DOI: 10.14457/tu.the.2015.1353
title: Measurement of antiretroviral drug levels prior to HIV-1 resistance testing to predict detection of HIV-1 resistance mutations for patients with virological failure

description: In Thailand more than 280,000 HIV infected patients are now receiving antiretroviral treatment (ART) under the National AIDS Program. For patients on ART with confirmed virologic failure (HIV-1 RNA &gt;1,000 copies/mL) HIV genotypic resistance testing is performed to select the subsequent drug regimen. It is critical that genotypic resistance testing is performed while patients are taking their treatment as prescribed in order to maximize the possibility of detecting any resistance mutations (i.e. selected under drug pressure). Treatment discontinuation prior to genotypic resistance testing can result in the outgrowth of wild-type virus and decrease the sensitivity to detect the resistant viruses. The Clinical Microbiology Service Unit (CMSU) at the Faculty of Associated Medical Sciences, Chiang Mai University provides HIV-1 genotypic resistance testing as part of the Thai National AIDS Program. Approximately 20% of samples sent to the CMSU between 2013 and 2014 had no HIV drug resistance mutations detected. We hypothesize that detecting the presence of antiretroviral drugs in plasma samples sent to CMSU before performing the genotypic resistance test may help ensure that the optimal sample is used for testing and prevent testing samples unnecessarily that will not be useful to determine the subsequent regimen.Our objective was to assess if detecting the presence of antiretroviral drugs in plasma prior to HIV-1 genotypic resistance testing can predict the detection of HIV drug resistance mutations. We performed a retrospective analysis using plasma samples sent to the CMSU for genotypic resistance testing between 2013 and-2014. Genotypic drug resistance testing was performed using the ViroSeq HIV-1 Genotyping System V2.8. Antiretroviral drug concentrations were measured in plasma samples of patients who had a drug resistance test performed and receiving a non-nucleoside reverse-transcriptase inhibitor (NNRTI) or protease inhibitors (PI) in combination with 2 nucleoside reverse-transcriptase inhibitors (NRTI). NNRTI and PI plasma drug concentrations were determined using validated reversed-phase high performance liquid chromatography (HPLC) assays. The sensitivity, specificity and predictive values of using the presence of antiretroviral drugs in plasma to predict the detection of drug resistance mutations (specific to the drug detected) by resistance testing were determined. Of 395 samples tested: 180 patients were receiving a NNRTI-based regimen and 215 were receiving a PI-based regimen.  Overall, 219 of 395 (55.4%) plasma samples had no detectable NNRTI or PI drug concentrations. Among these 219 samples, 187 (85%) had no NNRTI or PI drug resistance mutation detected. The sensitivity of detectable NNRTI or PI drug concentrations to predict the detection of associated resistance mutations was 79% and the specificity was 78%. The negative predictive value was 85%. An additional analysis was performed based on the presence of NNRTI or PI in patient’s regimen. The sensitivity, specificity and negative predictive value were 80%, 84% and 52%, respectively, for patients receiving an NNRTI, and 85%, 77% and 99% for those receiving a PI. In conclusion the presence of PI drug concentrations in plasma samples sent for resistance testing  provides a high negative predictive value to predict the detection of PI-associated resistance mutations by genotypic drug resistance testing in that sample. Further analyses, including a large sample size, and different PIs are needed to confirm the utility of drug measurement to predict the detection of resistance mutations prior to genotype testing.