April 8th, 2018

Latest DHHS Guidelines for Initial HIV Therapy Now Include 5 Choices — But Really 2 Are Best

On March 28, the Department of Health and Human Services Guidelines issued an update to the HIV treatment guidelines, with a focus on the recent approval of bictegravir/TAF/FTC:

BIC/TAF/FTC is an effective and well-tolerated INSTI-based regimen for initial therapy in adults with HIV, with efficacy that is noninferior to DTG/ABC/3TC and DTG plus TAF/FTC for up to 48 weeks. On the basis of these clinical trial results, the Panel classifies BIC/TAF/FTC as one of the Recommended Initial Regimens for Most Adults with HIV.

Based on this change, there are now five recommended initial regimens for most people:

  1. Bictegravir/TAF/FTC
  2. Dolutegravir/ABC/3TC
  3. Dolutegravir + TAF (or TDF)/FTC
  4. Elvitegravir/cobicistat/TAF (or TDF)/FTC
  5. Raltegravir + TAF (or TDF)/FTC

All are based on an integrase inhibitor and a pair of NRTIs. Four have tenofovir/FTC as the NRTI pair. Three are available as a single tablet, once daily.

But with the important caveat that what follows represents my opinion and not that of these or any other guidelines, one could easily argue that there are really two primary choices here, not five.

And those are dolutegravir + TAF (not TDF)/FTC and, now, bictegravir/TAF/FTC.

Here’s why:

  • Raltegravir and elvitegravir both have a lower resistance barrier than dolutegravir and bictegravir. Virologic failure with elvitegravir and raltegravir may select for integrase resistance, usually along with NRTI resistance. This hasn’t happened yet in any clinical trial of dolutegravir or bictegravir for initial therapy, at least when given with two NRTIs.
  • Elvitegravir requires the pharmacokinetic booster cobicistat. This greatly increases the drug interactions of this option, some of which are highly clinically significant.
  • Raltegravir is two pills. In addition, it cannot be coformulated.
  • The association between abacavir and cardiovascular disease has become stronger with recent research. In addition, abacavir requires pre-treatment HLA-B5701 testing and does not treat hepatitis B. Furthermore, the coformulation of dolutegravir/ABC/3TC is the largest of the single-pill options for HIV therapy.
  • TAF has a better renal and bone safety profile than TDF. There will likely be cost benefits of TDF/FTC over TAF/FTC eventually, but they are not yet realized in the clinic.

As of April 8, 2018 (the day I’m writing this post), the choice between the two remaining options reflects how we and our patients feel about two issues.

If giving one pill rather than two is most important, then go with bictegravir/TAF/FTC.

If accumulated safety and “real world” experience is most important, then go with dolutegravir plus TAF/FTC.

Hey, isn’t HIV treatment simple these days?

16 Responses to “Latest DHHS Guidelines for Initial HIV Therapy Now Include 5 Choices — But Really 2 Are Best”

  1. Pallavi Bhargava says:

    Your opinion on first line regimen options gave instant clarity, Thanks !

  2. Malika Mohabeer Hart says:

    Thank you Paul. Always a fan. Fantastic to hear about these combinations and the advantages they bring!
    I currently work in Mauritius where cost is what mostly guides treatment protocols. Dolutegravir is hopefully soon going to be approved and procured by our department of health. In the meantime, most of our patients are still lingering on toxic and difficult to tolerate PI-based regimens. Generics here bring with them a higher burden of toleratbility issues. Parent companies need to do more to make modern antiretrovirals more accessible to resource-limited countries.

  3. Dan Ross says:

    It seems like there is not general awareness of the drug interactions with the boosters, especially for injected corticosteroids administered in procedure settings– where the interaction checks don’t always occur as they (hopefully) do for prescribed medications.

  4. Britt Gayle says:

    Is there really sufficient evidence to conclude that bictegravir has a higher barrier to resistance, than non DTG integrase inhibitors? It appears that the DHHS guideline is still limiting their recommendation for BIC/TAF/FTC initiation to patients without any history of resistance mutations, and the evidence base for BIC resilience doesn’t appear to be anywhere as robust as the data for DTG (i.e. efficacy trials with INSTI experienced patients), largely due to the lack of data.

    • Paul Sax says:

      Agree that there are data of much longer duration with DTG. But there hasn’t been a single case of treatment-emergent resistance in any of the bictegravir initial therapy or switch therapy studies. If you couple that observation with the in vitro resistance data on bictegravir (where it is quite comparable, and perhaps slightly better than DTG), you certainly could conclude that it’s better than both EVG and RAL.

  5. EDUARDO XAVIER HIAS POZZOBON says:

    In Brazil FTC and TAF never arrived. The only two options we have for integrase Inhibitors is RAL or DTG, both combined with TDF+3TC. The first choice is DTG. RAL is reserved for patients with tuberculosis. ABC is hard to prescribe. It’s almost impossible to do the HLA test.

  6. Michel Rosenheim says:

    Thanks for your opinion but I wonder on which data you rely to say that TAF is less toxic than TDF.

  7. Britt says:

    But it appears that the study populations in the initial therapy and switch studies were very carefully selected. I would definitely select a BIC containing regimen over EVG and RAL containing regimens due to its other advantages. Since I have yet to see it in the wild, I was wondering if you know how the size of Biktarvy compares to Triumeq?

  8. Vasileios PAPASTAMOPOULOS says:

    Dear Paul,
    Here is the conclusion of the publication by Andrew Hill(Journal of Virus Eradication 2018; 4: 73–80):
    “TDF boosted with RTV or COBI was associated with higher risks of bone and renal adverse events, and lower HIV RNA suppression rates, compared with TAF. By contrast, when ritonavir and cobicistat were not used, there were no efficacy differences between TAF and TDF, and marginal differences in safety. The health economic value of TAF versus low-cost generic TDF may be limited when these drugs are used without cobicistat or ritonavir.”
    Does that approach changes anything to your conclusion about ” that there are really two primary choices” only?
    Thanks

  9. Poojan Sheth says:

    Paul,

    As per my knowledge there has been no study done on Pregnant mothers with bictegravir, and with Dolutegravir there is only one ARIA study. What should be the preference during pregnancy?

    Also with anti TB, DTG is preferred and till date no studies on TB with BIC (may be studies are going on, which i am not aware) So isn’t DTG better with TB Patients for now.

  10. Keith W Crawford says:

    Paul, I generally agree with your evaluation of these options for initial therapy. There is one consideration I will raise. At CROI 2018, Courtney Fletcher Pharm.D.presented some excellent work investigating integrase penetration into lymphoid tissues. Comparing raltegravir, dolutegravir and elvitegravir, only elvitegravir reached concentrations in lymph nodes and GALT that were adequate to suppress viral replication in these tissues. All integrase inhibitors reached adequate concentrations in plasma and PBMC’s. We know that viral replication dynamics in plasma do not necessarily reflect what is going on in tissue. Acheiving adequate plasma drug concentration in tissue are essential for any approach that could ultimately “cure” the infection. I suspect the higher concentrations reached by elvitegravir are due to it being boosted. Just a thought.

  11. Alejandro Ferro says:

    Would be very important to argentine that TAF will be available not only in the Genvoya component

  12. Karen Mello says:

    Hi Paul
    This is a little tangential but ..do you have any opinion about risk for lipodystrophy with these treatment options
    I have a longstanding hiv+ T2dm with worsening abdominal lipodystrophy , stage 4 CKD on darunavir/ ritonavir/ tivicay with excellent suppression .
    Thanks , as always , for your advice in caring !

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HIV Information: Author Paul Sax, M.D.

Paul E. Sax, MD

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