Tenofovir alafenamide

Detailed information

There are two formulations of tenofovir, each one available in several combination products. The original formulation is known as tenofovir disoproxil fumarate (TDF) and is marketed as Viread, as a generic product and in fixed-dose combination tablets. See Tenofovir disoproxil fumarate – detailed information for further details of this formulation.

The newer formulation is known as tenofovir alafenamide (TAF) and is available in several fixed-dose combination tablets. Like TDF, it is made by Gilead Sciences Inc.

TAF is a prodrug of TDF. It is converted into an active drug in the body and reaches higher concentrations in cells than TDF. As a result, a much smaller quantity of TAF is needed (25mg or 10mg).

TAF is now included in the following approved products:

  • Descovy (TAF/emtricitabine)
  • Genvoya (TAF/emtricitabine/elvitegravir/cobicistat)
  • Odefsey (TAF/emtricitabine/rilpivirine)
  • Symtuza (TAF/emtricitabine/darunavir/cobicistat)
  • Biktarvy (TAF/emtricibine/bictegravir).

Effectiveness

TAF has been compared to TDF in several large studies in previously untreated and treatment-experienced people.

There was no significant difference in virological or immunological response to TAF when compared to TDF in studies examining the use of either drug as part of first-line treatment in combination with other antiretroviral agents. (Sax, 2015)

People who switched from TDF-containing regimens to TAF-containing regimens continued to maintain viral suppression at the same rate as people taking TDF-containing regimens in a 48-week phase III study and showed modest improvements in kidney function and bone mineral density. (Mills)

Tenofovir is also active against hepatitis B and is recommended as a component of HIV treatment for anyone who is co-infected with hepatitis B.

See our pages on specific combination products for further information on effectiveness.

Taking it

See our pages on specific combination products for details.

Side effects

For side effects of TAF in combinations, see the specific drug combination listed above.

Concerns have been raised about the long-term effects of TDF treatment on the kidneys and bones (see Tenofovir disoproxil fumarate – detailed information for further details of research). As the average age of the population living with HIV increases, reducing exposure to drugs that exacerbate age-related health problems such as osteoporosis and declining kidney function becomes an essential element of HIV management.

TAF was developed, in part, to address these concerns. Studies have consistently shown that people taking TAF had less reduction in kidney function or bone density loss than people taking TDF. It is unclear if these reductions in laboratory measurements of kidney function and bone density will translate into long-term reductions in kidney damage or fewer fractures.

Fewer people taking TAF discontinued treatment due to kidney injury than people taking TDF in two phase III studies, although the number of events was small (4 vs 0). These studies of TAF in first-line treatment combined with elvitegravir and cobicistat also found a smaller reduction in bone mineral density in the first year after starting treatment in people taking TAF when compared to TDF. (Sax, 2015) (Mills)

Glossary

boosting agent

Booster drugs are used to ‘boost’ the effects of protease inhibitors and some other antiretrovirals. Adding a small dose of a booster drug to an antiretroviral makes the liver break down the primary drug more slowly, which means that it stays in the body for longer times or at higher levels. Without the boosting agent, the prescribed dose of the primary drug would be ineffective.

kidney

Organ that removes waste products from the blood through urine.

 

regimen

A combination of medications and the way it is taken.

association

An association means that there is a statistical relationship between two variables. For example, when A increases, B increases. An association means that the two variables change together, but it doesn't necessarily mean that A causes B. The relationship isn't necessarily causal.

antiretroviral (ARV)

A substance that acts against retroviruses such as HIV. There are several classes of antiretrovirals, which are defined by what step of viral replication they target: nucleoside reverse transcriptase inhibitors; non-nucleoside reverse transcriptase inhibitors; protease inhibitors; entry inhibitors; integrase (strand transfer) inhibitors.

A pooled analysis of 26 clinical trials of TAF- or TDF-containing regimens involving 12,519 person-years of exposure to TAF and 5947 person-years of exposure to TDF showed that TDF recipients were significantly more likely to experience acute renal tubulopathy and to discontinue TDF due to a renal adverse event (p < 0.0001). However, the number of clinical events was very low (24 in the TDF recipients vs 3 in the TAF recipients). (Gupta)

A meta-analysis of 14 clinical trials comparing TDF and TAF combined with boosted or unboosted agents confirmed a higher risk of discontinuation due to renal adverse events in recipients of TDF as part of a boosted regimen (where TAF was combined with a boosted protease inhibitor or elvitegravir boosted by cobicistat). TDF also showed inferior virological efficacy as part of a boosted regimen, but not when it formed part of an unboosted regimen. However, the study investigators noted that TDF is used predominantly in combination with unboosted agents in guideline-recommended antiretroviral regimens. (Pilkington)

Studies have reported conflicting results regarding the effects of regimens containing TAF or TDF on lipid levels. An analysis of a phase III study comparing the two agents when combined with elvitegravir boosted by cobicistat found that although TAF recipients experienced significantly greater increases in total cholesterol, LDL and HDL cholesterol, these changes were not sufficient to increase their ten-year projected risk of cardiovascular disease. (Huhn) Some, but not all, retrospective studies have reported worsening of cardiovascular risk profiles after switching from TDF to TAF. (Gazzola; Schwarze-Zander; Kauppinen)

Weight gain has been reported in people with HIV after starting antiretroviral treatment. Several studies have reported that TAF is associated with greater weight gain than TDF in people starting or switching treatment. A randomised study in South Africa which compared two dolutegravir-containing regimens (one combined with TAF, the other with TDF) to an efavirenz-containing regimen found that the combination of dolutegravir and TAF was associated with greater weight gain (+6kg in men and +9kg in women over 96 weeks) and the risk of substantial weight gain was greater in women than men. (Venter).

