Improved immune function after treatment with highly active antiretroviral therapy (HAART) does not lead to the regression of pre-cancerous anal lesions in HIV-positive men, or to the clearance of human papilloma virus (HPV) infection, according to a French study published in the February edition of Sexually Transmitted Diseases. Investigators also found that neither infection with HPV nor the presence of pre-cancerous lesions was related to current or lowest-ever CD4 cell count. Numerous studies have now shown that HAART does not lead to an improvement in pre-cancerous anal lesions, or anal cancer.
Between summer 1999 and October 2000, 45 HIV-positive men who had taken at least six months of protease inhibitor-containing HAART were recruited to a cross-sectional study at the Hôpital Européen Georges Pompidou in Paris. Swabs were obtained for anal cytology and HPV testing, and then, within two months of the anal swabbing, investigators recorded the CD4 cell count and viral load for the individuals. Information on each individual’s nadir CD4 cell count prior to commencing HAART was also recorded.
Of the 45 anal cytology samples obtained, 32 (71%) were abnormal, including 22 cases of low-grade pre-cancerous lesions, anal intraepithelial neoplasia (AIN) and six cases of high-grade AIN. A further four individuals had abnormal anal cytology of undetermined severity.
A total of 36 men were infected with HPV (80%), with 22 of these men infected with an HPV type known to be associated with a high risk of cancer. In addition, the investigators established that infection with multiple types of HPV was common, affecting 20 men (56%).
The presence of pre-cancerous anal lesions was not significantly different in men who had a CD4 cell count above or below 250 cells/mm3 at enrolment (p=0.7). Furthermore, the investigators did not find any difference in the prevalence of pre-cancerous lesions when they stratified individuals according to their nadir CD4 cell count (above or below 150 cells/mm3, p=0.3) prior to starting HAART, or according to the magnitude of their CD4 cell increase after starting treatment with HAART (above or below 150 cells/mm3, p=0.3).
"No significant difference was observed between patients with and without anal HPV infection or between patients with or without abnormal cytology with regard to median CD4 cell count, median nadir of CD4 cell count, median increase in CD4 cell count, median viral load… and median duration of previous protease inhibitor regimen," write the investigators.
They add, “our data suggest that immune restoration under HAART is not associated with a decrease in the prevalence of anal HPV or [A]IN.” They conclude that the prevalence of HPV infection and AIN in HIV-positive gay men has remained unchanged since the introduction of HAART, and express concern that “if HAART exhibits no or little effect on the restoration of specific immunity against HPV, there would be more time for [AIN] to progress to cancer. This could in turn lead to an increase in anogential cancer among men and women receiving HAART, because they would be living longer.”
Further information on this website
Human papilloma virus - overview
Consistent condom use associated with regression of CIN and clearance of HPV in Dutch studies - news story
Anal cancer bad news for HIV-positive gay men even in HAART era, but incidence is rare - news story
Piketty C et al. High prevalence of anal squamous intraepithelial lesions in HIV-positive men despite use of highly active antiretroviral therapy. Sexually Transmitted Diseases 31: 96 – 99, 2004.