Human papillomavirus (HPV) is a common sexually transmitted germ. Many different strains of HPV exist and can cause different complications such as ano-genital warts and anal, cervical and vulvar cancer, as well as cancers of the throat and tongue.
There are three licensed HPV vaccines as follows:
- Cervarix -- provides protection against HPV 16 and 18 (these can cause anal and cervical cancer)
- Gardasil -- provides protection against HPV 6 and 11 (these can cause ano-genital warts) as well as HPV 16 and 18
- Gardasil 9 (the newest vaccine) -- provides protection against a broad range of HPV including 6, 11, 16, 18, 31, 33, 45, 52 and 58
In tests with HIV-negative men and women all of these vaccines are effective. However, there are less data on their safety and effectiveness in HIV-positive women.
A team of researchers across Canada in collaboration with the CIHR HIV Clinical Trials Network has reported results from a clinical trial of Gardasil in 310 HIV-positive women. The researchers found that the vaccine was safe. Furthermore, women whose HIV viral load was undetectable when they received the first of three injections of Gardasil produced significantly more antibodies to HPV than women whose HIV viral load was not undetectable.
The study researchers encourage doctors and nurses to consider timing the use of Gardasil once their patients' HIV viral loads have become undetectable to "optimize" the response to this vaccine.
Researchers enrolled participants between 2008 and 2012.
The average profile of the 310 women upon entering the study was as follows:
- age -- 38 years
- major ethno-racial groups: black -- 44%; white -- 36%; Indigenous -- 13%
- duration of HIV diagnosis -- eight years
- CD4+ cell count -- 510 cells/mm3
- proportion with a viral load less than 50 copies/mL -- 72%
At the start of the study, participants received an injection of one dose of Gardasil into muscle. Subsequent doses were given two and six months later.
Note that Gardasil is not a live vaccine, it is made from proteins taken from HPV; it cannot cause HPV infection.
What Happened to Participants?
As with all clinical trials, some participants move, lose interest or stop making visits to their study clinic. In total, 310 participants received at least one dose of Gardasil. A smaller group, 277 (89%) participants, received all three doses of the vaccine. Of these, 272 were negative for HPV antibodies and its genetic material at the start of the study for at least one of the HPV strains that were targeted by the vaccine. This indicates that they were not likely infected with those strains of HPV.
After the seventh month of the study, the proportion of women with antibodies against HPV proteins found in Gardasil was more than 90% and in some cases as high as 98% (depending on the protein that represented HPV strains). The proportions of women with antibodies against specific HPV strains were distributed as follows:
- HPV 6 -- 93% of women had antibodies
- HPV 11 -- 94% of women had antibodies
- HPV 16 -- 98% of women had antibodies
- HPV 18 -- 67% of women had antibodies
Researchers found that, in general, HIV-positive women had significantly greater levels of antibodies to HPV compared to data collected in previous trials with HIV-negative women. The exception was levels of antibodies to HPV 18, which was lower in HIV-positive women than in HIV-negative women in previous trials.
Also, the study team found that HIV-positive women whose HIV viral load was suppressed at the time they were vaccinated subsequently had the best response to Gardasil. This link between a suppressed HIV viral load and response to Gardasil was independent of participants' CD4+ cell counts.
Nurses observed participants for 30 minutes after each vaccination for any side effects that might have immediately occurred. Furthermore, participants were telephoned 48 hours after each vaccination to discuss any potential side effects that might have occurred.
A total of 36% of participants reported one or more vaccine-related side effects, most commonly distributed as follows:
- pain at the injection site -- 30%
- redness at the injection site -- 6%
- swelling at the injection site -- 6%
Side effects affecting other parts of the body were as follows:
- 20% of participants had headache, fever and fatigue that were clearly linked to having received the vaccine
Note that all side effects were temporary and resolved without any serious consequences.
Two women died during the study: One death was caused by a drug overdose 129 days after her third vaccination; the other death occurred 22 days after her third vaccination and was caused by the AIDS-related illness PML (progressive multifocal leukoencephalopathy). Investigation found that the HPV vaccine was not associated with these deaths.
A total of 41 women had 44 pregnancies during the four-year study. The results of these pregnancies were as follows:
- 23 were live births
- 16 were terminated
- 4 were miscarriages
- in one case researchers did not know the outcome
The vaccine was not linked to any adverse effect on the course of pregnancy or birth defects.
The present Canadian study found that Gardasil is safe and effective at producing relatively high levels of antibodies against HPV strains 6, 11, 16 and 18 in HIV-positive women.
Women who had an undetectable HIV viral load when they received their first vaccination of Gardasil subsequently had significantly greater levels of antibodies to HPV compared to women who did not have an undetectable HIV viral load. This finding caused the study team to encourage doctors and nurses to help their HIV-positive patients achieve an undetectable viral load status before initiating HPV vaccination.
HPV, cervical dysplasia and cervical cancer -- CATIE fact sheet
Money DM, Moses E, Blitz S, et al. HIV viral suppression results in higher antibody responses in HIV-positive women vaccinated with the quadrivalent human papillomavirus vaccine. Vaccine. 2016 Sep 14;34(40):4799-806.