 | HIV
and Hepatitis.com
Coverage of
the 13th Annual Conference on Retroviruses and Opportunistic Infections February 5 - 8, 2006, Denver, CO |
Limited Impact of Antiretroviral Therapy on Risk of Liver-related Death: The D:A:D Study Antiretroviral (ARV) therapy has been highly effective at controlling HIV infection in many patients, but concerns regarding the potential for long-term toxicity, including liver toxicity, of this therapy persist. While studies performed to date have generally indicated that most ARV regimens – especially those that do not involve nevirapine (Viramune), stavudine (Zerit) or high-dose ritonavir (Norvir) – are relatively unlikely to cause liver toxicity, many of these studies did not have enough patients or long-term follow-up required to clearly document this, especially in those patients co-infected with hepatitis B (HBV) or C (HCV). The investigators in the D:A:D study – which had more than 23,400 HIV-infected patients who were prospectively followed for over 76,893 person-years (PY) –assessed whether an association exists between exposure to ARV therapy and the risk of liver-related deaths (LRD). In the study, 1248 (5.3%) persons died (1.6/100 PY) and 183 of these deaths (15%) were from liver-related causes. Among those with LRD, 16.9% had active HBV (HBs/eAg+ or HBV DNA+) and 66.1% HCV (HCVAb+ or HCV RNA+) with 7.1% having both. 97.3% had been exposed to cART for a median of 3.3 years. The
most frequently
reported immediate
causes of LRD
were hepatic
failure (n=124),
bleeding (38),
infection in
patients with
end stage-liver
disease (21
bacterial/8
opportunistic
infections),
and hepatocellular
carcinoma
(17). The independent
predictors of
LRD were lower
baseline CD4
count (RR 1.18
per two-fold
lower), older
age (RR 1.34
per 5 years
older), intravenous
drug use
(RR 2.49), HCV
(RR 7.30) and
active HBV (RR
3.66) infections.
A model adjusting for the risk factors above (including the CD4 count at study entry), suggested a non-significant trend with >4 years exposure to ARV therapy (p=0.23) and adjustment for the latest CD4 count strengthened the relationship (p=0.03). Stratification by HCV status revealed no significant relationship with ARV therapy exposure and LRD in either HCV- or HCV+ patients. The authors conclude, “No strong association was found between exposure to [ARV therapy] for up to 7 years and the rate of LRD. When controlling for the beneficial effect that [ARV therapy] has on the CD4 count, there was some evidence of an association suggesting an increased risk of LRD with extended [ARV therapy] use.” “However, the main risk factors for LRD were low CD4 counts, chronic co-infection with HBV/HCV and age. Additional follow-up will further inform whether [ARV therapy] (or components hereof) affects the risk of LRD.” 02/07/06 Reference
| ||
