scholarly journals Dynamics of HIV DNA reservoir seeding in a cohort of superinfected Kenyan women

2020 ◽  
Vol 16 (2) ◽  
pp. e1008286 ◽  
Author(s):  
Mark D. Pankau ◽  
Daniel B. Reeves ◽  
Elias Harkins ◽  
Keshet Ronen ◽  
Walter Jaoko ◽  
...  
Keyword(s):  
Hiv Dna ◽  
Kenyan Women ◽  
Dna Reservoir

scholarly journals Circulating HIV DNA Correlates With Neurocognitive Impairment in Older HIV-infected Adults on Suppressive ART

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Michelli Faria de Oliveira ◽  
Ben Murrell ◽  
Josué Pérez-Santiago ◽  
Milenka Vargas ◽  
Ronald J. Ellis ◽  
...  
Keyword(s):  
Inflammatory Markers ◽  
Neurocognitive Impairment ◽  
Neurocognitive Functioning ◽  
Neurocognitive Disorder ◽  
Prevention Strategies ◽  
Hiv Dna ◽  
Treatment And Prevention ◽  
Markers Of Inflammation ◽  
Underlying Mechanisms ◽  
Dna Reservoir

Abstract Older HIV-infected adults have a higher risk of neurocognitive impairment, but the underlying mechanisms are poorly understood. Here, we investigated the associations between levels of HIV DNA in peripheral blood, soluble markers of inflammation and cellular trafficking in blood and cerebrospinal fluid (CSF) and neurocognitive functioning among 18 younger (22–40 years) and 26 older (50–71 years) HIV-infected subjects, who were administered a comprehensive neurocognitive battery. Older HIV-infected individuals presented higher levels of inflammation in CSF and blood compared to younger individuals, but no difference was observed in HIV DNA levels. Among older participants, higher HIV DNA levels were significantly associated with more severe neurocognitive impairment (p = 0.005), particularly in the Executive Functions domain (p = 0.004). No association was observed between HIV DNA and neurocognition among younger individuals. Despite significantly increased inflammation observed in the older group, none of the inflammatory markers were associated with neurocognitive impairment among older HIV+ individuals (p > 0.05). Our study supports the involvement of peripheral HIV DNA reservoir in the pathogenesis of neurocognitive disorder during suppressive ART. Correlates of neurocognitive impairment might differ between younger and older adults, suggesting that future treatment and prevention strategies for HIV-associated neurocognitive disorders likely need to be tailored based on age.

scholarly journals Cytomegalovirus Replication in Semen Is Associated with Higher Levels of Proviral HIV DNA and CD4+T Cell Activation during Antiretroviral Treatment

2014 ◽  
Vol 88 (14) ◽  
pp. 7818-7827 ◽  
Author(s):  
Sara Gianella ◽  
Marta Massanella ◽  
Douglas D. Richman ◽  
Susan J. Little ◽  
Celsa A. Spina ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell Activation ◽  
Immune Activation ◽  
Genital Tract ◽  
Cell Activation ◽  
Future Studies ◽  
Hiv Rna ◽  
Hiv Dna ◽  
Dna Reservoir

ABSTRACTAsymptomatic cytomegalovirus (CMV) replication occurs frequently in the genital tract in untreated HIV-infected men and is associated with increased immune activation and HIV disease progression. To determine the connections between CMV-associated immune activation and the size of the viral reservoir, we evaluated the interactions between (i) asymptomatic seminal CMV replication, (ii) levels of T cell activation and proliferation in blood, and (iii) the size and transcriptional activity of the HIV DNA reservoir in blood from 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. We found that asymptomatic CMV shedding in semen was associated with significantly higher levels of proliferating and activated CD4+T cells in blood (P< 0.01). Subjects with detectable CMV in semen had approximately five times higher average levels of HIV DNA in blood CD4+T cells than subjects with no CMV. There was also a trend for CMV shedders to have increased cellular (multiply spliced) HIV RNA transcription (P= 0.068) compared to participants without CMV, but it is unclear if this transcription pattern is associated with residual HIV replication. In multivariate analysis, the presence of seminal plasma CMV (P= 0.04), detectable 2-long terminal repeat (2-LTR), and lower nadir CD4+(P< 0.01) were independent predictors of higher levels of proviral HIV DNA in blood. Interventions aimed at reducing seminal CMV and associated immune activation may be important for HIV curative strategies. Future studies of anti-CMV therapeutics will help to establish causality and determine the mechanisms underlying these described associations.IMPORTANCEAlmost all individuals infected with HIV are also infected with cytomegalovirus (CMV), and the replication dynamics of the two viruses likely influence each other. This study investigated interactions between asymptomatic CMV replication within the male genital tract, levels of inflammation in blood, and the size of the HIV DNA reservoir in 53 HIV-infected men on long-term antiretroviral therapy (ART) with suppressed HIV RNA in blood plasma. In support of our primary hypothesis, shedding of CMV DNA in semen was associated with increased activation and proliferation of T cells in blood and also significantly higher levels of HIV DNA in blood cells. These results suggest that CMV reactivation might play a role in the maintenance of the HIV DNA reservoir during suppressive ART and that it could be a target of pharmacologic intervention in future studies.

