IAS 2007 - Track B Late Breaker Session 1

Track B Late Breaker Session 1

WESS1

Type:

Special session

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Venue:

Bayside Auditorium B

Time:

13:00 - 14:00, Wednesday, 25.07.2007

Code:

WESS1

Chairpersons:

Luís Soto-Ramírez, Mexico
Stefano Vella, Italy

Click here to see a webcast of this session on kaisernetwork.org

Presentations in this session:
13:00
WESS101
Abstract
Powerpoint (218 KB) PREDICT-1: a novel randomised prospective study to determine the clinical utility of HLA-B*5701 screening to reduce abacavir hypersensitivity in HIV-1 infected subjects (study CNA106030)
Presented by Simon Mallal, Australia
Mallal S.¹, Phillips E.², Carosi G.³, Molina J.-M.⁴, Workman C.⁵, Tomažič J.⁶, Jägel-Guedes E.⁷, Rugina S.⁸, Kozyrev O.⁹, Flores Cid J.¹⁰, Hay P.¹¹, Nolan D.¹, Hughes S.¹², Hughes A.¹³, Thorborn D.¹⁴, Benbow A.¹⁴
¹Royal Perth Hospital, Perth, Australia, ²Murdoch University, Perth, Australia, ³Universita` degli Studi di Brescia, Brescia, Italy, ⁴Hopital Saint Louis, Paris, France, ⁵AIDS Research Initiative, Darlinghurst, Australia, ⁶University Medical Centre, Ljubljana, Slovenia, ⁷HIV Research and Clinical Care Centre, Munich, Germany, ⁸Spitalul Cl. De Boli, Infectioase, Constanta, Romania, ⁹Regional Center for AIDS, Volgograd, Russian Federation, ¹⁰Hospital Arnau de VIlanova, Valencia, Spain, ¹¹St George's Hosptial, London, United Kingdom, ¹²GlaxoSmithKline, Greenford, United Kingdom, ¹³GlaxoSmithKline, RTP, United States, ¹⁴GlaxoSmithKline, Brentford, United Kingdom

13:15
WESS102
Abstract
Powerpoint (348 KB) Efficacy and safety of NRTI´s switch to tenofovir plus emtricitabine (Truvada(R)) vs. abacavir plus lamivudine (Kivexa(R)) in patients with virologic suppression receiving a lamivudine containing HAART: the BICOMBO study
Presented by Jose M Gatell, Spain
Martinez E.¹, Arranz J.A.², Podzamczer D.³, Ribera E.⁴, Knobel H.⁵, Roca V.⁶, Gutierrez F.⁷, Llibre J.M.⁸, Barragan P.³, Clotet B.⁹, Dalmau D.¹⁰, Pich J.¹¹, de Lazzari E.¹², Gatell J.M.¹
¹Hospital Clinic Universitari, Infectious Diseases, Barcelona, Spain, ²Principe Asturias, Medicina, Oviedo, Spain, ³Bellvitge, Infectious Diseases, Barcelona, Spain, ⁴Vall d´Hebron, Infectious Diseases, Barcelona, Spain, ⁵Hospital del Mar, Infectious Diseases, Barcelona, Spain, ⁶Clinico San Carlos, Medicina, Madrid, Spain, ⁷Hospital de Elche, Medicina, Elche, Spain, ⁸Hospital Calella, Medicina, Calella, Spain, ⁹Fundacio IrsiCaixa, HIV, Barcelona, Spain, ¹⁰Mutua de Tarrasa, Medicina, Tarrasa, Spain, ¹¹Hospital Clinic Universitari, Pharmacology, Barcelona, Spain, ¹²Hospital Clinic Universitari, Biostatistics, Barcelona, Spain

13:30
WESS103
Abstract
Powerpoint (610 KB) Antiretroviral therapy initiated before 12 weeks of age reduces early mortality in young HIV-infected infants: evidence from the Children with HIV Early Antiretroviral Therapy (CHER) Study
Presented by Avy Violari, South Africa
Violari A.¹, Cotton M.², Gibb D.³, Babiker A.³, Steyn J.¹, Jean-Phillip P.⁴, McIntyre J.¹, on behalf of the CHER Study Team
¹Perinatal HIV Research Unit, University of Witwatersrand, Witwatersrand, South Africa, ²Children's Infectious Diseases Clinical Research Unit, Faculty of Health Sciences, Stellenbosch University, Stellenbosch, South Africa, ³MRC-Clinical Trials Unit, London, United Kingdom, ⁴Division of AIDS, NIAID, NIH, Bethesda, United States

