HIV-positive patients who are coinfected with hepatitis C virus (HCV) are less likely to discontinue anti-HIV therapy because of liver toxicities if they first receive six months of anti-HCV treatment, according to a small Italian study published in the June 1st edition of the Journal of Acquired Immune Deficiency Syndromes.
The study also found that discontinuation of HAART due to liver problems was predicted by baseline alanine aminotransferase levels (ALT) and that delaying the initiation of HAART to allow time initial HCV therapy did not lead to increases in HIV viral load.
In January 1996, investigators recruited 105 coinfected patients at the San Raffaele University Hospital in Milan. Patients were given the opportunity to defer anti-HIV treatment and start HCV therapy with a regimen of either interferon-alpha monotherapy or interferon-alpha and ribavirin. Thirty-six patients opted to receive interferon-alpha monotherapy, and 30 combination anti-HCV therapy. The remaining 39 patients refused anti-HCV therapy and opted to receive HAART.
After six months of anti-HCV therapy patients were followed for 24 months of HAART. Patients with normal ALT levels at baseline were considered to have progressed if their levels increased beyond the upper limit of the normal range. Progression was graded on a four point scale, point one being 1.25 to 2.5 times baseline and point four five times or above baseline levels.
There were no significant differences in the baseline characteristics between the patients who opted to accepted anti-HCV therapy and those who commenced HAART. Average age was 35 years and CD4 cell count 480 cells/mm3. The majority of patients were infected with HCV genotype 3 (n=74), with 27 infected with genotype 1.
Eleven patients (16.6%) who received anti-HCV therapy already had an undetectable HCV viral load at baseline.
After six months of HCV treatment, 50% of patients receiving monotherapy had seen an improvement in their ALT levels and 30% a decrease in their HCV load. Amongst patients receiving combination HCV therapy, 66.6% experienced an improvement in ALT levels and 64.4% a fall in HCV viral load. Only one patient receiving monotherapy maintained a sustained virological response compared to ten patients treated with interferon alpha and ribavirin, nine of whom were infected with HCV genotype 3.
Side-effects caused seven patients on monotherapy and nine on combination therapy to discontinue HCV treatment.
HIV viral load fell slightly in patients treated with combination HCV therapy.
After HAART was initiated, four of the 66 (6.1%) pretreated patients had to discontinue because of severe liver side-effects compared to six of the 39 (15.4%) patients who opted-out of HCV therapy. The investigators estimated that the probability of HCV pretreated patients staying on HAART for 24 months was 95% compared to 85% for those who did not receive HCV therapy, “thus suggesting that previous chronic active hepatitis treatment reduces the risk of severe antiretroviral therapy-related hepatotoxicity by 10%” (RR 10.4, 95% CI 1.6-66, p=0.0127).
The only other risk factor for the development of severe liver toxicities found by the investigators was elevated baseline ALT levels. The risk ratio for discontinuing anti-HIV therapy was 1.014 for every unit increase in ALT levels for patients pretreated for HCV and 10.4 for patients who did not receive anti-HCV drugs.
Commenting on their study, the investigators note “the patients who had never been treated for HCV infection had a significantly higher risk of being unable to tolerate anti-HIV drugs, and the protective effect of anti-HCV therapy was maintained after the discontinuation of therapy.” In addition, the only patients who received HCV treatment who subsequently discontinued HAART were those who did not achieve a sustained virological response.
They conclude, “our data allow us to suggest that anti-HCV therapy should be given before starting antiretroviral therapy, because this may reduce the risk of severe antiretroviral therapy-related liver toxicity and probably reduces the risk of progressing to liver failure.”
Further information on this website
Hepatitis C - overview
Hepatitis C - factsheet
Draft BHIVA guidelines for treatment of HIV/HCV coinfection
HIV and hepatitis - booklet in the information for HIV-positive people series (pdf)
Uberti-Foppa C et al. Pretreatment of chronic active hepatitis C in patients coinfected with HIV and hepatitis C virus reduces the hepatotoxicity associated with subsequent antiretroviral therapy. JAIDS 33: 146 – 152, 2003.