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  20th International AIDS Conference
July 20-25, 2014
Melbourne, Australia
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Raltegravir Regimen More Durable,
Atazanavir Less Durable, Than Single-Tablet Atripla

  20th International AIDS Conference, July 20-25, 2014, Melbourne IAC: Economic Burden of Adverse Events Associated With HIV Antiretroviral Therapy in the United States (07/30/14) this analysis considers the utility of and quantify healthcare costs associated with medical events attributable to HIV ART AEs.
Real-World Adherence among Patients Receiving Single versus Multiple Tablet Regimens for HIV-1 Infection, and Associations between Adherence and Viral Suppression: A Systematic Literature Review and Meta- Analysis (07/29/14)
IAC: Cost-Effectiveness of Single versus Multiple Tablet Regimens for Treatment of HIV-1 Infection in the US (07/29/14)
Mark Mascolini
Despite the convenience of single-tablet once-daily Atripla (efavirenz plus tenofovir/emtricitabine, TDF/FTC), a twice-daily multipill raltegravir regimen proved more durable as a first-line combination in a large Canadian cohort [1]. Atazanavir-based multipill regimens were less durable than Atripla, and darunavir-based regimens had similar durability.
(from Jules: this study used only 1 STR, Atripla, in its comparison, which has a well-known side effects profile associated with it including CNS adverse events. However, raltegravir although not an STR or once a day now has a history of a safe and tolerable safety profile, studies have just started examine a once a day raltegravir regimen: "First Patient Enrolled in New Phase 3 Trial Program Investigating a Once-Daily Dosing Regimen of ISENTRESS® (raltegravir)" - http://www.natap.org/2014/HIV/060914_10.htm).
Link to poster for this Canadian cohort:
IAC: Do Single Tablet Regimens Translate into More Durable HIV Treatments? Evidence from the Canadian Observational Cohort (CANOC) (07/29/14)
Once-daily single-tablet regimens--which now include Atripla, Complera (rilpivirine plus TDF/FTC), and Stribild (elvitegravir/cobicistat plus TDF/FTC)--have gained popularity because of their convenience. And research shows that convenience translates into better adherence. To see if single-tablet regimen convenience also means longer durability of first-line therapy, Canadian researchers assessed the staying power of four potent combinations in the 8-site CANOC cohort.
CANOC includes adults who started their first antiretroviral therapy (ART) after 1999. This analysis focused on people who began treatment with Atripla, raltegravir plus two NRTIs, atazanavir/ritonavir plus two NRTIs, or darunavir/ritonavir plus two NRTIs from 2007 to 2012. (from Jules: so the study did not compare other new Single-tablet regimens STRs). The primary endpoint was any change in the regimen (including the NRTI backbone) or treatment suspension for more than 30 days. To identify factors associated with that endpoint, the investigators used Cox proportional hazards models adjusted for age, gender, pre-ART CD4 count and viral load, HIV risk factors, study site, and year when ART began.
The analysis included 2965 people, 84% of them men, with a median age of 41 years and a median follow-up of 2.5 years. While 1420 people (48%) started Atripla, 1545 began a multipill combination. Average age when ART began was similar in the two groups (41 with Atripla, 40 with other regimens), and both groups had been diagnosed with HIV for an average 2 years. The Atripla group included a higher proportion of men (87% versus 81%), a lower proportion with a starting CD4 count below 200 (27% versus 37%), and a lower proportion with a starting viral load above 100,000 copies (33% versus 40%) (P < 0.001 for all comparisons). Follow-up since treatment started was shorter in the Atripla group (2 versus 3 years, P < 0.001).
During follow-up, 1449 people (49%) stopped their first-line regimen. Median duration of first regimens measured 41 weeks for Atripla (interquartile range [IQR] 34 to 48) and 21 weeks for atazanavir regimens (IQR 17 to 24). The researchers could not calculate median duration for the other two regimens because the probability of stopping those combinations did not reach 50%.
The Cox model determined that starting a raltegravir regimen versus Atripla cut the risk of stopping more than 40% in an association that stopped just short of statistical significance (adjusted hazard ratio [aHR] 0.58, 95% confidence interval [CI] 0.33 to 1.01, P = 0.06). Starting atazanavir versus Atripla boosted chances of quitting 16%, a significant association (aHR 1.16, 95% CI 1.03 to 1.30, P = 0.01). The model saw no difference in chances of stopping darunavir versus Atripla.
Cohort members infected during sex between men had almost a 20% lower risk of quitting their first regimen (aHR 0.82, 95% CI 0.70 to 0.97), whereas people infected while injecting drugs had almost a 50% higher risk of quitting (aHR 1.49, 95% CI 1.28 to 1.74). Men had almost a 30% lower risk of stopping their first regimen than women (aHR 0.72, 95% CI 0.63 to 0.83). Starting treatment with a viral load above 100,000 copies did not independently affect chances of quitting.
The CANOC team concluded that single-tablet regimens--at least Atripla--do not necessarily prolong first-line duration. The researchers did not assess possible reasons for durability differences, such as toxicity.
1. Machouf N, Szadkowski L, Trottier B, et al. AIDS 2014. Do single tablet regimens translate into more durable HIV treatments? Evidence from the Canadian Observational Cohort (CANOC). 20th International AIDS Conference. July 20-25, 2014. Melbourne. Abstract WEPDB0103.