article came out in lancet on a very effective and simple HIV regimen using the new integrase-inhibitor dolutegravir (see doi.org/10.1016/S0140-6736(14)60084-2). in the FLAMINGO study 484 patients naive to antiretroviral therapy were put on an investigator chosen background therapy of either tenofivir-emtricitabine (67% of the patients) or abacavir-lamivudine (33%), then randomized to either dolutegravir 50mg daily or the protease inhibitor darunavir 800mg plus ritonivir 100mg. primary endpoint was HIV viral load <50 copies/ml at 48 weeks. patients recruited from 64 research centers in eastern and western europe, US, puerto rico. results, after 48 weeks:
–baseline: 71% white, 25% of african origin; 85% men, CD4 was 395, 25% with viral load > 100K
–90% on dolutegravir and 83% on darunavir/ritonivir achieved <50 copies/ml (statistically significant)
–in those with baseline viral load >100K, significant difference in those on dolutegravir (94% vs 71%, esp significant in those on tenof/emtricit as background therapy, given higher “n” for this group)
—No patient developed drug resistance
–both well-tolerated: 3% in dolutegravir and 9% in darunavir/riton discontinued meds for nonvirologic reasons. mostly diarrhea, nausea, headache, nasopharyngitis, and most were grade 1-2
–higher treatment satisfaction scores with dolutegravir
so, several advantages of dolutegravir regimen:
–better efficacy at 48 weeks, statistically significant. part of this is that integrase-inhibitors (such as dolutegravir) reduce viral load much more rapidly than protease inhibitors (such as darunavir), with the former achieving viral suppression often in less than 8 weeks (in this study, 80% had viral suppression at 4 weeks, 85% by 8 weeks; vs 10% and 25% in the PI group). so possible that darunavir would be just as good if look further out than 48 weeks. esp in those with very high viral loads which take longer to decrease on meds
–the dolutegravir regimen is just 2 pills once a day (and combo may be coming out as a 1 pill regimen). the darunavir regimen was 4 pills once a day
–dolutegravir is really easy to take: few drug-drug interactions, can take with/without meals, better lipid profile
–one sort-of adverse reaction is increase in creatinine, which is related to decreased creatine secretion and NOT to decreasing the true GFR (ie, the calculated GFR looks worse than the true GFR, as also found with cimetidine and trimethoprim), and in this study no one had a concerning (grade 3-4) increase in serum creatinine.
–study not include patients co-infected with hep b or c, and few patients with advanced HIV disease (they consciously excluded pts with moderate to severe hepatic impariment or anticipated need for hep c treatment)
so, sounds like a really fantastic regimen (supported by some other posts I’ve made). some concern about the generalizability of the results to sicker or co-infected patients (hep b or c), nonwhite, women. and, no doubt, the price tag will be high — this may become much more of an issue when the older drugs, such as efavirenz, become available generically. a head-to-head trial of dolutegravir/abacavir/lamivudine was significantly superior to tenof-emtricit-efavirenz (atripla), though in my experience the vast majority of patients on atripla do really well and tolerate the regimen adequately. but the tolerability, efficacy, lack of resistance, lack of food restriction and drug-drug interactions of dolutegravir is really impressive.
geoff