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Switch and Stop Rates 25% and 12% in First ART Year in 18-Cohort Study
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18th Conference on Retroviruses and Opportunistic Infections, February 27-March 2, 2011, Boston
ART Cohort Collaboration investigators concluded that "some reasons for switching are important prognostic factors for subsequent AIDS or death: ART changes for treatment failure, patient decision and to a less extent side effects are associated with a higher risk of AIDS/death than switching for simplification." Treatment duration, CD4 count, and age when stopping or switching also clearly affected the risk of AIDS or death. But viral load at stopping or switching did affect AIDS or death risk.
Mark Mascolini
One quarter of adults who started antiretroviral therapy (ART) in the ART Cohort Collaboration switched antiretrovirals within the first year of treatment, and one eighth stopped treatment altogether [1]. Relatively high proportions of switches in this 2002-2010 study involved changes to unrecommended regimens, including 14% who switched to single or double antiretrovirals and 9% who switched to a triple-nucleoside regimen.
The ART Cohort Collaboration includes 18 prospective HIV cohorts in Europe and North America. This analysis involved 8600 adults starting their first antiretroviral combination with a nonnucleoside (NNRTI) plus two or more nucleosides and 6408 people starting a ritonavir-boosted protease inhibitor (PI) with two or more nucleosides. The researchers excluded anyone who stopped their first regimen within 1 month and anyone taking zalcitabine, etravirine, enfuvirtide, tipranavir, raltegravir, maraviroc, or vicriviroc. Everyone began treatment after 2001, and follow-up continued to June 30, 2010.
Most cohort members (79%) were men. One third acquired HIV during gay sex, one third heterosexually, and 15% when injecting drugs. Median age stood at 40 (interquartile range [IQR] 33 to 47), median CD4 count at 183 (IQR 76 to 280), and median viral load at 100,000 copies. One quarter of the study group had AIDS when treatment began. About one third of the cohort began treatment in each of three study periods: 2002-2003 (32%), 2004-2005 (37%), and 2006-2008 (31%).
During follow-up, 6301 people (42%) did not change or stop treatment, 6153 (41%) switched at least one antiretroviral, and 2554 (17%) stopped treatment. Switching was more frequent in people who started a PI than in those who started an NNRTI (46% versus 37%); the discontinuation rate was equivalent in the two group (16% and 18%). Median CD4 count at antiretroviral change was 316 (IQR 180 to 490). Median viral load measured 1.69 log (about 50 copies) at the switch and 2.30 log (about 200 copies) when treatment stopped. Among the 6153 people who changed antiretrovirals, 30% switched to a boosted PI plus two or more nucleosides, 5% switched to an unboosted PI plus nucleosides, 38% to an NNRTI plus nucleosides, 9% to three or more nucleosides, and 14% to one or two antiretrovirals.
The antiretroviral discontinuation rate plateaued around 2 years after follow-up began, while the switch rate continued to climb through 5 years of follow-up:
Stop rate: 7.9% at 6 months, 12.0% at 1 year, 15.7% at 2 years, 18.1% at 3 years, 21.2% at 5 years
Switch rate: 14.7% at 6 months, 24.9% at 1 year, 36.1% at 2 years, 44.0% at 3 years, 55.6% at 5 years
From the start of the first antiretroviral regimen to the end of follow-up, 721 people died. The overall death rate rose from 1.2% after 6 months of therapy to 2.3% at 1 year, 3.8% at 2 years, 5.0% at 3 years, and 7.7% at 5 years. Multivariate analysis adjusting for CD4 count and viral load at antiretroviral initiation, date of initiation, PI versus NNRTI and nucleosides in regimen, and periods of starting and switching treatment identified several independent predictors of AIDS or death after switching or stopping antiretrovirals, at the following adjusted hazard ratios (AHR) (and 95% confidence intervals):
-- Interrupting versus switching antiretrovirals: AHR 1.69 (1.46 to 1.97)
-- AIDS at stop/switch: AHR 1.94 (1.69 to 2.21)
Compared with switching or stopping for simplification:
-- Switch/stop for side effects: AHR 1.93 (1.09 to 3.42)
-- Switch/stop for patient decision: AHR 2.45 (1.33 to 4.51)
-- Switch/stop for treatment failure: AHR 3.80 (2.10 to 6.85)
-- Switch/stop for physician decision did not independently affect AIDS or death risk
Compared with duration of first regimen under 6 months at stop/switch:
-- Duration of first regimen 6 to 12 months: AHR 0.84 (0.70 to 1.00)
-- Duration of first regimen 12 to 24 months: AHR 0.67 (0.52 to 0.85)
-- Duration of first regimen more than 24 months: AHR 0.54 (0.39 to 0.76)
Compared with a CD4 count below 100 at stop/switch:
-- CD4 count 101 to 200 at stop/switch: AHR 0.65 (0.54 to 0.80)
-- CD4 count 201 to 350 at stop/switch: AHR 0.52 (0.41 to 0.65)
-- CD4 count 351 to 500 at stop/switch: AHR 0.46 (0.35 to 0.61)
-- CD4 count above 500 at stop/switch: AHR 0.46 (0.33 to 0.63)
Compared with gay HIV transmission:
-- Injection drug use HIV transmission in men: AHR 1.41 (1.09 to 1.83)
-- Injection drug use HIV transmission in women: AHR 1.47 (1.02 to 2.13)
-- Heterosexual transmission did not affect AIDS or death risk compared with gay sex
Compared with age 16 to 29 at stop/switch:
-- Age 30 to 39 at stop/switch: AHR 1.38 (1.07 to 1.78)
-- Age 40 to 49 at stop/switch: AHR 1.64 (1.27 to 2.12)
-- Age 50 or older at stop/switch: AHR 2.00 (1.53 to 2.61)
ART Cohort Collaboration investigators concluded that "some reasons for switching are important prognostic factors for subsequent AIDS or death: ART changes for treatment failure, patient decision and to a less extent side effects are associated with a higher risk of AIDS/death than switching for simplification." Treatment duration, CD4 count, and age when stopping or switching also clearly affected the risk of AIDS or death. But viral load at stopping or switching did affect AIDS or death risk.
Reference
1. Abgrall S, Cornish R, Mugavero M, Saag M, May M, Sterne J, and ART-CC. Outcomes after switch from or interruption to first ART regimen: the ART Cohort Collaboration. 18th Conference on Retroviruses and Opportunistic Infections. February 27-March 2, 2011. Boston. Abstract 578. Poster online at http://www.retroconference.org/2011/PDFs/578.pdf.
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