Abstract
Background: In the CARINEMO ANRS 12146 clinical trial, HIV-tuberculosis co-infected patients in Mozambique were randomized to nevirapine (NVP) or to efavirenz (EFV)-based antiretroviral therapy to compare these two non-nucleoside reverse transcriptase inhibitors (NNRTIs) in treatment naïve patients. Methods: In this sub study, we explored the relationship of NNRTI concentrations with virological escape and the possible emergence of resistance mutations at week 48. The virological escape was defined as an HIV-RNA above 400 copies/m at week 48. Results: Among the 570 randomized patients, 470 (82%) had an HIV-RNA result at week 48; 54 (12.1%) patients had a viral escape and 35 patients had at least one major resistance mutation detected. Low drug concentration at weeks 12 and 24 (below the 10th percentile) were independently associated with virologic escape at week 48 (adjusted odds ratio [aOR]=2.9; 95% CI: 1.1 -7.2; p=0.0312 and aOR=4.2; 95% CI: 1.8-9.8; p=0.0019, respectively), and independently associated with an increased risk of emergence of resistance mutation (aOR=4.5; 95% CI: 1.8-14.6; p=0.009 at week 12; aOR=5.1; 95% CI: 1.8-14.6 at week 24). Receiver operating characteristic curves analyses indicated a better predictability of the mid-dose concentration and of the HIV-1 RNA values on resistance mutations in contrast to virological escape. Conclusions: Very low drug plasma concentrations early after treatment initiation (week 12) were predictive factors of virological escape and the emergence of resistance mutations at week 48, and early monitoring of drug intake may prevent the occurrence of late virological escape and the selection of vial resistance mutations.
Highlights
Antiretroviral therapy (ART) aims to sustain virological suppression, which is associated with a clinical benefit and immune recovery
These results indicate a better predictability of the HIV-1 RNA values on resistance mutations in contrast to virological escape
In the present study, we used the data of a large randomized clinical trial assessing two drugs of the nucleoside reverse transcriptase inhibitors (NNRTIs) class in combination with anti-TB drugs
Summary
Antiretroviral therapy (ART) aims to sustain virological suppression, which is associated with a clinical benefit and immune recovery. It prevents HIV transmission and limits the emergence of antiretroviral (ARV) drug resistance. In 2016, 80% of the worldwide prescription of ART-included efavirenz (EFV), a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-class drug[2]. In the CARINEMO ANRS 12146 clinical trial, HIV-tuberculosis co-infected patients in Mozambique were randomized to nevirapine (NVP) or to efavirenz (EFV)-based antiretroviral therapy to compare these two non-nucleoside reverse transcriptase inhibitors (NNRTIs) in treatment naïve patients. Conclusions: Very low drug plasma concentrations early after treatment initiation (week 12) were predictive factors of virological escape and the emergence of resistance mutations at week 48, and early monitoring of drug
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.