Incidence of Hypertension in People With HIV Who Are Treated With Integrase Inhibitors Versus Other Antiretroviral Regimens in the RESPOND Cohort Consortium

Dathan M. Byonanebye; Mark N. Polizzotto; Bastian Neesgaard; Mario Sarcletti; Raimonda Matulionyte; Dominique L. Braun; Antonella Castagna; Stéphane de Wit; Ferdinand Wit; Eric Fontas; Jörg Janne Vehreschild; Jan Vesterbacka; Lauren Greenberg; Camilla Hatleberg; Harmony Garges; Joel Gallant; Alain Volny Anne; Angela Öllinger; Iwona Mozer-Lisewska; Bernard Surial; Vincenzo Spagnuolo; Coca Necsoi; Marc van der Valk; Amanda Mocroft; Matthew Law; Lene Ryom; Kathy Petoumenos


HIV Medicine. 2022;23(8):895-910. 

In This Article

Abstract and Introduction


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 receiving NNRTIs (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.


Hypertension is a major cause of premature death worldwide and is a growing problem in people living with HIV.[1] Globally, 35% of all adult people living with HIV receiving antiretroviral therapy (ART) have hypertension.[2] The increasing burden of hypertension is partly due to the increasing prevalence of risk factors and ageing of people living with HIV.[2,3] However, the recent improvement in ART access and the associated control of viraemia, together with safer ART, may negate some of the increase in risk factors of hypertension due to ageing. Like individuals without HIV, hypertension is associated with a higher risk of cardiovascular disease (CVD)[4,5] and mortality in people living with HIV.[5,6] The key risk factors for hypertension in the general population that are particularly important in people living with HIV include smoking, alcohol use, illicit drug use and dyslipidaemia.[7,8] In addition, uncontrolled HIV viraemia is an independent risk factor for hypertension[9] and CVD.[10]

The potential mechanisms of hypertension in people living with HIV are diverse and include an interaction of adipogenesis and lipodystrophy activation of the adipocyte renin-angiotensin system, immune reconstitution and metabolic changes, including dyslipidaemia, chronic systemic and vascular inflammation, and renal insufficiency.[1,7,8] Furthermore, ART plays a role in the mechanism of hypertension,[11–13] as has been reported with older protease inhibitors (PIs)[14,15] and non-nucleoside reverse transcriptase inhibitors (NNRTIs).[15,16] However, the risk due to PIs and NNRTIs has been of less clinical relevance in some studies[15] and the risk due to contemporary regimens remains unclear.

Clear evidence associates integrase strand transfer inhibitors (INSTIs) with weight gain,[17–20] but the data linking these agents with hypertension are conflicting. Analyses from selected populations and small cohorts have reported a higher risk of hypertension or elevated blood pressure (BP) in people living with HIV using INSTIs[21–23] despite evidence linking INSTI use with favourable lipid profiles[24–26] and lower levels of vascular disease markers.[27] Randomized controlled trials have also not reported a higher risk of hypertension in people living with HIV receiving INSTIs,[28,29] although this has been investigated in few studies. In addition, the results from clinical trials may be inconclusive because of the highly selected participants and brief durations of follow-up. The risk of hypertension in people living with HIV receiving INSTIs should be further investigated, especially in larger cohorts, since INSTIs are increasingly recommended as first-line ART agents.[30,31] In this analysis, we compared the incidence of hypertension in people living with HIV receiving INSTI-based regimens versus those receiving contemporary NNRTIs and PIs, within a large consortium of HIV cohorts.