V Rainone, D Trabattoni, F Penagini, et al. Efficacy of HPV vaccination in HIV+ adolescents and young adults for the induction of strong HPV-specific humoral and cell-mediated immune responses. 20th International AIDS Conference. Melbourne, Australia, July 20-25, 2014. Abstract WEAB0101.