Oral HPV Rate Rises in First 12 to 24 Weeks of Antiretroviral Therapy

Detection of oral human papillomavirus (HPV) rose during the first 12 to 24 weeks of antiretroviral therapy (ART) in a prospective observational study of 388 people starting their first ART regimen. Rates of HPV-related oral warts did not rise or fall substantially during the first 48 weeks of ART, according to the study.

Up to half of people with HIV have detectable oral HPV DNA, a prevalence higher than in HIV-negative individuals. Compared with HIV-negative men who have sex with men (MSM), HIV-positive MSM have higher prevalence and incidence of oral HPV DNA and oncogenic HPV genotypes.

To determine whether oropharyngeal HPV persists after people with HIV start ART, AIDS Clinical Trials Group (ACTG) investigators conducted this prospective analysis of antiretroviral-naive adults starting therapy in a controlled clinical trial. Participants gave throat-wash specimens before entering the study, at entry, between weeks 12 and 18 and at week 24. They underwent oral soft tissue exams at entry and at weeks 12-18, 24 and 48. Researchers used real-time PCR to detect HPV in throat-wash samples and probed specifically for high-risk genotypes 6, 11, 16 and 18.

The analysis involved 388 HIV-positive adults recruited in 2010-2012, all of whom had throat-wash HPV DNA results before entry, at entry and at two points after starting ART. Median age at study entry was 38 years, 81% of participants were men, 39% black, 36% white and 22% Hispanic. Almost one-third of enrollees (31%) had one oral sex partner in the six months before ART, and 43% had two or more oral sex partners in that time. In the 24 weeks after starting ART, 33% had one oral sex partner and 26% had two or more oral sex partners.

Median CD4 count rose from 328 cells/mm3 at study entry to 402 cells/mm3 at week four, to 447 cells/mm3 at weeks 12-18 and to 483 cells/mm3 at week 24. From study entry to week 24, median viral load fell from 4.68 log10 copies/mL to <1.60 log10 copies/mL (about 48,000 copies/mL to <40 copies/mL).

HPV DNA detectable in throat washes rose after ART began. Whereas 70 participants (18%) had detectable HPV DNA before ART, 93 participants (24%) did at ART weeks 12-18 or 24. These proportions did not differ substantially between men and women.

Among people without detectable oral HPV DNA before ART, 15% had an HPV-positive specimen at ART weeks 12-18 or 24. At those on-ART follow-up points, 20% of participants had a new HPV genotype not detected before ART. Among 68 people with typeable HPV DNA before ART, 46 cleared one or more HPV genotypes and 15 maintained at least one HPV genotype during ART. Six of 20 genotypes detected were high-risk oncogenic genotypes, including HPV-16, the third more prevalent genotype, found in 14%.

Prevalence of any oncogenic HPV genotype was 5% before ART and 5% after 12-24 weeks of ART. Among people with an oncogenic genotype before ART, 58% cleared that genotype after 12 to 24 weeks of therapy, while 42% kept that genotype or acquired another oncogenic genotype.

Change in plasma HIV RNA through week 24 was not associated with change in detectable oral HPV DNA during ART. Among people with undetectable oral HPV DNA before ART, median CD4 gain proved significantly greater through week four in those with detectable HPV DNA during follow-up.

Before ART began, 3% of study participants had oral warts. After 48 weeks of ART, oral warts developed in 2.5% of study participants without pre-ART warts.

The ACTG investigators believe their findings suggest two major conclusions: (1) ART for 24 weeks does not reconstitute immune control of HPV in the oral cavity. (2) Although oral warts did not increase after ART began, HPV DNA detection increased after 12 to 24 weeks of ART. The researchers propose that "the prevalence of HPV-associated oral malignancies may continue to increase in the modern ART era."