scholarly journals Subclinical Cytomegalovirus and Epstein-Barr Virus Shedding Is Associated with Increasing HIV DNA Molecular Diversity in Peripheral Blood during Suppressive Antiretroviral Therapy

2020 ◽  
Vol 94 (19) ◽  
Author(s):  
Antoine Chaillon ◽  
Masato Nakazawa ◽  
Stephen A. Rawlings ◽  
Genevieve Curtin ◽  
Gemma Caballero ◽  
...  
Keyword(s):  
Peripheral Blood ◽  
Epstein Barr Virus ◽  
Molecular Diversity ◽  
Viral Shedding ◽  
Barr Virus ◽  
Hiv Dna ◽  
Ebv Dna ◽  
Epstein Barr ◽  
Over Time ◽  
Dna Reservoir

ABSTRACT Cytomegalovirus (CMV) almost universally infects persons with HIV (PWH), and it is a driver of persistent inflammation and HIV persistence. The mechanisms underlying the association between CMV (and possibly other herpesviruses) and HIV persistence are unclear. Serially collected blood samples were obtained from men who have sex with men (MSM) who started antiretroviral therapy (ART) within 1 year of their estimated date of HIV infection (EDI). Total CMV and Epstein-Barr virus (EBV) DNA were quantified in peripheral blood mononuclear cells by droplet digital PCR (ddPCR). Deep sequencing of the HIV DNA partial env gene was performed, and the dynamics of viral diversity over time were analyzed in relation to CMV and EBV shedding status. In total, 37 MSM PWH were included and followed for a median of 23 months (IQR, 22 to 28). Participants started ART within a median of 3.1 months (IQR, 1.5 to 6.5) after EDI and remained virally suppressed thereafter. A total of 18 participants (48.6%) were classified as high EBV shedders, while 19 (51.4%) were classified as CMV shedders. In longitudinal analyses, normalized molecular diversity levels tended to increase over time among participants with detectable CMV and high EBV DNA (0.03 ± 0.02, P = 0.08), while they significantly declined among participants with no/low viral shedding (−0.04 ± 0.02, P = 0.047, interaction P < 0.01). Subclinical CMV and EBV shedding could contribute to the dynamics of the HIV DNA reservoir during suppressive ART. Whether persistent CMV/EBV replication could be targeted as a strategy to reduce the size of the latent HIV reservoir is an avenue that should be explored. IMPORTANCE As part of this study, we evaluated the molecular characteristics of the HIV DNA reservoir over time during antiretroviral treatment (ART) in relation to those of other chronic viral infections (i.e., cytomegalovirus [CMV] and Epstein-Barr virus [EBV]). We demonstrated that the presence of CMV and high-level EBV DNA in peripheral blood cells was associated with changes in HIV DNA molecular diversity. Specifically, HIV DNA molecular diversity increased over time among participants with detectable CMV and high-level EBV DNA, while it significantly declined among participants with no/low viral shedding. Although the current study design does not allow causality to be inferred, it does support the theory that persistent CMV and EBV shedding could contribute to the dynamics of the HIV DNA reservoir during suppressive ART, even when ART is initiated during the earliest phases of HIV infection.

scholarly journals Control of the HIV-1 DNA Reservoir Is Associated In Vivo and In Vitro with NKp46/NKp30 (CD335 CD337) Inducibility and Interferon Gamma Production by Transcriptionally Unique NK Cells

2017 ◽  
Vol 91 (23) ◽  
Author(s):  
Francesco Marras ◽  
Anna Casabianca ◽  
Federica Bozzano ◽  
Maria Libera Ascierto ◽  
Chiara Orlandi ◽  
...  
Keyword(s):  
Nk Cells ◽  
Interferon Gamma ◽  
Antiretroviral Treatment ◽  
Nk Cell ◽  
Transcriptional Signature ◽  
Hiv Dna ◽  
Ifn Γ ◽  
Hiv 1 ◽  
Dna Reservoir

