Incidence of hypertension in people with HIV who are treated with integrase inhibitors versus other antiretroviral regimens in the RESPOND cohort consortium

Abstract

Objective: To compare the incidence of hypertension in people living with HIV receiving integrase strand transfer inhibitor (INSTI)-based antiretroviral therapy (ART) versus non-nucleoside reverse transcriptase inhibitors (NNRTIs) or boosted protease inhibitors (PIs) in the RESPOND consortium of HIV cohorts. Methods: Eligible people with HIV were aged ≥18 years who initiated a new three-drug ART regimen for the first time (baseline), did not have hypertension, and had at least two follow-up blood pressure (BP) measurements. Hypertension was defined as two consecutive systolic BP measurements ≥140 mmHg and/or diastolic BP ≥90 mmHg or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension, overall and in those who were ART naïve or experienced at baseline. Results: Overall, 4606 people living with HIV were eligible (INSTIs 3164, NNRTIs 807, PIs 635). The median baseline systolic BP, diastolic BP, and age were 120 (interquartile range [IQR] 113-130) mmHg, 78 (70-82) mmHg, and 43 (34-50) years, respectively. Over 8380.4 person-years (median follow-up 1.5 [IQR 1.0-2.7] years), 1058 (23.0%) participants developed hypertension (incidence rate 126.2/1000 person-years, 95% confidence interval [CI] 118.9-134.1). Participants receiving INSTIs had a higher incidence of hypertension than those receivingNNRTIs (aIRR 1.76; 95% CI 1.47-2.11), whereas the incidence was no different in those receiving PIs (aIRR 1.07; 95% CI 0.89-1.29). The results were similar when the analysis was stratified by ART status at baseline. Conclusion:Although unmeasured confounding and channelling bias cannot be excluded, INSTIs were associated with a higher incidence of hypertension than were NNRTIs, but rates were similar to those of PIs overall, in ART-naïve and ART-experienced participants within RESPOND.

Change in body weight and risk of hypertension after switching from efavirenz to dolutegravir in adults living with HIV: evidence from routine care in Johannesburg, South Africa

“…Clinical trials have reported no increased risk of hypertension, 29 , 30 while analyses from observational cohorts, including our own, have reported a higher risk of hypertension or elevated blood pressure in PLWH using INSTIs. 31 , 32 , 33 , 34 There are a number of hypothesized pathways for this increased risk, primarily mediated through changes in BMI, 33 however INSTI use has also been linked to dyslipidaemia, adipogenesis, oxidative stress and insulin resistance, all of which have been associated with hypertension. 32 Though previous studies have also linked our comparative agent, efavirenz, to dyslipidaemia, 35 it was not shown to be associated with an increased risk of hypertension.…”

“… 31 , 32 , 33 , 34 There are a number of hypothesized pathways for this increased risk, primarily mediated through changes in BMI, 33 however INSTI use has also been linked to dyslipidaemia, adipogenesis, oxidative stress and insulin resistance, all of which have been associated with hypertension. 32 Though previous studies have also linked our comparative agent, efavirenz, to dyslipidaemia, 35 it was not shown to be associated with an increased risk of hypertension. 36 Further research is needed to delineate the metabolic pathway between INSTI use and hypertension.…”

Associations between HIV status and self-reported hypertension in a high HIV prevalence sub-Saharan African population: a cross-sectional study

“… 30 31 The use of newer integrase inhibitors may also increase weight gain among PLHIV and raise the prevalence of hypertension further. 32 33 Consequently, more prevention and treatment services may be required to avoid worsening outcomes.…”

Inflammation markers and the risk of hypertension in people living with HIV

“…Microbial translocation, chronic inflammation, immune reconstitution, and HIV-related renal disease all influence the development and progression of hypertension. In addition, the use of INSTIs has been reported to affect hypertension (60), due to the limited number of patients using INSTIs, we have not found the effect of drugs on hypertension for the time being. Indeed, the effect of drugs on blood pressure may require longer observation.…”