Evaluation of plasma human herpesvirus 8 DNA as a marker of clinical outcomes during antiretroviral therapy for AIDS-related Kaposi sarcoma in Zimbabwe.
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/microL at baseline to 281 cells/microL, the plasma HIV-1 RNA level decreased from 4.69 to <2.60 log(10) 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/10(6) 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; P = .04) and a better clinical response (odds ratio, 6.38; 95% confidence interval, 1.68-24.19; P = .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.
Borok
Margaret
M
Departments of Medicine, University of Zimbabwe College of Health Sciences, Harare, Zimbabwe. mborok@mweb.co.zw
Fiorillo
Suzanne
S
Gudza
Ivy
I
Putnam
Beverly
B
Ndemera
Buxton
B
White
Irene E
IE
Gwanzura
Lovemore
L
Schooley
Robert T
RT
Campbell
Thomas B
TB
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications / Q000188:drug therapy*; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D015415:Biomarkers; D004279:DNA, Viral / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D019288:Herpesvirus 8, Human / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D010949:Plasma / Q000821:virology*; D011446:Prospective Studies; D012514:Sarcoma, Kaposi / Q000188:drug therapy*; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load; D015030:Zimbabwe
D019380:Anti-HIV Agents; D015415:Biomarkers; D004279:DNA, Viral