This study presents a case-control nested analysis of cervical squamous intraepithelial lesions (SIL) in a cohort of 423 HIV-infected women with registered Pap smears between 1991 and 2004. Data on Pap smear results, CDC HIV classification, CD4 cell count and antiretroviral therapy were prospectively collected. Pap smears were classified using the Bethesda classification. Women had a median of three Pap smears registered in the database. The first Pap smear was registered <or=1996 for 57.7%. Two hundred and twenty women were diagnosed with SIL at least once, mainly at their first screening. Compared to women free of SIL and cancer at all Pap smear, they were younger, had lower CD4 cell count and were more likely included <or=1996 and less likely treated with HAART. These differences persisted in multivariate analysis. Among the 142 women with secondary Pap smears after SIL diagnosis, 43 (30.3%) worsen their Pap smear results. No specific characteristics could be identified for these patients compared to those who did not. Finally 21 women were diagnosed with cervix cancer, three at first Pap smear and the others after a previous SIL diagnosis in a median delay of three years. These results reflect the change in gynaecologic management of HIV-infected women after HAART introduction but also underline the necessity to maintain a regular gynaecologic screening for HIV-infected women.