BACKGROUND: Emtricitabine/tenofovir alafenamide fumarate (TAF) was approved for pre-exposure prophylaxis (PrEP) in the US in October 2019. Studies demonstrated weight gain potentially associated with TAF use which may increase the risk for hypertension. We evaluated the risk of incident hypertension in adults initiating TAF for PrEP compared with those who initiated emtricitabine/tenofovir disoproxil fumarate (TDF).
METHODS: Adults (=18 years) who initiated PrEP between October 2019-June 2022 were identified from Kaiser Permanente Southern California (KPSC), an integrated health system. Individuals with a hypertension diagnosis before and up to 30 days after the PrEP initiation were excluded. Initiation was defined as the first instance of TDF or TAF dispensing while enrolled in KPSC during the study period. Each person who initiated with TAF was matched to 4 individuals who started with TDF using the propensity score informed by baseline demographics, cardiovascular risk score, smoking history, comorbidities, medical center, neighborhood deprivation index, and PrEP initiation year. Odds ratios (OR) and risk differences (RD) of incident hypertension within two years of PrEP initiation between matched TAF and TDF users were estimated using logistic regression and g-computation, respectively. Missing covariates were handled with multiple imputation. The analysis was repeated in a subgroup of individuals =40 years of age at PrEP initiation due to higher hypertension risk in this age group.
RESULTS: There were 338 individuals who initiated with TAF: mean age of 36 years, 99% male, 31% Hispanic, 6% non-Hispanic Black, 43% non-Hispanic white, and 4% with baseline diabetes. There were 8 (1.7%) hypertension cases identified among TAF initiators and a mean of 19 cases (1.3%, 95%CI: 1.09, 1.95%) in matched TDF initiators (n=1,552) across imputations (m=50). Odds ratio (OR: 1.7, 95%CI: 1.3, 2.2) and risk difference (RD 0.82%, 95%CI: 0.31, 1.3%) showed higher hypertension risk in TAF initiators versus matched TDF initiators. Differences between TAF and TDF initiators were higher among the subset of those =40 years at PrEP initiation (OR: 2.2, 95%CI: 1.3, 3.8; RD: 2.6%, 95%CI: 0.41, 4.8%).
CONCLUSIONS: TAF initiators may be at increased risk for hypertension. Findings need to be confirmed with larger studies.

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