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The prevalence of human papillomavirus (HPV) is higher among HIV-positive women, but the prevalence of HPV prior to HIV acquisition has not been carefully evaluated.This study evaluated whether HPV infection is independently associated with heterosexual HIV acquisition in a cohort of Zimbabwean women.Case–control study nested within a large multicenter cohort study (HC-HIV).Cases consisted of Zimbabwean women with incident HIV infection observed during follow-up (n = 145). HIV-uninfected controls were selected and matched to cases (n = 446). The prevalence of cervical HPV infections was compared at the visit prior to HIV infection in the cases and at the same follow-up visit in the matched controls.The odds of acquiring HIV were 2.4 times higher in women with prior cervical HPV infection after adjustment for behavioral and biologic risk factors. There was no statistically significant difference in the risk of HIV acquisition between women infected with high-risk vs. low-risk HPV types. Loss of detection of at least one HPV DNA type was significantly associated with HIV acquisition [odd ratio = 5.4 (95% confidence interval 2.9–9.9)] (P < .0001).Cervical HPV infection is associated with HIV acquisition among women residing in a region with a high prevalence of both infections. Further studies are required to evaluate whether the observed association is causal.