Virologic and immunologic parameters that predict clinical response of AIDS-associated Kaposi's sarcoma to highly active antiretroviral therapy

The purpose of the work was to assess the predictive value of biologic fact ors on the efficacy of highly active antiretroviral therapy alone or combin ed with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-K aposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe init ial clinical status. Median followup was 652 d. The main outcome measures w ere as follows: best Kaposi's sarcoma clinical response; Kaposi's-sarcoma-a ssociated herpesviral load in peripheral blood mononuclear cells using real -time quantitative polymerase chain reaction (non-detectable if less than 1 00 copies per tg); human immunodeficiency viral charge in plasma (non-detec table if less than 200 copies per ml); and CD4 lymphocyte count. Time to un detectable Kaposi's-sarcoma-associated herpesviral load, time to undetectab le human immunodeficiency viral charge, and time to CD4 greater than or equ al to 150 per mul were also recorded over time, from 2 mo measurements. Pat ients were staged according to the AIDS Clinical Trials Group-based tumor, immune, systemic staging system criteria. At baseline, Kaposi's sarcoma was progressive for 25 (96%) of the 26 enrolled patients. Complete or partial response to highly active antiretroviral therapy alone or combined with che motherapy was achieved in 22 patients (85%). Median time to clinical respon se was estimated at 251 d. Clinical response was faster in patients without chemotherapy at baseline (p = 0.003) as well as in patients not previously treated with reverse transcriptase inhibitors (p = 0.0012). Using univaria ble analyses, predictive factors of clinical response were undetectable Kap osi's-sarcoma-associated herpesviremia (p = 0.013), undetectable human immu nodeficiency viremia (p = 0.03), and relative variation of CD4 lymphocytes (p = 0.004). Using multivariable analysis, undetectable Kaposi's-sarcoma-as sociated herpesviremia (p = 0.009) and relative variation of CD4 (p = 0.005 ) were independently selected as having a predictive value for clinical res ponse. Occurrence of nondetection of either Kaposi's-sarcoma-associated her pesvirus or human immunodeficiency virus was not associated with baseline C D4 value. Kaposi's-sarcoma-associated herpesvirus quantitative viral charge is an independent predictive factor of the efficacy of highly active antir etroviral therapy on AIDS-Kaposi's sarcoma. Our results support immune reco nstitution as a mechanism of response of Kaposi's sarcoma to highly active antiretroviral therapy.