Truvada vs. Descovy for HIV prevention
Truvada is the brand name of a pill containing two anti-HIV drugs:
- tenofovir disoproxil fumarate (TDF)
- emtricitabine (FTC)
Generic formulations of these drugs are also available in one pill.
When used as prescribed, the medicines inside Truvada are highly effective at reducing a person’s risk of getting HIV. This was the case in randomized clinical trials and in observational studies.
As mentioned, Truvada contains TDF. In some people this formulation of tenofovir is associated with an increased risk for kidney injury and, in some cases, thinner-than-normal bones. The manufacturer of Truvada, Gilead Sciences, has developed a new formulation of tenofovir called TAF (tenofovir alafenamide). TAF mostly concentrates inside cells of the immune system and is generally associated with a better safety profile than TDF. TAF is formulated with other medicines in one pill. The specific combination of TAF + FTC is sold under the brand name Descovy.
In a large randomized, placebo-controlled clinical trial sponsored by Gilead Sciences, called the Discover trial, HIV-negative participants were randomly assigned to receive one of the following pills taken once daily:
Participants did not know which formulation they received for the first 96 weeks. After this time, the study was unblinded and all participants were offered Descovy.
Most participants are gay or bisexual men and about 1% are transgender women.
The study is still ongoing; however, interim results have been released.
Overall, cases of HIV infection that occurred were distributed as follows:
- Truvada – 15 cases
- Descovy – seven cases
This difference between the two regimens was not statistically significant. What these results show is that when it comes to effectiveness, both regimens are similarly effective (the technical term for this is “non-inferior”) at reducing the risk for HIV infection.
It is important to note that additional analyses were done, particularly on blood samples from people who became infected during the study. These revealed that most people who became infected either were not taking the study drug exactly as directed or had become infected at the start of the study, perhaps within hours of the screening process. When these factors are taken into account (and such people are excluded from analysis), only one person on each formulation became infected.
However, safety analyses, particularly on bone thinning, show a clear difference in favour of Descovy.
Gilead Sciences plans to seek regulatory approval for using Descovy as part of a package of tools to reduce the risk of HIV infection in Canada, Australia, the European Union and the United States later this year.
The average profile of participants upon entering the study was as follows:
- age – 34 years (note that ages of people in the study were between 18 and 72)
- major ethno-racial groups: white – 60%; Hispanic – 24%; Black – 9%; Asian – 5%
Participants were required to have at least one of the following:
- condomless anal intercourse with at least two unique male partners in the past 12 weeks (partners must be either HIV positive or of unknown HIV status)
- documented history of syphilis in the past 24 weeks
- documented history of rectal gonorrhea or chlamydia in the past 24 weeks
After 96 weeks, the overall distribution of HIV infections was as follows:
- Truvada – 15 infections
- Descovy – seven infections
At first it appeared that Descovy reduced the risk of infection by at least 50%. However, when researchers subsequently analysed blood samples and other data they noted that most infections were likely caused by the following factors:
- Truvada – 10 infections were linked to less-than-ideal levels of tenofovir in the blood; this suggests that these participants were not taking Truvada every day
- Descovy – six infections were associated with less-than-ideal levels of tenofovir in the blood; this suggests that these participants were not taking Descovy every day
Suspected infection at the start of the study (baseline)
- Truvada – four infections
- Descovy – one infection
Thus, when this information about drug levels/adherence and very early infections is taken into account and the people with these issues removed from the analysis, the numbers of people infected on each formulation was as follows:
- Truvada – one infection
- Descovy – one infection
Overall, Truvada and Descovy were well tolerated. The proportions of people who developed drug-related side effects were as follows:
- Truvada – 23%
- Descovy – 20%
As most side effects were generally mild to moderate, perhaps a better indicator of tolerance is the proportions of people who left the study prematurely due to side effects, distributed as follows:
- Truvada – 2%
- Descovy – 1%
Diarrhea appeared to be a fairly common issue in the study, with about 16% of participants who took either study pill reporting it.
Changes to bone mineral density
Overall, about 383 participants were assessed for changes in bone mineral density. In general, people taking Descovy had a small increase in their bone mineral density in their spine and hips, as assessed by low-dose X-ray scans called DEXA (dual-energy X-ray absorptiometry). In contrast, a small decrease in bone mineral density (about 1%) occurred among Truvada users.
The increase in bone density occurred among Descovy users because many participants were young men in their late teens or early 20s whose bones were still developing. Their bone density would have naturally increased. What is important to note is that Descovy did not harm their bone development.
Focus on the kidneys
Several different tests were used to assess kidney health in this study:
- eGFR – estimated glomerular filtration rate
- the ratio of retinol-binding protein to creatinine in the urine
- the ratio of beta-2-microglobulin to creatinine in the urine
There were very small changes in eGFR, about a two-point increase among Descovy users and about a two-point decline among Truvada users, suggesting minor injury to the kidney’s ability to filter blood. Due to the large number of participants in the study, these small changes were statistically significant.
The ratio of retinol-binding protein to creatinine
This ratio increased during the study among participants using Truvada, suggesting very mild kidney injury. However, the increased ratios were still within the normal range. In contrast, the ratio remained stable among Descovy users. These differences in the ratios were statistically significant.
The ratio of beta-2-microglobulin to creatinine
Among Truvada users, levels of this ratio rose but remained within the normal range. Among Descovy users it remained stable. These differences in the ratios were statistically significant.
A note about tests
Both ratios involving retinol-binding protein and beta-2-microglobulin in the urine assess the ability of the kidneys to reabsorb nutrients from urine. Abnormalities in these ratios indicate that parts of the kidney called proximal tubules may be injured. However, doctors in clinics do not routinely use the ratios mentioned above when monitoring kidney health; these tests are research tools. To assess the possibility of injury to the proximal tubules, kidney specialists in the United States have suggested that doctors can use inexpensive and readily available tests such as monitoring the levels of phosphate and sugar in the urine of TDF users.
Bear in mind
The results from the Discover trial are very encouraging for Descovy; it has been shown to be similar in effectiveness to Truvada when it comes to preventing HIV infection. However, Descovy has a clear advantage when it comes to bone health: Most users had increased bone mineral density over the course of the study, while most Truvada users had a decrease. The kidney safety of Truvada over the course of the study was good, but there appear to be signals that a modest degree of kidney injury may be occurring over the long-term, so additional data from Discover is eagerly awaited.
Cost – Truvda vs. Descovy
A major issue for some people is cost. The price of a one-month supply of a generic formulation of Truvada is about $250 Canadian per person. In contrast, a month’s supply of Descovy is about $1000–$1200 Canadian per person. In Canada, many provincial and territorial ministries of health subsidize the cost of Truvada when it is used to reduce the risk of HIV infection. However, ministries of health will likely wait until Health Canada approves this use of Descovy to decide whether to subsidize its use for HIV prevention. Descovy is already approved in Canada as part of combination treatment for HIV infection but ministries of health have not subsidized it. The drug subsidy budgets of Canada’s provinces and territories are under pressure from many new medicines (for many conditions), all of which have high prices. It will be interesting to see what these ministries do once Descovy becomes approved as part of a package of HIV risk reduction tools.
—Sean R. Hosein
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- Amrhein V, Greenland S, McShane B. Scientists rise up against statistical significance. Nature. 2019 Mar;567(7748):305-307