Title

Finding the needle in the haystack: Progress in understanding the HIV reservoir

Code

OAA03

Session Type

Oral abstract session

Track

Track A: Basic and translational science

Format

Hybrid

CME accreditation

Yes

ROOM/CHANNEL

Room 517c/Channel 5

Date Time

01 August 14:15 - 15:15

Moderator

Lillian COHN, Fred Hutchinson Cancer Center, United States

14:15 2 min	Introduction Lillian COHN, Fred Hutchinson Cancer Center, United States

14:17 8 min	Scarcity of intact HIV genomes in vertically infected Thai children who initiated ART during the first months of life Caroline DUFOUR, Université de Montréal, Canada	Abstract Slides

14:25 8 min	HIV SMRTcap, a novel single molecule, long-read sequencing assay to characterize the HIV-1 reservoir in cells and tissues across multiple subtypes Melissa SMITH, University of Louisville, United States	Abstract Slides

14:33 8 min	Intact HIV proviruses persist in the central nervous system despite viral suppression with antiretroviral therapy Michael ROCHE, The University of Melbourne, Australia	Abstract Slides

14:41 8 min	SARS-CoV-2 mRNA vaccination exposes latent HIV to Nef-specific CD8+ T cells Brad JONES, Weill Cornell Medicine, United States	Abstract Slides

14:49 26 min	Q&A Lillian COHN, Fred Hutchinson Cancer Center, United States Caroline DUFOUR, Université de Montréal, Canada Melissa SMITH, University of Louisville, United States Michael ROCHE, The University of Melbourne, Australia Brad JONES, Weill Cornell Medicine, United States

AUTHOR

Guinevere Q. Lee

SUMMARY

In this session, four speakers presented their latest findings and new methods to study the HIV reservoir on under-studied tissue-types and donor populations.

HIGHLIGHTS

Caroline Dufour (L’Université de Montréal) summarized findings on the Thailand HIVNAT209 and HIVNAT194 HIV-infected newborn baby cohort. These infants were infected during pregnancy or delivery and were given ART immediately after birth. The study shows intact viruses decreased in frequency over time and clonal viral genomes increased over time in these infants. Melissa Smith (University of Louisville) reported a PacBio-based novel sequencing assay “SMRTcap”, which enables the detection of integration sites, clonal expansion, and genome-intactness, and could be applied to HIV-infected cell lines, donor-derived subtype A1, B, C, D HIV-1 DNA genomes, and in tissue samples. Michael Roche (University of Melbourne) reported that in post-mortem brain samples from 12 on-therapy and 6 off-therapy individuals, intact proviruses were detectable and were similar in frequencies in the central nervous system including frontal lobe, basal ganglia, cerebellum, and were predominantly harbored in myeloid cells instead of T cells. Brad Jones (Weill Cornell) reported that in 13 donors who received Moderna/Pfizer COVID-19 mRNA vaccines, cell-associated 3’ HIV mRNA increased after the prime dose, and negatively correlates with Nef-specific T cell responses. Neither total HIV DNA nor intact proviruses as measured by IPDA and TILDA showed reductions in the HIV reservoir size.

CRITICAL ASSESSMENT

Identification of genome-intact HIV genomes in the integrated DNA pool is key to our understanding of HIV persistence: our current knowledge is largely centered around subtype B HIV-1 isolated from blood that is derived from adult donors using labor-intensive molecular methods. This session presented new data on understudied aspects of the HIV reservoir including viral reservoirs in infants, reservoirs in the central nervous system, and reservoirs after COVID-19 mRNA vaccination. It also showcased a new sequencing method to study reservoir genetics.