ABSTRACT The size of lentiviral DNA reservoirs reflects the effectiveness of immune responses against lentiviruses. So far, abundant information has been gathered on the control of HIV-1 replication. Understanding the innate mechanisms contributing to containment of the HIV DNA reservoir, however, are only partly clarified and are relevant to guiding interventions for reservoir containment or eradication. We studied the contribution of natural killer (NK) cell functional features in HIV patients controlling replication either spontaneously (HIV controllers [HIC]) or after progression and antiretroviral treatment (progressor patients [PP]). An inverse correlation between HIV DNA copy numbers (either total or integrated) in circulating CD4+ cells and NK cell function was observed. Induced interferon gamma (IFN-γ) production and NKp46/NKp30 activating receptor-induced expression correlated inversely with reservoir size. The correlation was present not only for a homogeneous cohort of HIC patients but also when PP were included in the analysis. Adaptive (NKG2C+ CD57+) NK cell features were not associated with reservoir size. However, a distinct set of 370 differentially expressed transcripts was found to underlie functional differences in NK cells controlling HIV DNA reservoir size. In proof-of-principle in vitro experiments of CD4+ cell infection with HIV-1, purified NK cells with the above-mentioned functional/transcriptional features displayed 10- and 30-fold higher abilities to control HIV replication and DNA burdens in vitro, respectively, than those of other NK cells. Thus, NK cells with a specific functional and transcriptional signature contribute to control of the HIV reservoir in CD4+ cells. Their selection, expansion, and/or adoptive transfer may support strategies to eradicate HIV-1 infection or to safely deescalate antiretroviral treatment. IMPORTANCE The most relevant feature of HIV-1 infection is represented by its DNA reservoir size in the body, which guarantees lifelong infection and resumption of virus replication after antiretroviral treatment interruption. So far, there has been little success in the identification of factors contributing to HIV-1 reservoir containment. In this study, by studying quantitative total and integrated HIV-1 DNA levels and NK cells in HIV-1 patients with either progressive or nonprogressive disease, we observed that inducible IFN-γ and natural cytotoxicity receptor (NCR) expression in a specific subset of NK cells with a characteristic transcriptional signature represents a correlate for HIV-1 reservoir control. This represents an advance in our understanding of the mechanism(s) that controls the lentivirus reservoir. Monitoring, selection, expansion, and adoptive transfer of these NK cells may allow monitoring of treatment efficacy and the likelihood of reservoir control and may support protocols for HIV-1 eradication.

scholarly journals HIV DNA Reservoir Increases Risk for Cognitive Disorders in cART-Naïve Patients

PLoS ONE ◽  
2013 ◽  
Vol 8 (7) ◽  
pp. e70164 ◽  
Author(s):  
Victor G. Valcour ◽  
Jintanat Ananworanich ◽  
Melissa Agsalda ◽  
Napapon Sailasuta ◽  
Thep Chalermchai ◽  
...  
Keyword(s):  
Cognitive Disorders ◽  
Hiv Dna ◽  
Dna Reservoir

scholarly journals Correction: HIV DNA Reservoir Increases Risk for Cognitive Disorders in cART-Naïve Patients

PLoS ONE ◽  
2014 ◽  
Vol 9 (1) ◽  
Author(s):  
Victor G. Valcour ◽  
Jintanat Ananworanich ◽  
Melissa Agsalda ◽  
Napapon Sailasuta ◽  
Thep Chalermchai ◽  
...  
Keyword(s):  
Cognitive Disorders ◽  
Hiv Dna ◽  
Dna Reservoir

scholarly journals Oral ABX464 reduces the HIV DNA reservoir IN CD4+ peripheral blood T cells

2017 ◽  
Vol 3 ◽  
pp. 55
Author(s):  
J.-M. Steens ◽  
R. Cranston ◽  
J. Martinez-Picado ◽  
R. Paredes ◽  
B. Clotet ◽  
...  
Keyword(s):  
T Cells ◽  
Peripheral Blood ◽  
Hiv Dna ◽  
Dna Reservoir

scholarly journals Decay of HIV DNA in the Reservoir and the Impact of Short Treatment Interruption in Kenyan Infants

2017 ◽  
Vol 5 (1) ◽  
Author(s):  
Mark D Pankau ◽  
Dalton Wamalwa ◽  
Sarah Benki-Nugent ◽  
Kenneth Tapia ◽  
Evelyn Ngugi ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Treatment Interruption ◽  
Short Treatment ◽  
Hiv Reservoir ◽  
Hiv Dna ◽  
The Impact ◽  
Dna Reservoir

Abstract We compared change in HIV reservoir DNA following continued antiretroviral therapy (ART) vs short treatment interruption (TI) in early ART-treated Kenyan infants. While HIV DNA in the reservoir decayed with continued ART, HIV DNA levels were similar to pre-TI HIV DNA reservoir levels in most children after short TI.

Exploring Kenyan Women University Students’ Everyday Interaction with Information

2013 ◽  
Author(s):  
Brooke Shannon
Keyword(s):  
University Students ◽  
Nous Avons ◽  
Everyday Life ◽  
Information Literacy ◽  
Social Constructionist ◽  
Kenyan Women ◽  
Everyday Interaction

A social constructionist methodology was used to explore how Kenyan women university students interact with information in everyday life. Focus was on how participants interpret experiences within the historical, cultural, and material spaces they inhabit. Methods used were linguistics pragmatics, phenomenology, and hermeneutics. Conceptual implications for information literacy are discussed.Une méthodologie sociale constructioniste est utilisée pour explorer comment les étudiantes universitaires kenyanes interagissent avec l’information au quotidien. Nous avons insisté sur les façons dont les participantes interprètent leurs expériences dans les espaces historiques, culturels et matériels où elles habitent. Les méthodologies utilisées comprennent la pragmatique linguistique, la phénoménologie et l’herméneutique. Nous discutons finalement de leurs implications sur la maîtrise de l’information. 

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