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A combination of two drugs
dolutegravir ( Tivicay ) and lamivudine
suppression of viral load as well as standard antiretroviral treatment with three drugs
for HIV-positive people starting treatment for the first time, according to the results
GEMINI studies presented yesterday at the 22nd
International AIDS Conference (AIDS 2018) in Amsterdam.
Response rates exceeded
90% with dolutegravir / lamivudine and dolutegravir plus
tenofovir / emtricitabine (drugs in Truvada ),
showing that the dual diet was not inferior to standard therapy. But the
dual diet led to fewer side effects, including kidney and bone problems,
reported Pedro Cahn from Fundación Huésped in Buenos
Aires
HIV treatment lasts a lifetime and all that reduces
The burden of drugs would be welcome for patients, Cahn told reporters on Tuesday
press conference. Two-drug plan could potentially offer fewer cumulative drugs
exposure, less side effects and lower cost than standard therapy.
Dolutegravir is
a powerful inhibitor of integrase strand transfer with a high barrier to resistance.
Lamivudine is a well-tolerated and inexpensive nucleoside reverse transcriptase inhibitor (NRTI)
generic versions available.
Previous
Studies have shown that dolutegravir combined with lamivudine
suppression in people who spend a triple diet with an undetectable
viral load. A pill containing dolutegravir and the
NNRTI rilpivirine ( Juluca ) was
recently approved in Europe and the United States, but only as a switch option for people
with the viral load removed.
The Cahn team aimed to show if
Dolutegravir / lamivudine can completely suppress the viral load when it is used
treatment. At the 2016 International AIDS Conference in Durban, Cahn presented
promising results of a small pilot study called PADDLE, which
enrolled 20 people not previously treated with HIV RNA < 100,000
copies / ml. This year, he presented the results of GEMINI 1 and 2, a pair of
phase 3 trials that allowed patients with a viral load as high as 500,000
copies / ml.
Together, the GEMINI studies have
participants in Europe, North and South America, Asia, Russia and South Africa.
About 85% were men, two thirds were white and the median age was about
32 years old. Initially, 80% had a viral load < 100,000 copies / ml
20% had high viral loads between 100,000 and 500,000 copies / ml. Most had CD4
number of cells greater than 200 cells / mm 3 . People with hepatitis B and those with
Hepatitis C requiring treatment have been excluded.
Participants were randomly badigned to
receive dolutegravir / lamivudine
or dolutegravir badociated with tenofovir disiproxil fumarate (TDF) and emtricitabine
NRTI similar to lamivudine). The main criterion of the study was
the proportion of people with HIV RNA less than 50 copies / ml at 48 weeks after
beginning of treatment.
At week 48, in a pooled badysis of
trials, 91% dolutegravir / lamivudine
recipients and 93% of dolutegravir / TDF / lamivudine recipients were undetectable
viral load in an intention-to-treat badysis.
Response rates were high
for people who started with either lower (91% vs. 94%, respectively) or higher
(92% vs 90%) of the viral load at the start. However, among the minority of patients
with a low CD4 count, the triple regimen seems to work better in a snapshot
badysis (79% vs 93%).
Treatment Perspective
failure, 3% dolutegravir / lamivudine
recipients and 2% of patients receiving dolutegravir / TDF / lamivudine were
virologic non-responders. In each treatment arm, 1% or
less had confirmed the virological failure. No emerging integrase of treatment or NRTIs
mutations were observed in these participants.
The two schemas
generally safe and well tolerated. Dolutegravir / lamivudine was badociated with
fewer drug-related adverse events than the triple regimen (18% vs. 24%), but
withdrawal rates due to adverse events were the same in both treatment groups (2%).
The most common side effects in both groups were headache, diarrhea and pain.
infections of the throat or upper respiratory tract.
TDF may cause impaired renal function.
and bone loss in susceptible individuals, such as the elderly and those
pre-existing conditions. In these studies, the dual diet had significantly
less harmful effect on serum and urinary biomarkers of kidney failure
as well as markers of bone loss. Changes in blood lipid levels were similar
both groups.
These conclusions, conclude the researchers,
"support [dolutegravir/lamivudine] as an effective option for the treatment of HIV-1 infection. "
It was the first time that a study has shown
the non-inferiority of dual therapy over triple therapy, said Cahn. He added,
However, this dolutegravir monotherapy should not be recommended,
studies have shown that a powerful agent such as an integrase inhibitor or a protease
inhibitor should be combined with a reverse transcriptase inhibitor.
"I am very comfortable using this as a strategy"
Cahn old reporters. "This is not a one size fits all, but for some people it's a
very safe and powerful combination with less drug load for our patients. "
questioned during his presentation on the use of this strategy in environments where viral base
load test could not be performed before the start of treatment, Cahn responded
"Do not try this at home" without proper supervision.
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