icon-folder.gif   Conference Reports for NATAP  
  EACS - 12th European AIDS Conference
November 11-14, 2009
Cologne, Germany
Back grey_arrow_rt.gif
Later Year and Age Over 50 Tied to Better Response After Triple-Class Failure
  12th European AIDS Conference, November 11-13, 2009, Cologne, Germany
Mark Mascolini
After triple-class failure, new rescue regimens proved significantly more effective with each passing year in a 1999-person analysis of the multicohort COHERE database [1]. Compared with people under 40 years old, those 50 or older had a 17% better chance of getting their viral load under 50 copies after drugs from the first three antiretroviral classes stopped controlling HIV.
Failure of drugs in the first three antiretroviral classes carried a poor prognosis before development of new agents with activity against multidrug-resistant virus [2]. To gauge rescue regimen response trends, Dominique Costagliola and COHERE collaborators analyzed data on 1999 people in 33 European cohorts.
The study included adults who began antiretroviral in 1998 or later, when almost everyone started treatment with three or more antiretrovirals. Thus this analysis differs from most previous studies of triple-class failure, which included people who began treatment with one- and two-drug regimens. From 2000 through 2007, everyone in the COHERE study had a viral load above 500 copies after at least 4 months of treatment and "extensive triple-class resistance," which the researchers defined as virologic failure of at least two nucleosides, one nonnucleoside, and one ritonavir-boosted protease inhibitor. Of the 1999 cohort members, 1387 (70%) were men, 406 (25% were women), and 388 (17%) were injecting drug users. Median viral load at triple-class failure stood at 4.0 log (10,000 copies, interquartile range [IQR] 3.2 to 4.8 log), while median CD4 count measured 269 (IQR 140 to 412).
Among people who first had extensive triple-class resistance in 2000, only 15.4% reached a viral load below 50 copies on subsequent regimens. In contrast, 65.4% who first had extensive triple-class resistance in 2007 later reached an undetectable viral load. Multivariate analysis determined that, compared with people whose extensive triple-class resistance began in 2000-2003, those with extensive resistance in 2004-2005 had a 76% better chance of reaching a sub-50-copy load (incidence rate ratio [IRR] 1.76, 95% confidence interval [CI] 1.57 to 1.99), and those with extensive resistance starting in 2006-2007 had more than a doubled chance of subsequent viral control (IRR 2.30, 95% CI 2.02 to 2.62) (P < 0.0001).
Several other factors also independently raised or lowered the chance of regaining viral control after extensive triple-class resistance, including age over 49 years compared with under 40 years (IRR 1.17, 95% CI 1.01 to 1.35). Older age often correlates with better adherence, which may partly explain this result.
Costagliola reported these independent predictors of failure to reach a sub-50 load after extensive triple-class resistance:
· Heterosexual men (compared with gay men): IRR 0.83, 95% CI 0.71 to 0.96
· Heterosexual women (compared with gay men): IRR 0.76, 95% CI 0.66 to 0.88
· Three or more regimen changes since triple-class failure (compared with 1 or 2 changes): IRR 0.84, 95% CI 0.75 to 0.95
· No regimen changes since triple-class failure (compared with 1 or 2 changes): IRR 0.89, 95% CI 0.80 to 0.98
· New regimen containing no newer drugs (that is, enfuvirtide, raltegravir, maraviroc, etravirine, rilpivirine, darunavir, or tipranavir): IRR 0.80, 95% CI 0.70 to 0.92
· Not on antiretroviral therapy: IRR 0.20, 95% CI 0.11 to 0.38 Analyses using other definitions of virologic success reached similar conclusions.
Costagliola and colleagues cautioned that more modeling and further follow-up of people taking newer antiretrovirals are needed to exclude the possibility of selection bias. For example, people who started effective newer drugs after triple-class failure may also benefit from care by more forward-looking clinicians or treatment at centers with more HIV experience.
1. Costagliola D, for the PLATO II Project Team of COHERE. Viral load outcome after virologic failure of the three original antiretroviral drug classes in 2000-2007. 12th European AIDS Conference. November 11-13, 2009. Cologne, Germany. Abstract BPD2/8.
2. Ledergerber B, Lundgren JD, Walker AS, et al. Predictors of trend in CD4-positive T-cell count and mortality among HIV-1-infected individuals with virological failure to all three antiretroviral-drug classes. Lancet. 2004;364:51-62.