First-Line Antiretroviral Regimens and Risk of Incident Hypertension in People With HIV: A 15-Year Cohort Study
Abstract
Background: People with HIV (PWH) face a growing burden of cardiovascular disease. Integrase strand transfer inhibitors (INSTIs) have been linked to weight gain and possibly hypertension, but head-to-head data among contemporary regimens are scarce, and few studies analyze older and modern regimens together. We evaluated the incidence of hypertension in antiretroviral therapy (ART)-naive PWH initiating Spanish guidelines-recommended first-line regimens since 2009.
Methods: This study evaluated a retrospective cohort of ART-naive adults initiating first-line regimens from 2009 to 2024, grouped into non-nucleoside reverse transcriptase inhibitor (NNRTI), INSTI, and boosted protease inhibitor (PI)-based classes. Incident hypertension was defined by a composite of clinical diagnosis, antihypertensive initiation, or 2 consecutive measurements ≥ 140/90 mmHg. Time to hypertension was analyzed using Kaplan–Meir methods and Cox regression, with a prespecified INSTI subanalysis.
Results: Among 1134 participants (median age 34.1 years; 89.8% male), 205 (18.1%) developed hypertension over a median of 135.9 weeks (incidence 4.9/100 person-years). Hypertension-free survival differed by class (log-rank P = .005); INSTI-based ART was independently associated with higher risk than NNRTIs (adjusted HR 1.61; 95% CI 1.20–2.17). Within the INSTI subgroup (n = 437; incidence 7/100 person-years), 5-year cumulative hypertension ranged from 9% (EVG/c/FTC/TAF) to 37% (dolutegravir-based); dolutegravir-based regimens carried a >2-fold adjusted hazard versus EVG/c/FTC/TAF. Higher body mass index was independently predictive but did not abolish this signal.
Conclusions: In ART-naive PWH, INSTI-based regimens were associated with a higher incidence of hypertension than NNRTI-based regimens, whereas the comparison with PI-based regimens was not statistically significant. Dolutegravir-containing regimens were independently associated with incident hypertension supporting systematic blood pressure surveillance and further comparative studies.
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BibTeX
@article{bernardino2026firstline,
title = {{First-Line Antiretroviral Regimens and Risk of Incident Hypertension in People With HIV: A 15-Year Cohort Study}},
author = {José I Bernardino and C Busca and L Serrano and A de Gea-Grela and M M Arcos-Rueda and L Martin-Carbonero and M L Montes and R Montejano and J Llenas-García and R Mican and R de Miguel and J González-García and A Borobia and José R Arribas},
journal = {Open Forum Infectious Diseases},
year = {2026},
month = oct,
doi = {10.1093/ofid/ofag686},
url = {https://doi.org/10.1093/ofid/ofag686},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - First-Line Antiretroviral Regimens and Risk of Incident Hypertension in People With HIV: A 15-Year Cohort Study
AU - José I Bernardino
AU - C Busca
AU - L Serrano
AU - A de Gea-Grela
AU - M M Arcos-Rueda
AU - L Martin-Carbonero
AU - M L Montes
AU - R Montejano
AU - J Llenas-García
AU - R Mican
AU - R de Miguel
AU - J González-García
AU - A Borobia
AU - José R Arribas
PY - 2026
DA - 2026/10/24
JO - Open Forum Infectious Diseases
DO - 10.1093/ofid/ofag686
UR - https://doi.org/10.1093/ofid/ofag686
AB - Background: People with HIV (PWH) face a growing burden of cardiovascular disease. Integrase strand transfer inhibitors (INSTIs) have been linked to weight gain and possibly hypertension, but head-to-head data among contemporary regimens are scarce, and few studies analyze older and modern regimens together. We evaluated the incidence of hypertension in antiretroviral therapy (ART)-naive PWH initiating Spanish guidelines-recommended first-line regimens since 2009. Methods: This study evaluated a retrospective cohort of ART-naive adults initiating first-line regimens from 2009 to 2024, grouped into non-nucleoside reverse transcriptase inhibitor (NNRTI), INSTI, and boosted protease inhibitor (PI)-based classes. Incident hypertension was defined by a composite of clinical diagnosis, antihypertensive initiation, or 2 consecutive measurements ≥ 140/90 mmHg. Time to hypertension was analyzed using Kaplan–Meir methods and Cox regression, with a prespecified INSTI subanalysis. Results: Among 1134 participants (median age 34.1 years; 89.8% male), 205 (18.1%) developed hypertension over a median of 135.9 weeks (incidence 4.9/100 person-years). Hypertension-free survival differed by class (log-rank P = .005); INSTI-based ART was independently associated with higher risk than NNRTIs (adjusted HR 1.61; 95% CI 1.20–2.17). Within the INSTI subgroup (n = 437; incidence 7/100 person-years), 5-year cumulative hypertension ranged from 9% (EVG/c/FTC/TAF) to 37% (dolutegravir-based); dolutegravir-based regimens carried a >2-fold adjusted hazard versus EVG/c/FTC/TAF. Higher body mass index was independently predictive but did not abolish this signal. Conclusions: In ART-naive PWH, INSTI-based regimens were associated with a higher incidence of hypertension than NNRTI-based regimens, whereas the comparison with PI-based regimens was not statistically significant. Dolutegravir-containing regimens were independently associated with incident hypertension supporting systematic blood pressure surveillance and further comparative studies.
SN - 2328-8957
ER -