HIV-positive young women have adequate response to human papillomavirus vaccine

Published: 16 October 2013

HIV-positive girls did not respond as well to the quadrivalent human papillomavirus (HPV) vaccine as HIV-negative girls of the same age, but they responded as well as HIV-negative older women, probably giving them sufficient protection from infection, according to a late-breaker presentation at the IDWeek 2013 conference recently held in San Francisco.

Human papillomavirus can trigger abnormal cell proliferation and cause warts, tissue abnormalities (dysplasia or neoplasia) and malignancies including cervical and anal cancer.

Two effective HPV vaccines are available. The bivalent Cervarix vaccine protects against cancer-causing HPV types 16 and 18. The quadrivalent Gardasil vaccine protects against 16 and 18 as well as wart-causing types 6 and 11. HPV vaccines are recommended for girls and boys aged nine through to their mid-twenties. Most people become infected with HPV soon after they become sexually active, so vaccination is recommended by adolescence.

People with HIV who have substantial immune system damage may not produce as many antibodies in response to vaccination, but this has not been extensively studied in relation to HPV. It is an important issue because HIV-positive women and men have higher rates of HPV infection, dysplasia and cervical and anal cancer. 

Deborah Money from the University of British Columbia conducted a study to test the efficacy of a HPV virus-like particle quadrivalent vaccine in HIV-positive girls and women.

Among HIV-negative people, HPV vaccination is most effective for adolescents aged 9 to 13 and more than 99% of females and males achieve adequate antibodies after the standard three doses, the researchers noted as background.

This open-label multicentre study included 407 HIV-positive female adolescents enrolled at eleven sites in Canada between November 2008 and December 2012. Almost all were exposed to HIV through mother-to-child transmission. Most participants were in the 9 to 13 age group (mean 11 years) but 27 were younger; a majority had not yet started menstruation. Most (70%) were African-Canadian, 4% were white and 26% were 'other'.

Two-thirds of participants had undetectable HIV viral load at baseline. The mean baseline CD4 cell count was 710 cells/mm3 and the nadir (lowest-ever) level was 470 cells/mm3, indicating well-preserved immune function. All but one tested negative for the four HPV types in the vaccine (6, 11, 16 and 18) at baseline.

An HIV-negative comparison group included 825 girls and women ages 9 to 13 or 16 to 26 in another study comparing two versus three doses of the vaccine. In that study most participants (80%) were white and 18% were Asian. 

The HIV-positive girls received three vaccine doses, one at study entry with boosters at two and six months later; follow-up continued for two years.

All HIV-positive girls in the study completed the full vaccine schedule and all experienced seroconversion, or production of antibodies against all HPV types in the vaccine. The overall response rate for the entire cohort was 99%. 

Girls with HIV viral suppression achieved two- to three-fold higher antibody titres than those with unsuppressed HIV, but there were few girls in the latter group and differences did not reach statistical significance. There were no differences in response according to baseline or nadir CD4 count.

The HIV-positive girls had significantly lower geometric mean antibody titres (GMT) than HIV-negative girls aged 9 to 13 in the comparison study for all four HPV types in the vaccine at months 7 and 24. Looking at the older HIV-negative women (ages 16 to 26), however, antibody levels were similar and difference were not significant for any HPV type.

The quadrivalent vaccine was safe and well tolerated by HIV-positive girls. No serious adverse events considered related to the vaccine were reported. 

In this study there was a "high rate of seroconversion seen in HIV-positive girls given the quadrivalent HPV vaccine by standard dosing", the researchers concluded. "Lower peak GMT was observed in these HIV-positive girls compared to HIV-negative girls."

However, they continued, "levels of response were comparable to levels seen in older women for whom data is available[, suggesting] that these levels confer efficacy against HPV infection and disease".

They cautioned that "until an immune correlate of protection is defined in HIV-negative and HIV-positive persons, understanding of the meaning of antibody levels remains limited", and "the role of booster dosing remains to be evaluated".

Although this study looked only at HIV-positive girls, the trend in HPV vaccine research over the past several years has been that similar results are seen in boys and men.

Reference

Money D et al. Lower Immunogenicity of HPV Vaccine in HIV-infected Girls aged 9-13 Years. IDWeek 2013, San Francisco, abstract LB-5, 2013. View the abstract on the IDWeek conference website.

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