People With HIV More Likely to Develop Hypertension After Starting INSTI-Based ART vs NNRTI

People living with HIV receiving integrase strand transfer inhibitor (INSTI)–based antiretroviral therapy (ART) are more likely to develop hypertension after starting the treatment, compared with those receiving non-nucleoside reverse transcriptase inhibitors (NNRTIs).

These findings were part of RESPOND, a large international cohort published in HIV Medicine.

The study authors also found that adults living with HIV receiving boosted protease inhibitors (PIs) had a greater risk of developing hypertension compared with adults receiving INSTIs.

Hypertension or high blood pressure is a major cause of premature death and is associated with increased cardiovascular disease risk. Globally, 35% of adults living with HIV receiving ART have hypertension, making it a growing concern for this population.

To compare hypertension incidence between people using INSTIs, NNRTIs, and PIs, the authors pulled data from 17 cohorts that identified adults aged 18 or older with HIV who were starting or switching treatment with a 3-drug ART. Other eligibility criteria included not having hypertension and having at least 2 follow-up blood pressure (BP) measurements.

The authors defined hypertension as 2 consecutive systolic BP measurements of at least 140 mmHg and/or 2 consecutive diastolic BP measurements of at least 90 mmHg, or initiation of antihypertensives. Multivariable Poisson regression was used to determine adjusted incidence rate ratios (aIRRs) of hypertension.

Of 4606 people with HIV meeting the criteria, 2486 had received ART before, and 2120 were ART naïve. Out of the entire group, 3164 (68.7%) initiated INSTIs, 807 (17.5%) initiated NNRTIs, and 635 (13.8%) initiated PIs.

Of those who have received ART before, 2090 (84.1%) switched to INSTIs with 1289 switching from PIs, 305 switched to NNRTIs with 276 switching from PIs, and 91 switched to PIs with 81 switching from NNRTIs.

The median (IQR) baseline systolic BP was 120 mmHg (113-130) and median diastolic BP was 78 mmHg (70-82). The authors noted this did not differ based on initial treatment and, despite some characteristic differences between groups, baseline BPs were comparable between ART-experienced and ART-naïve individuals.

Of the entire 4606-person population, 1058 (23%) developed hypertension within 8380.4 person-years of follow-up (incidence rate [IR] 126.2 per 1000 person-years; 95% CI, 118.9-134.1), with a median (IQR) follow-up period of 1.5 (1.0-2.7) years.

Adults living with HIV receiving INSTIs had a 76% higher incidence of hypertension compared with adults receiving NNRTIs (adjusted incidence rate ratio [aIRR] 1.76; 95% CI, 1.47-2.11).

A univariable analysis showed hypertension incidence was 31% lower with INSTIs compared with PIs (aIRR 0.69; 95% CI, 0.58-0.81), but incidence was not significantly different after adjusting for previous ART use (aIRR 1.07; 95% CI, 0.75-1.06).

For ART-experienced adults specifically, 497 (20.4%) developed hypertension within 4894.5 person-years (IR, 101.5 per 1000 person-years; 95% CI, 93.0-110.95), and it was 43% more common in adults receiving INSTIs compared with NNRTIs (aIRR 1.43; 95% CI, 1.07-1.92).

For ART-naïve adults, 561 (26.5%) developed hypertension within 3485.8 person-years (IR, 160.9 per 1000 person-years; 95% CI, 148.2-174.8). Hypertension was much higher for adults receiving INSTIs in this group, with a 92% higher incidence compared with adults receiving NNRTIs (aIRR 1.92; 95% CI, 1.51-2.44).

Neither group had a notable difference in hypertension incidence between adults receiving INSTIs and adults receiving PIs.

These findings support a need for regular BP monitoring for adults living with HIV, according to the authors, especially for adults receiving INSTIs or PIs as they are at a higher risk of developing hypertension.

“The high incidence in the present study possibly reflects an ageing and predominantly ART-experienced population,” they noted. “Furthermore, participants with prior AIDS or traditional risk factors should be routinely monitored for hypertension.”

They further added that other studies have associated INSTI use with weight gain. Additionally, this study found type 2 diabetes and high body mass index, among several other factors, to be associated with increased hypertension incidence. However, the data linking INSTIs with hypertension are conflicting.

“Whether the higher risk of hypertension with INSTIs is associated with weight gain will be explored in a planned analysis within RESPOND,” the authors wrote. “Our results suggest that participants with prior AIDS or traditional risk factors should be monitored for hypertension at each visit, especially after initiating INSTIs and PIs.”

Reference

Byonanebye DM, Polizzotto MN, Neesgaard B, et al. The RESPOND study group. Incidence of hypertension in people with HIV who are treated with integrase inhibitors versus other antiretroviral regimens in the RESPOND cohort consortium. HIV Med. 2022;00:1-16. doi:10.1111/hiv.13273