The Impact of HAART on Treatment of HIV-HCV and HIV-HBV Coinfection 

By Marina Nunez, MD, PhD

Effect of HAART on ESLD-free Survival

Several reports suggest that the use of HAART counterbalances the negative impact of HIV infection on the course and outcome of HCV coinfection. In a study presented at the 13th CROI, the effect of HAART on progression to end-stage-liver-disease (ESLD) was evaluated in a cohort of hemophiliacs with known dates of HIV and HCV seroconversion, HAART use, and clinical outcomes [1].

ESLD developed in 17 out of 85 (20%) HIV-positive and in 8 of 72 (11.1%) HIV-negative patients. Median ESLD-free survival was significantly shorter in HIV-positive than in non-HIV patients [hazard ratio, HR, 3.00 (95% CI 1.27-7.08); p=0.009]. With each decade of HIV infection, ESLD risk increased 1.63-fold (95% CI 1.14-2.35; p=0.008).

ESLD-free survival was significantly longer among HAART-treated HIV+ (30.3 years) than in non-HAART HIV+ subjects (20 years) [HR 3.14 (95% CI 1.27-7.08); p=0.043], but was similar to that in non-HIV men. In like manner, HCV duration, age at death or present, median age at ESLD, overall mortality and ESLD mortality were similar in HAART-treated and HIV-negative patients.

These findings suggest that HAART slows progression of HCV-related liver disease to ESLD and results in decreased mortality. Nevertheless, the care of HIV-HCV coinfected patients should also contemplate the provision of specific anti-HCV drugs in addition to HAART in an attempt to eradicate the HCV infection in these patients.

The Role of HAART in Liver Enzyme Elevation

The negative effects of HAART on HIV-hepatitis virus-coinfected patients was the subject of a few studies presented at CROI 2006. The line between elevation of liver enzymes due to HAART toxicity and to the hepatitis coinfections (HCV and HBV) themselves is not clear. Italian investigators addressed this issue analyzing the I.Co.N.A. cohort [2].

HIV-infected patients with HCV-coinfection, defined by positive anti-HCV antibody, and/or with HBV-coinfection, defined by positive HBsAg, were examined. HAART was prescribed to 1,547 patients, while 937 others remained antiretroviral naïve. Non-coinfected patients (2,547) were also included in the analyses.

There was no evidence that HAART was differently used in coinfected and HIV monoinfected patients, after adjustment by age, sex, HIV risk factor and baseline ALT. Liver enzyme elevations were detected in 618 occasions in 353 patients. Patients on HAART were not at increased risk for liver enzyme elevations [RR 1.13 (95% CI 0.89-1.43); p=0.28]. The occurrence of liver enzyme elevations was significantly more frequent in intravenous drug users [RR 1.56 versus heterosexuals (95% CI 1.03-2.36); p=0.03].

The authors concluded, “Most of liver enzyme elevations observed during HAART in hepatitis viruses coinfected patients are probably related to the natural history of liver disease and not to direct drug hepatotoxicity.” These results challenge the concept of HAART hepatotoxicity in HIV-hepatitis coinfected patients. Nevertheless, the analysis could be further refined by a stronger definition of HCV coinfection and by taking into account the effect of anti-HBV active drugs as part of HAART in the case of HBV coinfection.

HAART Duration and Outcome in HIV, HIV-HBV and HIV-HCV Coinfection

The duration of first-line antiretroviral regimen may be decreased in HIV-hepatitis coinfected patients due to the development of HAART-related liver toxicity. Canadian authors presented the results of a study in which 526 HIV-only, 173 HIV/HCV-, and 30 HIV/HBV-coinfected subjects receiving HAART for the first time between January 2000 and December 2004 were evaluated [3].

The overall median duration of therapy was 14months. Those with HCV- coinfection had shorter duration of therapy (HCV 9 months) than those with HIV monoinfection (17 months) (p<0.001). In univariate analysis, longer HAART duration was predicted by HIV-monoinfection versus HCV coinfection [OR 1.64 (95% CI 1.35-1.99); p<0.001]. However, in multivariate Cox regression analysis, history of injection drug use (OR 1.59; p<0.001) but no HCV-coinfection (OR 1.19; p=0.19) predicted shorter duration of first HAART.

Poor adherence and substance abuse were major explanations for premature interruptions in HIV/HCV-coinfected subjects in this study.

02/21/06

References

1. R Schillo and others. HAART improves ESLD-free survival in HIV/HCV coinfection. 13th Conference on Retroviruses and Opportunistic Infections. February 5-8, 2006, Denver, CO Abstract 886.

2. P Cicconi and others. Is the increased risk of liver enzyme elevation in hepatitis coinfected patients greater in those on HAART than in antiretroviral naïve patients? 13th Conference on Retroviruses and Opportunistic Infections. February 5-8, 2006, Denver, CO. Abstract 888.

3. C L Cooper and others. Comparison of first ART duration and outcome in HIV, HIV/HBV, and HIV/HCV infection. 13th Conference on Retroviruses and Opportunistic Infections. February 5-8, 2006, Denver, CO. Abstract 890.