Judith Feinberg from the
University of Cincinnati and colleagues presented findings from the FLAMINGO
study comparing dolutegravir against ritonavir-boosted darunavir (Prezista), a potent protease inhibitor,
in people new to antiretroviral therapy (ART).
This multicentre, open-label, non-inferiority study enrolled 484
treatment-naive adults with HIV. Most participants (85%) were men, a majority
were white, about 20% were black and the median age was 34 years. At baseline,
the median CD4 cell count was 395 cells/mm3, with 10% having
<200 cells/mm3. One quarter had high viral load (HIV RNA
>100,000 copies/ml) at study entry.
Participants were randomly assigned to received 50mg once-daily
dolutegravir or 800/100mg once-daily darunavir/ritonavir. In addition, they
received investigator-selected NRTIs, with 75% using tenofovir/emtricitabine
(the drugs in Truvada) and 25% using
The researchers looked at the proportion of study participants with undetectable
viral load below 50 copies/ml at 48 weeks, along with safety, tolerability,
health outcomes and viral resistance. The randomised study will last through 96
weeks, followed by a non-randomised extension phase.
By 48 weeks, 7% of people taking dolutegravir discontinued treatment
compared with 12% taking darunavir/ritonavir. The most common reasons for
stopping in both arms were adverse events and loss to follow-up.
In a "snapshot" analysis, 90% of people taking dolutegravir
and 83% taking darunavir/ritonavir achieved undetectable viral load, with
dolutegravir meeting the criteria for statistical superiority (p = 0.025). Results
were similar in a per-protocol or as-treated analysis, 91% and 84%,
respectively. Week 48 CD4 cell gains were the same in both arms: 210 cells/mm3.
The dolutegravir advantage was especially apparent among people with high
pre-treatment viral load: 93 vs 70%, respectively. Among people with low viral
load, response rates were similar, 88 and 87%, respectively.
Virological non-response was uncommon in both the dolutegravir and
darunavir/ritonavir arms (6 and 7%, respectively). Dolutegravir's superiority
was attributable to fewer early withdrawals due to side-effects or other
reasons and better response among people with high viral laod. Among people
with virological failure, primary antiretroviral resistance mutations were rare
in both arms (<1%).
Both regimens were general safe and well-tolerated, with most
side-effects being mild to moderate. Fewer people in the dolutegravir arm, compared
with the darunavir/ritonavir, arm discontinued due to adverse events (1 vs 4%)
and serious drug-related adverse events were uncommon (one vs none). The most
frequent side-effects were diarrhoea (17 vs 29%), nausea (16 vs 18%) and
headache (15 vs 10%).
Laboratory abnormalities were uncommon in both arms. However, people in
the dolutegravir arm had significantly smaller increases in LDL 'bad
cholesterol' (3.1 vs 14.1mg/dl) and were less likely to have moderate or
worse LDL elevation (2 vs 7%). Small increases in serum creatinine – a
potential indicator of kidney toxicity – were seen in the dolutegravir arm,
which Dr Feinberg explained was due to its inhibition of a renal transporter
"Once-daily dolutegravir was superior to darunavir/ritonavir in
treatment-naive HIV-1 infected patients," the researchers concluded.
"Dolutegravir provides a potent and well-tolerated alternative to
darunavir/ritonavir for this naive population."
Dr Feinberg noted that while this open-label study was not double-blind
and did not include placebo controls in order to reduce pill burden, these
findings were "entirely consistent" with response rates seen in
previous trials. She also noted that response rates did not differ based on which
NRTIs were used.