Associations between change in BMI and the risk of hypertension and dyslipidaemia in people receiving INSTI’s and TAF. Lancet HIV
Byonanebye et al. on behalf of the RESPOND consortium aimed to compare the risk of new-onset hypertension or dyslipidaemia in people receiving integrase strand-transfer inhibitors (INSTIs), tenofovir alafenamide, or both versus regimens without INSTIs and tenofovir alafenamide, and established whether increases in BMI could explain any associations between antiretroviral therapy (ART) regimens and hypertension or dyslipidaemia.
Participants were eligible if receiving INSTI-containing ART regimens or a contemporary non-INSTI, did not have hypertension or dyslipidaemia at baseline, and had baseline and at least two follow-up BMI, lipid, and blood pressure measurements. Participants receiving non-ART medications associated with weight changes, including antipsychotics and mood stabilisers, corticosteroids, insulin, and insulin secretagogues were excluded.
Of the 35 941 RESPOND participants, 9’704 (7’327 [75·5 %] male and 2’377 [24·5%] female) were included in the hypertension analysis and 5’231 (3’796 [72·6%] male and 1’435 [27·4%] female) were included in the dyslipidaemia analysis. In the univariable model, hypertension was more common in individuals receiving an INSTI with tenofovir alafenamide (IRR 1·70, 95% CI 1·54–1·88) or an INSTI without tenofovir alafenamide (1·41, 1·30–1·53) compared with those receiving neither INSTIs nor tenofovir alafenamide. Adjustment for time-updated BMI and confounders attenuated risk in participants receiving an INSTI with (IRR 1·48, 1·31–1·68) or without (1·25, 1·13–1·39) tenofovir alafenamide. Similarly, dyslipidaemia was more common in participants using tenofovir alafenamide with an INSTI (IRR 1·24, 1·10–1·40) and tenofovir alafenamide alone (1·22, 1·03–1·44) than in participants using neither INSTI nor tenofovir alafenamide. Adjustment for BMI and confounders attenuated the risk in participants receiving tenofovir alafenamide with an INSTI (adjusted IRR 1·21, 1·07–1·37), whereas the risk in those receiving tenofovir alafenamide alone became non-significant (1·15, 0·96–1·38). The associations between increasing BMI and risk of hypertension and dyslipidaemia did not differ between participants receiving different ART regimens (pinteraction = 0∙46 for hypertension; pinteraction = 0∙31 for dyslipidaemia).
In conclusion, the study reports an association between weight gain, the concurrent or separate use of INSTIs or tenofovir alafenamide, and hypertension and dyslipidaemia. The association between INSTIs and hypertension appears to be partly mediated by weight gain. Furthermore, the association between weight gain and hypertension or dyslipidaemia was not different in regimens with INSTIs or tenofovir alafenamide than in other contemporary antiretroviral regimens. Interpreted with results that have linked INSTIs with increased cardiovascular risk, further research is warranted to fully understand the associations between the use of INSTIs and tenofovir alafenamide, weight gain, and cardiovascular risk.