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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Timing constraints of in vivo Gag mutations during primary HIV-1 subtype C infection
PLoS ONE, Volume 4, No. 11, Article e7727, Year 2009
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Description
Background: Aiming to answer the broad question "When does mutation occur?" this study examined the time of appearance, dominance, and completeness of in vivo Gag mutations in primary HIV-1 subtype C infection. Methods: A primary HIV-1C infection cohort comprised of 8 acutely and 34 recently infected subjects were followed frequently up to 500 days post-seroconversion (p/s). Gag mutations were analyzed by employing single-genome amplification and direct sequencing. Gag mutations were determined in relation to the estimated time of seroconversion. Time of appearance, dominance, and completeness was compared for different types of in vivo Gag mutations. Results: Reverse mutations to the wild type appeared at a median (IQR) of 62 (44;139) days p/s, while escape mutations from the wild type appeared at 234 (169;326) days p/s (p<0.001). Within the subset of mutations that became dominant, reverse and escape mutations appeared at 54 (30;78) days p/s and 104 (47;198) days p/s, respectively (p<0.001). Among the mutations that reached completeness, reverse and escape mutations appeared at 54 (30;78) days p/s and 90 (44;196) days p/s, respectively (p = 0.006). Time of dominance for reverse mutations to and escape mutations from the wild type was 58 (44;105) days p/s and 219 (90;326) days p/s, respectively (p<0.001). Time of completeness for reverse and escape mutations was 152 (100;176) days p/s and 243 (101;370) days p/s, respectively (p = 0.001). Fitting a Cox proportional hazards model with frailties confirmed a significantly earlier time of appearance (hazard ratio (HR): 2.6; 95% CI: 2.3-3.0), dominance (4.8 (3.4-6.8)), and completeness (3.6 (2.3-5.5)) of reverse mutations to the wild type Gag than escape mutations from the wild type. Some complex mutational pathways in Gag included sequential series of reversions and escapes. Conclusions: The study identified the timing of different types of in vivo Gag mutations in primary HIV-1 subtype C infection in relation to the estimated time of seroconversion. Overall, the in vivo reverse mutations to the wild type occurred significantly earlier than escape mutations from the wild type. This shorter time to incidence of reverse mutations remained in the subsets of in vivo Gag mutations that reached dominance or completeness. © 2009 Novitsky et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC2768328/bin/pone.0007727.s001.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2768328/bin/pone.0007727.s002.eps
https://efashare.b-cdn.net/share/pmc/articles/PMC2768328/bin/pone.0007727.s003.eps
https://efashare.b-cdn.net/share/pmc/articles/PMC2768328/bin/pone.0007727.s004.eps
https://efashare.b-cdn.net/share/pmc/articles/PMC2768328/bin/pone.0007727.s005.eps
https://efashare.b-cdn.net/share/pmc/articles/PMC2768328/bin/pone.0007727.s006.eps
https://efashare.b-cdn.net/share/pmc/articles/PMC2768328/bin/pone.0007727.s007.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC2768328/bin/pone.0007727.s008.pdf
Authors & Co-Authors
Novitsky, Vladimir A.
United States, Boston
Harvard T.h. Chan School of Public Health Aids Initiative
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Wang, Rui
United States, Boston
Harvard T.h. Chan School of Public Health
Margolin, Lauren
United States, Boston
Harvard T.h. Chan School of Public Health Aids Initiative
Baca, Jeannie
United States, Boston
Harvard T.h. Chan School of Public Health Aids Initiative
Kebaabetswe, Lemme Prica
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Rossenkhan, Raabya
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Bonney, Caitlin
United States, Boston
Harvard T.h. Chan School of Public Health Aids Initiative
Herzig, Michaela
United States, Boston
Harvard T.h. Chan School of Public Health Aids Initiative
Nkwe, David O.
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Moyo, Sikhulile M.
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Musonda, Rosemary Mubanga
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Woldegabriel, Elias
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
van Widenfelt, Erik
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Makhema, Joseph M.
United States, Boston
Harvard T.h. Chan School of Public Health Aids Initiative
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Lagakos, Stephen W.
United States, Boston
Harvard T.h. Chan School of Public Health
Essex, Max E.
United States, Boston
Harvard T.h. Chan School of Public Health Aids Initiative
Botswana, Gaborone
Botswana Harvard Aids Institute Partnership
Statistics
Citations: 30
Authors: 16
Affiliations: 3
Identifiers
Doi:
10.1371/journal.pone.0007727
e-ISSN:
19326203
Research Areas
Cancer
Environmental
Infectious Diseases
Study Design
Cohort Study