Tenofovir alafenamide (TAF) and tenofovir disoproxil fumarate (TDF), antiretroviral drugs used to treat HIV and hepatitis B, may be simultaneously depleting the energy of immune cells.
While TAF and TDF have been previously demonstrated the potential to alter immunometabolism, only limited research has been done in humans. It was unknown whether higher intracellular drug levels, observed in peripheral blood mononuclear cells (PBMCs) treated with TAF and/or TDF, altered mitochondria function and energy production in immune cells.
Mitochondria, affectionately called “the powerhouse of the cell” regulate immune and organ function. Utilizing both a human clinical trial and experimental lab studies, investigators from UCLA assessed how TAF and TDF affect the immune cells’ ability to make energy.
The study included 26 people living with HIV who switched antiretrovirals over the course of 9 months. The investigators assessed how the different drugs affected their cells’ energy production. They confirmed their findings in the lab, adding drugs to healthy immune cells and determining their impact on cell metabolism.
The investigators determined cellular bioenergetics in PBMCs from HIV-positive participants exposed to TAF versus TDF, at a comparable concentration to a clinically relevant plasma exposure. Observing as decrease in cellular oxygen consumption rate at baseline and under cellular stress, the investigators hypothesized there was mitochondrial dysfunction.
Surprisingly, the investigators found that TAF and TDF directly reduce energy produced by mitochondria, thus reducing the energy available to immune cells. Both TAF and TDF reduced cellular oxygen consumption rates, a critical measure of the mitochondria’s ability to produce energy.
PBMCs from HIV-positive patients exposed in vitro to a concentration of 0.12–3.3 μM for TAF and TDF reduced basal and maximal oxygen consumption rate, compared to the control patients.
Compared to TDF, TAF may alter bioenergetics in immune cells from people living with HIV both in vitro and in vivo.
In addition to treating patients currently living with HIV and HBV, TAF and TDF are used as pre-exposure prophylaxis (PrEP) to protect against HIV contraction. Thus, these drugs are vital to prevent both severe progression as well as new infections.
For future studies, the investigators recommended examining the clinical impact of TAF versus TDF on metabolism.