Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2002 Mar;76(5):2573-8.
doi: 10.1128/jvi.76.5.2573-2578.2002.

Contribution of peaks of virus load to simian immunodeficiency virus pathogenesis

Roland R Regoes  1 , Silvija I Staprans, Mark B Feinberg, Sebastian Bonhoeffer
Affiliations

Contribution of peaks of virus load to simian immunodeficiency virus pathogenesis

Roland R Regoes et al. J Virol. 2002 Mar.

Abstract

The mechanisms causing AIDS and subsequently death in human immunodeficiency virus type 1 infection are not yet fully understood. Nonetheless, correlates of accelerated progression to disease based on immunological and virological markers have been identified. The best correlate identified to date is the baseline virus load or the so-called viral set point. By focusing on a virus load measurement from a restricted time range, however, we ignore valuable information contained in the long-term profile of the virus load. Here, we investigate the relationship between virus load and survival with the aid of a statistical model. The model takes into consideration the virus load at every stage of the disease. In particular, we aim to determine the effect of peaks of virus load on disease progression. We fit our model to unique sequential viral load data of 12 simian immunodeficiency virus mac251-infected rhesus macaques which contain frequent measurements throughout the entire course of the infection until the development of simian AIDS. Our model enables us to predict the survival times of the animals more accurately than an equivalent model which considers the viral set point only. Furthermore, we find that peaks of the virus load contribute less to disease progression than phases of low virus load with the same amount of viral turnover. Our analysis implies that the total viral turnover is not the best correlate of survival. As a consequence, the direct cytopathic effects of virus replication may, by themselves, have less of an impact on disease progression than previously thought.

PubMed Disclaimer

Figures

FIG. 1.
FIG. 1.
Interpretation of model 1 for p = 0, p = 1, and p = ∞. For each case we show two hypothetical virus load progressions and the resulting times of death.
FIG. 2.
FIG. 2.
The fitting procedure of model 1.
FIG. 3.
FIG. 3.
Virus load in and as felt by host 21289 according to our analysis.
FIG. A1.
FIG. A1.
Fraction of the explained variation in survival times as a function of p. The best fit is determined as the value for the parameter p which maximizes the fraction of explained variation.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Antia, R., B. R. Levin, and R. M. May. 1994. Within-host population dynamics and the evolution and maintenance of microparasite virulence. Am. Nat. 144:457-472.
    1. Arnaout, R. A., A. L. Lloyd, T. R. O'Brien, J. J. Goedert, J. M. Leonard, and M. A. Nowak. 1999. A simple relationship between viral load and survival time in HIV-1 infection. Proc. Natl. Acad. Sci. USA 96:11549-11553. - PMC - PubMed
    1. Cheng-Mayer, C., D. Seto, M. Tateno, and J. A. Levy. 1988. Biologic features of HIV-1 that correlate with virulence in the host. Science 240:80-82. - PubMed
    1. Efron, B. 1979. Bootstrap methods: another look at the jackknife. Ann. Stat. 7:1-26.
    1. Efron, B., and R. J. Tishbirani. 1993. An introduction to the bootstrap. Chapman & Hall, New York, N.Y.

Publication types

MeSH terms