Adverse events to antiretrovirals in the Swiss HIV Cohort Study: effect on mortality and treatment modification.
BACKGROUND
Antiretroviral therapy (ART) decreases morbidity and mortality in HIV-infected patients but is associated with considerable adverse events (AEs).


METHODS
We examined the effect of AEs to ART on mortality, treatment modifications and drop-out in the Swiss HIV Cohort Study. A cross-sectional evaluation of prevalence of 13 clinical and 11 laboratory parameters was performed in 1999 in 1,078 patients on ART. AEs were defined as abnormalities probably or certainly related to ART. A score including the number and severity of AEs was defined. The subsequent progression to death, drop-out and treatment modification due to intolerance were evaluated according to the baseline AE score and characteristics of individual AEs.


RESULTS
Of the 1,078 patients, laboratory AEs were reported in 23% and clinical AEs in 45%. During a median follow up of 5.9 years, laboratory AEs were associated with higher mortality with an adjusted hazard ratio (HR) of 1.3 (95% confidence interval [CI] 1.2-1.5; P < 0.001) per score point. For clinical AEs no significant association with increased mortality was found. In contrast, an increasing score for clinical AEs (HR 1.11,95% CI 1.04-1.18; P = 0.002), but not for laboratory AEs (HR 1.07, 95% CI 0.97-1.17; P = 0.17), was associated with antiretroviral treatment modification. AEs were not associated with a higher drop-out rate.


CONCLUSIONS
The burden of laboratory AEs to antiretroviral drugs is associated with a higher mortality. Physicians seem to change treatments to relieve clinical symptoms, while accepting laboratory AEs. Minimizing laboratory drug toxicity seems warranted and its influence on survival should be further evaluated.
Keiser
Olivia
O
Institute of Social and Preventive Medicine (ISPM), University of Bern, Switzerland.
Fellay
Jacques
J
Opravil
Milos
M
Hirsch
Hans H
HH
Hirschel
Bernard
B
Bernasconi
Enos
E
Vernazza
Pietro L
PL
Rickenbach
Martin
M
Telenti
Amalio
A
Furrer
Hansjakob
H
D000328:Adult; D044966:Anti-Retroviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D023241:Antiretroviral Therapy, Highly Active; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D006678:HIV; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016019:Survival Analysis; D013557:Switzerland; D016896:Treatment Outcome; D028761:Withholding Treatment
D044966:Anti-Retroviral Agents