MD Conference Express ICAAC 2011 - (Page 15)
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Fighting HIV – New Antiretroviral Agents and Novel Regimens
Written by Rita Buckley
Improvements in antiretroviral therapy (ART) have made the treatment of HIV infection more potent and better tolerated. While current treatment regimens still have limitations, they are more effective, more convenient, and less toxic than those that were used in the early ART era. Joel E. Gallant, MD, MPH, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA, discussed studies that have shown the effectiveness of new and potential ART therapies, including single-tablet regimens, coformulations, nucleoside reverse transcriptase inhibitor (NRTI)-sparing regimens, CCR5 antagonists as initial therapy, and new entry inhibitors. ECHO [NCT00540449] and THRIVE [NCT00543725], two randomized Phase 3 trials, showed that the recently approved non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) has sustained efficacy that is noninferior to efavirenz (EFV) in ART-naïve adults who are infected with HIV-1 [Cohen CJ et al. Lancet 2011; Molina JM et al. Lancet 2011]. There were fewer discontinuations that were due to adverse events and fewer treatment-limiting side effects (especially neurological and dermatological) in the RPV arm but more virological failure and resistance compared with the EFV arm, most notably in participants with baseline viral loads >100,000 copies/mL (Figure 1). RPV has been approved both as a single agent and in a coformulation with tenofovir disoproxil fumarate (TDF) and emtricitabine (FTC). It is taken once daily with a meal and is contraindicated in patients who are taking proton pump inhibitors. Figure 1. ECHO/THRIVE Outcomes.
100 RPV 25 mg QD (n=686) EFV 600 mg QD n=682
Responders (Percent, 95% CI)
80
78% 78%
60
40
20
0
0
2 4
8
12
16
24
32
Time (weeks)
40
48
60
72
84
96
• More virologic failures (VF) with RPV vs EFV: 14% vs 7.6% - Difference due to more VF between Weeks 0 to 48; VF similar Weeks 48 to 96 - NRTI mutations more common with VF on RPV vs EFV - Cross-resistance to ETR more common with RPV failures (E138K mutation) • Discontinuations due to adverse events were more common with EFV vs RPV: 8.5% vs 4.1%
Peer-Reviewed Highlights from the
51st ICAAC
Reproduced with permission from The Lancet. Rilpivirine versus efavirenz with tenofovir and emtricitabine in treatment-naive adults infected with HIV-1 (ECHO): a phase 3 randomised double-blind active-controlled trial. Molina JM et al. July 16, 2011;378(9787)238-246.
In the MERIT study [NCT00098293], maraviroc (MVC) BID was not noninferior to EFV at <50 copies/mL in the primary analysis in ART-naïve patients with CCR5-tropic virus. However, 15% of patients in the original MERIT trial had dual/mixed-tropic virus, using the more sensitive tropism assay. After exclusion of data from those patients, the MVC arm met noninferiority criteria compared with EFV [Cooper DA et al. J Infect Dis 2010] (Figure 2). QD administration of MVC is also being studied. In a post hoc analysis from the original MOTIVATE trials, which initially included a QD MVC arm, virological suppression
Official Peer-Reviewed Highlights from the 51st ICAAC
15
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Table of Contents for the Digital Edition of MD Conference Express ICAAC 2011
MD Conference Express ICAAC 2011
Contents
Infectious Disease Genomics
Emerging Resistance Among Gram-Negative Pathogens
Procalcitonin-Guided Antibiotic Therapy In Patients with Lower Respiratory Tract Infections
Combination Therapy with Flucytosine Improves Survival in AIDS-Related Cryptococcal Meningitis
CXA-201 Effective Against Common ICU Pathogens
Tigecycline Plus Standard Therapy Is More Effective For Treating Infections in Febrile Neutropenic Cancer Patients
Interventions Aimed at Reducing MRSA BSIs Led to Decreased Rates of Nosocomial MSSA BSIs
Is the Effectiveness of aP Vaccine in Pre-Adolescents Insufficient?
TMC435 Effective in the Treatment of HCV Genotype 1 Infection
HIV
Vaccines
Antibiotic Resistance
Drug Discovery
The Conundrum of MDR TB and Combination Therapy
New Drugs to Treat MDR Pathogens
Immunizations in Reproductive Health
Why Can’t Microbes Just Get Along?
The Role of Adjunctive Steroids in the Treatment of Bacterial Meningitis
Human and Animal Viruses Share “One World” and Emerging Zoonotic Infections Continue to Threaten
MD Conference Express ICAAC 2011
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