Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART

Pasternak, Alexander; Grijsen, Marlous L.; Wit, Ferdinand W. N. M.; Bakker, Margreet; Jurriaans, Suzanne; Prins, Jan M.; Berkhout, Ben

doi:10.1172/jci.insight.134196

Cited by 70 publications

(66 citation statements)

References 73 publications

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“…Li et al reported that both NNRTI-based ART regimen and lower levels of cell-associated HIV RNA were associated with a longer time to viral rebound [164]. Our group recently reported that cell-associated HIV RNA was predictive of both time to and magnitude of viral rebound after discontinuation of ART initiated during primary HIV infection [165]. Although ART regimen was not directly associated with time to rebound in that study, our finding that levels of cell-associated HIV RNA and DNA were lower in individuals treated with NNRTI-based regimens [148] argues that further research is needed to determine the influence of ART composition on the clinical measures of the reservoir, such as the time to viral rebound.…”

Section: Future Perspectivesmentioning

confidence: 78%

Differences in HIV Markers between Infected Individuals Treated with Different ART Regimens: Implications for the Persistence of Viral Reservoirs

Darcis¹,

Berkhout

Pasternak

2020

Viruses

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In adherent individuals, antiretroviral therapy (ART) suppresses HIV replication, restores immune function, and prevents the development of AIDS. However, ART is not curative and has to be followed lifelong. Persistence of viral reservoirs forms the major obstacle to an HIV cure. HIV latent reservoirs persist primarily by cell longevity and proliferation, but replenishment by residual virus replication despite ART has been proposed as another potential mechanism of HIV persistence. It is a matter of debate whether different ART regimens are equally potent in suppressing HIV replication. Here, we summarized the current knowledge on the role of ART regimens in HIV persistence, focusing on differences in residual plasma viremia and other virological markers of the HIV reservoir between infected individuals treated with combination ART composed of different antiretroviral drug classes.

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Section: Future Perspectivesmentioning

confidence: 78%

Differences in HIV Markers between Infected Individuals Treated with Different ART Regimens: Implications for the Persistence of Viral Reservoirs

Darcis¹,

Berkhout

Pasternak

2020

Viruses

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“…Template sequence heterogeneity also often limits the design of qRT-PCR assays, which requires placement of primer and probe sequences in highly conserved regions. Third, in some diseases, tissue sites have been found to serve as better predictors of disease outcome and indicators of treatment efficacy [20], highlighting the value of sensitive detection of viruses in tissues from infected individuals or animal models. However, nucleic acid extracted from tissues can present challenges during qRT-PCR quantification due to co-purified inhibitors and significant amounts of background nucleic acid (i.e.…”

Section: Introductionmentioning

confidence: 99%

Development of a reverse transcription droplet digital PCR (RT-ddPCR) assay for sensitive detection of simian immunodeficiency virus (SIV)

Long¹,

Berkemeier²

2021

Virol J

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Background Simian immunodeficiency virus (SIV)-infected rhesus macaques constitute an excellent model of human HIV infection. Sensitive detection of SIV RNA in cell and tissue samples from infected animals subjected to treatment regimens becomes especially critical in determining which therapeutic attempts are successful, and consequently, which interventions should be prioritized in HIV cure research. Results In this report, we describe the design and testing of a Raindance ddPCR platform-based, sensitive SIV reverse transcription droplet digital PCR (RT-ddPCR) assay by exploring the combinations of various priming conditions and reverse transcriptases, and testing one-step vs. two-step procedures, to eliminate background signal(s) and enable detection and quantification of low level target signals. Conclusions Similar reaction conditions and assay validation procedures can be explored for potential development of additional assays for other applications that require sensitive detection of low-level targets in RNA samples.

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“…6 However, these measures fail as biomarkers when assessed during ART. 6 Levels of cell-associated HIV DNA 7 and RNA, 8,9 as well as features of plasmacytoid dendritic cells, 10 during ART, correlate with viral rebound after ART cessation, however, the correlations are generally modest. Thus, as of now, there are no su ciently reliable or validated biomarkers that can be leveraged to guide clinical decision making.…”

Section: Introductionmentioning

confidence: 99%

Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

Giron

Palmer

Liu

et al. 2020

Preprint

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Non-invasive biomarkers that predict HIV remission after antiretroviral therapy (ART) interruption are urgently needed. Such biomarkers can improve the safety of analytic treatment interruption (ATI) and provide mechanistic insights into the pathways involved in post-ART HIV control. We identified plasma glycomic and metabolic signatures of time-to-viral-rebound and probability-of-viral-rebound using samples from two independent cohorts. These samples include a large number of post-treatment controllers, a rare population demonstrating sustained virologic suppression after ART-cessation. The signatures remained significant after adjusting for key demographic and clinical confounders. We also confirmed a mechanistic link between biomarkers and HIV latency reactivation and myeloid inflammation in vitro. Finally, machine learning algorithms selected sets of biomarkers that predict time-to-viral-rebound with 74–76% capacity and probability-of-viral-rebound with 97.5% capacity. In summary, we fill a major gap in HIV cure research by identifying non-invasive biomarkers, with potential functional significance, that predict duration and probability of viral remission after treatment interruption.

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Cell-associated HIV-1 RNA predicts viral rebound and disease progression after discontinuation of temporary early ART

Cited by 70 publications

References 73 publications

Differences in HIV Markers between Infected Individuals Treated with Different ART Regimens: Implications for the Persistence of Viral Reservoirs

Differences in HIV Markers between Infected Individuals Treated with Different ART Regimens: Implications for the Persistence of Viral Reservoirs

Development of a reverse transcription droplet digital PCR (RT-ddPCR) assay for sensitive detection of simian immunodeficiency virus (SIV)

Non-Invasive Plasma Glycomic and Metabolic Biomarkers of Post-treatment Control of HIV

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