13:45
WESS104
Abstract
Powerpoint (444 KB) A multicenter, randomized, double-blind, comparative trial of a novel CCR5 antagonist, maraviroc versus efavirenz, both in combination with Combivir (zidovudine [ZDV]/lamivudine [3TC]), for the treatment of antiretroviral naive patients infected with R5 HIV 1: Week 48 results of the MERIT study
Presented by Michael Saag, United States
Michael Saag¹, Prudence Ive², Jayvant Heera³, Margaret Tawadrous³, Edwin DeJesus⁴, Nathan Clumeck⁵, David Cooper⁶, Andrej Horban⁷, Lerato Mohapi⁸, Horacio Mingrone⁹, Gustavo Reyes-Teran¹⁰, Sharon Walmsley¹¹, Frances Hackman¹², Elna van der Ryst¹², Howard Mayer³
¹University of Alabama at Birmingham, Birmingham, USA, ²University of the Witwatersrand, Clinical HIV Research Unit (CHRU), Johannesburg, South Africa, ³Pfizer Global Research and Development, New London, USA, ⁴Orlando Immunology Center, Orlando, Florida, USA, ⁵Saint-Pierre University Hospital, Infectious Diseases, Brussels, Belgium, ⁶University of New South Wales, National Centre in HIV Epidemiology and Clinical Research, Sydney, Australia, ⁷Hospital of Infectious Diseases, Warsaw, Poland, ⁸University of the Witwatersrand, Perinatal HIV Research Unit, Johannesburg, South Africa, ⁹HIV Outpatient Care Unit, Muñiz Hospital, Buenos Aires City, Argentina, ¹⁰Instituto Nacional de Enfermedades Respiratorias, Center for Research in Infectious Diseases, Tlalpan, Mexico, ¹¹University of Toronto, Ontario, Canada, ¹²Pfizer Global Research and Development, Sandwich, UK

Audio files:

audio file - low quality (mp3 format, 15.1 MB)

Rapporteur reports

Track B: Clinical Research, Treatment and Care report by Sarah Pett

Olson and colleagues reported on the safety and efficacy of a new humanised CCR5 monoclonal antibody PRO140. Patients were given a single IV dose (0.5, 2 & 5 mg/Kg) of PRO140 or placebo. Dose-dependent reductions in VL with 100% response in those receiving 5mg/Kg and mean reduction in viral load of 1.83 log cp/mL, maximal effects at day 10 sustained for 2-3 weeks. No drug related SAEs or dose limiting toxicities. Potential for SC delivery.

Jenkins reported on a new NNRTI, UK-453,061 which is active in vitro against virus with the K103N, Y181C/I, G190A/S mutations; the drug is predicted to penetrate CNS well and there is no CYP3A4 inhibitio. In a double blind dose-ranging study in 81 HIV-infected individuals, doses of 500mg bid and 750mg qd achieved 1.9 and 2.0 log₁₀ cp/mL declines in viral load at day 8 respectively. The drug was well tolerated.

Cahn and colleague reported on the phase II study (AVX-201) of apricitabine (ATC) vs. 3TC in treatment experienced patients failing a 3TC containing regimen who also had the M184V mutation. At 21 days, without any other changes in the OBR (equivalent to functional monotherapy), there was a -0.9 (p=0.06) and -0.71 (p=0.506) decline from baseline with the 600mg and 800mg dose of ATC respectively. In patients with >3 TAMS, there was a -0.75 log₁₀ cp/mL in patients taking the 800mg dose. The drug was well tolerated. The phase II/III studies continue.

