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Dolutegravir matches or surpasses other regimens for first-line HIV treatment
Liz Highleyman, 2013-10-30 13:50:00
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.
Bonaventura 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).
Results from 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).
Clotet's late-breaker 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%, respectively.
The larger 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."
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