Phase I study of low-dose zidovudine and acyclovir in asymptomatic human immunodeficiency virus seropositive individuals.
OBJECTIVE
The combination of zidovudine and acyclovir has shown in vitro antiretroviral activity and led to short-term improvement in patients with symptomatic human immunodeficiency disease (HIV) disease. We performed a phase I study of zidovudine (500 mg/day) plus acyclovir (2 or 4 g/day) in asymptomatic HIV-seropositive men to investigate pharmacokinetics, safety, tolerance, and immunologic effects of the combination.


METHODS
Fifty HIV-seropositive homosexual or bisexual men from the San Francisco City Clinic Cohort Study were recruited for the study; of these, 20 met the eligibility criteria. Treatment with zidovudine and acyclovir was open label. Pharmacokinetic, virologic, immunologic, and clinical data were collected periodically over a 24-week period.


RESULTS
Pharmacokinetic analysis showed no drug interaction. The combination was generally well tolerated, and hematologic parameters remained stable through 24 weeks. There were no significant changes in total lymphocytes, T4 lymphocytes, overall skin test reactivity, or ability to culture virus from peripheral blood.


CONCLUSIONS
This combination of agents is safe in this population for at least six months. Conclusions about long-term tolerance and efficacy await the results of larger trials with longer follow-up.
Hollander
H
H
Department of Medicine, University of California, San Francisco 94143.
Lifson
A R
AR
Maha
M
M
Blum
R
R
Rutherford
G W
GW
Nusinoff-Lehrman
S
S
D000212:Acyclovir / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D004334:Drug Administration Schedule; D004338:Drug Combinations; D004341:Drug Evaluation; D004357:Drug Synergism; D004906:Erythrocyte Count / Q000187:drug effects; D015658:HIV Infections / Q000188:drug therapy; D006679:HIV Seropositivity / Q000097:blood*; D006801:Humans; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D009000:Monocytes / Q000187:drug effects; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*
D004338:Drug Combinations; D015215:Zidovudine; D000212:Acyclovir