HIV-1 coreceptor switch during 2 years of structured treatment interruptions

2013 ◽  
Vol 32 (12) ◽  
pp. 1565-1570 ◽  
Author(s):  
S. Baroncelli ◽  
C. M. Galluzzo ◽  
M. Andreotti ◽  
M. F. Pirillo ◽  
V. Fragola ◽  
...  
Keyword(s):  
Treatment Interruptions ◽  
Coreceptor Switch ◽  
Hiv 1

High intrapatient HIV-1 evolutionary rate is associated with CCR5-to-CXCR4 coreceptor switch

2013 ◽  
Vol 19 ◽  
pp. 369-377 ◽  
Author(s):  
Mattias Mild ◽  
Rebecca R. Gray ◽  
Anders Kvist ◽  
Philippe Lemey ◽  
Maureen M. Goodenow ◽  
...  
Keyword(s):  
Evolutionary Rate ◽  
Coreceptor Switch ◽  
Cxcr4 Coreceptor ◽  
Hiv 1

scholarly journals Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir

2021 ◽  
Vol 17 (6) ◽  
pp. e1009686
Author(s):  
Taina T. Immonen ◽  
Christine M. Fennessey ◽  
Leslie Lipkey ◽  
Abigail Thorpe ◽  
Gregory Q. Del Prete ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Viral Replication ◽  
Rhesus Macaques ◽  
Treatment Strategies ◽  
Viral Reservoir ◽  
Virus Population ◽  
Analytical Treatment ◽  
Treatment Interruptions ◽  
The Impact ◽  
Hiv 1

Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI.

The Strategy of Immunologic Control of HIV-1 with Structured Treatment Interruptions (STIs)

2001 ◽  
Vol 1 (1) ◽  
pp. 11-17 ◽  
Author(s):  
Ronald Moss ◽  
Fred Jensen ◽  
Dennis Carlo ◽  
Mark. Wallace
Keyword(s):  
Treatment Interruptions ◽  
Immunologic Control ◽  
Hiv 1

scholarly journals Evolution of CCR5 Use before and during Coreceptor Switching

2008 ◽  
Vol 82 (23) ◽  
pp. 11758-11766 ◽  
Author(s):  
Mia Coetzer ◽  
Rebecca Nedellec ◽  
Janelle Salkowitz ◽  
Sherry McLaughlin ◽  
Yi Liu ◽  
...  
Keyword(s):  
Envelope Gene ◽  
Virus Population ◽  
Ccr5 Expression ◽  
Immunodeficiency Virus ◽  
Coreceptor Switch ◽  
Transmitted Sequence ◽  
Rapid Divergence ◽  
Selective Forces ◽  
Hiv 1

ABSTRACT The envelope gene (env) of human immunodeficiency virus type 1 (HIV-1) undergoes rapid divergence from the transmitted sequence and increasing diversification during the prolonged course of chronic infection in humans. In about half of infected individuals or more, env evolution leads to expansion of the use of entry coreceptor from CCR5 alone to CCR5 and CXCR4. The stochastic nature of this coreceptor switch is not well explained by host selective forces that should be relatively constant between infected individuals. Moreover, differences in the incidence of coreceptor switching among different HIV-1 subtypes suggest that properties of the evolving virus population drive the switch. We evaluated the functional properties of sequential env clones from a patient with evidence of coreceptor switching at 5.67 years of infection. We found an abrupt decline in the ability of viruses to use CCR5 for entry at this time, manifested by a 1- to 2-log increase in susceptibility to CCR5 inhibitors and a reduced ability to infect cell lines with low CCR5 expression. There was an abnormally rapid 5.4% divergence in env sequences from 4.10 to 5.76 years of infection, with the V3 and V4/V5 regions showing the greatest divergence and evidence of positive selection. These observations suggest that a decline in the fitness of R5 virus populations may be one driving force that permits the emergence of R5X4 variants.

Selection of drug-resistant HIV-1 mutants in response to repeated structured treatment interruptions

AIDS ◽  
2002 ◽  
Vol 16 (6) ◽  
pp. 895-899 ◽  
Author(s):  
Javier Martinez-Picado ◽  
Kristina Morales-Lopetegi ◽  
Terri Wrin ◽  
Julia G. Prado ◽  
Simon D. W. Frost ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Treatment Interruptions ◽  
Hiv 1 ◽  
Selection Of

scholarly journals Structured treatment interruptions (STIs) in HIV-1 infected pediatric populations increases interferon gamma production and reduces viremia

