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FEBRUARY 2008
News and Literature Reviews
Additional News from the 2008 Conference on Retroviruses and Opportunistic Infections (CROI) Resuming Therapy Doesn’t Reverse Progression Risk of Off-and-On Therapy Wafaa El-Sadr of the Harlem Hospital Center, New York presented additional data regarding the decision to halt the Strategies for Management of Anti-Retroviral Therapy (SMART) study. SMART, which ended two years ago, examined the impact of suspending antiretroviral therapy (ART) during periods of high CD4 counts. SMART consisted of two arms: one group continued ART throughout the study, while the other group discontinued ART when CD4 counts rose above 350/mm3 and resumed ART when the CD4 count fell below 250/mm3. The study was ended when it was determined that people in the interrupted ART group were at 1.8 times higher risk of death from any cause, as well as a 1.7 times higher risk of major cardiovascular, renal, or hepatic disease. The interrupted group continued to experience worse health outcomes even after the study’s termination in January 2006, at which time the investigators had counseled patients to resume uninterrupted treatment. Participants who had been assigned to the interrupted treatment group had a 24% higher risk of heart, kidney, or liver disease, a 37% higher risk of opportunistic disease or death, and a 41% higher risk of death than those in the control group of uninterrupted treatment. Members of the interrupted treatment group spent an average of 71% of the time on therapy, substantially less than the 91% of time spent on treatment in the control group. When researchers compared only people who had spent more than 85% of their time on ART, the risk of opportunistic infection or death appeared equivalent between the two groups. Three factors were postulated to explain the disparity in health outcomes between the study’s two arms. Some members of the interrupted treatment group did not resume ART therapy after the study’s completion, thus limiting the effectiveness of treatment. Secondly, CD4 counts stayed lower in members of the interrupted treatment group, even if they did restart therapy. Finally, opportunistic diseases diagnosed before the study’s completion may have had a long-term impact on the health of individuals. This study suggests that the impact of CD4-guided drug breaks may be long-lasting. Mascolini, Mark. Resuming Therapy Can’t Reverse Progression Risk With Off-and-On Therapy. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. 48-Week Results from BENCHMRK-2, a Phase III Study of Raltegravir (RAL) in Patients Failing Antiretroviral Therapy (ART) with Triple-Class Resistant HIV-1 Results from an ongoing double-blind Phase III study have demonstrated raltegravir’s effectiveness in suppressing HIV viral loads. The study found that patients who took 400 milligrams of raltegravir twice daily in combination with optimized background therapy (OBT) had lower viral loads than patients whose treatment regimens included OBT and a placebo. The results were gathered after 48 weeks of treatment amongst patients living with HIV-1 in North and South America. The success of this study offers hope to treatment-experienced individuals living with antiretroviral-resistant HIV, as well as the treatment-naive. Raltegravir, which acts as an HIV-1 integrase strand-transfer inhibitor, can be taken in combination with NRTIs, NNRTIs, PIs, and efuvirtide in order to combat multi-drug resistant strands of HIV. In addition, strains of HIV that become resistant to raltegravir may still remain sensitive to other types of antiretrovirals. Levin, Jules. 48-Week Results from BENCHMRK-2, a Phase III Study of Raltegravir (RAL) in Patients Failing Antiretroviral Therapy (ART) with Triple-Class Resistant HIV-1. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Immediate Antiretrovirals During Acute OI Lower Death Risk: ACTG A5164 A Stanford University research team headed by Andrew Zolopa presented data from a randomized trial of 282 patients that evaluated whether or not to complete treatment of AIDS-related opportunistic infections (OI) before beginning ART in HIV-infected patients. The study included individuals with acute OI including Pneumocystis pneumonia, bacterial pneumonia, cryptococcosis, Mycobacterium avium complex, or central nervous system toxoplasmosis. Participation was limited to patients who had never experienced antiretroviral failure and had not taken ART in the past 8 weeks or for more than 31 days in the past 6 months. The participants were evenly split into two treatment arms. While both groups received immediate treatment of their OI, one group also received immediate treatment with ART. The other group deferred ART until at least 28 days after enrollment in the study. 24.1% of those in the deferred group had a new AIDS diagnosis or had died, compared to 14.2% in the immediate treatment group. As such, participants who deferred antiretroviral treatment had twice the chance of progression as participants who began treatment immediately. Participants who received immediate treatment experienced a faster increase in CD4 count, thus limiting their period of vulnerability to new OIs or death. Differences in progression rates and death between the two groups were mainly limited to the first 6 months of the study, as there was little difference in the viral loads of the two groups by week 48. These findings emphasize the importance of immediate ART for patients suffering from acute AIDS-related OIs. Mascolini, Mark. Immediate Antiretrovirals During Acute OI Lower Death Risk: ACTG A5164. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Sustained Virological Response to Interferon plus Ribavirin Reduces Liver-related Complications and Mortality in HIV/HCV Co-infected Patients A recent analysis of the GESIDA 3603 Study Cohort provided new information on the impact of sustained virological response (SVR) on HIV/HCV coinfected patients. The study consisted of 711 patients who began interferon-ribavirin treatment between January 2000, and December 2005. Patients were seen every 6 months for 18 to 22 months, and clinical outcomes such as mortality, liver-related complications, and HIV progression were assessed. An estimated 31% of the study population achieved SVR during the course of this study. The health outcomes of this group were then compared to the remainder of the participants who did not achieve SVR. Among the 218 people who achieved a SVR, the death rate was only .9%. This compared to a death rate of 6.9% among the 493 patients who did not achieve SVR. Liver related complications affected 3.7% of the non-SVR group and .5% of the SVR group. 2.2% of the non-SVR group had liver transplants, compared to 0% of the SVR-achieving group. In total, members of the non-SVR group had a 9 times greater risk of death, 20 times greater risk of liver decomposition, and 4 times greater risk of new AIDS conditions. Levin, Jules. Sustained Virological Response to Interferon plus Ribavirin Reduces Liver-related Complications and Mortality in HIV/HCV-co-infected Patients. 15th Conference on Retroviruses and Opportunistic Infections. February 3-6, 2008. Boston. Compiled by Christine Devore, Duke University
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