XVIII International AIDS Conference

Late Breaker Track B - 2 THLBB2

Type:
Oral Abstract Session Back
Location: SR 1
Schedule: 14:30 - 16:00, 22.07.2010
Code: THLBB2
Chairs: Anton Pozniak, United Kingdom
Sharon Walmsley, Canada



Presentations in this session:

14:30
THLBB201
Abstract
Slides with audio
HAART initiation and clinical outcomes: insights from the CASCADE cohort of HIV-1 seroconverters on 'When to Start'
Presented by Joe Eron, United States
M. Jonsson Funk1, J.S. Fusco2, S.R. Cole1, J.C. Thomas1, K. Porter3, J.S. Kaufman4, M. Davidian5, A.D. White6, K.E. Hartmann7, J.J. Eron8, CASCADE Collaboration
1University of North Carolina at Chapel Hill, Dept of Epidemiology, Chapel Hill, United States, 2EpiQuest Sciences, Inc, Libertyville, United States, 3Medical Research Council Clinical Trials Unit, London, United Kingdom, 4McGill University, Department of Epidemiology, Biostatistics, and Occupational Health, Montreal, Canada, 5North Carolina State University, Department of Statistics, Raleigh, United States, 6GlaxoSmithKline, Worldwide Epidemiology, Research Triangle Partk, United States, 7Vanderbilt University Medical Center, Nashville, United States, 8University of North Carolina at Chapel Hill, School of Medicine, Chapel Hill, United States

14:40
THLBB202
Abstract
Slides with audio
Comparison of 48 week efficacy and safety of 400 mg QD nevirapine extended release formulation (Viramune XR) versus 200 mg BID nevirapine immediate release formulation (Viramune IR) in combination with Truvada® in antiretroviral (ARV) naïve HIV-1 infected patients (VERxVE)
Presented by Anne-Marie Quinson, United States
J. Gathe1, J. Bogner2, S. Santiago3, A. Horban4, M. Nelson5, P.E. Cahn6, J. Andrade7, D. Spencer8, C. Young9, T. Nguyen9, W. Zhang9, M. Drulak9, A.-M. Quinson9
1Therapeutic Concepts, Houston, United States, 2Ludwig-Maximilians University, Munich, Germany, 3Care Resource, Miami, United States, 4Warsaw Medical University and Hospital of Infectious Diseases, Warsaw, Poland, 5Chelsea & Westminster Hospital, London, United Kingdom, 6Fundacion Huesped, Buenos Aires, Argentina, 7Antiguo Hospital Civil de Guadalajara, Guadalajara, Mexico, 8Toga Labs, Edenvale, South Africa, 9Boehringer-Ingelheim Pharmaceuticals Inc, Ridgefield, United States

14:50
THLBB203
Abstract
Slides with audio
Safety and immunovirological activity of once daily maraviroc (MVC) in combination with ritonavir-boosted atazanavir (ATV/r) compared to emtricitabine 200mg/tenofovir 300mg QD (TDF/FTC) + ATV/r in treatment-naïve patients infected with CCR5-tropic HIV-1 (Study A4001078): A week 24 planned interim analysis
Presented by Simon Portsmouth, United States
A. Mills1, D. Mildvan2, D. Podzamczer3, G. Fätkenheuer4, M. Leal5, S. Than6, S. Valluri6, C. Craig7, J. Heera6, S. Portsmouth6
1Los Angeles, CA, Los Angeles, United States, 2Beth Israel Medical Center Division of Infectious Diseases, New York, United States, 3HIV Unit, Infectious Disease Service, Hospital Unversitari de Bellvitge, Barcelona, Spain, 4Universitaet Koeln, Koeln, Germany, 5Laboratory of Immunovirology, Biomedicine Institute of Seville (IBIS), Infectious Diseases Service, Virgen del Rocio University Hospital, Sevilla, Spain, 6Pfizer Inc, New York, United States, 7Pfizer Global Research and Development, Sandwich, United Kingdom

