Low frequency of severe hepatotoxicity and association with HCV coinfection in HIV-positive patients treated with HAART.
BACKGROUND
Highly active antiretroviral therapy (HAART) is strongly effective in reducing morbidity and mortality in HIV-1-positive individuals. Its main drawback is the potential toxicity. Data on the frequency and determinants of severe hepatotoxicity in a clinical setting are still sparse.


METHODS
This is a prospective study of HIV-1-positive individuals with known HBsAg and HCV-Ab serology. The study end point was progression to alanine aminotransferase (ALT) levels > or =200 IU/L after HAART initiation. Cumulative probability of progression to this end point was estimated by the Kaplan-Meier method. Crude and adjusted hazard ratios (HR) were estimated by proportional hazards regression model.


RESULTS
One thousand two hundred fifty-five patients were included. HBsAg was found in 91 (7.2%), HCV-Ab in 578 (46.5%) patients; almost all injection drug users (451 of 482; 93.6%) were HCV-Ab positive. Sixty-one individuals progressed to the end point with a probability of 7.9% (95% confidence interval [CI], 5.6-10.0) of progression at 24 months from starting. Independent factors predicting progression to the end point were baseline ALT levels (HR, 5.29; 95% CI, 3.24-8.65; every 10 IU/L higher), HCV-Ab positivity (HR, 4.01; 95% CI, 1.48-10.85) or both HBsAg and HCV Ab positivity (HR, 3.85, 95% CI, 1.01-14.61), and previous non-HAART therapy (HR, 1.84, 95% CI, 1.04-3.42). Patients receiving stavudine-containing regimens had a lower risk than those receiving zidovudine-containing regimens (HR, 0.30, 95% CI, 0.12-0.71).


CONCLUSIONS
There was a low risk of ALT > or =200 IU/L in our cohort. Hepatitis C coinfection and elevated ALT levels at HAART initiation are important predictors of progression to ALT > or =200 IU/L; stavudine-containing regimens were associated with a lower risk compared with zidovudine-containing regimens.
Monforte
A de A
Ade A
Institute of Infectious and Tropical Diseases, University of Milan, L Sacco H, Milan, Italy. adarmin@tin.it
Bugarini
R
R
Pezzotti
P
P
De Luca
A
A
Antinori
A
A
Mussini
C
C
Vigevani
G M
GM
Tirelli
U
U
Bruno
R
R
Gritti
F
F
Piazza
M
M
Chigiotti
S
S
Chirianni
A
A
De Stefano
C
C
Pizzigallo
E
E
Perrella
O
O
Moroni
M
M
D000410:Alanine Transaminase / Q000097:blood; D019380:Anti-HIV Agents / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D006679:HIV Seropositivity / Q000150:complications; D015497:HIV-1 / Q000302:isolation & purification; D006514:Hepatitis B Surface Antigens / Q000032:analysis; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D008297:Male; D016016:Proportional Hazards Models; D018119:Stavudine; D015215:Zidovudine / Q000627:therapeutic use
D019380:Anti-HIV Agents; D006514:Hepatitis B Surface Antigens; D015215:Zidovudine; D018119:Stavudine; D000410:Alanine Transaminase