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The D:A:D Study

The Data Collection on Adverse Events of Anti-HIV Drugs Study Group^*

Arch Intern Med. 2006;166:1632-1641.

Background  An increasing proportion of deaths among human immunodeficiency virus (HIV)–infected persons with access to combination antiretroviral therapy (cART) are due to complications of liver diseases.

Methods  We investigated the frequency of and risk factors associated with liver-related deaths in the Data Collection on Adverse Events of Anti-HIV Drugs study, which prospectively evaluated 76 893 person-years of follow-up in 23 441 HIV-infected persons. Multivariable Poisson regression analyses identified factors associated with liver-related, AIDS-related, and other causes of death.

Results  There were 1246 deaths (5.3%; 1.6 per 100 person-years); 14.5% were from liver-related causes. Of these, 16.9% had active hepatitis B virus (HBV), 66.1% had hepatitis C virus (HCV), and 7.1% had dual viral hepatitis co-infections. Predictors of liver-related deaths were latest CD4 cell count (adjusted relative rate [RR], 16.1; 95% confidence interval [CI], 8.1-31.7 for <50 vs 500/µL), age (RR, 1.3; 95% CI, 1.2-1.4 per 5 years older), intravenous drug use (RR, 2.0; 95% CI, 1.2-3.4), HCV infection (RR, 6.7; 95% CI, 4.0-11.2), and active HBV infection (RR, 3.7; 95% CI, 2.4-5.9). Univariable analyses showed no relationship between cumulative years patients were receiving cART and liver-related death (RR, 1.00; 95% CI, 0.93-1.07). Adjustment for the most recent CD4 cell count and patient characteristics resulted in an increased risk of liver-related mortality per year of mono or dual antiretroviral therapy before cART (RR, 1.09; 95% CI, 1.02-1.16; P = .008) and per year of cART (RR, 1.11; 95% CI, 1.02-1.21; P = .02).

Conclusions  Liver-related death was the most frequent cause of non–AIDS-related death. We found a strong association between immunodeficiency and risk of liver-related death. Longer follow-up is required to investigate whether clinically significant treatment-associated liver-related mortality will develop.

*Authors/Writing Committee: The following members of the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) Study Group take authorship responsibility for the D:A:D Study: Rainer Weber, MD; Caroline A. Sabin, PhD; Nina Friis-Møller, MD, PhD; Peter Reiss, MD, PhD; Wafaa M El-Sadr, MD, PhD; Ole Kirk, MD, DMSc; Francois Dabis, MD, PhD; Matthew G. Law, PhD; Christian Pradier, MD, PhD; Stephane De Wit, MD, PhD; Börje Åkerlund, MD; Gonzalo Calvo, MD; Antonella d’Arminio Monforte, MD, DMSc; Martin Rickenbach, MD; Bruno Ledergerber, PhD; Andrew N. Phillips, PhD; and Jens D. Lundgren , MD, DMSc.

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