Two doses of the widely used HPV vaccine Gardasil9 produced an immune response identical to the standard three-dose regimen in women with well-controlled HIV, according to a study by Dr Deborah Konopnicki and colleagues published in the journal Clinical Infectious Diseases.
The World Health Organization (WHO) currently recommends a three-dose schedule for people living with HIV as opposed to two doses in the general population, due to concerns about potentially reduced immune responses. However, the study explored whether two doses might be sufficient for women with HIV who have stable immune function. Their results showed that antibody levels − commonly used as a proxy for vaccine efficacy − were effectively the same in the two- and three-dose groups against all nine types of the virus the vaccine protects against.
Human papillomavirus (HPV), like HIV, exists in multiple genotypes (genetically distinct variants). While some types cause disturbing yet less impactful conditions such as genital warts, others are oncogenic and can lead to cancer. Persistent infection with these types is linked to cervical, anal, penile, and throat cancers. Transmission typically occurs through sexual contact.
Although some people naturally clear HPV infections, the virus often evades immune detection. Relying solely on the immune system is risky, hence the importance of preventive vaccination.
The Gardasil9 vaccine has nine valencies – in other words it protects against nine of the high-risk strains of the virus. It provides excellent protection when applied at the appropriate age. Timing is important because the vaccine is preventive, meaning it needs to prepare the immune system to counter the virus before it has got the chance to enter the system. Vaccination is recommended as early as nine years of age in girls, to ensure that the person has built proper immunity to the virus before their first sexual contact.
One flaw in vaccination programmes is that more than half of countries fail to include boys. Men who have anal sex are also at risk of anal HPV infection and potential anal cancer when unvaccinated; 90% of anal cancers are attributed to HPV infection.
The study
At Saint-Pierre University Hospital in Brussels, the researchers recruited 167 women with HIV between 15 and 40 years of age, who were on HIV treatment and had maintained a viral load below 400 copies for the preceding 6 months. Of all recruited women, 100 were randomised either to the two-dose or three-dose group. Of the remaining 67, 22 received two doses and 45 received three. However, as these participants weren’t randomised, their data were only used to corroborate trends that were observed in the randomised trial.
The median age of the participants was 35 years and most were born in African countries. They had been on HIV treatment for nearly six years on average and their CD4 count stood at the healthy number of 649 cells. All women had a viral load below 400 copies, while 92% were undetectable. At the start of the study, about a third of women had a high-risk HPV type detected in their cervical swabs. Liquid cytology showed that 72% had normal cells, and there were no precancerous lesions in any of the 30 biopsies taken.
In both groups, over 90% of the participants completed their vaccination schedule. No participant had previously received HPV vaccination.
The levels of protective antibodies against each of the types of HPV the vaccine is supposed to protect against were measured at the start of the study, before the first vaccine, and a month after the last vaccine dose.
The main outcomes the researchers looked for were that the two-dose regimen would lead to the production of antibodies against all nine types of HPV in at least 80% of the participants and that the concentrations of these antibodies were high enough compared to the three-dose group. They also looked at the rate of side effects (mainly injection-site reactions) in both groups.
The vaccines were delivered in the beginning of the study and at six months for the two-dose group, with an additional one at two months for the three-dose group.
A high rate of immune response to vaccination in both groups
Prior to vaccination, only around 10% of the participants had some levels of protective antibodies against any of the nine HPV types, with the exception of type 6, to which 26% had antibodies.
Measured at the seventh month – a month past the last dose – 97.7% of the participants in the randomised two-dose group and 97.9% in the randomised three-dose group produced antibodies to all nine HPV types, which was statistically identical.
A robust increase in protective antibody concentrations in both groups
The levels of the protective antibodies in either group increased by 17 to 259 times depending on the type of HPV. The levels of the antibodies were comparable to those seen in previous studies of women without HIV, reflecting the overall good health of the participants’ immune function.
More side effects in the three-dose group
Overall, there weren’t any serious side effects, however injection-site reactions were present in both groups, but were more frequent and longer-lasting in the three-dose group. The participants who received all three doses also reported more fatigue.
Concluding thoughts
There is currently no treatment for HPV and vaccination is the most effective way to prevent infection by this virus and possible pre-cancerous conditions and cancers. However, vaccination remains suboptimal in most parts of the world. Despite significant progress in gender-neutral vaccination programmes in most Central and Western European countries and North America, many countries are still failing to reach proper vaccination levels even for girls who are most at risk.
People who decide to get the vaccine as an adult usually have to pay for it and the price may be challenging. A two-dose schedule offers meaningful financial and logistical relief. For example, when only two doses are given six months apart, they could match the standard twice yearly clinic visits many people with HIV have, therefore not burdening the person or the healthcare system with the logistics and cost of extra visits. Two doses would also potentially mean fewer side effects, or at least only having to put up with them twice.
While the study brings overall good news, what it cannot tell us is whether men would respond to the vaccine in the same way, since some studies suggest a slightly weaker immune response in men with HIV, even at three doses. There is a need for a well-designed study, similar to the one described here, to explore the effects of two doses of the nine-valent HPV vaccine in men.