Secondary Logo

Journal Logo

Effect of interferon and ribavirin on HIV viral load

Landau, Alain; Batisse, Dominique; Piketty, Christophe; Kazatchkine, Michel D.

Correspondence
Free

Service d'hepatologie et gastroenterologie, and Service d'immunologie clinique, HBpital Broussais and UniversitE Pierre et Marie Curie, Paris, France.

Received: 26 August 1999; accepted 27 September 1999

Approximately 10% of HIV-seropositive individuals are co-infected with hepatitis C virus (HCV). Co-infection with HCV and HIV is particularly prevalent among HIV-seropositive injecting drug users. The course of chronic hepatitis C is more severe in HIV-seropositive patients than in HIV-seronegative individuals. Given the poor efficacy of IFN-α monotherapy in co-infected patients and the promising results of combination therapy with IFN and ribavirin in immunocompetent HIV-seronegative patients [1] we have engaged in the treatment with IFN and ribavirin of a cohort of HIV-seropositive patients with chronic hepatitis C in an open prospective trial.

Among the 46 patients so far enrolled in the study, four patients were na]ve of antiretroviral treatment (Table 1). Two of these patients had failed to respond to IFN and ribavirin at 36 weeks, whereas the two other patients were complete responders to therapy, as assessed by the lack of detectable circulating HCV RNA using the Amplicor Roche assay with a lower detection limit of 1000 copies/ml. Plasma levels of HIV RNA of the four patients, before the initiation of IFN and ribavirin, were 4.48 and 4.45 log copies/ml (Quantiplex HIV-RNA 2.0, threshold: 500 copies/ml; Chiron, Emeryville, CA, USA). At week 36 of IFN and ribavirin, the plasma levels of HIV RNA of the two responding patients decreased significantly to 1.79 and 1.76 log copies/ml, with a concomittant increase in the CD4 cells from 565 and 432 to 623 and 584 × 106/l, in the absence of antiretroviral treatment. In the two non-responding patients, plasma levels of HIV RNA (3.8 and 2.9 copies/ml) and CD4 cell counts (398 and 367 × 106/l) at 6 months of therapy did not differ from those at baseline.

Table 1

Table 1

Ribavirin is a nucleoside analogue that exhibited a poor antiviral activity against HIV in one previous clinical trial [2] IFN-α alone was also shown not to be an effective therapy for HIV disease. Facilitating interactions between hepatitis B virus (HBV) and HIV [3] and between HCV and HBV replication [4] through transactivation of viral genes, have been reported; however, there is no such report for HCV and HIV.

Our observations suggest a beneficial effect of IFN and ribavirin on plasma levels of HIV RNA in HIV-seropositive patients with moderate immunodeficiency, co-infected with HCV. Because immune reconstitution with highly active antiretroviral therapy has been associated with enhanced liver damage in co-infected patients with chronic hepatitis C, our data may encourage clinicians to delay the time of initiation of antiretroviral therapy in HIV-seropositive patients with chronic hepatitis C, in order first to achieve a remission of HCV disease. Future trials are needed to confirm these results and document the safety and efficacy of combination therapy with IFN and ribavirin in patients co-infected with HIV and HCV.

Alain Landau

Dominique Batisse

Christophe Piketty

Michel D. Kazatchkine

Back to Top | Article Outline

References

1. Reichard O Norkrans G FrydEn A et al Randomised, double blind, placebo-controlled trial of interferon a-2b with and without ribavirin for chronic hepatitis C. Lancet 1998 35183–87.
2. The Ribavirin ARC Study Group Multicenter clinical trial of oral ribavirin in symptomatic HIV-infected patients. J Acquired Immune Defic Syndr 1993 632–41.
3. Twu JS Chu K Robinson WS Hepatitis B X gene activates k-B like enhancer sequences in the long terminal repeat of human immunodeficiency virus 1. Proc Natl Acad Sci USA 1989 865168–5172.
4. Shih CM Lo SJ Miyamura T et al Suppression of hepatitis B virus expression and replication by hepatitis C virus core protein in HuH-7 cells. J Virol 1993 675823–5832.
© 2000 Lippincott Williams & Wilkins, Inc.