Low-dose oral recombinant interferon-alpha A in patients with HIV-1 infection: a blinded pilot study.

OBJECTIVE: To evaluate the efficacy of low-dose oral recombinant interferon-alpha (IFN-alpha A) on clinical parameters, body weight, CD4+ lymphocyte counts and natural killer cell cytolytic activity in HIV-infected patients. DESIGN: Blinded crossover trial with controls for the protein and diluent components of the drug preparation. SETTING: Medical school outpatient referral center. PATIENTS, PARTICIPANTS: Eight patients with HIV-1 infection and a CD4+ lymphocyte count between 150 and 600 x 10(6)/l. Concurrent use of zidovudine was permitted. INTERVENTIONS: Patients received (daily, by mouth) 10 ml of a study solution of 2.5% albumin for 6 weeks, 150 IU IFN-alpha A for 6 weeks, and normal saline for 6 weeks. MAIN OUTCOME MEASURES: After two baseline visits, clinical assessments, vital signs, body weight, and laboratory tests, including enumeration of number and percentage of CD4+ and CD8+ lymphocytes and natural killer cell cytolytic activity, were performed every 3 weeks. Complete physical examinations were conducted every 6 weeks. RESULTS: No significant clinical or laboratory changes were observed during treatment with IFN-alpha A. Peak CD4+ lymphocyte counts were achieved at baseline in one patient, during albumin treatment in two patients, during IFN-alpha A treatment in one patient, and during saline treatment in four patients. All patients remained HIV-seropositive. Treatments were well-tolerated. CONCLUSION: This blinded pilot study of orally administered IFN-alpha A (150 IU daily for 6 weeks) did not demonstrate clinical benefit in HIV-infected patients.

Human immunodeficiency virus type 1 pol gene mutations which cause decreased susceptibility to 2',3'-dideoxycytidine.

To investigate whether human immunodeficiency virus type 1 pol gene mutations are selected during prolonged 2',3'-dideoxycytidine (ddC) therapy, we used the polymerase chain reaction to amplify a portion of the reverse transcriptase segment of the pol gene from the peripheral blood mononuclear cell DNA of a patient with AIDS before and after an 80-week course of ddC therapy. The consensus sequence from the second sample contained a unique double mutation (ACT to GAT) in the codon for reverse transcriptase amino acid 69, causing substitution of aspartic acid (Asp) for the wild-type threonine (Thr). A mutation (ACA to ATA) also occurred in the codon for position 165, causing substitution of isoleucine (Ile) for Thr. The GAT (Asp) codon was introduced into the pol gene of a molecular clone of human immunodeficiency virus via site-directed mutagenesis. Following transfection, mutant and wild-type viruses were tested for susceptibility to ddC by a plaque reduction assay. The mutant virus was fivefold less susceptible to ddC than the wild type; cross-resistance to 3'-azido-3'-deoxythymidine or 2'3'-dideoxyinosine was not found. The Ile-165 mutation did not confer additional ddC resistance. The Asp-69 substitution may have contributed to the generation of resistant virus in this patient.