However, other randomised studies have not reported weight gain of similar magnitude and the extent of weight gain may be influenced by pre-treatment CD4 cell count, viral load, sex and race. (Sax 2019)

A cohort analysis of 6919 people living with HIV, representative of the population in care in the United States, found that switching to TAF was associated with significant weight gain, regardless of whether an integrase inhibitor formed part of the regimen or not. (Mallon)

Resistance

See Tenofovir disoproxil fumarate – detailed information.

Drug interactions

For potential drug interactions with TAF, see the specific drug combination listed above.

Pregnancy

The British HIV Association recommends that TAF should be used after the first 12 weeks of pregnancy owing to a lack of information about its effects on foetal development during the first trimester.

This recommendation is based on the findings of the IMPAACT 2010 study, which compared birth outcomes in pregnant women randomised to receive dolutegravir and emtricitabine with either TAF or TDF, or to efavirenz/TDF/ emtricitabine. Women began treatment between weeks 14 and 28 of pregnancy. The study found that significantly fewer women in the TAF arm had an adverse pregnancy outcome including stillbirth, premature delivery, infant death, or severe maternal adverse event, compared to women in the other study arms. (Chinula)

British and US treatment guidelines recommend against the use of two combinations containing TAF (Symtuza and Genvoya) during pregnancy owing to the risk of lower blood levels of antiretrovirals when boosted by cobicistat during pregnancy. US guidelines also advise against the use of another combination containing TAF (Biktarvy) in pregnancy due to limited information on its safety in pregnant women.

Children

See individual combination products for details of restrictions on use in children.

References

Sax P et al. Tenofovir alafenamide versus tenofovir disoproxil fumarate, coformulated with elvitegravir, cobicistat, and emtricitabine, for initial treatment of HIV-1 infection: two randomised, double-blind, phase 3, non-inferiority trials. The Lancet, 385: 2606-15, 2015. You can read more about this study in our news report.

Mills A et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide in antiretroviral regimens for virologically suppressed adults with HIV-1 infection: a randomised, active-controlled, multicentre, open-label, phase 3, non-inferiority study. The Lancet Infectious Disease, 16: 43-52, 2016. You can read more about this study in our news report.

Gupta S et al Renal safety of tenofovir alafenamide vs. tenofovir disoproxil fumarate: a pooled analysis of 26 clinical trials. AIDS, 33: 1455-1465, 2019.

Pilkington V et al. Tenofovir alafenamide vs. tenofovir disoproxil fumarate: an updated meta-analysis of 14 894 patients across 14 trials. AIDS, 34: 2259-2268, 2020. You can read more about this study in our news report.

Mallon P et al. Weight gain before and after switch from TDF to TAF. 23rd International AIDS Conference, abstract 3283, 2020. You can read more about this study in our news report.

Huhn G et al. Atherosclerotic cardiovascular disease risk profile of tenofovir alafenamide versus tenofovir disoproxil fumarate. Open Forum Infectious Diseases, 7: ofz472, 2019.

Gazzola L et al. Dyslipidaemia after switch to tenofovir alafenamide (TAF)-based cART regimens in a cohort of HIV-positive patients: what clinical relevance? HIV Medicine, 22: 140-145, 2021.

Schwarze-Zander C et al. Switching tenofovir disoproxil fumarate to tenofovir alafenamide in a real life setting: what are the implications? HIV Medicine, 21: 378-385, 2020.

Kauppinen K et al. Switching from tenofovir disoproxil fumarate to tenofovir alafenamide significantly worsens the lipid profile in a real-world setting. AIDS Patient Care STDS, 33: 500-506, 2019.

Chinula L et al. Safety and efficacy of DTG vs EFV and TDF vs TAF in pregnancy:IMPAACT 2010 trial. Conference on Retroviruses and Opportunistic Infections, abstract 130, 2020. You can read more about this study in our news report.

Venter W et al. Dolutegravir with emtricitabine and tenofovir alafenamide or tenofovir disoproxil fumarate versus efavirenz, emtricitabine, and tenofovir disoproxil fumarate for initial treatment of HIV-1 infection (ADVANCE): week 96 results from a randomised, phase 3, non-inferiority trial. The Lancet HIV, 7: e666-e676, October 2020. You can read more about this study in our news report.

Sax P et al. Weight gain following initiation of antiretroviral therapy: risk factors in randomized comparative clinical trials. Clinical Infectious Diseases, online ahead of print, 2019. You can read more about this study in our news report.

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