Lack of response of anal intra-epithelial neoplasia to highly active antiretroviral therapy

Anal human papillomavirus infection is found almost universally in HIV-1-infected homosexual men and has been implicated in the development of anal cancer. We studied the effect of antiretroviral agents on 23 HIV-1-infected homosexual men with symptomatic anal intra-epithelial neoplasia (AIN), by repeat biopsies. We found no evidence of a correlation between the successful treatment of HIV-1 infection and improvements in AIN. Anal and cervical cancer are thought to share aetiopathologies, and both have an increasing incidence, particularly in individuals infected with HIV-1. Both are thought to arise from the progression of squamous intra-epithelial lesions to invasive cancer [1,2]. A substantial body of literature has appeared concerning the relationship between cervical squamous intra-epithelial lesions in women treated with antiretroviral agents, and in some cases improvement has been observed [3]. The natural history of AIN has not, however, been established, nor has the effect of treatment with antiretroviral agents. We prospectively investigated the effect of highly active antiretroviral therapy in HIV-1-infected gay men with symptomatic AIN. Patients were included if they had repeat biopsies separated by more than 6 months of follow-up, and data from a total of 23 patients (median age 40 years, range 28–63) were collected. The median length of follow-up was 11.5 months (range 8–17). The presenting symptoms of AIN in this group, who were originally referred to an anoscopy service, were warts (12 patients), bleeding (six patients), pain (two), pruritis ani (one), ulcer (one), and a skin tag (one). Table 1 shows the results of repeat biopsy and changes in immune and HIV virological parameters over this time period. For all 23 individuals with AIN, eight (35%) improved their histological grade, 10 (43%) remained stable and five (22%) worsened. None of the patients with AIN-III, which is thought to represent the precursor lesion of squamous cell carcinoma, progressed during this follow-up period. In these three groups of patients, there were no significant correlations between changes in AIN and changes in HIV viral load and the CD4/CD8 cell count. Human papillomavirus sub-typing was performed on 18 patients, and no correlations were observed between these and progression, stability or regression of disease. In addition, patients found to have four or more papillomavirus sub-types did not appear to have a different outcome.Table 1: Immune and HIV virological parameters for patients who regress, remain stable or progress for anal intra-epithelial neoplasia grades I, II and III.We compared histology and cytology using a scale in which AIN-I, -II and -III (histology) referred to mild, moderate and severe dysplasia (cytology) in individuals in whom both were performed. In 65% of cases, cytological and histological results were matched. In 20% of cases, the cytology down-staged histological results and in 15% of cases it up-staged biopsy results. These data are in agreement with a previously published study [4]. There also remain issues concerning multi- versus uni-focal AIN and the number of biopsies taken. In this regard, there are data to suggest that single biopsies may miss affected areas, especially as AIN can affect visually normal skin and develop deep in the glands [5,6]. Physicians should be aware of AIN in patients with HIV and of the discordant results that biopsies and cytology may yield. For patients with confirmed AIN, the successful treatment of HIV-1 infection does not preclude progression. Follow-up with anoscopy (acetic acid staining and biopsies if necessary) is advised in this group.