Reverse engineered: Trial of a new HIV drug

Clinical Brief – October 13th

The Brief

Darunavir/cobicistat (Prezcobix or Rezolsta) is a combination therapy for HIV that’s taken with two other drugs as part of a complete treatment regimen.

A recent company-sponsored trial reported that a new 4-drug-combo therapy with darunavir + cobicistat + emtricitabine + tenofovir alafenamide mashed into 1 pill is no worse than older boosted protease-inhibitor combination therapies.

In translation: D/C/F/TAF (the acronym for the 4-drug combo) in 1 pill is no worse than taking the same type of drugs individually.

The upshot? If we can read the data backward, it may mean that the older regimen is no worse than the new D/C/F/TAF. Older = eventual genericization = lowered cost with no loss of efficacy. Win?


The trend in HIV drug development

HIV meds have seen some pretty amazing advancements in the last few decades. Trouble is, trials over the last few years that led to the approval of new drugs have nearly all been non-inferiority trials (some examples off the top of my head: Atripla, Complera, Genvoya, Stribild, Triumeq).

Non-inferiority trials are easier than equivalence trials and less risky than superiority trials to run, but they don’t tell us much more than the fact that a new drug is no worse than an existing one.

So basically, these trials are saying that there’s a new pill, it might not do much more to treat HIV than what we already have, but at least it won’t cause unacceptable harm and it might be easier to take.


The D/C/F/TAF trial

In this trial, researchers recruited over 1,100 patients from 106 hospitals across North American and Europe. Everyone was virally suppressed on a boosted protease-inhibitor regimen.

Patients were then randomized 2:1 to switch to the new D/C/F/TAF or stay on their original regimen. The researchers assumed a non-inferiority margin of 4%.

Basically, it’s ok if more patients on D/C/F/TAF loses control of their HIV viral load, as long as it’s not more than 4% higher than those taking the older regimen, error bars and all, for the trial to conclude that D/C/F/TAF isn’t worse than the older regimen.

After nearly a year of treatment, only 2.5% of patients on D/C/F/TAF lost control of their HIV viral load vs 2.1% on the older pills. The difference between the two treatments worked out to be 0.4%, with an error bar spanning -1.5 to 2.2, which meant that D/C/F/TAF was no worse than the older pills.


Let’s have a bit of fun with their data

Open-ended logic question: If A is not better and not worse than B, does that mean B is also not better and not worse than A?

Statistically speaking, if we take their data and flip it upside down, we get the comparison between the older protease-inhibitor regimen vs D/C/F/TAF instead.

In this scenario, the treatment difference between the old pills vs D/C/F/TAF would be negative 0.4% with error bars hitting -2.2 to 1.5; which would then mean that the older protease-inhibitor regimen is no worse than D/C/F/TAF.


Bottom line

This subtle difference is important because when a company claims that a new, simpler treatment is no worse than the tried-and-true combination regimen of the same class, we could very well come up with this as a counterbalance:

The tried-and-true combination, once genericized, will likely cost considerably less, and may possibly be no worse than the shiny new pill.

What kind of cost savings is considerable? If I take a conservative approach and estimate that the generic would cost 25% less than a new pill that may cost about $2,500 USD a month, it could mean savings of $7,500 USD a year.

For an American with an average income of about $35k USD, this is 1/5th their annual salary. How much quality life would that buy?

*Full disclaimer, the study authors did not suggest that reversing their statistics is advised. These calculations are my personal ruminations only and have not been subject to peer-review.


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The week in brief

August 28th – September 1st

Congratulations for making it through another week! Here are your recent updates in the world of medical research and policy.


A trial published last weekend during the 2017 European Society of Cardiology congress found that a blood thinner, rivaroxaban (Xarelto), failed to outperform aspirin at preventing cardiovascular death, stroke, or heart attack for patients who had hardened arteries.

The combination of rivaroxaban + aspirin did do better than aspirin alone, but also came at higher risk for uncontrolled bleeding.


