Journal zyxw of Medical Virology 40107-111 (1993) Treatment With Recombinant dnterferon of Chronic Hepatitis C in Anti-HIV-Positive Patients Eduardo Marriott, Sonia Navas, Jorge del Romero, Soledad Garcia, Inmaculada Castillo, Juan Antonio Quiroga, and Vicente Carreno zyxwvut Hepatology Unit, Department zyxwvutsrq of Gastroenterology, Fundacidn Jimdnez Diaz, (E.M., S.N., zyxw Z.C., zyxw J.A.Q., V.C.), Madrid, and Centro Sanitario Sandoval (J.R., S.G.), Madrid, Spain A pilot study of chronic hepatitis C treatment was conducted in 14 patients (13 had chronic active hepatitis and 1 had liver cirrhosis). All patients were asymptomatic for the human immunodefi- ciency virus (HIV)type 1 (mean CD4 count of 584 * 283 cells/mm3). Patients received 9 MU rlFN- a2A per day for three months. After this, patients received 9 MU three times weekly for three months, 6 MU for another three months on the same protocol, and finally 3 MU again three times weekly for the last three months. After the first month of ALT treatment in 9 patients (64%) returned to normal; a significant decrease in ALT levels was observed with respect to the pretreat- ment values (mean of 42 lU/l, range 15-75 vs 152 IUA, range 69-355; zyxwvutsr P < 0.01). Of the 9 patients who completed the treatment period, 5 had a complete response, and 4 zyxwvuts of these 5 continued with normal ALT values during follow-up (sus- tained response) while the other patient relapsed within one month after cessation of therapy. The remaining 4 patients were non-responders (in- cluding one case with a break-through of the re- sponse). HCV-RNA was not detectable in 3 of the 5 responders at the end of therapy while during follow-up viral RNA became undetectable in the other 2 patients. 2/4 non-responder patients had detectable HCV-RNA during follow-up. Liver his- tology improved in all the patients. No changes were observed in the immunological status or HIV infection. o 1993 Wiley-Liss, Inc. KEY WORDS: chronic hepatitis C, anti-HIV, a-i nterferon therapy INTRODUCTION The hepatitis C virus (HCV) genome has been identi- fied by molecular cloning and found to consist of an RNA molecule 9,400 base pairs in length [Choo et al., 19891. HCV is responsible for most cases of parenterally transmitted non-A,non-B (NANB) hepatitis and may result in a chronic carrier state. Chronic hepatitis C may progress to liver cirrhosis [Dienstag et al., 19831 zyxwv 0 1993 WILEY-LISS, INC. and to hepatocellular carcinoma [Hasan et al., 19901. Interferon treatment is efficient in patients with chronic hepatitis C [Davis et al., 1989; Di Bisceglie et al., 19891. However, previous studies on therapy of chronic hepatitis C did not include anti-HIV positive patients. The degree of deterioration of the immune system in patients with HIV infection may be variable and as- ymptomatic HIV carriers may have a relatively well preserved immune system [Lefson et al., 19881. In addi- tion, it has been shown that interferon-a (IFN-a) has an antiviral effect on HIV in in vitro studies [Ho et al., 19851. Although HIV infection might prove fatal before the complications of HCV infection, there is increasing evidence that HCV disease progresses more rapidly in the presence of HIV coinfection [Martin et al., 19891. This apparent cooperation of HIV and HCV might sug- gest IFN as an appropriate therapy in cases of coinfec- tion. The antiviral benefits of INF might outweigh its detrimental side effects. To investigate this possible therapy, we carried out a pilot study of treatment of chronic hepatitis C in patients who had anti-HIV anti- bodies but were asymptomatic. PATIENTS AND METHODS Patients Fourteen consecutive anti-HCV positive patients (9 male, 5 female) with a mean age of 29.0 & 5.9 years (range 21-39) were included. All the patients had been parenteral drug abusers, but had ended drug addiction at least 1 year prior to the study. All patients had a chronic hepatitis documented by biopsy obtained within 6 months prior to treatment (13 had a chronic active hepatitis and 1 had liver cirrhosis). All the pa- tients had abnormal ALT levels for the past 3 years before treatment and resulted negative for HBsAg, HBV-DNA, and anti-HDV. Other causes of liver dis- ease were excluded (alcohol abuse, autoimmune dis- ease, Wilson’s disease, haemochromatosis, porphyria, Accepted for publication September 25,1992. Address reprint requests to Dr. V. Carreno, Hepatology Unit, Department of Gastroenterology, Fundacion Jimenez Diaz, Avda. Reyes Catolicos, 2, E-28040 Madrid, Spain.