DOI: 10.5061/dryad.6980c06
title: Data from: Exploring an alternative explanation for the second phase of viral decay: infection of short-lived cells in a drug-limited compartment during HAART

description: 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 compartments. Results from numerical
 experiments of the short-term evolution of viral loads can reproduce the
 first two phases of viral decay when allowing new short-lived cell
 infections in an unidentified drug-limited compartment. Model long-term
 predictions are however less consistent with clinical observations. For
 the hypothesis to hold, efavirenz, tenofovir and emtricitabine drug
 exposure in the drug-limited compartment would have to be very low
 compared to exposure in peripheral blood. This would lead to significant
 long-term viral growth and the frequent development of resistant strains,
 a prediction not supported by clinical observations. This suggests that
 the existence of a drug-limited anatomical compartment is unlikely, by
 itself, to explain the second phase of viral load decay.
description: cART_ex1Long-term viral load decay (see SSanche - PLOS One - File descriptions.docx)cART_ex2Long-term viral load, file 2 (see SSanche - PLOS One - File descriptions.docx)cART_ex3Long-term viral load, file 3 (see SSanche - PLOS One - File descriptions.docx)Decay_KAR_Phi5_fu35see SSanche - PLOS One - File descriptions.docxDecay_KAR_Phi8_fu40see SSanche - PLOS One - File descriptions.docxDecay_P1_Phi5_fu47see SSanche - PLOS One - File descriptions.docxDecay_P2_Phi4_fu34see SSanche - PLOS One - File descriptions.docxDecay_P2_Phi10_fu40see SSanche - PLOS One - File descriptions.docxDecay_P3_Phi17_fu39see SSanche - PLOS One - File descriptions.docxDecay_P4_Phi5_fu36see SSanche - PLOS One - File descriptions.docxDecay_P5_Phi18_fu59see SSanche - PLOS One - File descriptions.docxDecay_P6_Phi13_fu20see SSanche - PLOS One - File descriptions.docxSPACE_FU_KLsee SSanche - PLOS One - File descriptions.docxSSanche - PLOS One - File descriptionsFile description