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Virologic Failure Rate Plummets From 31% to 5%
in France From 1997 Through 2009
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6th IAS Conference on HIV Pathogenesis, Treatment and Prevention, July 17-20, 2011, Rome
Mark Mascolini
Nearly one third of antiretroviral-treated people in France endured virologic failure in 1997-1998, but by 2008-2009 that rate had plunged to 5%, according to results of a nationwide study [1]. Higher current CD4 count correlated with a lower risk of failure.
Defining virologic failure as two consecutive viral loads above 500 copies while on treatment, French investigators tracked failure rates over 2-year intervals starting in 1997-1998 and ending in 2008-2009. All study participants took antiretrovirals for at least 6 months. The researchers eliminated viral loads recorded during treatment interruptions.
The study involved 72,978 people taking antiretrovirals in routine clinical practice from 1997 to 2009. Median follow-up on each patient was 96 months (interquartile range [IQR] 49 to 150), and the investigators analyzed a median of 11 viral loads (IQR 6 to 21) per patient.
Most study participants (69.4%) were male, and 12% came from sub-Saharan Africa. Median age at study entry stood at 38.4 years (IQR 32.4 to 44.3) and median CD4 count at 314 (IQR 186 to 468). About one quarter of cohort members (23.4%) had AIDS, while 42.9% had started therapy with a one- or two-drug regimen. Almost 14,000 people (19%) were positive for hepatitis C virus (HCV) antibody.
Numbers of cohort members in each study period were 31,950 in 1997-1998, 36,083 in 1999-2000, 37,997 in 2001-2002, 39,793 in 2003-2004, 42,683 in 2005-2006, and 46,602 in 2007-2009. Rates of exposure to protease inhibitors dipped from 70% in the first study period to 54% in 2003-2004, then climbed back to 70% in 2007-2009. Nonnucleoside exposure climbed from 14% in 1997-1998 to 43% in 2003-2004, and eased at 40% in 2007-2009. In that final study period, 11.5% of cohort members took raltegravir.
Through a median follow-up of 96 months, 40.6% of study participants had a virologic failure. The failure rate dropped consistently and significantly (P < 0.001) from one period to the next:
--1997-1998: 30.6%
--1999-2000: 28.8%
--2001-2002: 20.9%
--2003-2004: 15.7%
--2005-2007: 9.9%
--2008-2009: 4.6%
To figure the risk of virologic failure from period to period, the investigators devised a multivariate model that considered age, gender, place of origin, HCV status, AIDS, current CD4 count, type of initial antiretroviral regimen, duration of combination antiretroviral therapy, and number of antiretrovirals taken. This analysis determined that, compared with 1997-1998, the risk of virological failure rose slightly in 1999-2000, then fell 21% in 2001-2002 (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.77 to 0.82, P < 0.0001), 35% in 2003-2004 (OR 0.65, 95% CI 0.63 to 0.68, P < 0.0001), 55% in 2005-2006 (OR 0.45, 95% CI 0.43 to 0.47, P < 0.0001), and 77% in 2008-2009 (OR 0.23, 95% CI 0.22 to 0.24, P < 0.0001). Because of the large number of people in each study period, the confidence intervals are narrow.
Another multivariate analysis considering the same variables determined that the risk of virologic failures fell with each higher CD4 bracket. Compared with a current CD4 count under 200, failure risk dropped 33% for a current count of 200 to 350, 52% for a count of 350 to 500, and 71% for a count above 500 (P < 0.0001 for all comparisons). Starting antiretroviral therapy with one or two antiretrovirals raised the risk of failure.
The investigators attributed the steady decline in virologic failure to the availability of new antiretroviral drugs and classes, to better-tolerated and easier-to-take antiretrovirals, and to "national guidelines recommending rapid intervention in case of virologic failure since mid-2000."
Reference
1. Delaugerre C, Ghosn J, Lacombe JM, et al. Trend over calendar time in virological failure in HIV-infected patients treated for at least six months with combined antiretroviral therapy in France (FHDH ANRS CO04). 6th IAS Conference on HIV Pathogenesis, Treatment and Prevention. July 17-20, 2011. Rome. Abstract TUPDB0104.
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