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Switch On Your HIV Smarts.

Ask A Pharmacist: With a new tenofovir, should you switch to Descovy, Genvoya or Odefsey?

, by Jennifer Cocohoba, PharmD, AAHIVE

pharmacist-squareMany people living with HIV may be familiar with an HIV medication called tenofovir. Tenofovir disoproxil fumarate (brand name Viread, and also known as “TDF”) is an NRTI.

It is also one component in the following commonly-taken combination HIV pills:

  • Atripla (TDF/emtricitabine/efavirenz)
  • Complera (TDF/rilpivirine/emtricitabine)
  • Stribild (TDF/elvitegravir/cobicistat/emtricitabine)
  • Truvada (TDF/emtricitabine)

This year, a new version of tenofovir was released by the pharmaceutical company Gilead Sciences: tenofovir alafenamide (also known as “TAF”). It was approved for use by the Food and Drug Association to treat HIV in the following “updated” versions of Complera, Stribild and Truvada, which are:

  • Odefsey (TAF/rilpivirine/emtricitabine)
  • Genvoya (TAF/elvitegravir/cobicistat/emtricitabine)
  • Descovy (TAF/emtricitabine)

(An updated version of Atripla with TAF was likely not developed because the drug efavirenz is known to cause central nervous system problems like dizziness and impaired cognition. Fewer people, overall, are using efavirenz since it’s no longer a preferred initial regimen.)

Genvoya bottle and pillI’ve heard more than a few patients ask, what should I do? If I’m already taking Complera, Stribild or Truvada, should I switch to the newer drug formulation with TAF? I always encourage people to talk to their health care providers if they have questions about their medications. Here is some additional information that will be helpful if you’re considering asking your health care provider if switching is right for you.

So…what’s the difference between TDF and TAF?

Both TDF and TAF are prodrugs. This means that they’re not in their final, active form in pill form. Once they are in the body, they are converted by human enzymes into an active form of the medication.

Both TDF and TAF work exactly the same way to stop the HIV virus from replicating in the body (making copies of itself). Tenofovir blocks an HIV enzyme called “reverse transcriptase” and prevents HIV from converting RNA, the virus’s genetic blueprint, into DNA that can be integrated into our CD4 cells. Because the main ingredient in both TDF and TAF, tenofovir, is the same, we expect (and studies have demonstrated) that the medicines are equally effective.

But the chemical structures of TDF and TAF are different. TAF is more easily and quickly loaded into cells that HIV targets. TAF more efficiently gets to where it’s needed to prevent HIV replication. TDF does this less efficiently, which means TDF is more likely to wind up in higher concentrations in places where it’s not needed—like the plasma (our blood). When this happens, TDF can cause unwanted kidney and bone side effects.

What the research says about switching

Several studies have looked to see whether switching from TDF to TAF had beneficial effects on the kidneys, bones or other health measurements.

Gilead Study 109:

This study included 1,436 patients with undetectable viral loads. These participants switched from TDF/emtricitabine plus efavirenz, TDF/emtricitabine plus atazanavir/ritonavir, or TDF/emtricitabine/elvitegravir/cobicistat to TAF/emtricitabine/elvitegravir/cobicistat, or, they stayed on their current regimen. The study found that switching to TAF significantly increased bone mineral density (1.79% TAF vs 1.37% for TDF). It also found switching to TAF significantly increased total cholesterol, LDL cholesterol, and triglycerides (+22 points, +9 points, and +10 points).

A sub-analysis of Study 109:

This sub-analysis compared only people who had switched from cobicistat/elvitegravir/emtricitabine/TDF (Stribild) to cobicistat/elvitegravir/emtricitabine/TAF (Genvoya). In this smaller group, people who switched to TAF had less protein in their urine (-16% TAF vs. +14% TDF) and had fewer changes in bone mineral density. As in the other studies, those who took TAF had increased LDL, HDL and triglycerides as compared to those who took TDF.

Gilead Study 112:

This study included 242 people with undetectable viral loads, who switched from any ART regimen to cobicistat/elvitegravir/emtricitabine/TAF (Genvoya). People who switched from TDF to TAF had a significant decrease in urine protein (47% TDF vs. 13% TAF).

Study 311-1089:

This study included 663 people with undetectable viral loads who switched from TDF/emtricitabine (Truvada) to TAF/emtricitabine (Descovy). This study found small improvement in creatinine clearance (the rate at which your kidney filters) with TAF vs. TDF (+8.4 ml/min TAF vs. +2.8 ml/min TDF) and significantly less protein in the urine after switching to TAF (-14.6% TAF vs. +7.7% TDF).

