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Large Trial Finds Little Benefit in HPV Vaccine for Older HIV+ Adults
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Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston
Mark Mascolini
A 575-person placebo-controlled AIDS Clinical Trials Group (ACTG) study found that three doses of the quadrivalent human papillomavirus (HPV) vaccine did not protect HIV-positive adults older than 26 from anal HPV infection, though data did suggest protection against oral HPV [1]. The ACTG team says their findings "do not support HPV vaccination in older HIV-infected adults for prevention of anal HPV infection."
The quadrivalent HPV vaccine is safe and highly immunogenic in HIV-positive men and women and improves outcomes of treatment for anal high-grade squamous intraepithelial lesions (HSIL) [2]. US health authorities recommend HPV vaccination for all girls and boys starting at age 11 or 12 and for HIV-positive women and men and all men who have sex with men up to age 26 [3]. But older sexually active people acquire and carry HPV genotypes that put them at high risk for anal cancer, oral cancer, cervical cancer, and other cancers. Because there were no efficacy trials of HPV vaccination in older HIV populations who may be highly exposed to HPV, ACTG investigators conducted trial A5298, hypothesizing that the vaccine would prevent persistent anal infection with HPV types targeted by the vaccine in HIV-positive MSM and women.
Study participants had to be 27 or older and have no HPV-related cancers. Men had to practice receptive anal intercourse. ACTG investigators randomized them to three doses of the quadrivalent vaccine or placebo. The 472 men and 103 women enrolled had a median age of 47 (interquartile range 41 to 53), 46% were white, 31% black, and 20% Hispanic. Median CD4 count stood at 602, and 90% of participants had an HIV load below 200 copies. Most participants (60%) carried one or more of the four HPV types targeted by the vaccine in anal samples, as did 11% in oral samples.
After a median 2.6 years of follow-up, the trial Data and Safety Monitoring Board recommended stopping the study because results indicated the vaccine wasn't working. At that point no grade 3 or 4 adverse events related to the vaccine had developed. After 48 weeks there were 7 serious adverse events in the vaccine group and 22 in the placebo group.
As expected, the vaccine was highly immunogenic. For example, before vaccination 49.1% of participants in the vaccine group tested positive for HPV-16, the type most often linked to anal and cervical cancer, whereas 99.6% tested positive for HPV-16 at week 28, 4 weeks after the last dose. But this robust immune response did not translate into clinical benefit. Compared with the placebo group, the vaccine group did no better in rates of persistent anal HPV or anal HSIL. The ACTG team suggested that lack of protection against anal HPV probably reflected prior infection not detected by anal HPV DNA testing or serology.
One person in the vaccine group and 8 in the placebo group had persistent oral HPV infection during the trial, and the lower rate in the vaccine group reached statistical significance (hazard ratio 0.12, 95% confidence interval 0.02 to 0.98, P = 0.019). But when the researchers calculated oral HPV risk as persistent oral HPV or a single detection at the last visit, the vaccine group did no better than the placebo group.
The researchers concluded that their data "did not support routine vaccination of older HIV-positive adults for prevention of anal HPV infection or improving anal HSIL outcomes." They suggested that possible protection against oral HPV seen with the vaccine merits further study because there are no interventions to prevent HPV-related oropharyngeal cancer, which is a growing problem.
References
1. Wilkin TJ Chen H, Cespedes M, et al. ACTG A5298: A phase 3 trial of the quadrivalent HPV vaccine in older HIV+ adults. Conference on Retroviruses and Opportunistic Infections (CROI), February 22-25, 2016, Boston. Abstract 161.
2. Swedish KA, Factor SH, Goldstone SE. Prevention of recurrent high-grade anal neoplasia with quadrivalent human papillomavirus vaccination of men who have sex with men: a nonconcurrent cohort study. Clin Infect Dis. 2012;54:891-898. http://cid.oxfordjournals.org/content/54/7/891.long
3. Centers for Disease Control and Prevention. Human papillomavirus (HPV). Questions and answers. 2015. http://www.cdc.gov/hpv/parents/questions-answers.html
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