The recently approved HIV integrase inhibitor dolutegravir (Tivicay) provides at least equivalent
antiviral efficacy and better tolerability compared with approved
antiretroviral drugs for treatment-naive people, according to data reported at
the 14th European
AIDS Conference last week in Brussels and in the current edition of Lancet Infectious Diseases.
Clotet of Hospital Universitari Germans Trias i Pujol, Barcelona, presented a subgroup
analysis from the FLAMINGO trial comparing dolutegravir versus ritonavir-boosted
darunavir (Prezista) 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, 23% were black and the median age was 34 years. At
baseline, the median CD4 cell count was 395 cells/mm3 and
one quarter had high viral load (HIV RNA >100,000 copies/ml).
Participants were randomly assigned to receive 50mg
dolutegravir or 800/100mg darunavir/ritonavir, both once daily. In addition,
they received investigator-selected NRTIs, with 67% using
tenofovir/emtricitabine (Truvada) and
33% using abacavir/lamivudine (Kivexa).
the primary analysis, presented last month at the Interscience Conference on Antimicrobial Agents and
Chemotherapy (ICAAC), showed that 90% of people taking dolutegravir and 83% taking
darunavir/ritonavir achieved undetectable viral load in a 'snapshot' analysis,
with dolutegravir meeting the criteria for statistical superiority. CD4 cell
gains were the same in both arms at 210 cells/mm3. Fewer people in
the dolutegravir arm discontinued due to adverse events (1 vs 4%) and serious
drug-related adverse events were rare (one vs none).
presentation at EACS focused on pre-specified subgroups. Dolutegravir's
advantage was particularly notable amongst people with high viral load, with a
48-week response rate of 93%, compared to 70% in the darunavir/ritonavir arm.
The difference was smaller amongst people with lower viral load, 88 vs 87%,
difference in the high viral load strata was mainly driven by lower likelihood
of virological non-response (7 vs 18%) and fewer drop-outs due to adverse
events (0 vs 7%) in the dolutegravir arm.
Response rates for people with CD4 counts above and
below 350 cells/mm3 were similar to those seen in the primary
analysis as a whole (88 vs 80% for <350; 91 vs 84% for >350).
Response rates were comparable for younger and older patients, Clotet said (90
vs 81% for <50; 89 vs 92% for >50 years).
Rates for men (91 vs 85%) and for white patients (91
vs 84%) were similar to the overall primary analysis. Rates were lower for
women (84 vs 73%) and black patients (85 vs 77%), but with the same pattern
of differences favouring dolutegravir. There were no differences according to
NRTIs used (90 vs 85% with Kivexa;
90 vs 81% with Truvada).
Overall, side-effects in the subgroups were similar to
those observed in the analysis as a whole, with most subgroups reporting more
adverse events in the darunavir/ritonavir arm. There were no significant
differences in adverse events leading to withdrawal by subgroup. Dolutegravir
recipients experienced smaller rises in LDL ('bad') cholesterol. Some people
taking dolutegravir had small increases in serum creatinine, attributed to the
drug's effect on a transporter protein.
Based on these findings the researchers concluded,"Dolutegravir
provide a potent and well-tolerated new option for first-line HIV treatment."