Diminished responsiveness of male homosexual chronic hepatitis B virus carriers with HTLV-III antibodies to recombinant α-interferon

Abstract

In a randomized controlled trial, 41 chronic hepatitis B virus carriers were allocated, by opening numbered computerized randomization envelopes, to receive recombinant interferon-alpha 2A at three different doses: 2.5; 5.0, and 10.0 mU per m2. Thirty-two patients received treatment (6 for 3 months, 26 for 6 months), and 9 patients were controls (received no treatment). Ninety-three per cent of our patients were homosexual, and 41% had anti-HTLV-III in their serum. None of the control patients lost HBeAg. In contrast, six of the anti-HTLV-III-negative patients (33%) responded to treatment (p less than 0.02): five of these responders were homosexual (p less than 0.05). The response rate was greatest (44%) in the anti-HTLV-III-negative patients who received 10 mU per m2 of recombinant interferon-alpha 2A. None of the anti-HTLV-III-positive patients responded to treatment. The percentage reduction of hepatitis B virus DNA was significantly less in the anti-HTLV-III-positive group in comparison to the anti-HTLV-III-negative group at 1 and 4 months of treatment and at 3 months after the end of treatment (p less than 0.05). These patients were younger (33 vs. 42 years, p less than 0.02), had lower mean baseline AST values (42 vs. 80 IU per liter, p less than 0.02) and tended to have milder histological disease. Homosexual men with HBeAg-positive chronic liver disease who are anti-HTLV-III-positive appear to be less responsive to the direct antiviral and immunomodulatory effects of recombinant interferon-alpha 2A. This may be due to the subclinical immunosuppressive effects of co-infection with HTLV-III.

Long-term incidence of hepatitis B virus resistance to lamivudine in human immunodeficiency virus-infected patients

“…6,7 Lamivudine, an oral nucleoside analogue, is effective against both HIV and HBV replication. Lamivudine has promptly inhibited HBV replication in more than 80% of cases in both HIV-and non-HIV-infected patients.…”

A controlled trial of high dose interferon, alone and after prednisone withdrawal, in the treatment of chronic hepatitis B: long term follow up.

“…Several A large multicentre and multinational study has shown that interferon 10 MU three times weekly for three to six months has a greater efficacy than lower doses.3 Our randomised, controlled trial was designed to evaluate the efficacy and safety of high doses of interferon.…”

Treatment of Patients with Chronic Type B Hepatitis and Concurrent Human Immunodeficiency Virus Infection with a Combination of Interferon Alpha and Azidothymidine: A Pilot Study

“…Based on these considerations we have initiated a pilot study in patients with chronic type B hepatitis with concur rent HIV infection. As chronic type B hepa titis in HIV-infected individuals had a low or no response to IFN-a [3,4] with the excep tion of a recently published study [11], we have attempted to reduce HBV and HIV replication by a combination of AZT and IFN-a. As shown, the combined therapy of IFN-a and AZT, both given in quite low doses, was not able to eliminate the HBV in any of the patients treated.…”

“…type B hepatitis frequently becomes chronic [I, 2], Attempts to elimi nate the HBV indicated by the presence of hepatitis B e-antigen (HBeAg) and HBV deoxyribonucleic acid (HBV-DNA) in the serum from the serum of these patients by the use of interferon-a (IFN-a) have not been successful. In fact, these individuals have been shown to be non-or low responders to IFN-a therapy [3,4], Recently, it has been shown that HIV replication can be sup pressed by azidothymidine (AZT). a nucleo side analogue with a high affinity to the reverse transcriptase of the HIV and rather low affinity to eukaryotic DNA polymerases [5].…”