Highly Active Antiretroviral Therapy Enhances Regression of Cervical Intraepithelial Neoplasia in HIV-Seropositive Women

HIV infection is associated with an increased prevalence and severity and with a lower rate of regression of human papillomavirus (HPV)-associated cervical intraepithelial lesions. With increases in life expectancy due to antiretroviral treatment, one may speculate that HIV-positive women would be put at greater risk of developing cervical cancers from persistent cervical intraepithelial neoplasia (CIN). Alternatively, it is possible that immune restoration associated with antiretroviral treatment would enhance regression of CIN, thereby precluding the development of malignant disease. However, there has been limited and controversial data on the effect of highly active antiretroviral therapy (HAART).

The authors previously reported a regression rate of 35 percent of squamous intraepithelial lesions in 34 HIV-seropositive women with cervical disease who were receiving HAART for a median duration of 5 months. The current article discusses the long-term follow-up (17.7 months) of 168 HIV-positive women with CIN, of whom 96 were receiving HAART.

This was a prospective study of cervical disease in HIV-seropositive women attending two outpatient HIV clinics in Paris initiated in May 1993. The study included 168 HIV-infected women with evidence of CIN until regression to a lower grade or to normality (end-point) or until surgical treatment or last visit. Women were examined every 6 months by Papanicolaou smears, colposcopy, and biopsy if required. The probability of CIN regression was calculated using survival analysis. HAART was entered as a time-dependent covariate according to the date of first prescription of the medication.

The results indicate that there is a positive association of HAART with CIN regression that may be associated with some restoration of specific immune reactivity. Specific results included: regression of CIN in 67 (39.9 percent) women. The probability values for regression at 12 months were significantly higher for high-grade CIN (23 percent) than for low-grade lesions (14.8 percent). The risk of regression of CIN was twice as high in women receiving HAART as compared with women not receiving HAART. There was a trend for a larger increase in CD4 cell counts among those women taking HAART and who showed regression as compared with those who did not regress.

Importantly, however, according to the authors, the positive effect of HAART on the regression of CIN is not sufficient to modify the current recommendations for the gynecological follow-up of HIV-infected women, including systematic colposcopy and biopsy if indicated.

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