Short Communication: HIV-DRLink: A Tool for Reporting Linked HIV-1 Drug Resistance Mutations in Large Single-Genome Data Sets Using the Stanford HIV Database

Shao, Wei; Boltz, Valerie F.; Hattori, Junko; Bale, Michael J.; Maldarelli, Frank; Coffin, John M.; Kearney, Mary F

doi:10.1089/aid.2020.0109

Cited by 5 publications

(3 citation statements)

References 27 publications

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“…Viral sequences that lacked all mutations listed above were classified as “genome-intact” sequences. Proviral sequences identified as “genome-intact” with this algorithm were also classified as “genome-intact” using an alternative analysis procedure ( Shao et al., 2020 ). Sequence alignments were performed using MUSCLE ( Edgar, 2004 ) and Geneious Prime 2021.0.3 ( geneious.com ).…”

Section: Methodsmentioning

confidence: 99%

Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses

Einkauf

Osborn

Gao

et al. 2022

Cell

162

225

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Summary HIV-1-infected cells that persist despite antiretroviral therapy (ART) are frequently considered “transcriptionally silent,” but active viral gene expression may occur in some cells, challenging the concept of viral latency. Applying an assay for profiling the transcriptional activity and the chromosomal locations of individual proviruses, we describe a global genomic and epigenetic map of transcriptionally active and silent proviral species and evaluate their longitudinal evolution in persons receiving suppressive ART. Using genome-wide epigenetic reference data, we show that proviral transcriptional activity is associated with activating epigenetic chromatin features in linear proximity of integration sites and in their inter- and intrachromosomal contact regions. Transcriptionally active proviruses were actively selected against during prolonged ART; however, this pattern was violated by large clones of virally infected cells that may outcompete negative selection forces through elevated intrinsic proliferative activity. Our results suggest that transcriptionally active proviruses are dynamically evolving under selection pressure by host factors.

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Section: Methodsmentioning

confidence: 99%

Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses

Einkauf

Osborn

Gao

et al. 2022

Cell

162

225

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“…RAMs had been analyzed by Sanger sequencing of RNA. All mutations were included in the HIV drug resistance database (Stanford University) to determine the level of resistance to drugs [11]. In patients with more than one resistance test, the last available was considered.…”

Section: Methods Populationmentioning

confidence: 99%

Impact of preexisting nucleos(t)ide reverse transcriptase inhibitor resistance on the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide in treatment experience patients

Micán¹,

Grela²,

Cadiñanos

et al. 2022

Aids

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Introduction:Few clinical trials and cohort studies have evaluated the efficacy of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in people with HIV (PWH) with preexisting M184V/I or other nucleos(t)ide reverse transcriptase inhibitor (NRTI) resistance-associated mutations (RAMs). Real-world data are also scarce.Methods:Retrospective review of treatment-experienced patients who started B/F/TAF in a cohort of PWH. HIV-RNA less than 50 copies/ml was analyzed at 48 weeks in an intention-to-treat (ITT) analysis (missing=failure) and per protocol analysis (patients with missing data or changes for reasons other than virological failure were excluded). Results were compared in patients with and without previous NRTI-RAMs.Results:Five hundred and six PWH were included (16.2% women). Median age and time with HIV infection were 52.3 and 18.9 years, respectively. At baseline, viral load was less than 50 copies/ml in 440 patients (86.6%). Overall, 69 (13.6%) participants had documented preexisting NRTI-RAMs: 57 (11.2%) M184V/I and 30 (5.9%) tenofovir RAMs. In the ITT analysis, 83% (420/506) had HIV-RNA less than 50 copies/ml [82.2% (359/437) and 88.4% (61/69) in persons without and with NRTI-RAMs, respectively (P = 0.2)]. In the per protocol analysis 94.2% (420/445) had HIV-RNA less than 50 copies/ml [94.4% (359/380) vs. 93.8% (61/65); P = 0.2]. A total of 61 participants were excluded from the per protocol analysis (23 missing data, 19 discontinued B/F/TAF because of toxicity, 13 for other reasons, and 6 died).Conclusion:Switching to B/F/TAF is well tolerated and effective in the real-world setting, even in patients with preexisting NRTI RAMs, such as M184V and RAMs conferring resistance to tenofovir. These results confirm the robustness of this combination.

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“…Viral sequences without any of the mutations previously mentioned were classified as intact genome sequences. An alternative analysis was used to classify a sequence as intact, as previously reported (51). Phylogenetic distances between sequences were determined through maximum-likelihood trees in MEGA and visualized with Highlighter plots.…”

Section: Methodsmentioning

confidence: 99%

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers

Gasca-Capote,

Lian,

Gao

et al. 2024

Journal of Clinical Investigation

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BACKGROUND. Persistent controllers (PCs) maintain antiretroviral-free HIV-1 control indefinitely over time, while transient controllers (TCs) eventually lose virological control. It is essential to characterize the quality of the HIV reservoir in terms of these phenotypes in order to identify the factors that lead to HIV progression and to open new avenues toward an HIV cure. METHODS.The characterization of HIV-1 reservoir from peripheral blood mononuclear cells was performed using nextgeneration sequencing techniques, such as full-length individual and matched integration site proviral sequencing (FLIP-Seq; MIP-Seq). RESULTS.PCs and TCs, before losing virological control, presented significantly lower total, intact, and defective proviruses compared with those of participants on antiretroviral therapy (ART). No differences were found in total and defective proviruses between PCs and TCs. However, intact provirus levels were lower in PCs compared with TCs; indeed the intact/ defective HIV-DNA ratio was significantly higher in TCs. Clonally expanded intact proviruses were found only in PCs and located in centromeric satellite DNA or zinc-finger genes, both associated with heterochromatin features. In contrast, sampled intact proviruses were located in permissive genic euchromatic positions in TCs.CONCLUSIONS. These results suggest the need for, and can give guidance to, the design of future research to identify a distinct proviral landscape that may be associated with the persistent control of HIV-1 without ART.

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Short Communication: HIV-DRLink: A Tool for Reporting Linked HIV-1 Drug Resistance Mutations in Large Single-Genome Data Sets Using the Stanford HIV Database

Cited by 5 publications

References 27 publications

Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses

Parallel analysis of transcription, integration, and sequence of single HIV-1 proviruses

Impact of preexisting nucleos(t)ide reverse transcriptase inhibitor resistance on the effectiveness of bictegravir/emtricitabine/tenofovir alafenamide in treatment experience patients

The HIV-1 reservoir landscape in persistent elite controllers and transient elite controllers

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