Fw: NATAP/CROI: QUAD vs Atripla, Gilead Booster

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QUAD Four-in-One Pill asStrong as Atripla, But a Kidney Concern Arises17th Conference on Retroviruses andOpportunistic Infections, February 16-19, 2010, San FranciscoMark MascoliniA once-daily antiretroviral combining the integrase inhibitor elvitegravir witha non-ritonavir booster (GS-9350), tenofovir (TDF), and emtricitabine (FTC)proved as potent at Atripla (efavirenz plus TDF/FTC) after 24 weeks inpreviously untreated people [1]. This small double-blind, double-dummy phase 2 trial found substantially fewer overallside effects with the four-in-one pill (called Quad) than with Atripla. Butpresenter Calvin Cohen devoted a goodly number of slides to addressingpotential concerns about nephrotoxicity with GS-9350. Kidney trouble withGS-9350 would be a blow to Quad development because of TDF's well-known effecton creatinine clearance. But Cohen maintained the impact of GS-9350 oncreatinine approximates that of an over-the-counter ulcer drug.A separate phase 2 study by the same investigators found GS-9350 (now calledcobicistat) equivalent to ritonavir in boosting the protease inhibitoratazanavir with TDF/FTC in previously untreated people. No one in either studyhad virus resistant to nucleosides, nonnucleosides, or protease inhibitors whenthe trials began.The Quad-versus-Atripla trial involved 48 antiretroviral-naive peoplerandomized to Quad and 23 randomized to Atripla. Most were men and about threequarters were white. Age averaged 36 in the Quad group and 35 in the Atriplagroup. Both groups had an average viral load around 40,000 copies. Medianpretreatment CD4 count stood at 354 in the Quad group and 438 in the Atriplagroup. Fewer than 10% in either arm had AIDS.After 24 weeks 90% taking Quad and 83% taking Atripla had a viral load under 50copies in a missing-data-equal-failure analysis. In an intent-to-treat analysisthat excluded missing data, 96% taking Quad and 95% taking Atripla had a sub-50load at 24 weeks. CD4 counts climbed an average of 161 in the Quad group and113 in the Atripla group.Overall safety results favored Quad, with 37% having a study drug-relatedadverse event on Quad versus 57% on Atripla. The only two grade 3/4 safetyproblems occurred in the Atripla arm. However, by week 24 average serumcreatinine rose 0.14 mg/dL with Quad and 0.04 with Atripla. Glomerularfiltration rate estimated by the Cockcroft-Gault method was -18 mL/min withQuad versus -7 mL/min with Atripla. Estimated glomerular filtration rate atweek 24 averaged 111 mL/min with Quad and 126 mL/min with Atripla.Further analysis of a study of healthy volunteers suggested GS-9350 has noeffect on actual glomerular filtration rate, even though it lowers theestimated rate. Cohen explained that creatinine is excreted primarily byglomerular filtration, but about 10% to 15% is eliminated by active tubularsecretion. Thus he hypothesized that GS-9350 may inhibit tubular secretion ofcreatinine, as does the over-the-counter H2-receptor antagonist cimetidine.Certainly GS-9350 researchers will analyze these issues closely as clinicaldevelopment of Quad proceeds.Pretreatment characteristics in the trial comparing GS-9350 with ritonavir asan atazanavir booster were equivalent to those in the Quad-versus-Atriplastudy. This second trial randomized 50 people to GS-9350 and 29 to ritonavir. Twopeople dropped out of the GS-9350 group because of adverse events, comparedwith 1 dropout in the ritonavir arm. Two people taking GS-9350 had studydrug-related adverse events, compared with none taking ritonavir.By two intent-to-treat analyses, equivalent high proportions in both arms had asub-50 viral load at week 24. CD4 gains averaged 200 in both groups.Reference1. Cohen C, Shamblaw D, Ruane P, et al. Single-tablet, fixed-dose regimen ofelvitegravir/emtricitabine/tenofovir disoproxil fumarate/GS-9350 achieves ahigh rate of virologic suppression and GS-9350 is an effective booster. 17thConference on Retroviruses and Opportunistic Infections. February 16-19, 2010.San Francisco. Abstract 58LB.

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Is Atripla known to cause belly fat or the "pouch?"

Thanks, Ed