Persistent HIV-1 Viremia on Antiretroviral Therapy: Measurement and Mechanisms

Jacobs, Jana L.; Halvas, Elias K.; Tosiano, Melissa A.; Mellors, John W.

doi:10.3389/fmicb.2019.02383

Cited by 33 publications

(32 citation statements)

References 88 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Due to the lack of viral evolution in the released RNA-strands during blips, they are not believed to originate from replicating cells. However, some concern has been raised about how this was proven (102,124). With ART, HIV RNA strands detected during blips are not believed to infect and replicate in new cells, and are likely harmless for the infected individual.…”

Section: Discussionmentioning

confidence: 99%

Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations

Sörstedt

Carlander²,

Flamholc

et al. 2018

International Journal of Antimicrobial Agents

View full text Add to dashboard Cite

Until the introduction of dolutegravir (DTG), people living with HIV (PLWH) who have developed nucleoside reverse transcriptase inhibitor (NRTI) mutations have had few other treatment options outside of regimens based on ritonavir-boosted protease inhibitors (PI/r). Here we report treatment results among PLWH in Sweden with pre-existing NRTI mutations on antiretroviral treatment (ART) with DTG and one to two NRTIs. All PLWH on ART with DTG and one to two NRTIs with pre-existing NRTI mutations were retrospectively identified from the National InfCare HIV database. As controls, PLWH on PI/r and one to two NRTIs, matched according to Genotypic Susceptibility Score and observation time, were included. Data were collected as long as the study population was on treatment with DTG; controls were monitored for the same interval. Outcome was classified as either treatment success or failure. In total, 244 participants (122 individuals treated with DTG and 122 individuals treated with PI/r) were included. Median observation time was 78 weeks (interquartile range 50-98 weeks) for participants on DTG and 75 weeks (50-101 weeks) for individuals on PI/r. Viral failure was detected in four individuals treated with DTG and three individuals treated with PI/r, resulting in similar success rates of 96.7% and 97.5%, respectively. No new mutations were found among participants with treatment failure. DTG in combination with one to two NRTIs was as efficient as PI/r in individuals with pre-existing NRTI mutations in this setting. It may be considered an alternative to PI/r-based ART even in the presence of NRTI resistance.

show abstract

Section: Discussionmentioning

confidence: 99%

Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations

Sörstedt

Carlander²,

Flamholc

et al. 2018

International Journal of Antimicrobial Agents

View full text Add to dashboard Cite

show abstract

“…Using ultrasensitive RT-qPCR assays, most individuals with VLs below the limit of quantification of commercial assays still have detectable HIV RNA in plasma, averaging around 1-3 copies/mL [48][49][50][51][52][53][54]. A number of excellent reviews on persistent residual viremia (RV) in ART-treated individuals have been published [55][56][57][58][59][60][61][62][63], and a mathematical model of its origins has been put forward [64]. Importantly, RV can contribute to the viral rebound following ART interruption, at least in some cases [65].…”

Section: Sources Of Hiv Residual Viremia On Artmentioning

confidence: 99%

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

Darcis¹,

Berkhout

Pasternak

2020

Viruses

View full text Add to dashboard Cite

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.

show abstract

“…Most (95-98%) proviruses in individuals on long-term ART are defective, having large deletions or other lethal mutations [5][6][7][8][9]. A small subset of infected clones carry intact proviruses that can produce low-level viremia on ART [10,11] and may contribute to rebound viremia if ART is stopped [12][13][14][15]. Clones of cells that carry intact infectious proviruses, termed repliclones, are an important component of the HIV-1 reservoir and may constitute most of it.…”

Section: Introductionmentioning

confidence: 99%

Tracking HIV-1-Infected Cell Clones Using Integration Site-Specific qPCR

Brandt

Guo

Joseph

et al. 2021

Viruses

Self Cite

View full text Add to dashboard Cite

Efforts to cure HIV-1 infection require better quantification of the HIV-1 reservoir, particularly the clones of cells harboring replication-competent (intact) proviruses, termed repliclones. The digital droplet PCR assays commonly used to quantify intact proviruses do not differentiate among specific repliclones, thus the dynamics of repliclones are not well defined. The major challenge in tracking repliclones is the relative rarity of the cells carrying specific intact proviruses. To date, detection and accurate quantification of repliclones requires in-depth integration site sequencing. Here, we describe a simplified workflow using integration site-specific qPCR (IS-qPCR) to determine the frequencies of the proviruses integrated in individual repliclones. We designed IS-qPCR to determine the frequencies of repliclones and clones of cells that carry defective proviruses in samples from three donors. Comparing the results of IS-qPCR with deep integration site sequencing data showed that the two methods yielded concordant estimates of clone frequencies (r = 0.838). IS-qPCR is a potentially valuable tool that can be applied to multiple samples and cell types over time to measure the dynamics of individual repliclones and the efficacy of treatments designed to eliminate them.

show abstract

Persistent HIV-1 Viremia on Antiretroviral Therapy: Measurement and Mechanisms

Cited by 33 publications

References 88 publications

Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations

Effect of dolutegravir in combination with Nucleoside Reverse Transcriptase Inhibitors (NRTIs) on people living with HIV who have pre-existing NRTI mutations

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

Tracking HIV-1-Infected Cell Clones Using Integration Site-Specific qPCR

Contact Info

Product

Resources

About