Vaccine ◽  
2008 ◽  
Vol 26 (24) ◽  
pp. 3086-3089 ◽  
Author(s):  
William Borkowsky ◽  
Ram Yogev ◽  
Petronella Muresan ◽  
Elizabeth McFarland ◽  
Lisa Frenkel ◽  
...  
Keyword(s):  
Interferon Gamma ◽  
Treatment Interruptions ◽  
Pediatric Populations ◽  
Hiv 1

scholarly journals Modest de novo Reactivation of Single HIV-1 Proviruses in Peripheral CD4+ T Cells by Romidepsin

2021 ◽  
Vol 1 ◽  
Author(s):  
Kathrine Kjær ◽  
Steffen Leth ◽  
Christina V. Konrad ◽  
Jesper D. Gunst ◽  
Rasmus Nymann ◽  
...  
Keyword(s):  
Clinical Trials ◽  
T Cells ◽  
De Novo ◽  
Viral Rna ◽  
Viral Reservoir ◽  
Latent Reservoir ◽  
Host Immune System ◽  
Analytical Treatment ◽  
Treatment Interruptions ◽  
Hiv 1

A cure for human immunodeficiency virus (HIV-1) is restricted by the continued presence of a latent reservoir of memory CD4+ T cells with proviruses integrated into their DNA despite suppressive antiretroviral therapy (ART). A predominant strategy currently pursued in HIV-1 cure-related research is the “kick and kill” approach, where latency reversal agents (LRAs) are used to reactivate transcription from integrated proviruses. The premise of this approach is that “kicking” latent virus out of hiding allows the host immune system to recognize and kill infected cells. Clinical trials investigating the efficacy of LRAs, such as romidepsin, have shown that these interventions do induce transient spikes in viral RNA in HIV-1-infected individuals. However, since these trials failed to significantly reduce viral reservoir size or significantly delay time to viral rebound during analytical treatment interruptions, it is questioned how much each individual latent provirus is actually “kicked” to produce viral transcripts and/or proteins by the LRA. Here, we developed sensitive and specific digital droplet PCR-based assays with single-provirus level resolution. Combining these assays allowed us to interrogate the level of viral RNA transcripts from single proviruses in individuals on suppressive ART with or without concomitant romidepsin treatment. Small numbers of proviruses in peripheral blood memory CD4+ T cells were triggered to become marginally transcriptionally active upon romidepsin treatment. These novel assays can be applied retrospectively and prospectively in HIV-1 cure-related clinical trials to gain crucial insights into LRA efficacy at the single provirus level.

Emergence of drug-resistant HIV-1 variants in patients undergoing structured treatment interruptions

AIDS ◽  
2002 ◽  
Vol 16 (17) ◽  
pp. 2342-2344 ◽  
Author(s):  
Becky Schweighardt ◽  
Gabriel M Ortiz ◽  
Robert M Grant ◽  
Melissa Wellons ◽  
G Diego Miralles ◽  
...  
Keyword(s):  
Drug Resistant ◽  
Treatment Interruptions ◽  
Hiv 1

scholarly journals Early antiretroviral therapy in neonates with HIV-1 infection restricts viral reservoir size and induces a distinct innate immune profile

2019 ◽  
Vol 11 (520) ◽  
pp. eaax7350 ◽  
Author(s):  
Pilar Garcia-Broncano ◽  
Shivaali Maddali ◽  
Kevin B. Einkauf ◽  
Chenyang Jiang ◽  
Ce Gao ◽  
...  
Keyword(s):  
T Cell ◽  
Antiretroviral Therapy ◽  
Evolutionary Dynamics ◽  
T Cell Response ◽  
Innate Immune ◽  
Viral Reservoir ◽  
Viral Control ◽  
Immune Profile ◽  
Treatment Interruptions ◽  
Hiv 1

Neonatal HIV-1 infection is associated with rapidly progressive and frequently fatal immune deficiency if left untreated. Immediate institution of antiretroviral therapy (ART), ideally within hours after birth, may restrict irreversible damage to the developing neonatal immune system and possibly provide opportunities for facilitating drug-free viral control during subsequent treatment interruptions. However, the virological and immunological effects of ART initiation within hours after delivery have not been systematically investigated. We examined a unique cohort of neonates with HIV-1 infection from Botswana who started ART shortly after birth and were followed longitudinally for about 2 years in comparison to control infants started on treatment during the first year after birth. We demonstrate multiple clear benefits of rapid antiretroviral initiation, including an extremely small reservoir of intact proviral sequences, a reduction in abnormal T cell immune activation, a more polyfunctional HIV-1–specific T cell response, and an innate immune profile that displays distinct features of improved antiviral activity and is associated with intact proviral reservoir size. Together, these data offer rare insight into the evolutionary dynamics of viral reservoir establishment in neonates and provide strong empirical evidence supporting the immediate initiation of ART for neonates with HIV-1 infection.

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