15:00
THLBB204
Abstract
Slides with audio
The SPARTAN study: a pilot study to assess the safety and efficacy of an investigational NRTI- and RTV-sparing regimen of atazanavir (ATV) experimental dose of 300mg BID plus raltegravir (RAL) 400mg BID (ATV+RAL) in treatment-naïve HIV-infected subjects
Presented by Michael J. Kozal, United States
M.J. Kozal1, S. Lupo2, E. DeJesus3, J.-M. Molina4, C. McDonald5, F. Raffi6, J. Benetucci7, M. Mancini8, R. Yang8, V. Wirtz8, L. Percival8, J. Zhang8, A. Farajallah8, B.-Y. Nguyen9, R. Leavitt9, D. McGrath8, M. Lataillade8, for the SPARTAN study team
1Yale University School of Medicine and VA CT Healthcare System, New Haven, United States, 2Instittuto CAICI, Rosario, Argentina, 3Orlando Immunology Center, Orlando, United States, 4Department of Infectious Diseases, Saint-Louis Hospital and University of Paris Diderot Paris 7, Paris, France, 5Tarrant County Infectious Association, Fort Worth, United States, 6University Hospital, Nantes, France, 7FUNDAI and University of Buenos Aires, Buenos Aires, Argentina, 8Bristol-Myers Squibb, Global Development and Medical Affairs, Wallingford, United States, 9Merck Research Laboratories, North Wales, United States

15:10
THLBB205
Abstract
Slides with audio
Once-daily S/GSK1349572 as part of combination therapy in antiretroviral naïve adults: rapid and potent antiviral responses in the interim 16-week analysis from SPRING-1 (ING112276)
Presented by Garrett Nichols, United States
J. Arribas1, A. Lazzarin2, F. Raffi3, A. Rakhmanova4, G. Richmond5, J. Rockstroh6, J. van Lunzen7, B. Young8,9, S. Almond10, C. Brothers11, S. Min11, G. Nichols11
1Hospital La Paz, IdiPAZ, Madrid, Spain, 2Vita-Salute San Raffaele University, Milan, Italy, 3University Hospital, Nantes, France, 4Botkin Hospital of Infectious Diseases, St. Petersburg, Russian Federation, 5Broward Health, Ft. Lauderdale, United States, 6University of Bonn, Bonn, Germany, 7University Medical Center, Hamburg-Eppendorf, Germany, 8Rocky Mountain CARES/DIDC, Denver, United States, 9Health Connections International, Amsterdam, Netherlands, 10GlaxoSmithKline, Oakville, Canada, 11GlaxoSmithKline, Research Triangle Park, United States

15:20
THLBB206
Abstract
Slides with audio
Pooled week 48 efficacy and safety results from ECHO and THRIVE, two double-blind, randomised, phase III trials comparing TMC278 versus efavirenz in treatment-naïve, HIV-1-infected patients
Presented by Calvin Cohen, United States
C. Cohen1, J.-M. Molina2, P. Cahn3, B. Clotet4, J. Fourie5, B. Grinsztejn6, W. Hao7, M. Johnson8, M. Saag9, K. Supparatpinyo10, H. Crauwels11, L. Rimsky11, S. Vanveggel11, P. Williams11, K. Boven12
1Community Research Initiative of New England, Boston, United States, 2Saint-Louis Hospital and University of Paris, Department of Infectious Diseases, Paris, France, 3Hospital Juan A Fernández and Fundación Huesped, Buenos Aires, Argentina, 4Hospital Universitari Germans Trias i Pujol and irsiCaixa Foundation, Barcelona, Spain, 5Dr J Fourie Medical Centre, KwaZulu Natal, South Africa, 6Instituto de Pesquisa Clínica Evandro Chagas-Fiocruz, Rio de Janeiro, Brazil, 7Beijing You'an Hospital, Beijing, China, 8Royal Free Hospital, London, United Kingdom, 9University of Alabama at Birmingham, Infectious Diseases, Birmingham, United States, 10Chiang Mai University, Section of Infectious Disease, Chiang Mai, Thailand, 11Tibotec BVBA, Mechelen, Belgium, 12Tibotec Inc, Titusville, United States

