Switching to TAF-based PrEP improves kidney and bone markers – but does it raise cardiovascular risk?

People who switched from Truvada (tenofovir disoproxil fumarate/emtricitabine) to the newer Descovy (tenofovir alafenamide/emtricitabine) for pre-exposure prophylaxis (PrEP) experienced improvements in measures of kidney function and bone density, but adverse clinical outcomes were rare with either co-formulation, researchers reported at the recent IDWeek 2019 conference in Washington, DC.

However, another study looking at HIV treatment showed that switching from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide (TAF) led to weight gain and worsening cardiovascular risk scores.

TDF, one of the most widely used medications for HIV treatment and the first drug approved for PrEP, is generally safe and well tolerated, but it can cause kidney impairment and bone loss in susceptible individuals. Those with pre-existing kidney problems are advised not to use TDF and its co-formulations for HIV treatment or prevention.



Relating to the heart and blood vessels.

body mass index (BMI)

Body mass index, or BMI, is a measure of body size. It combines a person's weight with their height. The BMI gives an idea of whether a person has the correct weight for their height. Below 18.5 is considered underweight; between 18.5 and 25 is normal; between 25 and 30 is overweight; and over 30 is obese. Many BMI calculators can be found on the internet.


Relating to the kidneys.

bone mineral density (BMD)

The higher your bone mineral content, the denser your bones are. And the denser your bones, the stronger they are and the less likely they are to break. A bone density test uses X-rays to measure how many grams of calcium and other bone minerals are packed into a segment of bone. The bones that are most commonly tested are in the spine, hip and sometimes the forearm. 


An umbrella term for people whose gender identity and/or gender expression differs from the sex they were assigned at birth.

TAF is a newer pro-drug formulation that produces higher levels of the active drug (tenofovir diphosphate) in T-cells with smaller doses than TDF, which means lower concentrations in the blood and less drug exposure for the kidneys, bones and other organs.

Studies in the past few years have shown that antiretroviral therapy (ART) containing TAF has less detrimental effects on kidney and bone health than regimens containing TDF, and that switching from TDF to TAF leads to improvement in renal and bone biomarkers. However, kidney failure and fractures are uncommon with either medication. Gilead Sciences, which manufactures both drugs, has replaced TDF with TAF in its single-tablet regimens Biktarvy, Genvoya, Odefsey and Symtuza.

This month the US Food and Drug Administration approved Descovy as a second PrEP option for people at risk for sexually acquired HIV, with the exception of those who have receptive vaginal sex. Approval was based on findings from the DISCOVER trial, which showed that Truvada and Descovy were equally effective for HIV prevention in men who have sex with men and transgender women, but Descovy had less detrimental effects on kidney function and bone biomarkers.

At IDWeek, Dr Anthony Mills of the Men’s Health Foundation in Los Angeles presented findings from an analysis of kidney safety outcomes among DISCOVER participants, including a subset who switched from Truvada to Descovy. Dr David Wohl of the University of North Carolina at Chapel Hill presented a related analysis of bone safety outcomes.

DISCOVER enrolled more than 5300 at-risk men who have sex with men and a small number of trans women, but excluded cisgender women and trans men. Participants were randomly assigned to take Descovy or Truvada once daily for up to two years. Of these, 905 people were already taking Truvada before joining the trial, including 465 who were randomised to the Descovy arm and switched drugs.

Kidney outcomes

Kidney function assessments included urinalysis, estimated glomerular filtration rate (eGFR), urine protein-to-creatinine ratio, markers of proximal tubular function and investigator-reported renal adverse events. 

Overall, at 48 weeks, Descovy was associated with more favourable changes in eGFR and markers of proximal tubular function compared with Truvada, and proteinuria (protein in the urine) was less common (24% vs 21%, respectively), Dr Mills reported.

Participants taking Descovy had fewer drug-related renal adverse events (14 vs 26 cases), serious renal events (2 vs 3 cases) and were less likely to discontinue treatment for this reason (2 vs 6 cases). However, all these outcomes were uncommon in both groups (1% or less). One person taking Truvada but none taking Descovy developed proximal renal tubulopathy, or Fanconi syndrome, which is a type of serious kidney function impairment.

