Last data update: May 28, 2024. (Total: 46864 publications since 2009)
Records 1-3 (of 3 Records) |
Query Trace: Lipscomb JT [original query] |
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HIV immunocapture reveals particles expressed in semen under INSTI-based therapy are largely myeloid cell-derived and disparate from circulating provirus
Johnson JA , Li JF , Politch JA , Lipscomb JT , Santos Tino A , DeFelice J , Gelman M , Anderson DJ , Mayer KH . J Infect Dis 2024 As use of HIV integrase strand transfer inhibitors (INSTI) increases and formulations are being developed for maintenance therapies and chemoprophylaxis, assessing virus suppression under INSTI-based regimens in prevention-relevant biologic compartments, such as the male genital tract, is timely. We used cell-source marker virion immunocapture to examine amplification of particle RNA then assessed the phylogenetic relatedness of seminal and blood viral sequences from men with HIV who were prescribed INSTI-based regimens. Seminal plasma immunocaptures yielded amplifiable virion RNA from 13/24 (54%) men, and the sequences were primarily associated with markers indicative of macrophage and resident dendritic cell sources. Genetic distances were greatest (>2%) between seminal virions and circulating proviruses, pointing to ongoing low-level expression from tissue-resident cells. While the low levels in semen predict an improbable likelihood of transmission, viruses with large genetic distances are expressed under potent INSTI therapy and have implications for determining epidemiologic linkages if adherence is suboptimal. |
HIV reverse-transcriptase drug resistance mutations during early infection reveal greater transmission diversity than in envelope sequences.
Lipscomb JT , Switzer WM , Li JF , Masciotra S , Owen SM , Johnson JA . J Infect Dis 2014 210 (11) 1827-37 BACKGROUND: Drug resistance mutations (DRMs) can serve as distinct, non-polymorphic markers for evaluating diversity of expressed HIV-1. We screened for resistance mutations during early-acute viremia and examined the diversity in reverse transcriptase (RT) relative to envelope (env) in cases of transmitted drug resistance. METHODS: We evaluated 111 longitudinal plasma samples collected every 2-7 days from 15 individuals who seroconverted for HIV-1 infection in 1994-2000. The samples were screened with sensitive PCR assays for the commonly transmitted M41 L and K70R mutations, and for K65R, which was undetected by bulk sequencing. Mutation-positive samples were further characterized by clonal sequencing of RT and env V1-V3. RESULTS: Resistance mutations were detected in 4 of 15 seroconverters at 5-50 days of viral nucleic acid expression; most mutations disappeared around the time of seroconversion. Clonal sequencing verified low-level K65R at frequencies of 0.4%-4.9%. In each case, K65R co-existed unlinked with variants carrying 2-5 thymidine analog mutations at frequencies of 1.6%-23.0%. In one seroconverter, variants with M184 V and NNRTI mutations were also identified at first RNA expression. Each seroconverter displayed a homogeneous V1-V3 env population. CONCLUSIONS: Reverse transcriptase DRMs demonstrate that the breadth of variants in transmission may be greater than what is reflected in envelope sequences. |
Detection of low-level K65R variants in nucleoside reverse transcriptase inhibitor-naive chronic and acute HIV-1 subtype C infections.
Li JF , Lipscomb JT , Wei X , Martinson NA , Morris L , Heneine W , Johnson JA . J Infect Dis 2011 203 (6) 798-802 To substantiate reports of greater emergence of the K65R nucleoside reverse transcriptase inhibitor (NRTI) mutation in human immunodeficiency virus type 1 (HIV-1) subtype C, we examined natural low-level K65R expression in subtype C relative to subtypes B and AE. We used allele-specific polymerase chain reaction to screen HIV-1 amplified by reverse-transcription high-fidelity polymerase chain reaction from subtype C-infected South African women and infants and CRF01(subtype AE) from Thailand; all subjects were NRTI naive. We found low-level K65R of unknown clinical significance in NRTI-naive subtype C-infected women and infants at frequencies above the natural occurrence in subtypes B and AE. The frequent appearance of subtype C frameshift deletions at codon 65 supports a propensity for transcription error in this region. |
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