Hemophilia and nonprogressing human immunodeficiency virus type 1 infection.

Seven of 112 hemophiliacs infected with human immunodeficiency virus type-1 (HIV-1) before 1986 through contaminated plasma products are currently healthy, with CD4 T-cell counts above 500 cells/microL, and have never received antiretroviral therapy (long-term nonprogressors [LTNPs]). Seven age and sex-matched hemophiliacs infected in the same period but who have progressive HIV disease (progressors) and one additional slow-progressing individual were also studied. One hundred-fold, 20-fold, and 10-fold lower levels of full-length HIV RNA in plasma, peripheral blood mononuclear cells (PBMCs), and proviral DNA in PBMCs, respectively, were found in LTNPs compared with progressors. Plasma and cell-associated HIV RNA and proviral DNA were lower in LTNPs who tested negative for viral isolation from PBMCs or who were positive only after removal of CD8+ cells. No substantial differences were observed in the in vitro production of chemokines including RANTES, MIP-1 alpha, MIP-1 beta, MCP-1, and interleukin-8 (IL-8) in supernatants of activated PBMCs or CD8-depleted PBMCs of LTNPs, even when HIV isolation was simultaneously accomplished exclusively after removal of CD8+ cells. Low levels of HIV load and replication in peripheral blood are the strongest correlates of nonprogression in this small number of infected hemophiliacs.

Interferon-alpha is effective in the treatment of HIV-1-related, severe, zidovudine-resistant thrombocytopenia. A prospective, placebo-controlled, double-blind trial.

OBJECTIVE: To determine the effect of interferon-alpha for severe, zidovudine-resistant, HIV-1-related thrombocytopenia. DESIGN: Prospective, randomized, double-blind, placebo-controlled, multicenter, crossover trial. SETTING: Outpatient clinics in Central Northern Italy. PATIENTS: 15 sequential patients positive for HIV-1 with platelet counts less than 25 x 10(9)/L who were refractory to 1 month of full-dose (1000 mg/d) zidovudine. INTERVENTION: Interferon-alpha (3 million units) or placebo (1 mL saline) three times a week subcutaneously for 4 weeks, followed by a 4-week washout period. Patients were then switched to the alternative treatment for the next 4 weeks, followed by another 4 weeks of washout, and they were randomly assigned to either sequence of treatment. Patients received zidovudine (200 mg three times daily) throughout the study. MEASUREMENTS: The primary end point was the platelet count (measured weekly). Secondary end points were qualitative assessment of the platelet response; bleeding time; p24 antigen in serum; CD4/CD8 counts; beta 2-microglobulin in serum; and platelet-associated IgG. RESULTS: Interferon-alpha significantly increased platelet counts in the 12 patients who completed the study (baseline level, 15.6 +/- 7.1 x 10(9)/L; after 4 weeks of interferon-alpha therapy, 82.2 +/- 52.2 x 10(9)/L). The estimated increase in the platelet count after interferon-alpha compared with placebo was 60.0 x 10(9)/L (95% CI, 23.2 to 96.8 x 10(9)/L). The increase was already statistically significant after 3 weeks (66.6 +/- 49.7 x 10(9)/L) and remained significantly increased 1 week after discontinuing interferon-alpha therapy (58.2 +/- 45.0 x 10(9)/L). Placebo did not modify the platelet count. The bleeding time was significantly shortened by interferon-alpha. Four of 12 patients who had more serious alterations of some measures reflecting disease severity did not respond to interferon-alpha. No relevant side effects were observed. CONCLUSIONS: Interferon-alpha is a safe and effective treatment for zidovudine-resistant, HIV-related thrombocytopenia.