15:30
THLBB207
Abstract
Slides with audio
Safety and efficacy of treatment simplification to atazanavir/ritonavir plus lamivudine in patients on two NRTIs plus atazanavir/ritonavir with optimal virologic control: 24 weeks results from a pilot study (atazanavir and lamivudine simplification study, ATLAS)
Presented by Massimiliano Fabbiani
A. De Luca1,2, L. Bracciale1, M. Doino1, M. Fabbiani1, L. Sidella1, A. Marzocchetti1, S. Farina1, A. D'Avino1, R. Cauda1, S. Di Giambenedetto1
1Catholic University of Sacred Heart, Institute of Clinical Infectious Diseases, Rome, Italy, 2Universitary Hospital of Siena, Clinic of infectious Diseases, Siena, Italy

15:40
THLBB208
Abstract
Slides with audio
Similar times to virologic suppression and switching or stopping for abacavir(ABC)/3TC and tenofovir(TDF)/FTC in antiretroviral-naïve HIV-positive patients starting therapy
Presented by Curtis Cooper, Canada
M. Loutfy1,2,3, J. Raboud3,4, D. Tan5, S. Blitz4, K. Chan6, C. Cooper7, N. Machouf8, M. Klein9,10, D. Moore6,11, C. Tsoukas10, S. Rourke12,13, A. Palmer6, J. Montaner11,14, R. Hogg6,15, The Canadian Observational Cohort Collaboration (CANOC)
1Women's College Research Institute, Toronto, Canada, 2Maple Leaf Medical Clinic, Toronto, Canada, 3University of Toronto, Dalla Lana School of Public Health, Toronto, Canada, 4University Health Network, Infectious Diseases, Toronto, Canada, 5Toronto General Hospital, Toronto, Canada, 6British Columbia Centre for Excellence in HIV/AIDS, Drug Treatment Program, Vancouver, Canada, 7University of Ottawa, Ottawa, Canada, 8Clinique Medicale L'Actuel, Montreal, Canada, 9Montreal Chest Institute Immunodeficiency Service Cohort, Montreal, Canada, 10McGill University, Faculty of Medicine, Montreal, Canada, 11University of British Columbia, Faculty of Medicine, Vancouver, Canada, 12Ontario HIV Treatment Network, Toronto, Canada, 13University of Toronto, Faculty of Medicine, Toronto, Canada, 14British Columbia Centre for Excellence in HIV/AIDS, Vancouver, Canada, 15Simon Fraser University, Faculty of Health Sciences, Burnaby, Canada

15:50
THLBB209
Abstract
Slides with audio
The MONET trial 96 week analysis: darunavir/ritonavir monotherapy versus DRV/r + 2NRTIs, for patients with HIV RNA < 50 copies/mL at baseline
Presented by Armin Rieger, Austria
A. Rieger1, D. Banhegyi2, W. Schmidt3, A. Hill4, J. Arribas5, Y. van Delft6, C. Moecklinghoff7
1General Hospital, University of Vienna, Vienna, Austria, 2Belgyogyaszati Osztaly, Budapest, Hungary, 3Medizinisches Versorgungszentrum, Berlin, Germany, 4Liverpool University, Pharmacology, London, United Kingdom, 5Hospital la Paz, Madrid, Spain, 6Janssen-Cilag, Medical, Tilburg, Netherlands, 7Janssen-Cilag, Neuss, Germany





Rapporteur report

Track B report by Jose ARRIBAS


 

THLBB2 Late Breaker Track B – 2

This late breaker session was extremely interesting with many important clinical trials and cohorts presented.

 

Eron, et al. addressed the “when to start” question using data from the CASCADE cohort of HIV seroconverters. Using a novel method of sequential nested cohort analysis combined with inverse probability weighting, initiation of ART at CD4 <500 appears to reduce risk of death compared to deferring at baseline. At CD4 500-799, there was no apparent benefit to initiation for the population of patients with CD4s in this range. Eron discussed limitations to using observational data to address the question of “when to start”.

 

Quinson, et al. presented results of a RCT of nevirapine 400 mg QD in an extended release formulation versus NVP 200 mg BID that found the QD formulation to be non-inferior, and with a similar safety and tolerability profile to BID dosing of the immediate release formulation.

