Evaluation of plasma human herpesvirus 8 DNA as a marker of clinical outcomes during antiretroviral therapy for AIDS-related kaposi sarcoma in Zimbabwe
Clinical Infectious Diseases
University of Zimbabwe, College of Health Sciences, Dept of Medicine, Mazowe Street, Avondale, Harare, Zimbabwe; Department of Medical and Laboratory Sciences, University of Zimbabwe, College of Health Sciences, Harare, Zimbabwe; Division of Infectious Diseases, Department of Medicine, University of Colorado-Denver, Aurora, United States; University of California, San Diego, United States
Background. The usefulness of plasma human herpesvirus 8 (HHV-8) DNA as a marker of response to treatment for acquired immunodeficiency syndrome-associated Kaposi sarcoma (AIDS-KS) in an African setting is unknown. Methods. We conducted a prospective pilot study at the Parirenyatwa Hospital Kaposi Sarcoma Clinic (Harare, Zimbabwe) to investigate the hypothesis that the clinical response of AIDS-KS is associated with suppression of HHV-8 DNA. Antiretroviral therapy (ART) was provided as coformulation of abacavir, lamivudine, and zidovudine. Clinical response was defined as survival to week 96 with either complete or partial resolution of KS disease. Results. Ninety ART-naive participants (62 men and 28 women) aged >18 years who had human immunodeficiency virus type 1 (HIV-1) infection and biopsy-confirmed KS were studied; 82% had stage T1 disease. Fifty participants received adjunctive chemotherapy. The median CD4+ lymphocyte count increased from 124 cells/μL at baseline to 281 cells/μL, the plasma HIV-1 RNA level decreased from 4.69 to <2.60 log10 copies/mL, the plasma HHV-8 DNA level decreased from 660 to <25 copies/mL, and HHV-8 DNA level in peripheral blood mononuclear cells decreased from 2790 to 37 copies/106 cells (P<.001 for each comparison). There were 14 deaths (16%) and 13 patients (15%) lost to follow-up. The most common cause of death was infection. Clinical response of KS occurred in 17 participants (19%). Pretreatment plasma HHV-8 DNA levels of <660 copies/mL were associated with greater survival (odds ratio, 2.83; 95% confidence interval, 1.07-7.53; Pp.04) and a better clinical response (odds ratio, 6.38; 95% confidence interval, 1.68-24.19; Pp.006). Conclusions. AIDS-KS tumor responses after ART initiation were limited. Pretreatment plasma HHV-8 DNA level may be a surrogate for KS disease that is in need of intensive clinical management. © 2010 by the Infectious Diseases Society of America. All rights reserved.
abacavir; bleomycin; cotrimoxazole; doxorubicin; etoposide; lamivudine; nevirapine; vincristine; virus DNA; zidovudine; anti human immunodeficiency virus agent; biological marker; virus DNA; acquired immune deficiency syndrome; adult; aged; anemia; article; bacterial arthritis; cause of death; CD4+ T lymphocyte; clinical trial; cohort analysis; cryptococcal meningitis; drug hypersensitivity; female; follow up; gastrointestinal infection; hepatitis; human; Human herpesvirus 8; Human immunodeficiency virus 1; Kaposi sarcoma; lower respiratory tract infection; major clinical study; malaria; male; mortality; neutropenia; nonhuman; peripheral blood mononuclear cell; pilot study; Pneumocystis jiroveci; pneumonia; priority journal; prospective study; real time polymerase chain reaction; soft tissue infection; Stevens Johnson syndrome; stomatitis; survival; treatment duration; treatment outcome; tuberculosis; urinary tract infection; Zimbabwe; Acquired Immunodeficiency Syndrome; blood; complication; drug monitoring; genetics; highly active antiretroviral therapy; Human herpesvirus 8; isolation and purification; middle aged; plasma; procedures; Sarcoma, Kaposi; virology; virus load; Zimbabwe; Acquired Immunodeficiency Syndrome; Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Biological Markers; DNA, Viral; Drug Monitoring; Female; Herpesvirus 8, Human; Humans; Male; Middle Aged; Pilot Projects; Plasma; Prospective Studies; Sarcoma, Kaposi; Survival Analysis; Treatment Outcome; Viral Load; Zimbabwe; Acquired Immunodeficiency Syndrome; Adult; Aged; Anti-HIV Agents; Antiretroviral Therapy, Highly Active; Biological Markers; DNA, Viral; Drug Monitoring; Female; Herpesvirus 8, Human; Humans; Male; Middle Aged; Pilot Projects; Plasma; Prospective Studies; Sarcoma, Kaposi; Survival Analysis; Treatment Outcome; Viral Load; Zimbabwe