title: Virologic and immunologic parameters that predict clinical response of AIDS-associated Kaposi's sarcoma to highly active antiretroviral therapy.
abstract: The purpose of the work was to assess the predictive value of biologic factors on the efficacy of highly active antiretroviral therapy alone or combined with chemotherapy on AIDS-associated Kaposi's sarcoma. Twenty-six AIDS-Kaposi's sarcoma patients who started therapy with protease inhibitors were investigated. No baseline chemotherapy was associated with less severe initial clinical status. Median follow-up was 652 d. The main outcome measures were as follows: best Kaposi's sarcoma clinical response; Kaposi's-sarcoma-associated herpesviral load in peripheral blood mononuclear cells using real-time quantitative polymerase chain reaction (non-detectable if less than 100 copies per microg); human immunodeficiency viral charge in plasma (non-detectable if less than 200 copies per ml); and CD4 lymphocyte count. Time to undetectable Kaposi's-sarcoma-associated herpesviral load, time to undetectable human immunodeficiency viral charge, and time to CD4 >or= 150 per microl were also recorded over time, from 2 mo measurements. Patients 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 chemotherapy was achieved in 22 patients (85%). Median time to clinical response 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 univariable analyses, predictive factors of clinical response were undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.013), undetectable human immunodeficiency viremia (p = 0.03), and relative variation of CD4 lymphocytes (p = 0.004). Using multivariable analysis, undetectable Kaposi's-sarcoma-associated herpesviremia (p = 0.009) and relative variation of CD4 (p = 0.005) were independently selected as having a predictive value for clinical response. Occurrence of nondetection of either Kaposi's-sarcoma-associated herpesvirus or human immunodeficiency virus was not associated with baseline CD4 value. Kaposi's-sarcoma-associated herpesvirus quantitative viral charge is an independent predictive factor of the efficacy of highly active antiretroviral therapy on AIDS-Kaposi's sarcoma. Our results support immune reconstitution as a mechanism of response of Kaposi's sarcoma to highly active antiretroviral therapy.
authors.affiliation: Laboratory of Pharmacology, Hôpital Saint-Louis, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Pellet
authors.forename: S
authors.initials: S
authors.lastname: Chevret
authors.forename: L
authors.initials: L
authors.lastname: Blum
authors.forename: C
authors.initials: C
authors.lastname: Gauvillé
authors.forename: M
authors.initials: M
authors.lastname: Hurault
authors.forename: G
authors.initials: G
authors.lastname: Blanchard
authors.forename: F
authors.initials: F
authors.lastname: Agbalika
authors.forename: C
authors.initials: C
authors.lastname: Lascoux
authors.forename: D
authors.initials: D
authors.lastname: Ponscarme
authors.forename: P
authors.initials: P
authors.lastname: Morel
authors.forename: F
authors.initials: F
authors.lastname: Calvo
authors.forename: C
authors.initials: C
authors.lastname: Lebbé
mesh_terms: D000163:Acquired Immunodeficiency Syndrome / Q000150:complications* / Q000821:virology; D023241:Antiretroviral Therapy, Highly Active; D001426:Bacterial Proteins; D015704:CD4 Antigens / Q000032:analysis; D005500:Follow-Up Studies; D006360:Heat-Shock Proteins / Q000097:blood; D006566:Herpesviridae Infections / Q000209:etiology / Q000821:virology; D006801:Humans; D009000:Monocytes / Q000378:metabolism / Q000821:virology; D011379:Prognosis; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000209:etiology* / Q000276:immunology / Q000821:virology; D019562:Viral Load; D014766:Viremia / Q000821:virology
chemical_list: D001426:Bacterial Proteins; D015704:CD4 Antigens; D006360:Heat-Shock Proteins; C406264:orf29 protein, Listeria monocytogenes