Hypertension, dyslipidemia in HIV linked with INSTIs, tenofovir alafenamide

The use of integrase strand transfer inhibitors (INSTIs) and tenofovir alafenamide (TAF) is associated with incident risk for hypertension and dyslipidemia, indicating the need to screen for both conditions in patients with HIV infection. These study findings were published in The Lancet HIV.

Researchers conducted a multicenter, prospective observational study using data sourced from an international consortium of 19 ongoing observational cohort studies. They aimed to determine whether associations between BMI changes and incident risk for hypertension and dyslipidemia in patients with HIV infection differ by antiretroviral therapy (ART) regimen. The analysis included adult patients receiving INSTI- and non-INSTI-based ART who were enrolled at HIV clinics and hospitals in Europe and Australia. The primary outcomes were the incidence of hypertension and dyslipidemia. Outcomes were compared between patients receiving INSTIs, TAF, or both and those receiving other contemporary ART regimens. Multivariable Poisson regression was used to assess incidence rate ratios (IRRs) and the effect of time-updated BMI changes over the follow-up period.

The researchers performed separate analyses for hypertension (N=9704) and dyslipidemia (N=5231). Across both patient populations, the median ages were 44 (IQR, 36-51) and 43 (IQR, 35-50) years, 75.5% and 72.6% were men, 71.7% and 70.8% were White, and 77.5% and 74.6% reported prior ART use, respectively.

During a median follow-up period of 3.9 years, the rate of hypertension was 30.7% (IR, 74 per 1000 person-years; 95% CI, 72-77). Stratified by ART regimen, the researchers observed higher hypertension rates in patients on INSTIs with and without TAF and in those on TAF without INSTIs (IR, 102, 84, and 73 per 1000 person-years, respectively) compared with those on regimens without INSTIs or TAF (IR, 60 per 1000 person-years).

During a median follow-up of 3.2 years, the rate of dyslipidemia was 51.4% (IR, 138 per 1000 person-years; 95% CI, 133-143). Similar to hypertension, dyslipidemia incidence was higher among patients on INSTIs with TAF, INSTIs without TAF, or TAF without INSTIs (IR, 161, 139, and 157 per 1000 person-years, respectively) than in those on ART regimens without INSTIs or TAF (IR, 129 per 1000 person-years).

In fully adjusted analyses, hypertension risk was associated with the use of INSTIs with TAF (adjusted IRR, 1.48; 95% CI, 1.31-1.68), TAF without INSTIs (aIRR, 1.33; 95% CI, 1.14-1.55), and INSTIs without TAF (aIRR, 1.25; 95% CI, 1.13-1.39). However, dyslipidemia risk was only associated with the use of INSTIs with TAF (aIRR, 1.21; 95% CI, 1.07-1.37).

Stratified by specific ART agent, hypertension risk was associated with the use of bictegravir (aIRR, 1.77; 95% CI, 1.41-2.20), raltegravir (aIRR, 1.62; 95% CI, 1.36-1.94), dolutegravir (aIRR, 1.38; 95% CI, 1.20-1.59), and darunavir (aIRR, 1.27; 95% CI, 1.06-1.52). Incident dyslipidemia risk was associated with the use of darunavir (aIRR, 1.57; 95% CI, 1.33-1.85), elvitegravir (aIRR, 1.50; 95% CI, 1.25-1.79), raltegravir (aIRR, 1.43; 95% CI, 1.17-1.75), and efavirenz (aIRR, 1.18; 95% CI, 1.01-1.38).

After adjustment for changes in BMI over the study period, the association between INSTI use and hypertension risk was attenuated and the association between TAF use and dyslipidemia was no longer significant.

Limitations of this analysis include insufficient data on BMI, blood pressure, and lipid concentrations, the predominance of White patients, the relatively short follow-up period, nonstandardized blood pressure and lipid monitoring, and the lack of data on diet, physical activity, and family history.

“[F]urther researcher is warranted to fully understand the associations between the use of INSTIs and tenofovir alafenamide, weight gain, and cardiovascular risk,” the researchers concluded.

Disclosures: Multiple study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.

By Jessica Nye, PhD

References:

Byonanebye DM, Polizzotto MN, Maltez F, et al; on behalf of the RESPOND study group. Associations between change in BMI and the risk of hypertension and dyslipidaemia in people receiving integrase strand-transfer inhibitors, tenofovir alafenamide, or both compared with other contemporary antiretroviral regimens: a multicentre, prospective observational study from the RESPOND consortium cohorts. Lancet HIV. 2024;11(5):e321-e332. doi:10.1016/S2352-3018(23)00328-4