Initial treatment for HIV is three times more likely to fail if a person is infected with transmitted drug resistant (TDR) HIV compared to non-resistant HIV, according to a European-wide study involving CBRC and UCL investigators.
People with HIV (Human Immunodeficiency Virus) are normally treated with drugs known as antiretroviral drugs which slow down the growth of the virus. However some strains of HIV are drug resistant.
Results from the EuroCoord-CHAIN study, published in ‘Online First’ in the Lancet Infectious Diseases, show how important it is to test people for drug resistance before they begin treatment for HIV in order to work out which antiretroviral drugs are likely to work for them. The results also suggest which combinations of drugs are likely to work best for people with TDR HIV. This is particularly important when there are so many drug choices for treating HIV.
The study, funded by an EU FP7 grant held by University College London, assessed the effect of TDR on treatment outcomes during the first year of combination antiretroviral therapy (cART) in a large European dataset of over 10,000 patients.
Evidence from the study has important implications for resource-poor regions of the world where resistance testing is routine but where TDR is likely to increase as HIV treatment is rolled out. In Europe and the USA, 10-15% of patients who have not yet started treatment (‘treatment-naïve patients’) are infected with TDR HIV that already has at least one drug-resistant mutation.
Senior author, Professor Deenan Pillay, and Director of the UCLH/UCL NIHR Comprehensive Biomedical Research Centre said: “This is one of the very clearest examples to date of stratified, or individualised medicine, whereby routine testing of the genetic makeup of the virus directly leads to optimising the 1st line therapy with antiretroviral drugs for individual patients”.
More details about the study
10,056 patients from 25 cohorts across Europe underwent genotypic testing before the start of cART to determine resistence to nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (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.
Findings include:
- Poor virological and immunological response may be more common in TDR patients who take NNRTI-based regimens.
- 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.”
- 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.
- Patients infected 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 study authors said: “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 concluded: “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.”
