The contribution of viral genotype to plasma viral set-point in HIV infection.
Disease progression in HIV-infected individuals varies greatly, and while the environmental and host factors influencing this variation have been widely investigated, the viral contribution to variation in set-point viral load, a predictor of disease progression, is less clear. Previous studies, using transmission-pairs and analysis of phylogenetic signal in small numbers of individuals, have produced a wide range of viral genetic effect estimates. Here we present a novel application of a population-scale method based in quantitative genetics to estimate the viral genetic effect on set-point viral load in the UK subtype B HIV-1 epidemic, based on a very large data set. Analyzing the initial viral load and associated pol sequence, both taken before anti-retroviral therapy, of 8,483 patients, we estimate the proportion of variance in viral load explained by viral genetic effects to be 5.7% (CI 2.8-8.6%). We also estimated the change in viral load over time due to selection on the virus and environmental effects to be a decline of 0.05 log10 copies/mL/year, in contrast to recent studies which suggested a reported small increase in viral load over the last 20 years might be due to evolutionary changes in the virus. Our results suggest that in the UK epidemic, subtype B has a small but significant viral genetic effect on viral load. By allowing the analysis of large sample sizes, we expect our approach to be applicable to the estimation of the genetic contribution to traits in many organisms.
Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom.
Emma
E
Hodcroft
Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom.
Jarrod D
JD
Hadfield
MRC Clinical Trials Unit Aviation House, London, United Kingdom.
Esther
E
Fearnhill
Infection and Population Health, University College London, Royal Free Hospital, London, United Kingdom.
Andrew
A
Phillips
MRC Clinical Trials Unit Aviation House, London, United Kingdom.
David
D
Dunn
Department of Infectious Diseases, King's College London, London, United Kingdom.
Siobhan
S
O'Shea
Research Department of Infection, University College London, London, United Kingdom.
Deenan
D
Pillay
Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh, United Kingdom.
Andrew J
AJ
Leigh Brown
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000097:blood / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D010802:Phylogeny; D019562:Viral Load / Q000235:genetics*; D055815:Young Adult