Can a Two-Drug Treatment Regimen Keep HIV Under Control?
An antiretroviral regimen consisting of just two drugs—dolutegravir and lamivudine—led to sustained viral suppression for most people starting HIV treatment for the first time, according to findings from a small study presented in a late-breaker session at the recent 21st International AIDS Conference (AIDS 2016) in Durban, South Africa. Two-drug regimens would potentially be easier to take and less expensive compared to the standard three-drug HIV treatment regimens.
ViiV Healthcare’s drug dolutegravir (Tivicay, also in the Triumeq combination pill) is a potent HIV integrase inhibitor with a high barrier to resistance. Lamivudine (3TC or Epivir) is an inexpensive nucleoside reverse transcriptase inhibitor (NRTI) with minimal side effects and no known drug interactions.
Pedro Cahn, MD, from Fundacion HUESPED in Buenos Aires reported findings from the PADDLE trial, a small proof-of-concept study evaluating dolutegravir plus lamivudine for first-line HIV treatment (abstract FRAB0104LB).
PADDLE enrolled 20 previously untreated adults living with HIV who had no known NRTI drug resistance mutations. All but one were men and the median age was 34 years. At baseline, the median CD4 count was approximately 500 cells/mm3 and the median viral load was about 24,000 copies/mL; the study entry criteria called for baseline viral load below 100,000 copies/mL, but four participants actually had viral loads that were higher than 100,000 copies/mL.
All participants in this open-label 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, then every two weeks through the third month. Treatment was supposed to be intensified if a person did not have at least a 1 log drop in viral load by week 8, if virus levels remained above 1,000 copies/mL at week 12 or above 400 copies/mL at week 24, or if virus rebounded after becoming undetectable.
Cahn presented preliminary 24-week results at the European AIDS Conference last October and 48-week results at AIDS 2016. The study will continue through 96 weeks of follow-up.
Virus levels declined rapidly after starting treatment, similar to declines seen with standard three-drug ART. Most participants had viral suppression below 50 copies/mL by week 3. All participants—including the four who started with the highest levels—did so from week 8 onward.
While everyone had undetectable viral load at the 24-week analysis, at 48 weeks one participant experienced virological failure and one committed suicide, resulting in an overall response rate of 90%.
Cahn explained that the patient with virological failure discontinued the study, but his physician kept him on the same regimen and he achieved viral re-suppression without changing or adding drugs. But to be safe, the investigators eventually convinced him to intensify to a standard three-drug regimen.
Dolutegravir plus lamivudine was generally safe and well tolerated, with few side effects or laboratory abnormalities. The only serious adverse event was a suicide after a traumatic life event that was considered unrelated to the study drugs.
“If confirmed in a well-powered randomized clinical trial, this two-drug regimen might be considered as a simple, potent, well-tolerated, and potentially cheap strategy for HIV treatment initiation,” the study investigators concluded.
Cahn said more data from larger trials is needed to determine if this kind of dual therapy is a safe and effective strategy. The Phase 3 GEMINI trial, which screened its first participant last month, is comparing dolutegravir plus lamivudine against a three-drug regimen of dolutegravir plus tenofovir/emtricitabine (the drugs in Truvada).
“Don’t do this at home until we have the results,” Cahn cautioned.
Liz Highleyman is a freelance medical writer and editor-in-chief of HIVandHepatitis.com.
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