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Background. Studies analyzing the impact of combination antiretroviral therapy (cART) on cervical infection with high-risk human papillomavirus (HR-HPV) have generated conflicting results. We assessed the long-term impact of cART on persistent cervical HR-HPV infection in a very large cohort of 652 women who underwent follow-up of HIV infection for a median duration of 104 months.Methods. Prospective cohort of HIV-infected women undergoing HIV infection follow-up who had HR-HPV screening and cytology by Papanicolaou smear performed yearly between 2002 and 2011.Results. At baseline, the median age was 38 years, the race/ethnic origin was sub-Sarahan Africa for 84%, the median CD4+ T-cell count was 426 cells/µL, 79% were receiving cART, and the HR-HPV prevalence was 43%. The median interval of having had an HIV load of <50 copies/mL was 40.6 months at the time of a HR-HPV–negative test result, compared with 17 months at the time of a HR-HPV–positive test result (P < .0001, by univariate analysis). The median interval of having had a CD4+ T-cell count of >500 cells/µL was 18.4 months at the time of a HR-HPV–negative test result, compared with 4.45 months at the time of a HR-HPV–positive test result (P < .0001). In multivariate analysis, having had an HIV load of <50 copies/mL for >40 months (odds ratio [OR], 0.81; 95% confidence interval [CI], .76–.86; P < .0001) and having had a CD4+ T-cell count of >500 cells/µL for >18 months (OR, 0.88; 95% CI, .82–.94; P = .0002) were associated with a significantly decreased risk of HR-HPV infection.Conclusion. Sustained HIV suppression for >40 months and a sustained CD4+ T-cell count of >500 cells/µL for >18 months are independently and significantly associated with a decreased risk of persistent cervical HR-HPV infection.