- Category: Approved HIV Drugs
- Published on Monday, 04 November 2013 00:00
- Written by DHHS
The U.S. Department of Health and Human Services antiretroviral therapy guidelines panel has updated its list of preferred regimens for first-line treatment to include 2 additional HIV integrase inhibitors, elvitegravir (part of the Stribild single-tablet regimen) and dolutegravir (Tivicay).
Integrase inhibitors -- also known as integrase strand transfer inhibitors or INSTIs -- prevent HIV from inserting its genetic material into host cell chromosomes. They are among the most well-tolerated antiretrovirals as they do not interfere with the functioning of human cells.
The first approved drug in this class, raltegravir (Isentress), was included as a preferred first-line option in the February 2013 revision of the Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. That version also included Stribild (elvitegravir/cobicistat/tenofovir/emtricitabine) as an alternative regimen for patients with normal kidney function.
In the latest change, released October 30, 2013, the guidelines now recommend 4 integrase inhibitor-based combinations as preferred regimens for initial antiretroviral treatment:
- Raltegravir 400 mg twice-daily plus tenofovir/emtricitabine;
- Stribild (elvitegravir/cobicistat/tenofovir/emtricitabine) once-daily for patients with estimated creatinine clearance >70 mL/min;
- Dolutegravir 50 mg once-daily plus abacavir/lamivudine once-daily for patients who test negative for the HLA B*5701 abacavir hypersensitivity gene variant;
- Dolutegravir 50 mg once-daily plus tenofovir/emtricitabine once-daily.
Raltegravir is currently indicated only for twice-daily dosing, though recent data suggest once-daily administration may be adequate as maintenance therapy for people with suppressed viral load.
The Stribild single-tablet regimen was approved in August 2012. Elvitegravir and cobicistat alone and in an elvitegravir/cobicistat fixed-dose combination pill are awaiting regulatory approval.
The panel upgraded Stribild to a preferred regimen on the basis of favorable 96-week data from Phase 3 clinical trials as well as additional data through 144 weeks presented at recent conferences. The combination remained non-inferior to Atripla (efavirenz/tenofovir/emtricitabine) with no further serum creatinine increases and no cases of proximal renal tubulopathy beyond 24 weeks.
Dolutegravir was approved in August of this year, and a single-tablet-regimen containing dolutegravir/abacavir/lamivudine -- the first all-in-1 pill with abacavir rather than tenofovir -- is currently under consideration.
Dolutegravir was added as a preferred integrase inhibitor on the strength of data from Phase 3 randomized controlled trials in which it compared favorably to existing preferred regimens using raltegravir, Atripla, or ritonavir-boosted darunavir (Prezista).
Overall, dolutegravir has been shown to be safe and generally well-tolerated in clinical trials, with insomnia and headache being the most frequently reported adverse events. Although dolutegravir can cause an early increase in serum creatinine due to decreased tubular secretion, no discontinuations for drug-related kidney toxicity have been reported to date.
AIDSinfo. Recommendation on Integrase Inhibitor Use in Antiretroviral Treatment-Naive HIV-Infected Individuals from the HHS Panel on Antiretroviral Guidelines for Adults and Adolescents. October 30, 2013.