Thymidine Analogues, Didanosine Associated With Cardiovascular Risk

Results published in the journal AIDS suggest that there may be a potentially irreversible and harmful association of thymidine analogues and didanosine with increased visceral adipose tissue accumulation in people living with HIV (PLWHIV) who are exposed to these medications. The visceral adipose tissue accumulation further appears to be involved in increased risks for hypertension, hypercholesterolemia, and low high-density lipoprotein (HDL) level.

The study was conducted using data collected from 761 PLWHIV from the COCOMO study and 2283 age- and sex-matched controls from the Copenhagen General Population Study. The group of PLWHIV was stratified according to prior exposure and both visceral adipose tissue and subcutaneous adipose tissue distributions, which were determined using computer tomography scan.

According to regression analysis results, exposure to thymidine analogues and/or didanosine in PLWHIV was associated with 21.6 cm² larger visceral adipose tissue (95% CI, 13.8-29.3) compared with tissue in those with HIV infection without exposure. The results from individuals without HIV were associated with similar visceral adipose tissue compared with PLWHIV and unexposed individuals. Cumulative exposure was associated with visceral adipose tissue 3.7cm² larger (95% CI, 2.3-5.1) but time since discontinuation was not. An excess risk for hypertension (adjusted odds ratio [aOR] 1.11 per 20 cm² increase of visceral adipose tissue), hypercholesterolemia (aOR 1.17), and low HDL (aOR 1.13) were also associated with prior thymidine analogue and/or didanosine exposure in PLWHIV.

The main limitation to this work was the cross-sectional design, whereby exposure and outcome are measured at the same time. This meant causal relationships of the associations of cumulative exposure and the time since discontinuation with the study outcomes could not be drawn. It is also possible, according to the study investigators, that minor differences in ethnicity between the 2 populations may explain some differences in adipose tissue distribution. However, steps were taken to reduce possible confounding effects by adjusting variables such as region of origin in the multivariable analysis.

The researchers concluded that if their work can be confirmed with further prospective studies, these results may help identify a subgroup of PLWHIV who may benefit from more intensive cardiovascular prevention interventions.

Reference

Gelpi M, Afzal S, Fuchs A, et al. Prior exposure to thymidine analogues and didanosine is associated with long-lasting alterations in adipose tissue distribution and cardiovascular risk factors [published online December 21, 2018]. AIDS. doi: 10.1097/QAD.0000000000002119.