Journal Article

Patterns and rates of viral evolution in HIV-1 subtype B infected females and males

Westfall, Dylan H., Hall, Breana M., Chen, Lennie, Deng, Wenjie, Chen, Natalie, Anastos, Kathryn, Mullins, James I., Kim, Katie, Dapp, Michael J., Zhao, Hong, Au, Lily, Kober, Kord M., Sibley, Thomas, Wong, Kim, Cohen, Mardge, Ghorai, Suvankar, McHugh, Sarah

2017

Overview

Biological sex differences affect the course of HIV infection, with untreated women having lower viral loads compared to their male counterparts but, for a given viral load, women have a higher rate of progression to AIDS. However, the vast majority of data on viral evolution, a process that is clearly impacted by host immunity and could be impacted by sex differences, has been derived from men. We conducted an intensive analysis of HIV-1 gag and env-gp120 evolution taken over the first 6-11 years of infection from 8 Women's Interagency HIV Study (WIHS) participants who had not received combination antiretroviral therapy (ART). This was compared to similar data previously collected from men, with both groups infected with HIV-1 subtype B. Early virus populations in men and women were generally homogenous with no differences in diversity between sexes. No differences in ensuing nucleotide substitution rates were found between the female and male cohorts studied herein. As previously reported for men, time to peak diversity in env-gp120 in women was positively associated with time to CD4+ cell count below 200 (P = 0.017), and the number of predicted N-linked glycosylation sites generally increased over time, followed by a plateau or decline, with the majority of changes localized to the V1-V2 region. These findings strongly suggest that the sex differences in HIV-1 disease progression attributed to immune system composition and sensitivities are not revealed by, nor do they impact, global patterns of viral evolution, the latter of which proceeds similarly in women and men.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Acquired immune deficiency syndrome / AIDS / Antiretroviral agents / Antiretroviral therapy / Biological evolution / Biology and Life Sciences / CD4 antigen / Cohort Studies / Comparative analysis / Computer and Information Sciences / Development and progression / Disease Progression / Dosage and administration / Drug resistance / Drug therapy / Evolution / Evolution, Molecular / Female / Females / gag Gene Products, Human Immunodeficiency Virus - metabolism / Gag protein / Gender aspects / Glycoprotein gp120 / Glycosylation / Health aspects / HIV / HIV Envelope Protein gp120 - genetics / HIV infections / HIV Infections - genetics / HIV Infections - virology / HIV patients / HIV-1 - physiology / Human immunodeficiency virus / Humans / Immune system / Immunity / Infections / Likelihood Functions / Load distribution / Male / Males / Medicine and Health Sciences / Men / Nucleotides - genetics / Phylogeny / Research and analysis methods / Sex / Sex Characteristics / Sex differences / Sex differences (Biology) / Sexually transmitted diseases / STD / Studies / Time Factors / Virus replication / Viruses