In July 2017, the Trump Administration announced funding cuts and an end to its Teen Pregnancy Prevention Program.

In a commentary, the potential consequences of these cuts are laid bare: Lowering the age of first intercourse, increasing the rate of premarital sex among teens, increasing the number of unintended pregnancies, and increasing the number of abortions.


A new study found that taking excessive amounts of vitamins B6 and B12 is linked to significantly elevated risk of lung cancer in men.

It doesn’t mean B6 and B12 causes cancer, but the data showed signs that men who intentionally seek B6 and B12 supplementation may be at increased risk of lung cancer.


Graft-vs-host disease (aka GVHD) is where the stem cell transplant develops into white blood cells that “rejects” the recipient.

To help predict what happens after an acute GVHD, a new study turned to some common biomarkers which are simple to test. Their risk score, EASIX, also came with an online calculator.


TB (or tuberculosis) is a potentially lethal infection which is particularly serious for patients living with HIV.

To circumvent the high cost of genetic tests used to screen for active TB, a new study showed that a simple finger-prick test for CRP may do the job at less than a fifth the cost.


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Back to basics. TB screening

Clinical Brief – September 1st

The Brief

TB (or tuberculosis) is a potentially lethal infection which is particularly serious for patients living with HIV.

To circumvent the high cost of genetic tests used to screen for active TB, a new study showed that a simple finger-prick test for CRP may do the job at less than a fifth the cost. Continue reading “Back to basics. TB screening”

The week in brief

August 21st – 25th

A study from Germany found that for patients with binge eating disorder, face-to-face therapy is better than internet-based self-help intervention from a medical perspective, but in terms of improving the patients’ quality of life and stabilizing their BMI, either option should work.


A small study by the Michael J Fox Foundation confirmed that a drug used to treat type 2 diabetes may help patients with Parkinson’s control motor symptoms. The trial is too small to change how Parkinson’s treated today, but the drug they tested is due to go off patent this year, lowering the cost barrier to larger trials.


A group at UC San Francisco developed PREPARE, a website to help people with advance care planning. Their latest study with veterans showed that using the website together with a simple legal form helped more patients document their end-of-life plans.


Immunotherapies are important advances in the treatment of cancers like melanoma. As we are seeing them used more in clinics, we are starting to get a sense of their safety profile and the types of new side effects that can happen.

A Sloan Kettering study profiled the safety and tolerability of a pair of immunotherapies used to treat melanoma. They found that 3 in 5 patients didn’t make it to their fourth dose because of side effects or cancer progression, but noted that patients may still benefit with less than four doses.

 


Kaposi sarcoma is a type of skin cancer often linked to AIDS. Patients with Kaposi sarcoma are at greater risk of other cancers.

A new study found that the rate of Kaposi sarcoma has come down since the advent of HIV meds. The types of secondary cancers have also changed over time, notably with fewer non-Hodgkin lymphomas and more acute lymphocytic leukemias.


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Changing times: HIV-related cancer risk

Clinical Brief – August 25th

The Brief

Kaposi sarcoma is a type of skin cancer often linked to AIDS. Patients with Kaposi sarcoma are at greater risk of other cancers.

A new study found that the rate of Kaposi sarcoma has come down since the advent of HIV meds. The types of secondary cancers have also changed over time, notably with fewer non-Hodgkin lymphomas and more acute lymphocytic leukemias. Continue reading “Changing times: HIV-related cancer risk”

Flu shots for pregnant mothers ≠ durable protection for infants

  • Infants younger than 6 months are too young for flu shots.1
  • To protect infants younger than 6 months, the Centers for Disease Control and Prevention (CDC) suggests that pregnant mothers get the shot instead.2
  • Contrary to the CDC, a study showed that flu shots only protect infants for less than 2 months after birth.3

Continue reading “Flu shots for pregnant mothers ≠ durable protection for infants”