||ARV Therapy: Clinical Trials
Oral Abstract Session : Track B
||Session Room 1
||24.07.2012, 11:00 - 12:30
Christine Katlama, France
Michael Saag, United States
|ARV therapy: evolving concepts and new drugs|
R. Gulick, United States
|Once-daily maraviroc in combination with ritonavir-boosted atazanavir in treatment-naïve patients infected with CCR5‑tropic HIV-1 (study A4001078): 96‑week results|
A. Mills1, D. Mildvan2, D. Podzamczer3, G. Fätkenheuer4, M. Leal5, S. Than6, S.R. Valluri7, C. Craig8, M. Vourvahis7, J. Heera6, H. Valdez7, T. Brown9, A. Rinehart10, S. Portsmouth7
1Anthony Mills MD Inc., Los Angeles, United States, 2Beth Israel Medical Center Division of Infectious Diseases, New York, United States, 3HIV Unit, Infectious Disease Service, Hospital Universitari de Bellvitge, Barcelona, Spain, 4First Department of Internal Medicine, University Hospital of Cologne, Köln, Germany, 5Infectious Disease Service, Virgen del Rocio University Hospital, Seville, Spain, 6Pfizer Inc., Groton, United States, 7Pfizer Inc., New York, United States, 8Pfizer Inc., Sandwich, United Kingdom, 9Division of Endocrinology and Metabolism, Johns Hopkins University, Baltimore, United States, 10ViiV Healthcare, Research Triangle Park, United States
A. Mills, United States
|Cobicistat versus ritonavir as pharmacoenhancers in combination with atazanavir plus tenofovir disoproxil fumarate/emtricitabine: phase 3 randomized, double blind, active-controlled trial, week 48 results|
J. Gallant1, E. Koenig2, J. Andrade-Villanueva3, P. Chetchotisakd4, E. DeJesus5, F. Antunes6, K. Arastéh7, G. Moyle8, G. Rizzardini9, J. Fehr10, Y.-P. Liu11, L. Zhong11, C. Callebaut11, S. Ramanathan11, J. Szwarcberg11, M. Rhee11, A. Cheng11
1Johns Hopkins School of Medicine, Baltimore, United States, 2Instituto Dominicano de Estudios Virologicos -IDEV-, Santo Domingo, Dominican Republic, 3Hospital Civil, Guadalajara, Mexico, 4Khon Kaen University, Muang District, Thailand, 5Orlando Immunology Center, Orlando, United States, 6Hospital de Santa Maria, Lisboa, Portugal, 7EPIMED / Vivantes Auguste-Viktoria-Klinikum, Berlin, Germany, 8Chelsea & Westminster Hospital, London, United Kingdom, 9Ospedale Luigi Sacco, Milano, Italy, 10University Hospital Zurich, Zurich, Switzerland, 11Gilead Sciences, Foster City, United States
J. Gallant, United States
|SPIRIT study: switching to emtricitabine/rilpivirine/tenofovir df (FTC/RPV/TDF) single-tablet regimen (STR) from a ritonavir-boosted protease inhibitor and two nucleoside reverse transcriptase inhibitors (NRTIS) maintains HIV suppression and improves seru|
F. Palella1, P. Tebas2, B. Gazzard3, P. Ruane4, D. Shamblaw5, J. Flamm6, M. Fisher7, J. van Lunzen8, R. Ebrahimi9, K. White9, B. Guyer9, H. Graham9, T. Fralich9
1Northwestern University, Feinberg School of Medicine, Chicago, United States, 2University of Pennsylvania, Division of Infectious Diseases, Clinical Trials Unit, Philadelphia, United States, 3Chelsea and Westminster Hospital Foundation Trust, London, United Kingdom, 4Peter J. Ruane, MD, Inc., Los Angeles, United States, 5La Playa Medical Group and Clinical Research, San Diego, United States, 6Kaiser Permanente, Sacramento, United States, 7Brighton and Sussex University Hospitals, Brighton, United Kingdom, 8University Medical Center Hamburg-Eppendorf, Hamburg, Germany, 9Gilead Sciences, Foster City, United States
F. Palella, United States
|Efficacy and safety results from a randomized, double blind, active controlled trial of elvitegravir (once-daily) versus raltegravir (twice-daily) in treatment-experienced HIV-positive patients: long term 96-week data|
R. Elion1, J.-M. Molina2, J.-R. Arribas-Lopez3, D. Cooper4, F. Maggiolo5, E. Wilkins6, B. Conway7, Y.-P. Liu8, L. Zhong8, N. Margot8, J. Szwarcberg8, M. Rhee9, A. Cheng8
1Whitman-Walker Health, Washington, United States, 2Hopital Saint Louis, Service des Maladies infectieuses, Paris, France, 3Hospital Universitario La Paz, Servicio de Medicina Interna, Unidad VIH, Madrid, Spain, 4Kirby Institute, University of New South Wales, Sydney, Australia, 5Ospedali Riuniti di Bergamo, Bergamo, Italy, 6North Manchester General Hospital, Manchester, United Kingdom, 7Vancouver ID Research & Care Centre, Vancouver, Canada, 8Gilead Sciences, Foster City, United States, 9Gilead Sciences, HIV Clinical Research, Foster City, United States
R. Elion, United States
CPC report by Garry Brough
Despite the intense focus on treatment as prevention at this conference, less than 15% of the 3000 studies presented relate to basic research or clinical studies. In this session, however, Dr Roy Gulick sought to provide an overview of how far we have come and to examine some current and future prospects for HIV treatment. AZT was the first HIV medication to be approved, 25 years ago, and since then we have seen a further 25 approved ARVs in 6 classes. He noted the huge increases in effective viral suppression which help prevent morbidity and mortality, with life expectancy (at age 20) increasing from 27 years in 1996 to 52 years in 2006.
