Human papillomavirus (HPV)-infection belongs to the most common sexually transmitted diseases worldwide. HIV-infected men having sex with men (MSM) are strongly associated with a higher prevalence of genital HPV-infection, a higher incidence of anal intraepithelial neoplasia (AIN), and, consecutively, an increased risk for anal cancer. Since the introduction of highly active antiretroviral therapy (HAART), the incidence of several viral-associated neoplasias has significantly fallen in HIV-infected individuals. At the beginning of the era of HAART, a justified hope existed that genitoanal HPV-related neoplasias would also decrease based on the success of HAART-induced immune restoration. However, HAART seems to have only a small impact on the natural history of AIN as observed in a cohort of HIV-positive MSM before and after the initiation of HAART.