Abstract
Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350–550 cells/mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with HIV infection.
Highlights
HIV genetic diversity generally increases with duration of infection [1, 2] and is influenced by viral factors and the host immune response [3, 4]
Baseline high resolution melting (HRM) scores were obtained for six regions of the HIV genome (GAG1, GAG2, POL, ENV1, ENV2, and ENV3) for 86 (90.5%) of the 95 participants; nine participants were excluded from analysis
After correcting for multiple comparisons, we did not observe any association between baseline HIV diversity and any of the demographic, laboratory, or clinical characteristics evaluated
Summary
HIV genetic diversity generally increases with duration of infection [1, 2] and is influenced by viral factors and the host immune response [3, 4]. Higher pre-treatment HIV diversity has been associated with high viral load [6], less effective control of viremia after strategic treatment interruption [7], and more rapid disease progression [8]. The HRM diversity assay measures the melting range of DNA amplicons generated from viral RNA and generates a single numeric HRM score that reflects the level of diversity in the genomic region analyzed [9]. Higher HRM scores are associated with higher viral diversity [10] and are highly correlated with diversity measures obtained using next-generation sequencing [10]. The following factors did not have a significant impact on results obtained with the HRM assay: HIV viral load, plasma sample volume, and number of HIV RNA copies used for DNA template preparation [11]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: 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.
