TAF vs. TDF: Measuring Lipid Levels in HIV Treatment

As antiretroviral therapy (ART) allows people with HIV to live normal or near-normal lifespans, their chances of dying from non-AIDS conditions such as cardiovascular disease, kidney and liver dysfunction, and cancer have risen significantly. Therefore, clinicians must weigh the potential toxicities of ART medications when selecting the appropriate regimens for patients so as not to create or exacerbate undesirable side effects at the expense of viral suppression.

People living with HIV have double the risk of cardiovascular disease compared with the general population, making their choice of ART medications a consequential one. A team of investigators in a recent trial examined the lipid profiles of subjects randomized to 2 different ART therapies, tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF). While other studies have found that TDF lowers lipid levels in users—for reasons that are not completely clear—TDF also may negatively impact kidney function and cause lower bone density. For this reason, TAF has emerged as a popular alternative to TDF; however, TAF is known to raise cholesterol levels, which may be problematic for some users.

The current study involved 1733 people living with HIV between the ages of 40 and 79 years who had never taken ART before. Their fasting lipid profiles were measured at baseline, week 48, and week 96. The participants who began a regimen of TAF did see a rise in their fasting lipid levels over the course of the study. Their total cholesterol averaged 191 mg/dL vs. 177 mg/dL for those taking TDF; their LDL (low-density lipoprotein) levels averaged 119 mg/dL vs. 112 mg/dL in the TDF group; and their HDL (high-density lipoprotein) levels averaged 51 mg/dL vs. 48 mg/dL in those taking TDF.

However, because HDL is considered protective when it comes to cardiovascular risk, the higher LDL and total cholesterol levels in the TAF subjects were offset by the higher HDL levels when it came to overall cardiovascular risk.

“Total cholesterol to HDL ratios, often viewed as a clinically relevant surrogate for prediction of future cardiovascular events, were identical (3.7) at week 96, with the higher total cholesterol balanced by the higher HDL in participants taking TAF,” Gregory Huhn, MD,

Gregory Huhn, MD, MPHTM

MPHTM, an infectious disease specialist at the Ruth M. Rothstein CORE Center, a collaboration between Cook County Hospital and Rush University Medical Center in Chicago, and the lead author of the study, told Contagion®.

There’s no single right answer to the question of which ART medication is best for each patient, according to Huhn, who suggests that health care providers take into consideration the study data, clinical guidelines, and any comorbidities patients may have when making prescribing decisions.

The changes in the lipid profiles of this study’s subjects did not substantially change their cardiovascular risk profiles, he noted, adding, “It is clear that early and uninterrupted antiretroviral therapy is essential for optimizing HIV control as well as limiting off-target complications such as cardiovascular disease.”

Also important for HIV-positive patients whose cardiovascular risk profiles suggest trouble ahead? Statins. One-fifth of subjects in the study qualified for statins based on their lipid profiles, yet only a fifth of those subjects were prescribed the drugs.

“Statins play a central role in cardiovascular disease risk reduction in the general population, and the benefit of statins is believed to extend to people living with HIV, with lipid-lowering properties more pronounced than any lipid-lowering effect of TDF,” Huhn said. His team recommends that clinicians not hesitate to prescribe statins at standard doses for people taking ART.