Background

Safety of tenofovir disoproxil fumarate/emtricitabine (TDF-FTC) has been studied more

extensively among HIV-infected patients than among HIV-uninfected people. Using data

from a pre-exposure trial – FEM-PrEP –, we determined the cumulative probabilities of grade

1+ ALT, AST and creatinine and grade 2+ phosphorus toxicities; ALT/AST toxicities by

baseline hepatitis B status; and change in mean creatinine, phosphorus, ALT and AST levels

controlling for TDF-FTC adherence.

Methods and findings

FEM-PrEP was a randomized, blinded, placebo-controlled trial of daily TDF-FTC among

women in Africa. Enrolled women were in general good health, HIV antibody negative, 18 to

35 years old, hepatitis B surface antigen negative, and had normal hepatic and renal function

at baseline. AST, ALT, phosphorus and serum creatinine were measured regularly throughout

the trial. TDF-FTC concentrations were measured to assess adherence to TDF-FTC. The

cumulative probabilities of grade 1+ creatininemia and grade 2+ phosphatemia toxicities

were not statistically different between TDF-FTC and placebo arms. The cumulative

probabilities of grade 1+ ALT and AST toxicities were higher among participants in the

TDF-FTC arm than in the placebo arm (p = 0.03 for both). The proportions of grade 1+ and

grade 2+ ALT or AST toxicities were significantly higher in participants who were hepatitis

B virus surface antibody (HBsAb) positive than in those who were HBsAb-negative. Women

with good adherence had higher mean change from baseline to week 4 in their AST levels

(2.90 (0.37, 5.42); p = 0.025) than women with less than good adherence.

Conclusions

We did not observe a significant relationship between randomization to TDF-FTC and

creatinine or phosphorus toxicities. Women randomized to TDF-FTC had higher rates of mild

to moderate ALT/AST toxicities, especially women with prior hepatitis B virus exposure. We

also observed a significant increase in AST from baseline to week 4 among women who had

higher adherence to TDF-FTC during that interval.