Participants who switched from Truvada to Descovy at study entry saw significant increases in eGFR as early as week 4 after changing drugs, as well as decreased proteinuria.

"The improvements observed in these important markers of kidney health in the overall study population and in those who switched from Truvada to Descovy point to the potential for Descovy to be a preventive option for appropriate people at risk for HIV who may require longer-term PrEP use, including those who have previously taken Truvada for PrEP," Dr Mills said in a Gilead press release.

Bone outcomes

Dr Wohl reported results from a bone mineral density (BMD) sub-study that included 383 DISCOVER participants. Within this group, 53 were on Truvada at study entry, 26 of whom were randomized to switch to Descovy.

People assigned to the Descovy arm experienced small increases in bone density at the hip and spine at 48 weeks, while Truvada was associated with declines – especially among younger participants. Those who switched from Truvada to Descovy had significant improvements in spine and especially hip BMD compared with those who continued on Truvada.

Further, Descovy recipients were less likely to develop osteopenia (bone thinning) or osteoporosis (more severe bone loss) of the spine, but these were rare in both groups (under 1%). Fractures were uncommon and occurred with similar frequency in both groups (53 cases, or 2%).

Weight and cardiovascular risk

While TAF is less harmful to the kidneys and bones, TDF may have the advantage when it comes to cardiovascular risk. Tenofovir is known to lower blood lipid levels, but this effect is not as great with TAF as it is with TDF because of TAF's lower concentration in the blood. However, TAF's impact on other cardiovascular risk factors and outcomes has been less well studied.

Jason Schafer of Jefferson College of Pharmacy in Philadelphia presented findings from a retrospective analysis of HIV-positive people who switched from TDF to TAF without changing any other components of their combination antiretroviral regimen.

This observational study included 110 people age 40 to 75 years who had been taking TDF for at least a year and maintained viral suppression (below 200 copies/ml) before switching to TAF.

Most (80%) were men, 64% were African American and a third were white. The average age was 50 years; they had been diagnosed with HIV for a median of 12 years and on ART for a median of 8 years. The median CD4 count was high, at 628 cells/mm3. About half were taking integrase inhibitors, 29% were on NNRTIs and 16% were on protease inhibitors.

Weight, body mass index (BMI), cholesterol levels and atherosclerotic cardiovascular risk scores were collected for the year prior to and following the switch from TDF to TAF. Before switching, 31% were classified as normal weight, 28% as overweight, 37% as obese and 4% as underweight.

People who switched from TDF to TAF experienced significant increases in weight, BMI and cholesterol (total, LDL and HDL) after the change, although the total-to-HDL ratio did not change significantly. The median weight gain was 1.36kg, or +9.2%. The median cardiovascular risk score rose from 6.9 to 8.1 (+1.9%) after the switch.

After adjusting for potential confounding factors, the researchers calculated that switching from TDF to TAF was associated with a 13% increase in the average cardiovascular risk score. This shifted more than half of the participants above the American Heart Association threshold for recommending statins to manage cardiovascular risk.

"It is unlikely that the BMI changes we observed represent a 'return to health' since patients had longstanding HIV infection that was persistently controlled by ART prior to switching," they concluded. "BMI changes were modest, but could be clinically relevant as even small changes in BMI can influence a patient's lifetime risk for developing diabetes and atherosclerotic cardiovascular disease."

Further research is needed to determine if these kinds of changes are also seen in people taking TAF for PrEP, which tends to be a younger population.


Mills A et al. Renal outcomes for participants taking F/TAF versus F/TDF for HIV PrEP prep in the DISCOVER trial. IDWeek, Washington, DC, abstract 1962, 2019.

Wohl DA et al. Bone safety outcomes with F/TAF vs. F/TDF for PrEP in the DISCOVER trial. IDWeek, Washington, DC, abstract 1288, 2019.

Schafer J et al. BMI and ASCVD risk score changes in virologically suppressed patients with HIV switching from TDF to TAF containing ART. IDWeek, Washington, DC, abstract 979, 2019.

The last study has also been published in a peer-reviewed journal:

Schafer JJ et al.  Changes in Body Mass Index and Atherosclerotic Disease Risk Score After Switching From Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide. Open Forum Infectious Diseases 6: ofz414, 2019 (open access).