Switching from protease inhibitors to dolutegravir in virologically suppressed patients with HIV did not have an impact on blood pressure changes or incidence of hypertension, according to post-hoc analysis published in Clinical Infectious Diseases.
Investigators aimed to assess incident hypertension at 48 weeks in virologically suppressed patients with HIV. Secondary outcomes were factors associated with incident hypertension, discontinuations and adverse events associated with high blood pressure, and changes in systolic (SBP) and diastolic (DBP) blood pressure.
They initiated a post-hoc analysis of the NEAT022 randomized trial, (ClinicalTrials.gov Identifier: NCT02098837) which was conducted between May 2014 and November 2015 across 6 European countries at 32 clinical sites. Individuals at least 18 years of age with plasma HIV RNA of less than 50 copies/mL for at least the previous 6 months and with a Framingham cardiovascular disease (CVD) risk score of greater than 10% at 10 years receiving 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus 1 boosted protease inhibitor (PI/r) and patients with HIV who were aged at least 50 years were eligible for the study.
Participants were randomly assigned 1:1 to treatment groups (open label) stratified by country and either switched PI/r therapy to dolutegravir immediately (DTG-I) or continued PI/r therapy for 48 weeks then switched to dolutegravir (delayed; DTG-D) with all participants continuing on dolutegravir for another 48 weeks (to week 96).
Incidence of new diagnosis of hypertension at 48 weeks was the primary endpoint of the study. Participants with hypertension or who were receiving antihypertensive drugs at baseline were excluded from the study. Hypertension was defined as at least 130 mm Hg SBP or at least 85 mm Hg DBP. All outcomes were analyzed on a modified intention-to-treat (mITT) basis.
Baseline factors independently associated with higher hypertension risk at week 48 included lack of daily exercise, Black race, male gender, and being over 60 years of age. Baseline factors independently associated with hypertension risk at week 96 included daily exercise, smoking status, female gender, and 10-year Framingham CVD risk score of greater than 15%.
The investigators found there were 412 patients with HIV who received at least 1 dose of dolutegravir (DTG-I, n=204; DTG-D, n=208). Among all participants, 191 (46.4%) had hypertension at baseline and 24 received antihypertensive medications for other reasons. Among the remaining 197 participants not receiving hypertensive medications at baseline or without hypertension (DTG-I, n=98; DTG-D, n=99) incident rates at 48 weeks for DTG-I vs DTG-D were 40.3 vs 34.7 per 100 person years (P =.5755) and at 96 weeks they were 36.3 vs 52.0 per 100 person years (P =.2347). Between baseline and 48 weeks, there were 56 participants in this population with incident hypertension and between 48 and 96 weeks there were 45 additional participants with incident hypertension.
There was no between-group difference in SBP or DBP changes. Significant increases were noted in the first 48 weeks of exposure to dolutegravir in DBP in the DTG-I group (mean, +2.78 mm Hg; 95% CI, 1.07-4.50; P =.0016) and in the DTG-D group (mean, +2.29 mm Hg; 95% CI, 0.35-4.23; P =.0211). Significant increases were noted from baseline to week 96 in DBP in the DTG-I group (mean, +3.28 mm Hg; 95% CI, 1.36-5.19; P =.0009) and in the DTG-D group (mean, +3.71 mm Hg; 95% CI, 1.78-5.64; P =.0002).
There was no independent association between treatment arms and incident hypertension at weeks 48 or 96.
Study drugs were discontinued by 3 participants receiving dolutegravir therapy and 1 receiving PI/r therapy due to adverse high blood pressure events. Overall, there were 19 participants who reported adverse events associated with high blood pressure or hypertension (DTG-I, 11 [all under dolutegravir exposure]; DTG-D, 8 [3 under dolutegravir exposure]).
Limitations of the study include the study population having a high risk for cardiovascular disease, which limits generalizability. There is also a lack of women and Black patients. Additionally, the study reduced the NEAT022 population by half for this analysis.
“…the population with HIV of the NEAT022 study at high risk for CVD showed a high prevalence of hypertension at baseline and a remarkably high incidence of hypertension during 96 weeks of follow-up,” the investigators wrote. “Switching to dolutegravir did not negatively impact on the incidence of hypertension relative to continue protease inhibitors.”
Disclosure: This research was supported by ViiV Healthcare. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Sempere A, Assoumou L, González-Cordón A, et al.; on behalf of the NEAT-022 Study Group. Incidence of hypertension and blood pressure changes in persons with HIV at high risk for cardiovascular disease switching from boosted protease inhibitors to dolutegravir: a post-hoc analysis of the 96-week randomized NEAT-022 trial. Clin Infect Dis. Published online May 19, 2023. doi:10.1093/cid/ciad297