Interferon-alpha in patients with asymptomatic human immunodeficiency virus (HIV) infection. A randomized, placebo-controlled trial.
OBJECTIVE
To evaluate the toxicity and clinical efficacy of interferon-alpha 2b (IFN-alpha) in patients with asymptomatic human immunodeficiency virus (HIV) infection.


METHODS
Randomized, placebo-controlled, and double-blind study.


METHODS
Outpatient clinic of a government referral-based research hospital.


METHODS
Volunteer sample of 34 patients with asymptomatic HIV infection who had CD4 counts of 400 cells/mm3 or more, positive peripheral blood mononuclear cell cultures for HIV, or p24 antigenemia.


METHODS
Patients were randomly assigned to receive either IFN-alpha or placebo, 35 x 10(6) units per day subcutaneously. Doses of IFN-alpha or placebo were modified according to predefined laboratory and clinical criteria. Therapy lasted at least 12 weeks.


RESULTS
Seventeen patients were randomly assigned to each group. The two groups had similar mean CD4 counts at study entry. Thirty-five percent of patients assigned to receive IFN-alpha withdrew from the study because of toxicity. The average daily dose of IFN-alpha was 17.5 x 10(6) units. All patients receiving IFN-alpha reported flu-like symptoms; other toxicities included granulocytopenia (55%) and elevated liver enzyme levels (45%). While receiving IFN-alpha, 7 patients (41%) became HIV culture negative (three or more consecutive negative peripheral blood mononuclear cell cultures taken at least 2 weeks apart). In contrast, 2 patients in the placebo group (13%) became culture negative while on study (P = 0.05). During the treatment period, CD4 lymphocyte percentages were sustained at or above the baseline level in patients receiving IFN-alpha and declined slightly in patients receiving placebo. Of the 32 study patients followed after study (range, 5 to 33 months), no patients in the IFN-alpha group developed an acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection, compared with 5 patients in the placebo group (P = 0.02).


CONCLUSIONS
Treatment of early-stage HIV infection with IFN-alpha can result in a decrease in frequency of viral isolation. Although its use may be accompanied by dose-dependent toxicities, IFN-alpha may have a role in slowing progression of HIV disease.
Lane
H C
HC
National Institutes of Health, Bethesda, Maryland.
Davey
V
V
Kovacs
J A
JA
Feinberg
J
J
Metcalf
J A
JA
Herpin
B
B
Walker
R
R
Deyton
L
L
Davey
R T
RT
Falloon
J
J
D000293:Adolescent; D000328:Adult; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D004311:Double-Blind Method; D015683:Gene Products, gag / Q000097:blood; D016655:HIV Core Protein p24; D015658:HIV Infections / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007370:Interferon Type I / Q000627:therapeutic use*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007958:Leukocyte Count / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009894:Opportunistic Infections / Q000453:epidemiology; D011020:Pneumonia, Pneumocystis / Q000453:epidemiology; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D013223:Statistics as Topic; D014758:Viral Core Proteins / Q000097:blood
D015683:Gene Products, gag; D016655:HIV Core Protein p24; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D014758:Viral Core Proteins