In Europe and the USA, 10% of treatment-naïve patients are infected with transmitted drug resistant (TDR) HIV that already has at least one drug-resistant mutation. These patients are more than three times as likely to experience treatment failure, according to an Article published Online First in The Lancet Infectious Diseases. These findings confirm the need for drug resistance testing of treatment-naïve patients to determine which antiretroviral drugs are likely to work.
The findings also show that poor virological and immunological response might be more common in patients with transmitted resistance who take non-nucleoside reverse transcriptase inhibitor (NNRTI)-based regimens. The data show, for the first time, the optimal first line therapy to use in such cases and will be important in resource poor regions of the world where genotypic resistance testing is not routinely available but where TDR may increase with rollout of HIV treatment.
Current treatment guidelines recommend pre-treatment genotypic testing to detect the presence of resistance mutations and establish which first-line drugs are likely to work. However, the effect of TDR on virological and immunological response is controversial and more evidence is needed to better inform choice of drug regimens in an era of multiple drug choices for treatment of HIV.
The EuroCoord-CHAIN study was designed to assess the effect of TDR on treatment outcomes during the first year of combination antiretroviral therapy (cART) in a large European dataset.
10 056 patients from 25 cohorts were enrolled from across Europe. Genotypic testing was done before the start of cART to determine the presence of resistance to nucleoside reverse transcriptase inhibitors (NRTIs), NNRTIs, and protease inhibitors. Patients were categorised into three resistance categories—no TDR (9102 patients, 90.5%), at least one mutation and receiving fully-active cART (475 patients, 4.7%), or at least one mutation and resistant to at least one prescribed drug (479 patients, 4.8%)—and time to virological failure was assessed.
Patients with TDR and resistance to at least one prescribed drug were more than three times as likely to experience virological failure compared with patients without TDR, confirming: "the need for at least three fully-active antiretroviral drugs to optimise the virological response to a first-line regimen."
However, the risk of virological failure was not significantly different between patients with TDR taking a fully-active cART regimen (containing drugs not compromised by resistance) and those without TDR.
Additionally, patients with TDR who were taking two NRTIs plus one NNRTI and were predicted to be on a fully active treatment had a higher risk of virological failure than patients on protease inhibitor-based regimens who had a similar likelihood of virological failure to that of patients with no TDR.
The authors say: "If drug-resistant mutations are detected before treatment initiation, a ritonavir-boosted protease inhibitor can be included in the first treatment regimen, which, because of its higher genetic barrier, could better protect from the risk of virological failure than could NNRTI."
They conclude: "These findings confirm present treatment guidelines for HIV, which state that the initial treatment choice should be based on resistance testing in treatment-naive patients."
Dr Linda Wittkop, INSERM U897, ISPED, University Bordeaux Segalen, Bordeaux, France. E) Linda.wittkop@isped.u-bordeaux2.fr
Professor Geneviève Chêne, INSERM U897, ISPED, University Bordeaux Segalen, Bordeaux, France. T) +33 (0)5 57 57 12 57 (direct) or +33 (0)5 57 57 13 92/11 29 (secretary) E) genevieve.chene@isped.u-bordeaux2.fr
Professor Deenan Pillay, Director, UCL/UCLH Comprehensive Biomedical Research Centre, University College London. T) +44 (0)7711 440650 (direct) or +44 (0)7956 656656 (PA) E) d.pillay@ucl.ac.uk
For full Article see: http://press.thelancet.com/tlidarteurusa.pdf
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Journal
The Lancet Infectious Diseases