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A Year of ART Does Not Ease Anal Cancer Harbingers in Men
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XVIII International AIDS Conference, July 18-23, 2010, Vienna
Mark Mascolini
Rates of anal squamous intraepithelial lesions (ASIL) and high-risk human papillomavirus (HPV) infection were high before antiretroviral therapy in 94 gay men and remained high after 1 year of successful antiretroviral therapy (ART) [1]. ASIL is a precursor of anal cancer, and the new diagnosis rate of HPV-associated anal cancer is high in gay men with and without HIV [2].
French investigators enrolled 94 HIV-infected men who had not started ART and tested anal samples for ASIL and HPV DNA before they began treatment. They retested study participants after 12 and 24 months of ART and presented 12-month findings at the conference.
Study participants had a median age of 39.7 years (interquartile range [IQR] 33.2 to 43.5). While 53% started a protease inhibitor regimen, 42% began treatment with a nonnucleoside. Median viral load stood at 4.8 log copies/mL (about 65,000 copies) before ART and dropped to 1.6 log (below 50 copies/mL) after 12 months of therapy. Median CD4 count rose from 299 (IQR 242 to 342) before treatment to 500 (IQR 411 to 575) after 12 months.
Despite these good virologic and immunologic responses to ART, the proportion of men with detectable ASIL rose from 54% before treatment to 58% after 12 months of therapy. The proportion with high-grade SIL climbed from 8% to 17%. Whereas 40% of men had high-risk HPV-16 before therapy, 34% had HPV-16 after 12 months. Median number of HPV genotypes stayed flat at 5 through 1 year of therapy, as did median number of high-risk HPV genotypes, at 3.
Among 29 men with normal anal cytology and/or histology before ART, 13 (44%) had ASIL at month 12. Among 41 men with ASIL before treatment, 20 (49%) had ASIL regression by month 12. Anti-HPV-specific T-cell responses were rarely detectable either before ART or after 12 months of therapy.
The investigators believe their findings suggest that 1 year of effective ART had (1) no effect on the incidence of anal HPV infection, (2) no effect on the incidence of ASIL, and (3) no effect in restoring anti-HPV T-cell responses. They proposed that the findings help explain reported increases in new diagnoses of invasive anal cancer among HIV-infected men in the current antiretroviral era.
The researchers argued that "HIV-positive men who have sex with men remain at risk of ASIL despite immune restoration" with ART--at least through the first year of treatment. They called for development of anal screening programs for HIV-infected people regardless of antiretroviral treatment status.
References
1. Piketty C, Si-Mohamed A, Lanoy E, et al. Lack of regression of anal squamous intraepithelial lesions and anal HPV infection despite immune restoration under cART. XVIII International AIDS Conference. July 18-23, 2010. Vienna. Abstract WEAB0103.
2. Park IU, Palefsky JM. Evaluation and management of anal intraepithelial neoplasia in HIV-negative and HIV-positive men who have sex with men. Curr Infect Dis Rep. 2010;12:126-133.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2860554/?tool=pubmed
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