Human papillomavirus infection in the oral cavity of HIV patients is not reduced by initiating antiretroviral therapy

Abstract

Objective:The incidence of human papillomavirus (HPV)-related oral malignancies is increasing among HIV-infected populations, and the prevalence of oral warts has reportedly increased among HIV patients receiving antiretroviral therapy (ART). We explored whether ART initiation among treatment-naive HIV-positive adults is followed by a change in oral HPV infection or the occurrence of oral warts.Design:Prospective, observational study.Methods:HIV-1 infected, ART-naive adults initiating ART in a clinical trial were enrolled. End points included detection of HPV DNA in throat-washes, changes in CD4+ T-cell count and HIV RNA, and oral wart diagnosis.Results:Among 388 participants, 18% had at least one HPV genotype present before initiating ART, and 24% had at least one genotype present after 12–24 weeks of ART. Among those with undetectable oral HPV DNA before ART, median change in CD4+ count from study entry to 4 weeks after ART initiation was larger for those with detectable HPV DNA during follow-up than those without (P = 0.003). Both prevalence and incidence of oral warts were low (3% of participants having oral warts at study entry; 2.5% acquiring oral warts during 48 weeks of follow-up).Conclusion:These results suggest: effective immune control of HPV in the oral cavity of HIV-infected patients is not reconstituted by 24 weeks of ART; whereas ART initiation was not followed by an increase in oral warts, we observed an increase in oral HPV DNA detection after 12–24 weeks. The prevalence of HPV-associated oral malignancies may continue to increase in the modern ART era.

Oral Human Papillomavirus in Youth From the Pediatric HIV/AIDS Cohort Study

“…Despite our low rate of detection, we did find associations with low CD4 count and high VL similar to that reported in adults [2, 3, 5]. In a recent study of 388 treatment-naïve HIV-infected adults, men showed a higher rate of oral HPV than women (20% vs 11%, respectively, p=0.06) however, no difference was seen with respect to oral shedding of oncogenic HPV subgenotypes (4% and 5%, respectively) similar to our findings [14]. Another possible reason we observed low rates of HPV is that these sexually active HIV-infected youth entered puberty on ART with relatively well controlled HIV infection.…”

Modeling the Mechanisms by Which HIV-Associated Immunosuppression Influences HPV Persistence at the Oral Mucosa

“…A recent clinical trial has investigated the effect of HIV in HPV infection in the presence and absence of combination antiretroviral therapy [41]. The levels of oral HPV DNA in the co-infected patients, which was monitored for 24 weeks after the start of cART, remained elevated throughout therapy.…”

“…Equilibrium values for HIV RNA per ml and HIV-specific uninfected CD4+ T cells per ml were reported in an HIV/HPV co-infection study to be = 4.8x10 4 virions per ml and = 3.3x10 5 cells per ml [41]. Since the patient is in a chronic HIV steady state, we derive , β and s from steady state conditions , and , to be = 2.4x10 3 cells per ml, β = 1.5x10 -7 ml per cells per day and s = 5.6x10 3 cells per ml per day.…”

The Oral HIV/AIDS Research Alliance Program: lessons learned and future directions

“…A5264 was a comparison of ART alone • To evaluate the effect of ART initiation on oral HPV shedding and occurrence of oral warts • To evaluate the association between the development of oral warts and (i) CD4+ T cell count changes; and (ii) plasma HIV-RNA load at 4-week, 16-week, and 24-week follow-ups after ART initiation Study completed. (Shiboski et al, 2015b; CROI and manuscript submitted) a AMC052 is a protocol of the AIDS Malignancy Consortium that is conducted in collaboration with the ACTG.…”

“…Among the protocols that focused on HPV, protocol A5272 sought to explore whether ART initiation among treatment-na€ ıve HIV-positive adults was followed by an increase in oral wart incidence or a decrease in oral HPV shedding (Shiboski et al, 2015b). The rationale for this work was that previous studies have suggested an increase in the incidence of oral warts following antiretroviral therapy (ART) initiation.…”