Mills and Katlama presented the results of the DUET 1 and 2 studies. Both studies were double-blind randomised placebo-controlled studies exploring the efficacy and safety of etravirine (TMC125) in treatment experienced HIV-1 infected patients (triple class experienced, >3 primary PI mutations, >1 NNRTI resistance (RAM) and plasma HIV VL of >5000 copies/mL). 24 weeks data was presented. All patients received ritonavir-boosted darunavir as part of their optimised background regimen. 612 and 591 patients were enrolled in DUET-I and DUET -2 respectively. Results were similar, in the ITT, 56% vs. 39% (p=0.005) in the etravirine and placebo groups achieved plasma HIV RNA <50 cp/mL respectively in DUET-1. CD4+ T-cell gains were significantly higher i.e. increased by 89 vs. 69 (p=0.0002). In DUET-2: 62% of the etravirine and 44% of the placebo arm had plasma HIV RNA <50 cp/mL at week 24 (p=0.0003). Enfuvirtide use was well balance between the two arms in both studies, and de novo use of T-20 did not impact in a significant way on response to etravirine. There was no difference in response whether the viral load at study entry was >100,000 copies/mL; responses were independent of the number of active drugs in the OBR (not including darunavir) and the number of NNRTI mutations at baseline (note only 13% of patients had ≥3 NNRTI RAMS at baseline). However, 13 NNRTI RAMS were associated with a decreased response to TMC125, when 3 TMC125 RAMS were present, responses were similar to placebo especially if there were 2 TM125 RAMS in addition to the Y181C. The overall incidence of rash was 17% with TMC-125 vs. 9% with placebo with no association with either CD4+ count or prior history of NNRTI rash. Labs were similar between the arms. Conclusion: etravirine is a welcome addition to the new drugs that can be used in treatment experienced patients.

Track B: Clinical Research, Treatment and Care report by Nick Paton

Simon Mallal presented the results of PREDICT-1, a massive international enterprise to assess the value of HLA-B*5701 testing to avert abacavir hypersensitivity reactions. In this multinational trial, 1956 naïve patients starting an ABC-containing ART regimen were randomized to start ART or to have HLA testing prior to starting ART. The incidence of ABC hypersensitivity was significantly reduced in the prospective screening arm. This study is a landmark study in that it is the first time a randomized controlled trial has shown the value of a genetic screening test in clinical practice. The accuracy of the test in non-white populations was raised as an issue, and this was addressed in a separate abstract session (the SHAPE study).

Jose Gatell presented findings the results of the BICOMBO study, in which patients who had been virologically suppressed for at least 6 months on a 3TC-containing ART regimen had their nucleoside backbone switched to either Kivexa (ABC + 3TC) or Truvada (TDF + FTC). The primary endpoint was failure (any reason) at week 48, and the objective was to demonstrate non-inferiority of Kivexa versus Truvada using a standard limit of 95% confidence interval of 12.5%. Treatment failure occurred in 13.3% of patients in the Truvada arm, and 19.2% of the Kivexa arm (difference -5.9%, -2 to –14%) so non-inferiority of Kivexa could not be accepted. The rate of discontinuation due to side effects was greater in the Kivexa arm, mainly driven by 9 patients interrupting therapy due to suspected ABC hypersensitivity reaction. Virologic failure occurred in none of those taking Truvada and 4 in the Kivexa arm (2.4%), and on this endpoint Kivexa was within limits of non-inferiority. Prospective HLA testing was not done in this study, but if it had been included then this might have altered the findings on treatment failure findings.

A Violari presented the results of the CHER study conducted in South Africa in which 375 infants under the age of 12 weeks were randomized to deferred ART until CD4 count fell below 20% (arm 1), ART until 1^st birthday (arm 2) or ART until the 2^nd birthday (arm 3). The ART regimen used in arms 2 and 3 was AZT + 3TC + LPV/r as per local guidelines. The DSMB recommended discontinuing arm 1 in June 2007 and releasing the combined results of arms 2 or 3 (which continue under study). The finding was that early ART lead to a dramatic 75% reduction in the rate of death. Many of the deaths occurred at home of unknown cause, but of those in which cause could be determined most were due to infectious causes. These findings have obvious implications for paediatric treatment guidelines as well as reinforce the potential advantages associated with effective prevention of mother to child transmission and voluntary counseling and testing programmes.

Michael Saag presented results from the pivotal phase 3 trial of maraviroc in ART naïve patients. Patients were randomised to receive MVC or EFV with a nucleoside backbone of AZT and 3TC. The hypothesis being tested was non-inferiority of MVC for VL<50 copies based on a very stringent non-inferiority 95% confidence interval boundary of 10%. The overall rate of treatment discontinuation was similar in the two arms. The proportion of patients with VL<50 copies at week 48 was 65.3% in MVC arm and 69.3% in EFV arm, difference –4.2% with a boundary of the 95% confidence interval of 10.9%. Thus the non-inferiority criterion was not met. However, the CD4 count increase was greater in the MVC arm. Other interesting findings were an apparent difference in results when stratified by north and southern hemisphere, which at present seems to have no logical explanation. As Dr Saag pointed out, this data is hot-off-the-press and needs a great deal of further scrutiny to fully interpret the nature of the findings. However, the message is not good news for those looking forward to having MVC available as a licensed first-line treatment option.

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