Quantifying the HIV reservoir with dilution assays and deep viral sequencing

Lotspeich, SC; Richardson, BD; Baldoni, PL; Enders, KP; Hudgens, MG

Author(s): Lotspeich, SC; Richardson, BD; Baldoni, PL; Enders, KP; Hudgens, MG;
Details: Publication Year 2024-01-29,Volume 80,Issue #1,Page ujad018
Journal Title: Biometrics
Abstract: 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, that is, 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.
Publisher: Oxford Academic
Keywords: Humans; Virus Latency; *HIV-1/genetics; *HIV Infections; CD4-Positive T-Lymphocytes; Computer Simulation; Viral Load; Poisson distribution; distinct viral lineages; infectious units per million; maximum likelihood estimation; missing data; serial limiting dilution assay
Research Division(s): Bioinformatics
PubMed ID: 38364812
Publisher's Version: https://doi.org/10.1093/biomtc/ujad018
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2024-02-29 09:16:11

Last Modified: 2024-02-29 09:21:58