Truvada PrEP causes only mild loss of bone mineral density

Benefits outweigh risks, say researchers
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Treatment with tenofovir/emtricitabine (Truvada) as pre-exposure prophylaxis (PrEP) is associated with small but significant decreases in bone mineral density (BMD), investigators from the landmark iPrEx study report in the online edition of Clinical Infectious Diseases.

Changes in bone mineral density were compared between people randomised to receive Truvada and individuals in the control arm. Treatment with Truvada was associated with decreases in bone mineral density in both the spine and hip. However, these decreases occurred only during the first 24 weeks of treatment and bone mineral density in the spine recovered after therapy was discontinued. Moreover, the small reductions observed in the people taking Truvada did not appear to increase the risk of fractures.

“These results demonstrate the effect of FTC/TDF [emtricitabine/tenofovir] that is independent of HIV infection or other ART [antiretroviral therapy],” comment the authors. “The relatively small bone loss associated with FTC/TDF PrEP is offset by the prevention of HIV infection, which requires combination ART that is associated with relatively greater loss of BMD.”


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. 


A pill or liquid which looks and tastes exactly like a real drug, but contains no active substance.

dual energy x-ray absorptiometry scan (DXA or DEXA)

A test that uses low-dose x-rays to measure bone mineral density, including calcium content, in a section of bone. They are used to detect osteoporosis and predict the risk of bone fracture. 


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

control group

A group of participants in a trial who receive standard treatment, or no treatment at all, rather than the experimental treatment which is being tested. Also known as a control arm.

There is now robust evidence that daily Truvada PrEP significantly reduces the risk of HIV infection. But there are ongoing concerns about the safety of this therapy. In some people living with HIV, therapy with tenofovir has been associated with impaired kidney function and/or reductions in bone mineral density.

HIV infection can also have a negative impact on bone health and there is a high prevalence of other risk factors for low bone mineral density among people with HIV. The true impact of tenofovir-containing PrEP on bone mineral density in HIV-negative people is therefore open to question.

A sub-analysis of the iPrEx study was designed to address this question. Approximately 500 patients – 50% on PrEP and 50% a placebo – underwent dual-energy X-ray absorptiometry (DEXA) scanning at baseline and then at intervals of 24 weeks until 96 weeks of follow-up were completed. Changes in bone mineral density in the lumbar spine and left hip were compared between the treatment and control groups.

The iPrEX study recruited HIV-negative men who have sex with men and transgender women. At baseline, low bone mineral density in the spine and hip was observed in 12% and 2%, respectively.

Spine bone mineral density decreased in the Truvada group during the first 24 weeks of treatment, and further small decreases were observed through to week 94. The differences with the placebo group were small but significant (week 24, p = 0.001).

Truvada therapy was also associated with small but significant decreases in hip bone mineral density. In contrast, bone mineral density in the hip tended to increase among people in the placebo arm.

Decreases in bone mineral density at week 24 in the treatment arm were correlated with intracellular levels of tenofovir.

DEXA scans performed 24 weeks after the completion of therapy indicated that bone mineral density recovered in people receiving Truvada. Moreover, analysis of the entire study population of 2500 people showed that Truvada PrEP did not increase the risk of fractures (incidence, 1.7% Truvada vs 1.4% placebo).

Overall, the investigators were encouraged by their findings, concluding “the results of the current study provide no reason to modify the Centers for Disease Control’s recommendation that routine DEXA monitoring during FTC/TDF for PrEP is not warranted unless there are additional risk factors for fracture.” But they suggest that people starting PrEP should receive information about factors that can affect bone health, “including limiting use of alcohol and tobacco, increasing weight-bearing exercise, and assuring adequate dietary intake of calcium and vitamin D.”

In an editorial, Dr Julian Falutz of McGill University Hospital Cenre, Montreal, stated that the study filled important knowledge gaps about the safety of Truvada PrEP. He was also reassured that loss of bone mineral density during PrEP was minimal and reversible.


Mulligan K et al. Effects of emtricitabine/tenofovir on bone mineral density in HIV-negative persons in a randomized, double-blind, placebo-controlled trial: DXA results from iPrEx. Clin Infect Dis, 2015.

Falutz J The bare bones of HIV pre-exposure prophylaxis. Clin Infect Dis, online edition, 2015.