CTN 236: HPV vaccine in HIV positive girls and women

About the Study

The purpose of this study is to investigate the safety and immunogenicity of the human papillomavirus (HPV) vaccine in girls and women age 9 years and older who are infected with HIV. Immunogenicity refers to the ability of a treatment to stimulate different immune system responses needed to fight a virus. Specifically, this research is looking at a vaccine that protects against four strains of HPV, known as a quadrivalent vaccine (Gardasil). Through this study, researchers have attempted to determine the antibody responses to the four types of HPV covered by the vaccine, the rate of adverse events in girls and women after receiving Gardasil, and secondarily, the efficacy of the vaccine in preventing HPV-associated cervical cancer and genital warts in women living with HIV. The initial phase of this research included eight planned visits, beginning with three vaccination visits where an injection containing .5 ml of the vaccine was administered to participants. Participants were followed for approximately 24 months after the first dose of vaccine. A secondary follow-up study is underway to examine the long-term response to the HPV vaccine over an additional 3-year period.

About The Disease

HPV is common and has about 30 different types that infect the genital area. HPV is the leading cause of cervical cancer and genital warts, although only a small number of people infected with HPV will go on to develop cervical cancer or genital warts. HPV is spread through close skin and/or sexual contact. HIV-positive women are known to have higher rates of HPV and more rapid progression to cervical cancer, which is believed to be caused by a decrease in immune function. In addition, HIV-positive women with HPV can suffer from severe cases of genital warts that are very difficult to treat.

Study Approach

The qHPV vaccine protects against new infections of four types of HPV: two of these types are associated with genital warts while the other two are the high-risk, cancer-causing HPV types. Previous studies of qHPV have shown effective protection against these types of HPV in HIV-negative girls and women who were not previously exposed to the four types of HPV that the vaccine protects against. When CNT 236 began, no previous studies had evaluated the safety and efficacy of qHPV in HIV-positive people. Researchers are seeking to determine whether girls and women with HIV can be protected from some or all of the types of HPV that the vaccine protects against. The initial phase of CTN 236 is no longer enrolling. Currently, the secondary phase of CTN 236 is enrolling women that participated in the initial study. This long-term follow-up study will assess the ability of the Gardasil vaccine to maintain a protective immune response to four HPV strains in HIV-positive girls and women over an additional 3 years (3 study visits).

Results

Results from the initial phase of the study showed that women living with HIV had a comparable immune response to the qHPV vaccine compared to published data on HIV-negative women. The study highlighted the impact of HIV viral load on HPV vaccine immune response. Dr. Money and her team found that women with a fully suppressed HIV viral load had a better immune response compared to women without a fully suppressed viral load. The study also showed that this vaccine may be beneficial to older women living with HIV, who are above the typical age range for vaccination.

A second publication analyzing data of girls aged 9–13 living with HIV in the same cohort showed that their immune response to the vaccine was lower compared with their HIV-negative peers. In both girls and women, virologic suppression of HIV predicted a stronger vaccine immune response.

A follow-up paper published in the summer of 2018 demonstrated the vaccine’s efficacy over a two-year period. The publication showed that the rate of HPV infection was greatly diminished compared with rates seen in unvaccinated women living with HIV.

The research team then investigated how the qHPV vaccine dose schedule could impact the immune response among girls and women living with HIV, as an efficient dose schedule could benefit the accessibility and feasibility of HPV vaccination worldwide. Their research found that differential qHPV vaccine dose spacing did not significantly impact immune response.

Looking at pre-vaccination testing data, the researchers found that the participants in the study had a wide range of potentially cancer-causing HPV types, highlighting the importance of cervical cancer screening in these women and girls. Data collected post-vaccination showed that some of the women and girls in the study continued to have HPV infections with virus types not covered by available vaccines, showing the importance of continued screening after vaccination.

Most recently, the researchers studied whether the vaginal microbiome or infection with herpes simplex virus-2 (HSV-2) were associated with HPV-related outcomes, including incidence and persistence. They found that there may be a weak association between the vaginal microbiome (specific microbial species, including Gardnerella, Porphyromonas, and Prevotella) and HPV infection. In addition, while it was determined that HSV-2 infection was common among women living with HIV, it was not associated with HPV-related outcomes. However, anti-HSV medications (a marker of active HSV) were associated with more HPV types being detected and an increased risk of pre-cancerous lesions.

Additional Information

If you would like more information on this clinical study, please refer to a participating site or the national project manager:

Nancy Lipsky
nlipsky@cw.bc.ca
604-875-2424 Ext. 4877