 

Portsmouth, et al. presented the 24 week results of a pilot, open label RCT comparing MVC 150mg daily with ATV/r versus TDF/FTC/ATV/r in 112 treatment naïve patients. At week 24, VL<50 achieved in MVC arm: 80% versus TDF/FTC arm: 89%. Of the 5 participants with virologic failure who could be evaluated for drug resistance, no resistance was detected. A phase III study is now planned.

 

There is interest among clinicians to have available an antiretroviral regimen which is both ritonavir and nucleoside sparing. Before this conference several uncontrolled studies had suggested that unboosted Atazanavir 300 mg BID plus Raltegravir 400 mg BID could be a useful regimen in antiretroviral naive patients to avoid at the same time nucleosides and ritonavir associated toxicities. Kozal and colleagues (THLBB204) have reported the results of SPARTAN which is a multicenter, randomized, open-label, non-comparative pilot study to evaluate the efficacy and safety of atazanavir 300mg BID plus RAL 400mg BID in treatment-naïve HIV-infected patients. Subjects were randomized 2:1 to ATV+RAL (n=63) or a reference regimen of ATV/RTV 300/100mg QD + tenofovir/emtricitabine (TVD) 300/200mg QD (n=31). By the primary analysis at week 24 (HIV-RNA < 50c/ mL) that used confirmed virologic response (CVR NC=F) 74.6% of the patients randomized to ATV+RAL had undetectable viral load compared to 63.3% of patients receiving the control regimen.

 

Through week 24, 7 patients on ATV+RAL and one on ATV/RTV +TVD met criteria for resistance testing. 57.1% of the virologic failures on ATV +RAL developed RAL resistance. No ATV resistance was observed in either arm.  Grade 4 hyperbilirubinemia were 20.6% and 0%, respectively. The study supports the antiviral efficacy of the combination but poses the question if the risk of resistance to RAL is increased with this nucleoside and ritonavir sparing combination. Based on these data Dr. Kozal informed the audience that the study has been stopped. 

 GSK1349572 (ING572) is an integrase inhibitor in preclinical development which is administered once daily and without boosting. At this conference Arribas et al (THLBB205) communicated the results of a phase IIb dose-ranging, partially-blinded trial which included 205 antiretroviral naïve HIV-infected patients. All patients received a 2 drug NRTI backbone given once daily and were randomized to receive ING572 10 mg QD, ING572 25 mg QD, ING572 50 mg QD or EFV 600 mg QD. Mean baseline viral load was 4.46 log10 copies/mL and mean baseline CD4 cell count was 324 cells/µL. After 16 weeks, proportions of patients with less than 50 copies/mL (TLOVR) were 90-96% in the three ING572 groups and 60% in the EFV group. At week 16 only two confirmed virologic failures were identified (one in each arm). There were not severe adverse events related to ING572. Treatment-emergent laboratory abnormalities of grade 3 or higher were rare. Changes from baseline in lipids were more favorable in the ING572 groups than in the EFV group. Based upon this data, 50mg has been selected for Phase 3 studies of integrase inhibitor naïve subjects

 Rilpivirine (TMC278) is a non-nucleoside reverse transcriptase inhibitor which had shown promising results in dose-finding studies. In this conference Cohen and colleagues have reported (THLBB206) two important phase III trials of rilpivirne (ECHO and THRIVE) in antiretroviral naïve patients

These two trials include patients receiving (1:1) rilpivirne 25mg qd or efavirenz 600mg qd, plus either tenofovir (TDF)/emtricitabine (ECHO) or TDF/emtricitabine, lamivudine/zidovudine or abacavir/lamivudine (THRIVE). The primary objective was to demonstrate non-inferiority of TMC278 to efavirenz in confirmed virologic response (viral load < 50 copies/mL ITT-TLOVR algorithm) at Week 48. A total of 1368 patients were randomised to the study arms. Median baseline viral load was 5.00 log10 copies/mL and median CD4 256 cells/mm3. Rilpivirine showed non-inferior efficacy versus efavirenz. At week 48 proportion of patients with less than 50 copies/mL were 84.3% in the Rilpivirine groups and 82.3 % in the Efavirenz groups. The virologic failure rate was 9.0% in the TMC278 group and 4.8% in the efavirenz group. This difference was compensated by a lower rate of discontinuations due to side effects in the Rilpivirine groups. Lipid changes were more favorable with Rilpivirine than with Efavirenz. Half of the patients who failed rilpivirine with resistance were also cross-resistant to etravirine. This results support the use of Rilpivirine in antiretroviral naïve patients but also support the high efficacy of efavirenz based combinations.

