Regimen of two dolutegravir drugs and the well tolerated Reverse Transcriptase Inhibitor Analog Nucleoside, lamivudine led to sustained viral suppression for most people in the first antiretroviral therapy (ART) intervention in a small pilot study, according to one speaker late presentation at the XXI International Conference on AIDS (AIDS 2016) last week in Durban.
As people with HIV live a lifelong treatment, researchers continue to seek out therapies that are better tolerated, easier to take, and more affordable.
ViiV Healthcare dolutegravir (Tivicay, also in the unique Triumeq tablet scheme) is a potent integrase inhibitor with a high resistance barrier. Lamivudine (3TC; Epivir) is an inexpensive and well-tolerated reverse transcriptase nucleoside analogue (NRTI) with minimal known side effects of drug interactions and widely available generic versions of low cost.
Study GARDEL l previously showed promising results using a double combination of lopinavir / ritonavir (Kaletra) plus lamivudine. But dolutegravir is a more attractive option, like IT, has fewer toxicities and drug-to-drug interactions than protease inhibitors.
Pedro Cahn from the HUESPED Foundation demonstrated the findings reported in Buenos Aires from the PADDLE study, a "concept study" trial evaluating dolutegravir plus lamivudine for initial treatment of HIV.
This 4 phase of the pilot study has twenty participants previously untreated, adults with low baseline viral load (criterion <100.000 copies / ml, although 4 were actually above this threshold) and resistance mutations to unknown NRTIs. All but one were men and the median age was 34 years. The median baseline viral load was about 24.000 copies / ml and CD4 count was approximately 500 cells / mm3. People with hepatitis B were excluded (lamivudine is also active against the hepatitis B virus).
Participants in the current open study were treated with 50 mg dolutegravir plus 300 mg lamivudine once daily for 48 weeks. To ensure safety the viral load was initially measured every few days and then every two weeks until the third month. The first ten participants were evaluated at 8 weeks before the next group of ten had started therapy. Treatment has been discontinued if patients
reached at least a decrease in 1 log in viral load at week 8, and if viral load remained above 1000 copies / ml at week 12 or above 400 copies / ml at week 24, or if viral load recurred later become undetectable.
Andrew Cahn presented a preliminary report of the study after 24 weeks in the Conference Parliament on AIDS last October and the results after 48 week in 2016 AIDS. The ongoing study has 96 weeks deadline.
- Viral load declined rapidly after initiation of therapy, similar to the decline seen with 3 pattern to ART drugs.
- Most participants had HIV RNA below 50 copies / ml in the third week and everyone - including 4 who started with viral load above 10.000 copies / ml - did so from the eighth week onwards.
- While all had undetectable viral load in 24 weeks, in 48 weeks 1 person experienced with, in the protocol, the defining line of therapeutic failure and 1 committed suicide, resulting in a% 90 response rate.
- Treatment was generally safe and well tolerated, with few side effects or laboratory abnormalities.
Andrew Cahn explained that the patient with failed therapy had the study discontinued, but his doctor kept the same scheme and he achieved viral suppression without altering the therapy. Finally the researchers convinced him to insert a standard scheme.
The only serious adverse event was a suicide following a traumatic life event by an individual who later found to have had a previously undisclosed history of suicide attempts; this was considered unrelated to the study of drugs.
"In this pilot, proof-of-concept study, dual therapy with Dolutegravir plus lamivudine obtained rapid viral suppression induced with a favorable safety / tolerability profile in the treatment of HIV-1 infection - virally HIV-infected individuals," the researchers concluded:
"It has been confirmed in a well-fed randomized clinical trial that this two-drug regimen can be considered as a simple, potent, well-tolerated and potentially cost-effective strategy for initiating treatment for HIV infection."
Andrew Cahn said more data from larger trials are needed to determine whether dual therapy is a safe and effective strategy. The 3 phase of the GEMINI study (NCT02831673), who screened their first participant last week, will compare dolutegravir plus lamivudine versus the standard regimen of dolutegravir plus tenofovir / emtricitabine (Truvada drugs).
"We have to wait and see," Cahn warned. "Do not do this at home until we have the results."
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Translated by Claudio Souza's original Aidsmap: AIDS 2016: dolutegravir Plus Lamivudine Works Well as First-Line HIV Treatment
Reviewed by Mara Macedo