Together, these studies suggest that TAF may be safer for your kidneys and bones in the long run than TDF. People who participated in these switching studies showed improvements in urine protein and albumin (which shows better kidney function), and also had improvements in bone mineral density. But, they did not find big improvements in creatinine clearance—one of the main ways clinicians measure kidney health—after switching. These studies also found that TAF caused some people’s cholesterol to increase, which may be an unwanted side effect for many.

Is switching right for me?

Here are a few practical considerations if you’re thinking about switching:

How are my kidneys doing right now?

If your kidneys are healthy, great. Switching to TAF may help minimize damage to your kidneys caused by tenofovir. If your kidneys are not healthy it is not clear whether you should switch to TAF or not.  Switching to TAF can minimize exposure to tenofovir, but your doctor may also need to do other things—like take ultrasounds of your kidney, look at other medications you’re taking, or talk to a renal expert—to determine why your kidneys are not healthy before making the decision on whether to switch or not. We also don’t yet know what the right dose of TAF should be for persons who are on hemodialysis.

How’s my cholesterol?

Most of the switch studies found that when TDF was changed to TAF, all forms of cholesterol: total, LDL, HDL, and triglycerides increased. For some people this might be OK. For others who already have high cholesterol, or for those who are having a hard time controlling their cholesterol with medications, switching to TAF may not be the best idea.

What will my regimen look like after I switch?

Right now, TAF is only available in three forms: as Genvoya, Odefsey, and Descovy. For many people, switching to a TAF regimen would be an easy change. For example, going from Stribild to Genvoya means staying on one pill, taken once a day. But for some people, switching to a TAF containing regimen might require taking more pills, or might require you to switch off another drug in your regimen to keep it as compact as possible. Be sure to check in with your doctor or pharmacist about what your regimen would look like if you wanted to use TAF instead of TDF.

Will my insurance cover TAF?

This is an important consideration, because HIV medications can be expensive! Check with your insurance company or talk with your pharmacist to find out whether switching to TAF will cost you more money. If it does, you may qualify for some patient assistance programs that can help with co-pays. Your doctor and pharmacist may also have to submit a prior authorization so that the medication will be covered by your insurance.

The bottom line

If you’re wondering whether switching to a TAF-regimen is right for you, schedule some time to talk with your doctor or pharmacist. Together, you and your healthcare team can look at all your individual factors to decide on the best regimen to keep your HIV virus suppressed with the fewest short and long-term side effects possible.

Jennifer Cocohoba, PharmD, is an associate clinical professor in the School of Pharmacy at the University of California, San Francisco (UCSF). Since 2004, she has worked as the clinical pharmacist for the UCSF Women’s HIV Program, where she provides adherence support and medication information to patients and providers.

Sources

Gallant J., and others. Switching tenofovir DF to tenofovir alafenamide in virologically suppressed adults. Program and abstracts of the 2016 Conference on Retroviruses and Opportunistic Infections; February 22-25, 2016; Boston, Massachusetts. Abstract 29.

Gupta S., and others. Subjects with renal impairment switching from tenofovir disoproxil fumarate to tenofovir alafenamide have improved renal and bone safety through 48 weeks. Program and abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention; July 19-22, 2015; Vancouver, Canada. Abstract TUAB0103.

Thompson M., and others. Switching from a tenofovir disoproxil fumarate (TDF) to a tenofovir alafenamide (TAF)-based single tablet regimen (STR): week 48 data in HIV-1 infected virologically suppressed adults. Program and abstracts of ID Week 2015; October 7-11, 2015; San Diego, California. Abstract 725.

Mills T., and others. Switching from a tenofovir disoproxil fumarate (TDF)-based regimen to a tenofovir alafenamide (TAF)-based regimen: data in virologically suppressed adults through 48 weeks of treatment. Program and abstracts of the 8th IAS Conference on HIV Pathogenesis, Treatment & Prevention; July 19-22, 2015; Vancouver, Canada. Abstract TUAB0102.

Sax P., and others. Renal and bone safety of tenofovir alafenamide vs tenofovir disoproxil fumarate. Program and abstracts of the 2015 Conference on Retroviruses and Opportunistic Infections; February 23-26, 2015; Seattle, Washington. Abstract 143LB.

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