518   Impact of Highly Active Antiretroviral Therapy (HAART) on Cervical Intraepithelial Neoplasia (CIN) in HIV-Seropositive Women.

I. Heard*¹, J. M. Tassie², M. D. Kazatchkine¹, and G. Orth³.
¹INSERM U430 and Hosp. G. Pompidou;²Epicentre; and³Inst. Pasteur, Paris, France.

Background:The impact of HAART on the natural history of CIN in HIV-seropositive women is poorly documented. Our objective was to estimate the influence of HAART on the regression of CIN.

Methods:A prospective study of CIN in HIV-positive women with a semestrial follow-up including colposcopy, Pap smears and biopsy was initiated in 1993. All women with biopsy-proven CIN were included in the present substudy. During follow-up, regression of CIN was defined as reversion to normality or change from high-grade to low-grade biopsy-proven CIN. Survival analyses were used to assess the risk of regression of CIN associated with antiretroviral treatment. Protease inhibitor (PI) or non-nucleoside reverse transcriptase inhibitor (NNRTI) treatment was entered as a time-dependent covariate according to the date of first prescription, with CD4 cell counts and CIN grade at inclusion.

Results:One hundred sixty-eight women were included: 80 with high-grade CIN (HGCIN) and 88 with low-grade CIN (LGCIN). The median CD4 cell count at inclusion was 250/mm³. Eighty-six women were treated with PI and 10 with NNRTI in combination with NRTI. After a median follow-up of 17.7 months, regression was observed in 67 women (39.9%): from LGCIN to normal in 30 women, from HGCIN to normal in 6 and from HGCIN to LGCIN in 31. Progression to HGCIN was observed in 20 women with LGCIN. The regression rate at 12 months was estimated to be 23.8% (95% confidence interval [CI]: 14.2—33.5) for HGCIN and 14.8% (95% CI: 7.0—22.6) for LGCIN. In women receiving PI or NNRTI, the risk of regression was twice as high as for women without HAART (adjusted relative hazard: 2.09; 95%CI: 1.26—3.48).

Conclusions:HAART modified the course of CIN in HIV-infected women by significantly increasing the reversion to normality or the change to a lower grade. Current studies are being conducted to further evaluate the impact of HAART on cervical HPV infections.