Two-drug regimen of dolutegravir and the well-tolerated Nucleoside Analogue Reverse Transcriptase Inhibitor, lamivudine led to sustained viral suppression for most people in the first antiretroviral therapy (ART) intervention in a small pilot study, according to a speaker. late presentation at the 2016st International AIDS Conference (AIDS XNUMX) last week in Durban.
As people with HIV experience lifelong treatment, researchers continue to look for therapies that are better tolerated, easier to take and more accessible.
ViiV Healthcare dolutegravir (Tivicay, also in the unique Triumeq tablet) is a potent integrase inhibitor with a high barrier to resistance. Lamivudine (3TC; Epivir) is an inexpensive and well-tolerated form of nucleoside analog reverse transcriptase (NRTI) with minimal known side effects from drug interactions and widely available low-cost generic versions.
The study GARDEL l previously showed promising results using a double combination of lopinavir / ritonavir (Kaletra) plus lamivudine. But dolutegravir is a more attractive option, as TI, has less toxicities and drug-drug interactions than protease inhibitors.
Pedro Cahn of the HUESPED Foundation demonstrated the findings reported in Buenos Aires from the PADDLE study, a “concept study” test evaluating dolutegravir plus lamivudine for initial HIV treatment.
This phase 4 of the pilot study has twenty previously untreated participants, adults with low baseline viral load ( <100.000 copies / ml, although 4 were actually above this threshold) and unknown NRTI resistance mutations. All but one were men and the median age was 34 years. The median baseline viral load was around 24.000 copies / ml and the 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 present open study were treated with 50 mg dolutegravir plus 300 mg lamivudine once daily for 48 weeks. To ensure safety, 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 started therapy. Treatment was discontinued if patients were not
achieve at least a 1 log decrease in viral load in the eighth week, and whether the viral load remained above 1000 copies / ml at week 12 or above 400 copies / ml at week 24, or if the viral load reappeared later to become undetectable.
Andrew Cahn presented a preliminary report of the study after 24 weeks at the Parliament of the AIDS Conference last October and the results after 48 weeks in AIDS 2016. The current study is for 96 weeks.
- The viral load decreased rapidly after the initiation of therapy, similar to the decline seen with ART 3 drug pattern.
- Most participants had HIV RNA below 50 copies / ml in the third week and all - including the 4 who started with a viral load above 10.000 copies / ml - did so from the eighth week onwards.
- While everyone had an undetectable viral load at 24 weeks, at 48 weeks 1 person with the protocol defines the therapeutic failure definition line and 1 committed suicide, resulting in a 90% response rate.
- The treatment was generally safe and well tolerated, with few side effects or laboratory abnormalities.
Andrew Cahn explained that the patient with therapeutic failure had the study discontinued, but his doctor maintained the same schedule and he achieved viral suppression without changing the therapy. Finally, the researchers convinced him to insert a standard scheme.
The only serious adverse event was suicide after a traumatic life event by an individual who was 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 achieved rapid viral suppression induced with a favorable safety / tolerability profile in the treatment of HIV-1 infection - ART-naïve individuals,” the researchers concluded:
"It was confirmed in a well-fed randomized clinical trial, that this two-drug regimen can be considered as a simple, potent, well-tolerated and potentially inexpensive strategy for starting HIV infection treatment."
Andrew Cahn said more data from larger trials is needed to determine whether dual therapy is a safe and effective strategy. Phase 3 of the GEMINI study (NCT02831673), which tracked its first participant last week, will compare dolutegravir plus lamivudine versus the standard dolutegravir plus tenofovir / emtricitabine regimen (drugs in Truvada).
"We have to wait and see," Cahn warned. "Don't do it at home until we have the results."
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Medicament 2016 enter into the third line treatment of HIV infection
The dolutegravir Antiretroviral was incorporated into the SUS from the decision of the National SUS Technology Incorporation Commission (Conitec) as third-line drug in the treatment of HIV infection.
The third line of treatment is known as a rescue line. That is, the one indicated on failure patient care with the first and second lines. .. read more
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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