Exploring an alternative explanation for the second phase of viral decay: Infection of short-lived cells in a drug-limited compartment during HAART

PloS One
Steven SancheFahima Nekka

Abstract

Most HIV-infected patients who initiate combination antiretroviral therapy experience a viral load decline in several phases. These phases are characterized by different rates of viral load decay that decrease when transitioning from one phase to the next. There is no consensus as to the origin of these phases. One hypothesis put forward is that short- and long-lived infected cells are responsible for the first and second phases of decay, respectively. However, significant differences in drug concentrations are observed in monocytes from various tissues, suggesting the first two phases of decay in viral loads could instead be attributed to short-lived cells being differently exposed to drugs. Compared to a well-exposed compartment, new cell infection can be expected in a compartment with limited drug exposure, thus leading to a slower viral load decay with potential virologic failure and drug resistance. In the current study, the latter hypothesis was investigated using a model of viral kinetics. Empirical datasets were involved in model elaboration and parameter estimation. In particular, susceptibility assay data was used for an in vitro to in vivo extrapolation based on the expected drug concentrations inside physiological c...Continue Reading

References

Sep 20, 2000·Proceedings of the National Academy of Sciences of the United States of America·W S HlavacekA S Perelson
Jan 31, 2002·Annual Review of Medicine·Joel N BlanksonRobert F Siliciano
Jan 20, 2006·The New England Journal of Medicine·Joel E GallantUNKNOWN Study 934 Group
Aug 21, 2007·Journal of Medical Virology·Bernd KupferRolf Kaiser
Mar 12, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sarah PalmerMartin S King
Jul 20, 2010·Immunological Reviews·K Kai McKinstrySusan L Swain
Jul 28, 2010·Journal of Virology·Michael E AbramStephen H Hughes
Sep 9, 2010·PLoS Computational Biology·Rob J De BoerAlan S Perelson
Nov 26, 2010·AIDS Research and Human Retroviruses·Adam M SpivakRobert F Siliciano
Sep 8, 2011·Antimicrobial Agents and Chemotherapy·Almudena SánchezUNKNOWN Tormes Group
Sep 8, 2011·Antimicrobial Agents and Chemotherapy·Gautam BahetiCourtney V Fletcher
Dec 14, 2011·The Journal of Antimicrobial Chemotherapy·Aylin YilmazMagnus Gisslén
Feb 22, 2012·Nature Medicine·Benjamin L JilekRobert F Siliciano
Sep 4, 2012·Nature Medicine·Daniel I S RosenbloomMartin A Nowak
Sep 12, 2012·Antimicrobial Agents and Chemotherapy·Edward P AcostaChristos J Petropoulos
Jan 29, 2014·Proceedings of the National Academy of Sciences of the United States of America·Courtney V FletcherTimothy W Schacker
Feb 5, 2014·Antimicrobial Agents and Chemotherapy·Elodie ValadeDéborah Hirt
Nov 21, 2014·AIDS Patient Care and STDs·Cecilia T Costiniuk, Mohammad-Ali Jenabian
Jan 28, 2016·Nature·Ramon Lorenzo-RedondoSteven M Wolinsky
Jan 31, 2017·HIV Clinical Trials·Maile Y KarrisUNKNOWN California Collaborative Treatment Group (CCTG) 589 Study Team
May 31, 2017·CPT: Pharmacometrics & Systems Pharmacology·S SancheF Nekka

❮ Previous
Next ❯

Software Mentioned

WebPlotDigitizer

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.