When to start: all guidelines around the world now recommend treatment initiation at a CD4 count of 350, while US guidelines recommend treatment at any point.
What to start: standard backbone of 2 NRTIs - Truvada is recommended option everywhere, although WHO and the IAS also recommended Kivexa. All guidelines offer a choice of NNRTI, PI or II as third agent, apart from WHO, who only combines the NRTIs with an NNRTI, due to cost.
Dr Gulick touched upon research trials of NRTI-sparing regimens and while tree of the seven have been halted early, Dr Anthony Mills presented good data on once daily maraviroc and boosted atazanavir.
There are several promising drugs in current trials, with Integrase Inhibitors elvitegravir and dolutegravir closest to approval, as well as new NRTIs, CCR5 antagonist and a CD4 attachment inhibitor in phase 1 and 2 stages.
Cobicistat is a booster rather than an anti-HIV drug and Dr Joel Gallant presented comparative data showing its improved lipid profile in comparison to current PI booster ritonavir. Similarly Dr Frank Palella presented data on switching from a boosted PI to the one pill combo of rilpivirine/truvada, showing a marked lowering of lipids and improvements in long-term cardiovascular risk.
One-pill formulations look set to increase from our current range of two, with a further four in development, including the quad pill already mentioned as well as the first combination to co-formulate Kivexa (with dolutegravir) rather than Truvada. The prospect of long-acting formulations is also promising, with rilpivirine and another new drug pushing dosage intervals to between 26-55 days, though this is more likely be an injection than a pill.
Track B report by Dr. Federico Pulido
TUAB01. Oral Abstract Session - ARV Therapy: Clinical Trials
Roy Gulick started the session reviewing the state of the art of the antiretroviral therapy, emphasizing the most recent changes (including data to be presented in this conference) about the classical questions: When and What to start? And When and What to change? Also making a reference to the new drugs and combinations under development.
TUAB0102 - Once-daily maraviroc in combination with ritonavir-boosted atazanavir in treatment-naïve patients infected with CCR5 tropic HIV-1 (study A4001078): 96 week results.
96 week data of this Phase 2b, randomized, open-label study comparing MVC 150 mg QD (n=60) or tenofovir/emtricitabine (TDF/FTC) 200/300 mg QD (n=61) with ATV/r 300/100 mg QD show a trend to a lower efficacy of the dual therapy (82 vs. 67.8% with viral load [VL] <50 copies/mL, ITT M=F). However, most of the failing patients had VL<400 copies/mL and no one developed resistance. Patients on MVC+ATV/r had higher proportion of hyperbilirubinemia (grade 3-4, 70 vs. 55.7%) and lower decrease in creatinine clearance (-1 vs -21 ml/min). Based on this results a full powered study comparing DRV/r + MVC vs DRV/r + TDF/FTC has been launched.
TUAB0103 - Cobicistat versus ritonavir as pharmacoenhancers in combination with atazanavir plus tenofovir disoproxil fumarate/emtricitabine: phase 3 randomized, double blind, active-controlled trial, week 48 results.
Cobicistat was non-inferior to ritonavir when used as a booster for ATV [85% (ATV/co) and 87% (ATV/r) (difference: -2.2%; 95% CI: -7.4 to 3.0) with HIV-1 RNA < 50 copies/mL at Week 48 by snapshot algorithm]. Patients on ATV/co presented more hyperbilirubinemia (65 vs. 57%), higher decrease of estimated glomerular filtration (-13 vs -9 mL/min) and a non-significant trend to lower cholesterol and triglycerides.
TUAB0104 - SPIRIT study: switching to emtricitabine/rilpivirine/tenofovir df (FTC/RPV/TDF) single-tablet regimen (STR) from a ritonavir-boosted protease inhibitor (PI/r)and two nucleoside reverse transcriptase inhibitors (NRTIS) maintains HIV suppression and improves serum lipids in HIV-1-positive subjects
At 24 weeks, the proportion of patients maintaining viral load <50 copies/mL was non-inferior in patients switched to (FTC/RPV/TDF) as compared with those who continue receiving two NRTIs + PI/r (93.4% vs. 89.9%; 95% CI [-2.0%, 8.9%] by Snapshot analysis). All 17 participants (100%) with pre-existing K103N (all transmitted) who switched to FTC/RPV/TDF at baseline maintained HIV-1 RNA <50 copies/mL. Overall total cholesterol, LDL, TC:HDL ratio and triglycerides decreased to a greater extent among FTC/RPV/TDF than PI recipients.
TUAB0105 - Efficacy and safety results from a randomized, double blind, active controlled trial of elvitegravir (once-daily) versus raltegravir (twice-daily) in treatment-experienced HIV-positive patients: long term 96-week data
At Week 96, once-daily EVG in combination with a fully active PI/r and another second agent was non-inferior to twice-daily RAL in efficacy ( 47.6% in EVG and 45.0% in RAL with viral load <50 copies/mL; difference 2.6% [95% CI: -4.6 to 9.9] by TLOVR) in treatment-experienced patients. A similar rate of treatment emergent integrase resistance was reported (7% in both groups). Patients on EVG had significantly lower rates of grade 3-4 ALT, AST and GGT increases (2 vs. 6%; 2 vs. 5% and 3 vs. 7% respectively) and higher rates of diarrhea (13 vs. 8%).