Kaposi’s Sarcoma, Cervical Dysplasia Both Improve With Anti-HIV Therapy

GENEVA--Kaposi’s sarcoma (KS) and cervical dysplasia are common problems in HIV-infected patients. Research presented at the 12th World AIDS Conference shows that strong suppression of HIV replication with highly active antiretroviral therapy (HAART) also leads to recovery from these two neoplastic conditions.

Most patients with KS whose plasma HIV RNA levels were reduced below 500 copies/mL had complete resolution of KS lesions in a small series reported by Sara Santambrogio, MD, and her colleagues at the Institute of Infectious and Tropical Diseases, University of Milan.

This study included nine patients with KS. None had visceral KS. The median baseline plasma HIV level was 59,000 copies. All were treated with HAART including indinavir (Crixivan) plus two reverse transcriptase inhibitors. Median follow-up was 16 months.

Following HAART, seven of the nine patients had complete remission of KS, one had a partial remission, and one had KS progression. "HAART exerts a beneficial effect on the clinical course of AIDS-related Kaposi’s sarcoma, probably through immune function restoration," Dr. Santambrogio concluded.

This possibility was further supported in work reported as a "late breaker" presentation, which showed not only that HAART reduces the risk of KS but also that this improvement increases with the duration of HAART treatment.

Philippe Saiag, MD, and his colleagues in Boulogne, France, studied 38 patients with KS treated with HAART (at least one protease inhibitor plus two nucleoside analogs) for a median of 18 months.

Dr. Saiag reported, "KS improved progressively, with a response rate (complete response plus partial response) of 86% at month 18, by which time only seven patients were still receiving cytotoxic drugs for their KS." He suggested that cytotoxic drugs can be safely discontinued in patients on HAART whose KS goes into complete remission.

Patients with complete remissions had higher CD4 counts (median, 348/mL vs 189/mL) but did not have significantly lower plasma HIV RNA levels than those who did not have complete remissions. Dr. Saiag concluded that the beneficial effect on KS therefore "seems to be related to the restoration of immune function rather than to decreased HIV plasma load."

Cervical Dysplasia

Vitamin A deficiency is common in HIV-infected women and is associated with cervical squamous intraepithelial lesions (SILs). There was an inverse linear relationship, similar to a dose response, between vitamin A level and the prevalence of cervical SILs, even in women with vitamin A levels that are considered normal, Audrey French, MD, reported.

Dr. French and her colleagues at Cook County Hospital, Chicago, measured vitamin A levels by high performance liquid chromatography in 129 HIV-infected women enrolled in the Women’s Interagency HIV Study.

They found cervical SILs in 50% of women with vitamin A concentrations below 0.7 micromol/L, compared with 13% of women with normal vitamin A levels. The association between low vitamin A levels and cervical SILs was independent of CD4 levels, viral load, and human papillomavirus (HPV) infection.

As is the case with Kaposi’s sarcoma, suppressing HIV with HAART appears to allow the body to recover from cervical dysplasia in some cases. Isabelle Heard, MD, and her colleagues at Hôpital Broussais in Paris studied 85 women with advanced HIV disease who were beginning treatment with a protease inhibitor-containing HAART regimen.

"The prevalence of squamous intra-epithelial lesions decreased from 66% to 49% after a median duration of 5 months of HAART," Dr. Heard reported. "Partial regression to a lower grade was observed in 7 of 20 women who initially presented with high-grade lesions. Total regression to normal was observed in one woman who initially presented with high-grade disease and in 16 women who presented with low-grade disease."

Dr. Heard said that this improvement was due presumably to improvement in immune function, not to clearing of HPV-infected cells, even though HAART can reduce the clinical expression of HPV disease in some HIV-infected women.