Natural selection favoring more transmissible HIV detected in United States molecular transmission network

Joel O Wertheim,William M Switzer,Chenhua Zhang,Walid Heneine,Neeraja Saduvala,Alexandra M Oster,Ellsworth Campbell,Jeffrey A Johnson,Nivedha Panneer

doi:10.1038/s41467-019-13723-z

Abstract

HIV molecular epidemiology can identify clusters of individuals with elevated rates of HIV transmission. These variable transmission rates are primarily driven by host risk behavior; however, the effect of viral traits on variable transmission rates is poorly understood. Viral load, the concentration of HIV in blood, is a heritable viral trait that influences HIV infectiousness and disease progression. Here, we reconstruct HIV genetic transmission clusters using data from the United States National HIV Surveillance System and report that viruses in clusters, inferred to be frequently transmitted, have higher viral loads at diagnosis. Further, viral load is higher in people in larger clusters and with increased network connectivity, suggesting that HIV in the United States is experiencing natural selection to be more infectious and virulent. We also observe a concurrent increase in viral load at diagnosis over the last decade. This evolutionary trajectory may be slowed by prevention strategies prioritized toward rapidly growing transmission clusters.

Highlights

human immunodeficiency virus (HIV) molecular epidemiology can identify clusters of individuals with elevated rates of HIV transmission
Of the 251,754 individuals in the National HIV Surveillance System (NHSS) database with a reported HIV-1 polymerase sequence, 41,409 were antiretroviral therapy (ART)-naïve at diagnosis and had a reported HIV-1 subtype B resistance genotype performed within three months of diagnosis
Using pol sequences from these 41,409 individuals (31,285 of whom had wild-type virus containing no drug resistance-associated mutations (DRAMs)), we inferred a total of 4366 molecular transmission clusters using a genetic distance threshold of ≤0.015 substitutions/site in HIV-TRACE (HIV TRAnsmission Cluster Engine)[31], comprising 17,688 persons (42.7%)

Summary

Introduction

HIV molecular epidemiology can identify clusters of individuals with elevated rates of HIV transmission. The concentration of HIV in blood, is a heritable viral trait that influences HIV infectiousness and disease progression. Viral load is higher in people in larger clusters and with increased network connectivity, suggesting that HIV in the United States is experiencing natural selection to be more infectious and virulent. 0.3 log[10] and 0.5 log[10] increase per-event transmission risk by 20% and 40%, respectively, underscoring the potential impact of viral load on HIV spread at the population level[20]. Higher infectiousness due to increased viral load may not necessarily result in more transmission at the population level, because higher SPVL comes with an associated increase in the rate of disease progression that limits the duration of time over which transmission can occur[1,2]. Clustering in an HIV-1 molecular transmission network can serve as a proxy for transmission rate of the virus across multiple individuals and, for efficiency of spread in a population[23,24,25,26]

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Results

Conclusion