Background
Several studies have suggested an increased risk for hypertension (HTN) associated with initiation of integrase strand transfer inhibitors (INSTIs) for HIV treatment that may be mediated by weight gain. We investigated whether CAB-LA was associated with an increased incidence of HTN in a post-hoc analysis of the HPTN 084 trial.
Methods
HPTN 084 evaluated the effectiveness of long-acting injectable cabotegravir (CAB-LA) compared to daily oral TDF/FTC for PrEP in individuals born female aged 18-45 years in eastern and southern Africa. Of 3224 participants enrolled, 3071 (1543 CAB, 1528 TDF/FTC) with study drug exposure and without pre-existing HTN were analyzed. Incident HTN was defined as a new diagnosis of HTN or new initiation of anti-HTN treatment through 161 weeks of follow-up. Cox regression was used to estimate the hazard ratio (HR) for incident HTN by study arm, unadjusted and adjusted for age, baseline BMI, enrolment region (South Africa, southern or east Africa). Modelling also evaluated time-updated risk factors including percent weight change from baseline (TUWC), incident pregnancy and contraceptive method.
Results
Study arms were balanced with 51% of participants <25 years of age, 55% with a BMI ≥ 25 kg/m2, and 41% from South Africa. Median BMI increase was similar across both groups (2.2 kg/m2 CAB and 2.1 kg/m2 TDF/FTC). Over 8252 person-years of follow up, 234 (8%) had incident HTN (127/1543 CAB, 107/1528 TDF/FTC). Cumulative HTN incidence over 3 years was 8.6% for CAB and 7.2% for TDF/FTC. In unadjusted analyses, incident HTN was higher with CAB compared to TDF/FTC use (HR 1.20, 95% CI 0.93-1.55, p=0.16) and largely unchanged (HR 1.17, 95% CI 0.91-1.50, p=0.26) after adjustment for enrolment region, age, and baseline BMI. The hazard for HTN increased with >10% weight gain (HR 1.58, 95% CI 1.05-2.38), pregnancy (HR 2.20, 95% CI 1.14-4.25), enrolment from the southern Africa region (Botswana, Eswatini, Zimbabwe) (HR 2.24, 95% CI 1.58-3.19), pre-existing obesity (HR 2.35, 95% CI 1.63-3.36), and older age (HR per 10 years 2.50, 95% CI 2.03-3.08).
Conclusions
Overall, HTN incidence in this population without HIV was low. Observed HTN incidence was numerically higher with CAB compared to TDF/FTC PrEP use, but this was not statistically significant and slightly diminished with adjustment for key risk factors. Incident HTN is more likely explained by other risk factors like age, BMI, weight gain, pregnancy and enrolment region.