CROI 2024 Abstract eBook

Abstract eBook

Poster Abstracts

27 years (Q1, Q3: 22,33) and 20.7% were male. Few differences were observed between resistant and sensitive variants when looking at V1-V4 loop lengths, except for VRC26.25 and NIH45-46 where V1 loop was shorter in resistant compared to sensitive strains (p<0.01 and p=0.04) respectively. The most significant differences in variable regions between resistant and sensitive strains were observed with V5 loop length; where CD4 bnAb 2G12, DH270.5 and FP interface 35O22 resistant strains had shorter V5 loop lengths; p = <0.01, <0.01 and 0.02 consecutively. V1 charge distributions were significantly different for VRC26.25 (p =0.01), PGT121(p <0.01) and VRC01 (p = 0.01) resistant strains. In terms of mutations, E164 was observed and associated with resistance to both CH01 and PGT145. We observe the mutation T234N in sequences resistant to 3BNC117 and b12. We did not record mutations N671T, W672L, WG80G and F673L among all 2F5 resistant strains. We did however observe K683R mutation in all strains resistant to 2F5. Conclusion: Our findings further highlight the need to evaluate VC from sequence data, to determine the optimal vaccine design and best bnAb combinations to use for neutralization of highly variable HIV-1 subtype C. Cannabis Use Enhances Mucosal Immunity and the Microbiome in Individuals With HIV Robert Langat 1 , Ryan K. Cheu 2 , Christopher Basting 1 , Courtney A. Broedlow 1 , Michael Louella 3 , Nina Isoherranen 4 , Ann C. Collier 4 , Peter W. Hunt 5 , Jennifer A. Manuzak 6 , Nichole R. Klatt 1 1 University of Minnesota, Minneapolis, MN, USA, 2 Emery Pharma, Almeda, CA, USA, 3 defeatHIV, Seattle, WA, USA, 4 University of Washington, Seattle, WA, USA, 5 University of California San Francisco, San Francisco, CA, USA, 6 Tulane University, Metairie, LA, USA Background: Cannabis is widely used by people living with HIV (PLWH) both recreationally and to mitigate HIV- or antiretroviral therapy (ART)-associated nausea, pain, anorexia, or other symptoms. Here, we evaluated immune function and intestinal health among a cohort of ART-treated, cannabis using, and non-using PLWH. We hypothesized that cannabis using PLWH would have reduced inflammation and immune activation linked with a more immunomodulatory gastrointestinal (GI) microbiome. Methods: Colon single-cell suspensions from cannabis-using and non using ART-treated PLWH were analyzed for cellular immune function by multiparameter flow cytometry. Plasma levels of short-chain fatty acids (SCFA) as indicators of colonic function were assessed by GC-MS. GI microbial communities were profiled through colonic mucosa 16s rRNA sequencing. Cannabis use or non-use was verified in all participants by LC-MS. Results: Although overall frequencies of CD4+ and CD8+ T-cells were unchanged (p=0.692 and p=0.204, respectively), the frequencies of activated HLA-DR+CD38+ CD4+ and CD8+ T-cells were significantly decreased in the colon of ART-treated cannabis-using as compared to non-using PLWH (p<0.0001 for both subsets). Frequencies of colon IgA+ and IgG+ B cells were significantly increased in cannabis users vs. non- users (p=0.0006 and p=0.0259, respectively). Cannabis users had significantly lower frequencies of colon TNF- α+CD20+B cells as compared to non-users (p=0.0001). Plasma concentrations of the SCFAs acetate (p<0.0001), propionate (p=0.0034), butyrate (p=0.0001), and isobutyric acid (p=0.0043) but not valeric acid and isovaleric acid were increased in cannabis users vs. non-users. Lastly, ART-treated cannabis using PLWH possessed colonic mucosa microbiomes dominated by Prevotella, followed by Bifidobacterium, Faecalibacterium, Succiniclasticum, and Collinsella. No differences in alpha diversity were observed between ART-treated cannabis-using and non-using PLWH. Conclusion: ART-treated cannabis using PLWH had significantly lower frequencies of activated CD4+ and CD8+ T-cells and TNF-α+CD20+B cells, suggesting lower inflammation and immune activation as compared to non-cannabis users. Cannabis use has the potential to alleviate HIV-associated inflammation through alterations in microbial community structure and function. Overall, this study provides important insights into the impact of cannabis use on immunity and the microbiome of PLWH.

