Transmitted HIV Resistance Ups Risk of Tx Failure

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	Transmitted resistance to HIV drugs sharply increases the risk that a patient's first anti-retroviral regimen will fail, researchers reported. In an analysis of more than 10,000 treatment-naive patients, transmitted resistance to at least one drug in the first regimen increased the risk of virological failure by a factor of three, compared with patients with no resistance mutations, according to Linda Wittkop, MD, of the University Bordeaux Segalen in Bordeaux, France, and colleagues. On the other hand, patients who had transmitted resistance but were still placed on a fully active combination therapy were not significantly less likely to fail treatment, Wittkop and colleagues reported online in The Lancet. Action Points   Explain that in a multi-cohort study of over 10,000 patients, transmitted resistance to HIV drugs sharply increases the risk that a patient's first anti-retroviral regimen will fail. Note that in contrast, patients who had transmitted resistance but were still placed on a fully active combination therapy were not significantly less likely to fail treatment. Note that the vast majority of the patients, 90.5%, had no transmitted resistance on baseline testing. The finding confirms recommendations that physicians and patients should choose an initial three-drug treatment regimen after resistance testing, Wittkop and colleagues argued. Drug resistance is a continuing problem in HIV treatment, especially in the context of poor adherence, and if the resistant strains are transmitted, they are known to make treatment difficulty, the researchers noted. But the effect of transmitted drug resistance has not been fully quantified in large numbers of patients, they reported. To help fill the gap, they studied outcomes of 10,056 anti-retroviral-naïve patients who started combination therapy after Jan. 1, 1998, and had at least one sample for a genotypic test taken before the start of treatment. The good news from the so-called EuroCoord-CHAIN study was that the vast majority of the patients -- 90.5% -- had no transmitted resistance, the researchers reported. Another 4.7% had at least one resistance mutation but still got fully active therapy. And 4.8% had at least one mutation and were resistant to at least one of the drugs they were initially given, Wittkop and colleagues reported. For the analysis, virological failure was defined as two consecutive viral loads over 500 copies for HIV RNA per milliliter of blood after six months of treatment, with the date of the first high viral load being the date of failure. The researchers found that the cumulative Kaplan-Meier estimates for virological failure at 12 months were: 4.2% for patients without resistance. 4.7% for those with resistance but still fully active therapy. And 15.1% for those with resistance to at least one of the drugs they were prescribed. In a multivariate analysis, the hazard ratio for virologic failure was 1.47 when the patients who had resistance but active therapy were compared with the patients who had no treatment resistance. However the difference did not reach significance. On the other hand, the hazard ratio for virologic failure was 3.13, with a 95% confidence interval from 2.33 to 4.20, when the patients with resistance to at least one drug in their first regimen were compared with those who had no resistance, the researchers reported. The difference was significant at P<0.0001. While all the samples were taken before treatment started, not all were tested before a regimen was prescribed, the researchers noted, something that might have accounted for some of the sub-optimal regimens. Primary source: The Lancet Infectious Diseases Source reference: Wittkop L, et al "Effect of transmitted drug resistance on virological and immunological response to initial combination antiretroviral therapy for HIV (EuroCoord-CHAIN joint project): A European multicohort study" Lancet Infect Dis 2011; DOI: 10.1016/S1473-3099(11)70032-9.