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

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.