viremia occurs despite good ART adherence due to viral release from a large, clonally-expanded reservoir of HIV-infected CD4 cells. We describe two PWH on ART with persistent, high-level viremia that failed to fully suppress for >10 months, and was associated with persistent macrophage-tropic virus. Methods: Two PWH (NP1, NP2) initiated ART with high HIV-1 viral load and low CD4 counts. Both were adherent to ART regimen, by observation and drug levels and no evidence of resistance emergence by Sanger and deep sequencing. Plasma samples were collected from both participants, and total PBMCs from one. Viral RNA was sequenced using MiSeq with Primer ID on portions of pol and the env V1/V3 region. Near-full length sequencing was conducted on proviral DNA from PBMCs and viral RNA from the plasma. Full length env were cloned from plasma RNA and proviral DNA for pseudoviral assays to assess infection efficiency at low CD4 density as a predictor of macrophage tropism. Results: No DRMs were detected in either participant and a diverse plasma RNA population was seen in the V1V3 region. In NP1, a viral lineage representing ~50% of the total sequences rapidly declined, leaving a single, diverse persistent lineage, with no evidence of ongoing replication. In both participants, pseudoviruses generated from HIV envelopes of the persistent viremia were able to infect Low CD4 density cells to a similar degree as other described macrophage tropic viruses. In NP1, the plasma viral lineage that disappeared with ART initiation and that was present in total PBMC DNA did not infect at low CD4 density, consistent with T cell tropic viruses. Sequencing of PBMC DNA in NP1 found 2% of proviruses recovered were of the macrophage tropic lineage. Viral integration site analysis suggested intact proviral DNA from PBMCs was not clonal. Curiously, in this participant all M-tropic viruses were also found to have mutations in Vpr that abolished its open reading frame. Conclusion: We describe two PWH with persistent high-level plasma viremia derived likely from infected macrophages with a long half-life, with additional studies being explored to confirm this. This has both clinical significance as the treatment regimens are still effective at preventing further infection, and has implications to the persistence of the reservoir in long-lived macrophages.

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Poster Abstracts

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Variable HIV-1 C Env Characteristics Associated With Predicted bNAb Resistance in Botswana Natasha O Moraka 1 , Wonderful T. Choga 1 , Marea Pema 1 , Irene Gobe 2 , Margaret Mokomane 2 , Ontlametse T. Bareng 1 , Lynnette Bhebhe 1 , Molly Pretorius Holme 3 , Terence Mohammed 1 , Catherine K. Koofhethile 3 , Joseph M. Makhema 1 , Roger Shapiro 3 , Shahin Lockman 3 , Sikhulile Moyo 1 , Simani Gaseitiswe 1 1 Botswana Harvard AIDS Institute Partnership, Gabarone, Botswana, 2 University of Botswana, Gaborone, Botswana, 3 Harvard TH Chan School of Public Health, Boston, MA, USA Background: Characterizing HIV-1 early founder viruses is essential for informing vaccine design and broadly neutralizing antibody (bnAb) design. We analyzed variable region characteristics (VC) in HIV-1 seroconverters and compared them with predicted bnAb resistance/sensitivity using machine learning techniques. Methods: We analyzed HIV-1 near-full-length proviral sequences from 140 adults with documented recent HIV-1 seroconversion who were enrolled in a previous population-based household study (BCPP, 2013-2018). We determined the variable loop (V1-V5) length and net charge patterns using the Variable Region Characteristics (VC) tool in the LANL HIV sequence database (hiv.lanl. gov). VC were stratified by bNAb resistance predicted using the bNAb-ReP algorithm (https://github.com/RedaRawi/bNAb-ReP). Wilcoxon ranksum test was used for assessment of variables between predicted bnAb resistance or sensitivity. We also assessed the presence of signature mutations associated with predicted resistance. Results: A total of 140 consensus sequences were included in this analysis. Median log viral load (VL) of participants was 3.9 (Q1, Q3: 3.2, 4.4), median age

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CROI 2024