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Dolutegravir plus lamivudine dual therapy works well as initial HIV treatment
Liz Highleyman, 2016-07-25 08:50:00
A two-drug regimen of
dolutegravir and the well-tolerated NRTI lamivudine led to sustained viral
suppression for most people starting antiretroviral therapy (ART) for the first
time in a small pilot study, according to a late-breaker presentation at the 21st International AIDS Conference (AIDS 2016) last week in Durban, South Africa.
As people with HIV face lifelong treatment,
researchers continue to look for therapies that are better tolerated, easier to
take and more affordable.
ViiV Healthcare's dolutegravir (Tivicay, also in the Triumeq
single-tablet regimen) is a potent integrase inhibitor with a high barrier to
resistance. Lamivudine (3TC; Epivir)
is an inexpensive, well tolerated nucleoside reverse transcriptase inhibitor
(NRTI) with minimal side effects, no known drug interactions and widely
available low-cost generic versions.
The GARDEL trial previously showed promising results using a
dual combination of lopinavir/ritonavir (Kaletra)
plus lamivudine. But dolutegravir is a more attractive option as it has fewer toxicities
and drug-drug interactions than protease inhibitors.
Pedro Cahn of Fundacion
HUESPED in Buenos Aires reported findings from the PADDLE trial, a
proof-of-concept study evaluating dolutegravir plus lamivudine for initial HIV
This phase 4 pilot study
enrolled 20 previously untreated adults with low baseline viral load (criterion
of <100,000 copies/ml, though four were actually above this threshold)
and no known NRTI resistance mutations. 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
co-infection were excluded (lamivudine is also active against hepatitis B
Participants in this
open-label study were treated with 50mg dolutegravir plus 300mg lamivudine once
daily for 48 weeks. To ensure safety, viral load was initially measured every
few days, then every couple weeks through the third month. The first 10
participants were evaluated at 8 weeks before the next group of 10 started
therapy. Treatment was discontinued if patients did not have at least a 1 log10
decrease in viral load ay week 8, if HIV RNA remained above 1,000 copies/ml at
week 12 or above 400 copies/ml at week 24, or if viral load rebounded after
Cahn presented preliminary 24-week results at the European AIDS Conference last October and 48-week results at
AIDS 2016. The study is on-going through 96 weeks.
Viral load declined rapidly after starting therapy,
similar to declines seen with standard three-drug ART. Most participants had
HIV RNA below 50 copies/ml by week 3 and all - including the four who started
above 10,000 copies/ml - did so from week 8 onward.
While everyone had undetectable viral load at 24
weeks, at 48 weeks one person experienced protocol-defined virological failure
and one committed suicide, resulting in a response rate of 90%.
Dr 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 therapy. Eventually the
investigators convinced him to intensify to a standard regimen.
Treatment was generally safe and well tolerated, with
few side effects or laboratory abnormalities. The sole serious adverse event
was a suicide after a traumatic life event by an individual who was later found
to have had a prior non-disclosed suicide attempt; this was deemed unrelated to
the study drugs.
"In this pilot, proof of concept study, dual
therapy with dolutegravir plus lamivudine induced rapid virologic suppression
with a favourable safety/tolerability profile in HIV-1 infected, treatment-naive
individuals," the researchers concluded. "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
Dr Cahn said more data from larger trials is needed to
determine if dual therapy is a safe and effective strategy. The phase 3 GEMINI trial, which screened
its first participant last week, will compare dolutegravir plus lamivudine
versus the standard regimen of dolutegravir plus tenofovir/emtricitabine (the
drugs in Truvada).
"We need to wait and see," Dr Cahn
cautioned. "Don’t do this at home until we have the results."