Stribild, New One Pill Per Day Treatment of HIV and Drug Interactions

I’m writing a series of short blogs on the new one pill per day treatment of HIV/AIDS, Stribild.  Stribild has four HIV medications in a single pill, and is also popularly known as the quad pill.

One of the components of Stribild is cobicistat.  Cobicistat is also known as an enhancer of other drugs because it can increase their concentration or level in plasma, part of your blood.  It is a pharmacokinetic enhancer. 

In Stribild, cobicistat enhances elvitegravir, another one of the tablet’s four components.  It does this by inhibiting an enzyme in the liver known as CYP3A.  Because of cobicistat’s effect on CYP3A, elvitegravir drug levels become higher and it lasts longer it the body (known as half-life).  This effect makes it possible to take Stribild just once a day.

The disadvantage of cobicistat is that it also affects other drugs that metabolized by CYP3A, including other HIV medicines, such as protease inhibitors (Prezista, Reyataz, others), non-nucleoside reverse transcriptase inhibitors, (Sustiva, Edurant, Intelence, others), and maraviroc (Selzentry).

Stribild should not be combined with ritonavir (Norvir) or medications containing ritonavir (Kaletra) because both ritonavir and cobicistat inhibit CYP3A.

In addition, giving Stribild with other HIV medications is not recommended at this time.

Tomorrow we’ll continue exploring presciption medications to use with caution and monitoring if combined with Stribild.  Many of these potential drug interactions are a result of the CYP3A-inhibiting effects of cobicistat.

Sound complicated?  It may be complicated for some.  My best advice is to tell your doctor all the medications and herbal products you take, even if different doctors prescribed them, so that he or she can carefully review the list for possible drug interactions.  You can also ask your HIV pharmacist for help.

Who do you go to for help with drug interaction questions?

Have a great day!

Bill

Stribild, New One Pill Per Day Treament of HIV: What are the Precautions?

This week I’m writing about the new one pill per day treatment of HIV  150 mg elvitegravir, 150 mg of cobicistat, 200 mg emtricitabine, and 300 mg tenofovir. The dosasge of Stribild, formerly known as “quad” because it contains four medications, is just one tablet once a day.

The other two one pill per day medications for HIV, Atripla and Complera, contain three medications.

Are there any precautions for using Stribild?  The answer is yes, but nothing really unexpected or alarming.

Stribild has the same “black box” warning about lactic acidosis and enlarged liver as other HIV medications in its class.  It is not approved for treatment of chronic hepatitis B, and the hepatitis B could get worse if you were treated with Stribild and then stopped it.

It does have an interesting warning about its use in people with  kidney problems.  If  you doctor has told you that you have mild or moderate kidney changes and your creatinine clearance is below 70 ml per minute, you should not start Stribild.  Creatinine is a blood test that your doctor can easily order. If you start Stribild and your creatinine clearance drops below 50 ml per minute, you should stop Stribild.  This is because the dosages of two of the component medications, emtricitabine and tenofovor, should be adusted dowwnard, and that is not possible with a single tablet formulation.

Gilead recommends that your doctor check your estimated creatinine clearance, urine glucose, and urine protein before starting Stribild.  These are all standard lab tests.

Cobicistat, one of the components of Stribild, may cause a slight increase in serum creatinine and make it appear that your kidneys are not working  as effectively.  However, it does not actually affect how the kidney glomeruli function.  Still, if your creatinine increased more than 0.4 mg/dl from when you started Stribild, your  kidney function should be more closely monitored.

Any other warnings?

Tenofovir (Viread), part of Stribild, has been associated with decreases in bone mineral desnsity.  The effects of these changes on future bone fractures are unknown.  Supplmentation with calcium and vitamin D is a good idea, so discuss this with your doctor.

Fat redistribution, including central obesity, thinning of your arms and legs, and facial wasting, has been observed in patients who take HIV medications.  We don’t know what causes this, but  it could happen with any HIV medication or from the illness itself.  People with HIV get understandably freaked out about these changes, but in my opinion, these are not reasons to avoid an otherwise life-saving medication.

Immune Reconstitution Syndrome may occur when starting any HIV medication.  This is due to an inflammatory response of your immune system to certain infections that lay dormant while you were untreated, such as Mycobacterium avium infection, cytomegalovirus, or Pneumocystis jirovecii penumonia, better known as PCP pneumonia.

So that’s about it for the scary stuff.  Overall, there’s nothing alarming in this list, other than to make sure your doctor is following your kidney function both before and during treatment with Strilbild, but this is a good idea for any HIV medication regimen.

Tomorrow, we’ll look at adverse effects from Stribild.

Yours,

Bill

Stribild, a New Treatment for HIV-Comparing it to Atripla

This week I’m writing about Stribild, a new one pill per day treatment for HIV that contains four medications.

One of the questions on everyone’s mind is, “Does it work as well as the other medications?  Is it better?”

Let’s compare it to Atripla, one of the most used treatments for HIV, and a preferred treatment according to DHHS recommendations. The other one pill per day treatment for HIV is Complera, and the two medications have not been compared in a study to my knowledge.

In a study presented at CROI in 2012, a big US conference on HIV and related infections, Dr. Paul Sex from Boston reported 48-week data from a Phase 3 trial comparing Stribild and Atripla.  The study enrolled 700 participants.  Ninety percent of the participants were men.  Two-thirds were white, and the average age was 38 years.  All were starting HIV treatment for the first time.  Participants were randomly assigned to Atripla or Stribild.

Both Atripla and Stribild performed well through 48 weeks.  The study concluded  that Stribild demonstrated non-inferior efficacy to Atripla, meaning it worked as well as Atripla.  Similar numbers of participants had viral loads <50 copies, virologic failure was the same, and both were safe and well-tolerated.  Both Atripla and Stribild performed equally well in demographic subgroups.

Both Atripla and Stribild were similarly effective in people with high baseline viral loads, but Stribild did just a bit better in people with CD4 counts above 350 cells/mm3.

Similar proportions of participants from both the Atripla and Stribild group discontinued the study early, but fewer in the Stribild group stopped early due to adverse events (12 vs 18).

A little more nausea was reported with Stribild compared to Atripla (21% vs 14%)

Several other side effects occurred more often in the Atripla group, such as abnormal dreams, insomnia, and dizziness.  These are well-known side effects from efavirenz, contained in Atripla and Sustiva.  Skin rash occurred more frequently with Atripla than Stribild.

Stribild particiants had smaller increases in total, LDL (bad) and HDL (good) cholesterol compared to Atripla, with similar increases in triglycerides.

Stribild participants had a larger increase in serum creatinine, which is a marker of possible kidney damage, early on, but this stabilized and did not progress over time.  This is likely due to cobicistat, the new boosting agent, which affects how the kidneys handle creatinine.  Cobicistat does not appear to cause kidney damage, however.  I’ll be writing more about cobicistat and the kidney in upcoming blogs.

So compared to Atripla, Stribild did at least as well in this study.  I could see Stribild being used in people who do not like the way Atripla makes them feel, such as the dizziness, sleep disturbances, and vivid dreams often seen with Atripla.  In many people, these side effects of Atripla go away or get better over time, but sometimes they persist.

If you are on Atripla on, would you consider switching to Stribild?

In future blogs, I’ll write about how Stribild compares to Reyataz in a different study.

Yours,

Bill