CROI 2016 Abstract eBook

Abstract Listing

Poster Abstracts

940 Should NNRTIs Remain As the First-Line Therapy Choice in Resource-Limited Settings? Viviane D. Lima 1 ; MarkW. Hull 1 ; David McVera 2 ; P. Richard Harrigan 1 ;William Chau 1 ; Julio Montaner 1 1 BC Cntr for Excellence in HIV/AIDS, Vancouver, BC, Canada; 2 Univ of British Columbia, Vancouver, BC, Canada

Background: In many resource-limited settings, treatment failure is usually diagnosed clinically or immunologically. As such, there is a high likelihood that patients will stay on a failing regimen for a long period of time, with increased risk for resistance. In this study, we compared the long-term effectiveness of non-nucleoside reverse transcriptase inhibitors (NNRTIs) and boosted protease inhibitors (bPIs) among patients remaining on their initial failing regimens. Methods: We followed prospectively 3925 ART-naïve patients who started on regimens containing either NNRTIs (N=1963, 50%) or boosted protease inhibitors (bPIs) (N=1962; 50%) from January 1, 2000 until June 30, 2013 in British Columbia, Canada (Figure). At six months, we assessed whether patients virologically failed therapy (a viral load >50 copies/mL), and we classified these patients as those who failed with a viral load ≤500 versus >500 copies/mL. We then followed these patients for 12 months and calculated their probability of achieving subsequent viral suppression (two consecutive viral loads <50 copies/mL) and of developing drug resistance to any ART class. These probabilities were adjusted for fixed and time-varying factors, including ART adherence. Patients did not change regimen during the study period. Results: At six months, the virologic failure rate of those on NNRTI and bPI was, respectively, 15.5 and 23.0 cases per 100 person-years. Patients on NNRTI-based regimens who failed therapy with a viral load ≤500 copies/mL had a 16% higher probability of achieving subsequent suppression at 12 months than those on bPI (0.81 (Q1-Q3 0.70-0.87) versus 0.70 (0.64-0.74)). However, if patients on NNRTI-based regimens failed therapy with a viral load >500 copies/mL, they had a 30% lower probability of suppressing at 12 months than those on bPI (0.31 (0.31-0.56) versus 0.44 (0.41-0.50)). In terms of resistance, those who failed on NNRTI performed worse than bPI in all scenarios, especially if they failed with a viral load >500 copies/mL. Conclusions: Our results showed that patients who failed with a high viral load and continued on their first-line NNRTI regimen, in comparison to those on bPI, had a lower probability of subsequently achieving viral suppression. These patients had a higher chance of acquiring drug resistance in all scenarios. Thus, if NNRTI continues to be the preferred choice for first-line therapy, these results highlight the importance of improving access to regular virologic monitoring of these patients.

Poster Abstracts

941 Lower Mortality Among Patients Starting ART From 2008 to 2010 Than Earlier in the ART Era Adam Trickey 1 ; Margaret May 1 ; Julia Del Amo 2 ; Niels Obel 3 ; Heidi M. Crane 4 ; Sophie Abgrall 5 ; Colette Smith 6 ; Suzanne Ingle 1 ; Jonathan Sterne 1 ; for the AntiretroviralTherapy Cohort Collaboration 1 Univ of Bristol, Bristol, UK; 2 Inst de Salud Carlos III, Madrid, Spain; 3 Copenhagen Univ Hosp, Rigshospitalet, Copenhagen, Denmark; 4 Univ of Washington, Seattle, WA, USA; 5 Univ Hosp Antoine-Béclère, Clamart, France; 6 Univ Coll London, London, UK Background: Antiretroviral drugs available at the beginning of the ART era were inferior (in terms of both toxicity and efficacy) compared with those recommended in current guidelines. Other aspects of health care for HIV-1 positive patients have also improved since 1996. The implications of these changes for survival after starting ART are unclear. Methods: We analysed all-cause and cause-specific mortality in previously ART-naïve adults from 19 European and North American cohorts contributing to the ART Cohort Collaboration (ART-CC) who started triple ART between 1996 and 2010 and had at least 3 years potential follow up. We used Cox models, stratified by cohort, to estimate adjusted (for age, sex, AIDS diagnosis, IDU risk group, CD4 count and HIV-1 RNA at start of ART) hazard ratios (HR) for calendar period of starting ART (2000-03, 2004-07, 2008-10 compared with 1996-99) during (1) the 1st year and (2) the 2 nd and 3 rd years of ART. Results: Of 88,504 eligible patients, 2,106 died during the 1st year and 2,302 during the 2nd and 3rd years of ART. One-year all-cause mortality was notably lower among patients starting ART in 2008-10 than in previous years [adjusted HR (aHR) 0.70 (95% CI 0.60-0.82) compared with 1996-9] (see table). Declines in 2 and 3 year all-cause mortality were even more marked [aHR 0.47 (95% CI 0.40-0.55)]. Improvements were similar in men and women and consistent across Europe and North America. Trends in 2 and 3 year mortality were consistent across most subgroups and were partially explained by response to ART [HR for 2008-10 vs 1996-9 additionally adjusting for 12 month CD4 count and viral load 0.75 (0.63, 0.90)]. Rates of AIDS [aHR 0.63 (95% CI 0.49, 0.82) for 2008-10 vs 1996-9], suicides, accidents and overdoses [aHR 0.47 (95% CI 0.22, 0.99)] and cardiovascular [aHR 0.21 (95% CI 0.06, 0.73)] mortality were lower during the 1st year of ART. Rates of all specific causes of death examined were lower in the 2 nd and 3 rd years of follow-up for those starting 2008-10 vs 1996-99. Overall life-expectancy at age 35 improved by nearly 10 years between 1996-99 and 2008-10. Conclusions: Marked improvements in survival during the first 3 years of ART likely reflect availability of better antiretrovirals, more options for patients who develop resistance, and improvements in health care for HIV-positive patients. Prognostic models should be updated to account for these improvements.

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CROI 2016