 Toxicities associated with TDF and Abacavir have increased the interest for nuc-sparing regimens. A “middle way” to avoid these toxicities would be to use dual therapy using 3TC or FTC as the only nucleoside. Both 3TC and FTC have a very benign toxicity profile. In this conference De Luca and collaborators have presented (THLBB207) an interesting single-arm study about the safety and efficacy of treatment simplification to atazanavir/ritonavir plus lamivudine in patients on two NRTIs plus atazanavir/ritonavir with optimal virologic control (ATLAS study).

Patients receiving atazanavir/ritonavir + 2NRTI, without previous treatment failure or resistance to PI and/or lamivudine, with HIV-RNA< 50 copies/mL for >3 months, CD4>200cells/µL for >6 months, HBsAg-negative and with atazanavir plasma levels above efficacy thresholds were eligible. At baseline, regimens were simplified to atazanavir/ritonavir + lamivudine at recommended doses.

Study enrolled 40 patients with prolonged HIV suppression (medina 663 days) and high CD4 cell counts (98cells/µL). Thirty-nine patients discontinued tenofovir and one abacavir. At the time of analysis, 36/40 patients had reached week 24 visit. All patients maintained an HIVRNA< 50 copies/mL. Atazanavir concentration and total bilirubin did not show significant modifications. Median change from baseline total cholesterol was +19mg/dL and  LDL +15mg/dL, HDL +4mg/dL without significant modification of Total cholesterol/HDL ratio. A significant increase of GFR was observed. This is an interesting preliminary finding that should be confirmed in larger studies.

Clinical trials have suggested that abacavir might be less efficacious than tenofovir in patients with baseline viral load above 100.000 copies/mL. Partially for this reason ABC/3TC is now an “alternative” NRTI option for treating ART-naïve patients in the DHHS guidelines. In this conference Loufty and colleagues (THLBB208) present a cohort study looking at time to virologic suppression (two consecutive VL< 50 copies/mL>1 month apart) and time to switch or stop of ABC/3TC or TDF/FTC (not due to virologic failure) in ART-naïve patients who started HAART. 783 patients were included in the analysis. Investigators did not find a difference between the time to virologic suppression and stopping or switching first time use of ABC/3TC and TDF/FTC. Main limitation of the study is that is not randomized

 Rieger and colleagues communicated the 96 weeks results of the MONET clinical trial (THLBB209). To be included in the trial patients have to be naïve to Darunavir/ritonavir and had to be virologically suppressed (less than 50 copies/mL) for more than 6 months while receiving HAART (NNRTI or PI based). Patients with prior virological failures were excluded.

Patients were randomized to receive darunavir/ritonavir QD monotherapy or Darunavir/ritonavir QD plus two nucleosides. At 48 weeks (primary endpoint) this clinical trial demonstrated the non-inferiority of darunavir/ritonavir monotherapy. At this conference investigators have presented the 96 week update. At this time point in the switch = failure analysis (TLOVR) 80.6% of the patients randomized to triple therapy had less than 50 copies/mL compared to 74.8% of the patients randomized to monotherapy. The lower limit for the 95% CI for this difference is -16.0% and consequently the monotherapy arm did not achieve non-inferiority.

Authors performed a multivariate analysis looking for predictors of failure during the trial and interestingly Hepatitis C co infection was significantly associated with failure in both arms. One possible explanation for the lower efficacy of monotherapy at 96 weeks is that the proportion of patients with HCV/HIV co-infection at baseline was higher in the monotherapy group (19%) than in the triple therapy group (12%). After 96 weeks of follow up protease inhibitor resistance was found only in one patient per group.

 




   

    The organizers reserve the right to amend the programme.


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