HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time

@article{Perelson1996HIV1DI,
  title={HIV-1 Dynamics in Vivo: Virion Clearance Rate, Infected Cell Life-Span, and Viral Generation Time},
  author={Alan S. Perelson and Avidan U. Neumann and Martin Markowitz and John M. Leonard and David D. Ho},
  journal={Science},
  year={1996},
  volume={271},
  pages={1582 - 1586}
}
Key MethodA new mathematical model was used to analyze a detailed set of human immunodeficiency virus-type 1 (HIV-1) viral load data collected from five infected individuals after the administration of a potent inhibitor of HIV-1 protease. Productively infected cells were estimated to have, on average, a life-span of 2.2 days (half-life t 1/2 = 1.6 days), and plasma virions were estimated to have a mean life-span of 0.3 days (t 1/2 = 0.24 days). The estimated average total HIV-1 production was 10.3 x 10…
Short communication: HIV type 2 dynamics.
TLDR
The viral dynamics of HIV-1 and HIV-2 appear to have similar rates of production and clearance in vivo, and the large differences in plasma virus levels, virulence, and natural course of the disease between the two infections are due to other factors that are yet to be identified.
Decay characteristics of HIV-1-infected compartments during combination therapy
TLDR
It is estimated that 2.3–3.1 years of a completely inhibitory treatment would be required to eliminate HIV-1 from these compartments, and even longer treatment may be needed because of the possible existence of undetected viral compartments or sanctuary sites.
Reassessing the Human Immunodeficiency Virus Type 1 Life Cycle through Age-Structured Modeling: Life Span of Infected Cells, Viral Generation Time, and Basic Reproductive Number, R0
TLDR
Age-structured models of the viral decay dynamics in which viral production rates and death rates depend on the age of the infected cells are described and it is demonstrated that an exponential increase in viral production with infected-cell age is perfectly consistent with the data.
Quantification of in vivo replicative capacity of HIV-1 in different compartments of infected cells.
Based on a mathematical model, we analyze the dynamics of CD4+ cells, actively, latently, persistently, and defectively infected cells and plasma virus after initiation of antiretroviral therapy in
Viral Dynamics of Acute HIV-1 Infection
TLDR
The first estimates of the basic reproductive number (R 0), the number of cells infected by the progeny of an infected cell during its lifetime when target cells are not depleted are reported, to support the validity of the simian immunodeficiency virus macaque model of acute HIV infection.
Quantification of In Vivo Replicative Capacity of HIV‐1 in Different Compartments of Infected Cells
TLDR
Analysis of the dynamics of CD4+ cells, actively, latently, persistently, and defectively infected cells and plasma virus after initiation of antiretroviral therapy in 14 HIV‐1‐infected asymptomatic patients finds that only in actively infected cells the virus can maintain an ongoing infection.
Patterns of viral dynamics during primary human immunodeficiency virus type 1 infection. The Sydney Primary HIV Infection Study Group.
TLDR
Analysis of individual virus load curves revealed highly variable viral kinetics, and virus load and CD4 lymphocyte counts were similar in all patterns at 12 months, but the interval from infection to achievement of steady state virus load varied significantly.
Influence of follicular dendritic cells on HIV dynamics.
TLDR
It is shown that loss of virus from FDCs during therapy can make a much larger contribution to plasma virus than production of virus by infected cells, challenging the notion that long-lived infected cells are a significant source of HIV-1 during drug therapy.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 29 REFERENCES
Viral dynamics in human immunodeficiency virus type 1 infection
TLDR
Almost complete replacement of wild-type virus in plasma by drug-resistant variants occurs after fourteen days, indicating that HIV-1 viraemia is sustained primarily by a dynamic process involving continuous rounds of de novo virus infection and replication and rapid cell turnover.
Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection
TLDR
Treatment of infected patients with ABT-538 causes plasma HIV-1 levels to decrease exponentially and CD4 lymphocyte counts to rise substantially, indicating that replication of HIV- 1 in vivo is continuous and highly productive, driving the rapid turnover ofCD4 lymphocytes.
Quantitation of human immunodeficiency virus type 1 in the blood of infected persons.
TLDR
The levels of HIV-1 in plasma and PBMC are much higher than previous estimates, raising the possibility that the direct cytopathic effect of this retrovirus alone may be sufficient to explain much of the pathogenesis of AIDS.
HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy
TLDR
Results lead to a simple steady-state model in which infection, cell death, and cell replacement are in balance, and imply that the unique feature of HIV is the extraordinarily large number of replication cycles that occur during infection of a single individual.
A preliminary study of ritonavir, an inhibitor of HIV-1 protease, to treat HIV-1 infection.
TLDR
The protease inhibitor ritonavir is well tolerated and has a potent antiviral effect, as shown by substantial decreases in plasma viremia and significant elevations in CD4 cell counts.
Quantitative analysis of the human immunodeficiency virus type 1 (HIV- 1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: differential CTL responses to HIV-1 and Epstein- Barr virus in late disease
TLDR
CTL precursors were detected against all three HIV-1 structural gene products in patients with CD4+ lymphocyte counts > 400/microliters, at frequencies that are high compared with those reported for other persistent viruses.
Lower in vivo mutation rate of human immunodeficiency virus type 1 than that predicted from the fidelity of purified reverse transcriptase
TLDR
In vivo mutation rates for HIV-1 are three and seven times higher than those previously reported for two other retroviruses, spleen necrosis virus and bovine leukemia virus, respectively, and the calculated in vivo mutation rate is about 20-fold lower than the error rate of purified HIV- 1 reverse transcriptase, with the same target sequence.
Clinical evaluation of branched DNA signal amplification for quantifying HIV type 1 in human plasma.
  • Y. Cao, D. Ho, M. Saag
  • Biology, Medicine
    AIDS research and human retroviruses
  • 1995
TLDR
The close quantitative correlation between bDNA and QC-PCR results, and their significant association with other viral markers and CD4+ counts, support the use of plasma viral RNA measurement in HIV-1 clinical trials.
ABT-538 is a potent inhibitor of human immunodeficiency virus protease and has high oral bioavailability in humans.
  • D. Kempf, K. Marsh, X. Kong
  • Biology, Medicine
    Proceedings of the National Academy of Sciences of the United States of America
  • 1995
TLDR
It is demonstrated that high oral bioavailability can be achieved in humans with peptidomimetic inhibitors of HIV protease with potent in vitro activity against laboratory and clinical strains of HIV.
Rapid and precise quantification of HIV-1 RNA in plasma using a branched DNA signal amplification assay.
  • C. Pachl, J. Todd, B. Irvine
  • Biology, Medicine
    Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association
  • 1995
TLDR
Plasma RNA levels were found to change with disease stage, and in response to antiviral therapy, and may be a useful method for monitoring HIV-1 disease progression and therapeutic response.
...
1
2
3
...