Comparing HIV PrEP medications: Study explores hypertension risk in adults on TAF vs. TDF

In a recent study published in JAMA Network Open, a group of researchers assessed the risk of hypertension and statin initiation in adults starting Human Immunodeficiency Virus (HIV) Pre-exposure prophylaxis (PrEP) with emtricitabine/tenofovir alafenamide fumarate (TAF) compared to those taking emtricitabine/tenofovir disoproxil fumarate (TDF), using data from Kaiser Permanente Southern California (KPSC).

Study: Use of Tenofovir Alafenamide Fumarate for HIV Pre-Exposure Prophylaxis and Incidence of Hypertension and Initiation of Statins. Image Credit: PENpics Studio/Shutterstock.com

Background 

PrEP reduces Human Immunodeficiency Virus (HIV) infection risk and is pivotal for HIV elimination in the United States (US). As of 2023, two daily PrEP regimens received US Food and Drug Administration (FDA) approval: TDF in 2012 and TAF in 2019.

While both demonstrate similar HIV prevention efficacy, the DISCOVER trial revealed those on TAF showed improved bone and kidney health but increased weight. 

Conversely, TDF users had lowered cholesterol. TAF usage for HIV therapy also indicated weight and cholesterol increases, factors associated with cardiovascular disease. The trial showed no significant difference in lipid-modifying agent initiation but did not assess other cardiometabolic conditions.

Observational studies from the TriNetX database suggest higher statin initiation and blood pressure elevation with TAF. 

Further research is needed due to inconsistencies between clinical trial data and real-world evidence regarding the cardiometabolic effects of TAF and TDF, with concerns about underestimating outcomes in observational studies.

About the study

The present study was conducted on adults starting PrEP within the KPSC system. The integrated healthcare system in Southern California serves a wide demographic, with members' healthcare journeys meticulously documented in electronic health records (EHRs).

Researchers identified adults who began PrEP between October 1, 2019, and May 31, 2022, excluding those with prior HIV diagnosis, chronic kidney disease, signs of kidney, liver, or blood abnormalities, or those who were members for less than 30 days post-PrEP initiation.

Two distinct analytic cohorts emerged from this population, focusing on the risk of developing hypertension and the initiation of statins. Participants without a history of hypertension or statin use were included and subsequently formed into matched cohorts for more in-depth analysis.

The primary exposure was the initiation of PrEP with either TAF or TDF within KPSC. Researchers consulting outpatient pharmacy records identified the first filled PrEP prescription between the designated dates.

Primary outcomes of interest were the onset of hypertension and the start of statins within two years after beginning PrEP. The means of ascertaining these outcomes involved various methods, such as diagnostic codes, outpatient measurements, and pharmacy records.

Baseline variables considered in the study included race, age, gender, socio-economic markers, insurance details, body measurements, lab results, and associated risk scores. The present study used multiple statistical methods to analyze the data, such as propensity score matching, logistic regression, and time-to-event analysis.

Sensitivity analyses were also executed, especially for those aged 40 or above, as this group has an elevated risk of hypertension and is often recommended for statin initiation.

Study results 

The present study analyzed 6,824 individuals eligible to start PrEP, with an average age of 34 years and 97% male.

When contrasting the eligible individuals with those excluded from the study, it was found that the eligible participants were generally younger, had a lower likelihood of having Medicare/Medicaid insurance, were more frequently on TDF, and had fewer initial cardiometabolic issues.

Out of the pool, 5,523 participants did not have hypertension when the study began. When comparing those taking TDF to those taking TAF, the latter were generally older, predominantly non-Hispanic White, and had a higher probability of having diabetes from the outset.

They were, however, less likely to be Hispanic or insured by Medicare/Medicaid or commercial insurance providers. The TAF group also displayed a lower estimated Glomerular Filtration Rate (eGFR) and a shorter average follow-up time.

Once matching was completed, the analysis cohort consisted of 1,855 individuals on PrEP, with 20% on TAF and 80% on TDF. This matching process minimized differences in baseline metrics between TAF and TDF takers.

Interestingly, within two years of starting PrEP, 2.2% of the TAF group developed hypertension, compared to the TDF group's rate of 1.3%. This reveals that TAF usage is correlated with a slightly higher risk of hypertension within two years of starting PrEP compared to TDF use.

The present study also conducted a sensitivity analysis, considering a specific blood pressure level as the cutoff for hypertension diagnosis, and identified 3,454 individuals fitting the criteria. This test again found that those on TAF had a higher incidence of hypertension than those on TDF, supporting the study's primary findings.

In another aspect of the study concerning statin initiation, 6,149 participants with no prior statin usage history were identified. Upon comparing TDF users to TAF users, the latter were older on average, more frequently non-Hispanic White, and less likely to be Hispanic or have certain types of insurance.

They were also less likely to have hypertension at the outset. However, TAF takers had a higher Atherosclerotic Cardiovascular Disease (ASCVD) risk score and shorter average follow-up time.

Of the matched cohort for this aspect, 1,855 participants were included. Within two years of starting PrEP, 1.6% of the TAF group began statin treatment, compared to the TDF group's rate of 1.0%.

This suggests that those taking TAF might have a slightly higher probability of initiating statins within two years post-PrEP commencement. When focusing solely on participants aged 40 or older, the risk disparity associated with TAF was even more pronounced.

Written by

Susha Cheriyedath

Susha has a Bachelor of Science (B.Sc.) degree in Chemistry and Master of Science (M.Sc) degree in Biochemistry from the University of Calicut, India. She always had a keen interest in medical and health science. As part of her masters degree, she specialized in Biochemistry, with an emphasis on Microbiology, Physiology, Biotechnology, and Nutrition. In her spare time, she loves to cook up a storm in the kitchen with her super-messy baking experiments.