Related Experiment Video
Updated: Jun 16, 2026

Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Connection domain mutations in treatment-experienced patients in the OPTIMA trial
Birgitt Dau1, Dieter Ayers, Joel Singer
1AIDS Research Center, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA 94304, USA. birgitt.dau@gmail.com
Objectives:
To determine the frequency of mutations in the connection domain (CD) of HIV reverse transcriptase in treatment-experienced patients in the Options in Management with Antiretrovirals trial, their impact on susceptibility to antiretroviral (ARV) drugs, and their impact on virologic outcomes.
Methods:
Baseline plasma ARV genotypes and inferred resistance phenotypes were obtained. Frequencies of E312Q, Y318F, G333D, G333E, G335C, G335D, N348I, A360I, A360V, V365I, A371V, A376S, and E399G were compared with a treatment-naive population. The association of CD mutations with inferred IC50 fold changes to nucleos(t)ide reverse transcriptase inhibitors was evaluated. Univariate and multivariate analyses examined the association of CD mutations with a >1 log10 per milliliter decrease in HIV viral load after 24 weeks on a new ARV regimen.
Results:
Higher CD mutation rates were seen in Options in Management with Antiretrovirals patients (n = 345) compared with a treatment-naive population. CD mutations were associated with increased inferred IC50 fold changes to abacavir, stavudine, tenofovir, and zidovudine. On univariate analysis, A371V was associated with lack of virologic response, as was having any CD mutation on multivariate analysis.
Conclusions:
CD mutations are frequent in treatment-experienced populations. They are associated with reduced susceptibility to some nucleos(t)ide reverse transcriptase inhibitors and with a diminished response to ARV therapy.
Related Concept Videos
Clinical Trials: Overview
Treatment Resistent Cancers
Treatment Resistant Cancers
Clinical Trials
There are four phases in a clinical trial. A phase one...
Therapeutic Drug Monitoring: Affecting Factors
Bioavailability Study Design: Healthy Subjects Versus Patients