Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: a multi-cohort collaboration.
BACKGROUND
Whether nucleoside reverse transcriptase inhibitors increase the risk of myocardial infarction in HIV-infected individuals is unclear. Our aim was to explore whether exposure to such drugs was associated with an excess risk of myocardial infarction in a large, prospective observational cohort of HIV-infected patients.


METHODS
We used Poisson regression models to quantify the relation between cumulative, recent (currently or within the preceding 6 months), and past use of zidovudine, didanosine, stavudine, lamivudine, and abacavir and development of myocardial infarction in 33 347 patients enrolled in the D:A:D study. We adjusted for cardiovascular risk factors that are unlikely to be affected by antiretroviral therapy, cohort, calendar year, and use of other antiretrovirals.


RESULTS
Over 157,912 person-years, 517 patients had a myocardial infarction. We found no associations between the rate of myocardial infarction and cumulative or recent use of zidovudine, stavudine, or lamivudine. By contrast, recent-but not cumulative-use of abacavir or didanosine was associated with an increased rate of myocardial infarction (compared with those with no recent use of the drugs, relative rate 1.90, 95% CI 1.47-2.45 [p=0.0001] with abacavir and 1.49, 1.14-1.95 [p=0.003] with didanosine); rates were not significantly increased in those who stopped these drugs more than 6 months previously compared with those who had never received these drugs. After adjustment for predicted 10-year risk of coronary heart disease, recent use of both didanosine and abacavir remained associated with increased rates of myocardial infarction (1.49, 1.14-1.95 [p=0.004] with didanosine; 1.89, 1.47-2.45 [p=0.0001] with abacavir).


CONCLUSIONS
There exists an increased risk of myocardial infarction in patients exposed to abacavir and didanosine within the preceding 6 months. The excess risk does not seem to be explained by underlying established cardiovascular risk factors and was not present beyond 6 months after drug cessation.
Sabin
Caroline A
CA
Worm
Signe W
SW
Weber
Rainer
R
Reiss
Peter
P
El-Sadr
Wafaa
W
Dabis
Francois
F
De Wit
Stephane
S
Law
Matthew
M
D'Arminio Monforte
Antonella
A
Friis-Møller
Nina
N
Kirk
Ole
O
Pradier
Christian
C
Weller
Ian
I
Phillips
Andrew N
AN
Lundgren
Jens D
JD
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016049:Didanosine / Q000009:adverse effects* / Q000627:therapeutic use; D015224:Dideoxynucleosides / Q000009:adverse effects* / Q000627:therapeutic use; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced*; D016012:Poisson Distribution; D018894:Reverse Transcriptase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D012307:Risk Factors; D000099227:Abacavir
D016049:Didanosine; D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; D000099227:Abacavir