  People living with HIV on antiretroviral therapy often have undetectable
virus levels by standard assays, but "latent" HIV still persists in viral
reservoirs. Eliminating these reservoirs is the goal of HIV cure research. The
quantitative viral outgrowth assay (QVOA) is commonly used to estimate the
reservoir size, i.e., the infectious units per million (IUPM) of HIV-persistent
resting CD4+ T cells. A new variation of the QVOA, the Ultra Deep Sequencing
Assay of the outgrowth virus (UDSA), was recently developed that further
quantifies the number of viral lineages within a subset of infected wells.
Performing the UDSA on a subset of wells provides additional information that
can improve IUPM estimation. This paper considers statistical inference about
the IUPM from combined dilution assay (QVOA) and deep viral sequencing (UDSA)
data, even when some deep sequencing data are missing. Methods are proposed to
accommodate assays with wells sequenced at multiple dilution levels and with
imperfect sensitivity and specificity, and a novel bias-corrected estimator is
included for small samples. The proposed methods are evaluated in a simulation
study, applied to data from the University of North Carolina HIV Cure Center,
and implemented in the open-source R package SLDeepAssay.
