The quadrivalent human
papillomavirus (HPV) vaccine worked as well for teens and young adults living with HIV
as it did for their HIV-negative counterparts, according to study findings
presented the 20th International AIDS Conference last week in Melbourne, Australia.
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 people living with HIV tend to harbour 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 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
living with HIV, especially those who are not on effective antiretroviral therapy
This prospective, open-label study included 46
HIV-positive young women and men (age 13-27 years) and 47 HIV-negative control participants (age 14-27). Participants had well-controlled HIV disease: they had
been on ART for at least 10 years, had two or more undetectable HIV viral load
measurements (<37 copies/ml) during the previous six months and had CD4
counts above 350 cells/mm3. Those with a history of prior HPV
vaccination or with anal or genital warts or other HPV-related lesions were
All participants received a standard regimen of three
doses of the Gardasil vaccine at
baseline and at 2 and 6 months later.
Blood samples were collected at enrolment and one
month after each vaccine dose, with follow-up continuing through 18 months. The researchers evaluated humoral
immunity as indicated by IgG antibody titres against HPV types 6, 8, 11 and 18.
Cell-mediated immunity was determined by T-cell patterns, immune activation and
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 stabilised by the end of follow-up at 18
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.
HIV-positive and -negative participants demonstrated 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 the 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 living with HIV reached a
higher percentage of activated CD4 cells.
Likewise, both HIV-positive and -negative
participants showed significant increases in HPV-specific CD4 cells producing
interleukin 2 and interferon-gamma, and HPV-specific CD8 cells producing
interferon-gamma and tumour necrosis factor-alfa. Levels
of the cytokines perforin and granzyme B also increased in both groups, again
with no significant differences.
were monitored for adverse events after each vaccine dose. 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 more likely than HIV-negative
people to report localised 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 summarised.
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."
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," they concluded.