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Cervical Intraepithelial Neoplasia and Cervicovaginal Shedding of Human Immunodeficiency Virus

From the Departments of ¹Obstetrics and Gynecology, ²Microbiology, and ³Infectious Diseases, IRCCS Policlinico S. Matteo, University of Pavia, Pavia, Italy.

OBJECTIVE: Although human immunodeficiency virus (HIV) infection is a well-known risk factor for cervical intraepithelial neoplasia (CIN), the influence of CIN on cervicovaginal shedding of HIV is poorly understood. The purpose of this study was to evaluate the association between CIN and the shedding of HIV in cervicovaginal secretions.

METHODS: Two hundred sixteen HIV-seropositive patients were followed up by Pap test, colposcopy, and targeted cervical biopsies for a median of 16 months (range 0–94). A diagnosis of low-grade CIN was made on the basis of Pap test and either colposcopy or cervical biopsy. High-grade CIN was diagnosed solely on the basis of cervical biopsy. At each follow-up visit, we measured HIV-1 RNA in plasma, proviral HIV-1 DNA, and cell-associated and cell-free HIV-1 RNA in cervicovaginal secretion by competitive polymerase chain reaction (cRT-PCR) and reverse transcriptase PCR. The univariable and multivariable associations between the occurrence of CIN and the presence of HIV-related nucleic acids in cervicovaginal secretions were evaluated with logistic generalized estimating equations.

RESULTS: Overall, at enrollment and during the follow-up period, a diagnosis of either low-grade or high-grade CIN was made in 14.4% (99/689) and 6.7% (46/689) of the visits, respectively. The presence of measurable levels of plasma HIV-1 RNA was a significant risk factor for the detection of cervicovaginal HIV-1 DNA (odds ratio [OR] 1.86, 95% confidence interval [CI] 1.32–2.61, P < .001), cell-associated (OR 1.69, 95% CI 1.18–2.43, P = .004), and cell-free HIV-1 RNA (OR 1.84, 95% CI 1.28–2.63, P = .001). After the adjustment for the effect of plasma HIV-1 RNA, CD4⁺ positive cell counts less than 200 mm³, and bacterial vaginosis, the detection of cell-associated (OR 1.75, 95% CI 1.23–2.49, P = .006) and cell-free HIV-1 RNA (OR 2.0, 95% CI 1.39–2.87, P = .001) in cervicovaginal secretions was significantly associated with the diagnosis of CIN.

CONCLUSION: The presence of CIN lesions is a significant risk factor for genital HIV shedding. Given the high prevalence of cervical disease among HIV-positive women, this finding could have important epidemiological implications in both heterosexual and perinatal transmission of HIV.

LEVEL OF EVIDENCE: II-2