PrEP does not raise lipids or alter body fat, safety study finds

Using pre-exposure prophylaxis (PrEP) does not raise lipid levels or have any substantial effect on body fat, investigators from the iPrEX trial report this month in the journal Clinical Infectious Diseases.

They followed almost 500 PrEP users and a placebo group for a year and a half within the larger iPrEX randomised study of tenofovir/emtricitabine (Truvada) to prevent HIV infection and concluded that PrEP users did not suffer long-term fat loss. PrEP users experienced modest reductions in total cholesterol, 'bad' LDL cholesterol and 'good' HDL cholesterol.

The same sub-study previously reported that bone mineral density declined by 1% in the hip and 1.81% in the spine during the study but recovered within six months of stopping PrEP in those with detectable drug levels at each bone scan.

This report looked at the metabolic effects of using tenofovir/emtricitabine in HIV-negative people.

Some antiretroviral drugs have been associated with harmful metabolic effects including increases in lipids, especially 'bad' LDL cholesterol, and fat redistribution (lipodystrophy). Tenofovir has been widely adopted as a replacement for the nucleoside reverse transcriptase inhibitors zidovudine and stavudine, both of which cause subcutaneous fat loss (lipoatrophy).

But, say the investigators, it can be difficult to disentangle the effects of one antiretroviral drug from another, and also from effects of HIV infection and immune reconstitution after starting treatment.

The randomised iPrEX trial of tenofovir/emtricitabine (Truvada) PrEP included a metabolic sub-study which monitored body composition and lipid levels, so as to evaluate the long-term effects of PrEP in HIV-negative men who have sex with men and transgender women.

The sub-study recruited 498 iPrEX study participants in Chiang Mai, Cape Town, Lima, Rio de Janeiro and San Francisco. Almost half of the study participants were recruited in Lima (Peru) (44%), 19% in Thailand, 14% in the United States, 11% in Brazil and 12% in South Africa.

Participants underwent whole-body, hip and spine dual X-ray absorptiometry (DXA) scans to measure body composition and fasting lipid evaluations at baseline, every 24 weeks during the study and 24 weeks after stopping the study drug. Drug concentrations were measured from samples provided at each visit after starting PrEP.

The study population was young (median age 25) and 86% had cholesterol within the healthy range (< 200mg/dl or < 5.1mmol/l). The median total cholesterol was 161 mg/dl (4.16 mmol/l).

The median weight was 66kg and the body mass index was 23 (28% of the tenofovir group and 32% of the placebo group had a body mass index over 25, indicating that they were overweight or obese). The median body fat content was 12.4 kg.

Of the 498 participants, 419 had at least one follow-up DXA scan (median 3.4) and 418 had at least one follow-up lipid measurement (median = 4).

The median exposure to Truvada lasted 64 weeks. After 24 weeks of follow-up, participants in the tenofovir/emtricitabine group had experienced a very small, but statistically significant, reduction in weight (-0.8% compared to the placebo group) but this difference had disappeared by week 96.

This small difference in weight did not appear to be attributable to nausea experienced by people taking tenofovir/emtricitabine. Investigators found no significant difference in weight change at week 24 in the tenofovir/emtricitabine group between those who reported nausea and those who did not.

The change in weight represented fat loss; whereas the placebo group gained body fat during the study (+6.4%), and did so steadily during the study, participants in the tenofovir/emtricitabine group showed no gain in fat at weeks 24 or 48. At week 24 body fat content was 3.8% lower in the tenofovir/emtricitabine group than the placebo group. By week 96, after stopping the study drug, the difference in fat content between the two groups had narrowed and the difference was no longer significant.

To check if drug exposure was related to fat loss, investigators looked at fat changes according to drug concentrations. They found that within the tenofovir/emtricitabine group, people with detectable drug concentrations at week 24 had a -4.9% decrease in body fat compared to the placebo group (p = 0.003). This represents a difference of approximately 600 grams (1.3 lbs) from baseline. This difference disappeared by week 72.

There were no differences in total cholesterol or LDL cholesterol between the tenofovir/emtricitabine and placebo groups, but participants in the tenofovir/emtricitabine group did have small but significant reductions in HDL cholesterol by week 48 (-3.9mg/dl (0.1 mmol/l)). But, when lipid changes were evaluated according to whether people had detectable drug levels or not, differences for all lipid measurements were significant.

The researchers concluded that “these data provide additional reassurance on the modest, apparently benign and possibly transient metabolic effects of TDF/FTC [tenofovir/emtricitabine] as PrEP.” However, they caution that because the cohort was young and followed for between one and two years, “longer-term effects in older populations merit further evaluation.”