HAART -- Especially Nevirapine -- May Slow Progression of Liver Fibrosis in HIV-HCV Coinfected Individuals

The effect of HAART on the progression of liver disease in people with HIV-HCV coinfection is not well understood. Studies have shown that people with more advanced immune compromise tend to experience more rapid fibrosis progression, suggesting that antiretroviral therapy that controls HIV and enables CD4 cell recovery may have a beneficial impact on liver disease.

On the other hand, several antiretroviral drugs can cause liver toxicity, signaled by elevated liver enzymes and in rare cases life-threatening liver failure. The non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine can cause a hypersensitivity reaction involving the liver, the nucleoside reverse transcriptase inhibitors (NRTIs) d4T and ddI can cause enlarged fatty liver (steatosis) associated with mitochondrial toxicity, and protease inhibitors (PIs) can also cause liver problems. Studies suggest that the risk of drug-related liver toxicity is highest among people with pre-existing liver disease, including chronic hepatitis B or C.

As reported at the 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) last week in Chicago, researchers analyzed the effect of exposure to NNRTIs and PIs on liver fibrosis progression in HIV-HCV coinfected individuals.

Three-quarters were men, the median age was 39 years, 32% had a prior AIDS diagnosis, all were on HAART for a median of 4.3 years, the median CD4 count was 460 cells/mm3, and 72.8% had an HIV viral load below 50 copies/mL. The estimated median time since HCV infection was 21.3 years and 57% had HCV genotype 1.

The investigators analyzed liver biopsy samples from 201 consecutive coinfected patients who acquired HIV through injection drug use. Fibrosis was scored using the METAVIR system. By multinomial logistic regression, they assessed the association between time on a NNRTI or PI and both fibrosis stage and fibrosis progression index (FPI), the ratio of fibrosis stage to years of HCV infection.

Results

• The distribution of liver fibrosis was as follows:
- F0 (no fibrosis): 0.5%;
- F1 (minimal fibrosis): 37.1%;
- F2 (moderate fibrosis): 31.9%;
- F3 (advanced fibrosis): 18.8%;
- F4 (severe fibrosis/cirrhosis): 11.7%.
• The association between time on HAART and fibrosis stage (using F ? 3 as a reference) and with the FPI (FPI > 0.1 as a reference) is summarized in the table below:

	F ≤ 1 vs F ≥ 3	F2 vs ≥ F3	FPI ≤ 0.1 vs > 0.1
Per year on	OR (CI 95%)	OR (CI 95%)	OR (CI 95%)
HAART	1.32 (1.04-1,67)	1.20 (0.95-1.53)	1.31 (1.07-1.60)
PI	1.24 (0.99-1.54)	1.00 (0.79-1.26)	1.14 (0.95-1.38)
NNRTI	1.64 (1.18-2.27)	1.51 (1.08-2.10)	1.33 (1.03-1.70)
Efavirenz	1.54 (1.03-2.30)	1.42 (0.94-2.16)	1.18 (0.86-1.62)
Nevirapine	1.72 (1.15-2.78)	1.58 (1.06-2.37)	1.44 (1.07-1.95)

Conclusion

Based on these findings, the researchers concluded that, "Exposure to HAART reduced the FPI and development of bridging fibrosis and cirrhosis. Nevirapine was found to be the most beneficial drug for fibrosis progression whereas PIs were not."

The investigators acknowledged that this finding contradicts reports to date, which indicate that nevirapine is among the drugs most likely to cause liver problems.

"Prospective studies are needed to assess the effects of different antiretroviral agents on fibrosis progression in HIV-HCV coinfected patients," they added.

Hosp. Gregorio Marañón, Madrid, Spain; Hosp Gregorio Marañón, Madrid, Spain.

09/25/07

Reference
J Berenguer, S Resino, P Miralles, and others. Association Between Nevirapine Exposure and Reduced Liver Fibrosis Progression and Development of Bridging Fibrosis and Cirrhosis in HIV/HCV-Coinfected Patients. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy. Chicago, September 17-20, 2007. Abstract V-1385.

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