Human Immunodeficiency Virus (HIV)-Antibody Repertoire Estimates Reservoir Size and Time of Antiretroviral Therapy Initiation in Virally Suppressed Perinatally HIV-Infected Children

Rocca, Salvatore; Zangari, Paola; Cotugno, Nicola; Rossi, Anita De; Ferns, Bridget; Petricone, Davide; Rinaldi, Stefano; Giaquinto, Carlo; Bernardi, Stefania; Rojo, Pablo; Rossi, Paolo; Pahwa, Savita; Nastouli, Eleni; Palma, Paolo; Klein, Nigel; Gibb, Diana; Watters, Sarah A.; Chan, M.K.; McCoy, Laura E; Babiker, Abdel; Marcelin, Anne‐Geneviève; Cálvez, Vincent; Muñoz, Mercedes; Wahrén, Britta; Foster, Caroline; Cotton, Mark F.; Robb, Merlin L.; Ananworanich, Jintanat; Claiden, Polly; Pillay, Deenan; Persaud, Deborah; Boer, Rob J. de; Schröter, Juliane; Anelone, Anet J. N.; Puthanakit, Thanyawee; Ceci, Adriana; Giannuzzi, Viviana; Luzuriaga, Kathrine; Chomont, Nicolas; Cameron, Mark J.; Cancrini, Caterina; Yates, Andrew J.; Kuhn, Louise; Violari, Avy; Otwombe, Kennedy; Pepponi, Ilaria; Rocchi, Francesca; Tagarro, Alfredo; Lain, Maria Grazia; Vaz, Paula; Lopez, Elisa; Nhampossa, Tacita

doi:10.1093/jpids/piy080

Cited by 28 publications

(30 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A more recent publication demonstrated significant association of anti-gp160 and anti-gp41 antibody levels with HIV-1 DNA level in PBMCs [28]. In an analysis of 69 children from the EPIICAL cohort, a Western blot band intensity score correlated directly with the time of cART initiation (P < .001) and with HIV-1 DNA (P = .032) [29]. In our study, antibody level correlated more robustly with HIV-1 DNA level than with inducible virus level.…”

Section: Discussionmentioning

confidence: 94%

Clinical Correlates of Human Immunodeficiency Virus–1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years

Ransy

Hawkes

Annabi

et al. 2019

Clinical Infectious Diseases

Self Cite

View full text Add to dashboard Cite

Background The Early Pediatric Initiation Canada Child Cure Cohort (EPIC4) study is a prospective, multicenter, Canadian cohort study investigating human immunodeficiency virus–1 (HIV-1) reservoirs, chronic inflammation, and immune responses in children with perinatally acquired HIV-1 infection. The focus of this report is HIV-1 reservoirs and correlates in the peripheral blood of children who achieved sustained virologic suppression (SVS) for ≥5 years. Methods HIV-1 reservoirs were determined by measuring HIV-1 DNA in peripheral blood mononuclear cells and inducible cell-free HIV-1 RNA in CD4+ T-cells by a prostratin analogue stimulation assay. HIV serology was quantified by signal-to-cutoff ratio (S/CO). Results Of 228 enrolled participants, 69 achieved SVS for ≥5 years. HIV-1 DNA, inducible cell-free HIV-1 RNA, and S/COs correlated directly with the age of effective combination antiretroviral therapy (cART) initiation (P < .001, P = .036, and P < .001, respectively) and age when SVS was achieved (P = .002, P = .038, and P < .001, respectively) and inversely with the proportion of life spent on effective cART (P < .001, P = .01, and P < .001, respectively) and proportion of life spent with SVS (P < .001, P = .079, and P < .001, respectively). Inducible cell-free HIV-1 RNA correlated with HIV-1 DNA, most particularly in children with SVS, without virologic blips, that was achieved with the first cART regimen initiated prior to 6 months of age (rho = 0.74; P = .037) or later (rho = 0.87; P < .001). S/COs correlated with HIV-1 DNA (P = .003), but less so with inducible cell-free HIV-1 RNA (P = .09). Conclusions The prostratin analogue stimulation assay, with its lower blood volume requirement, could be a valuable method for evaluating inducible HIV-1 reservoirs in children. Standard commercial HIV serology may be a practical initial indirect measure of reservoir size in the peripheral blood of children with perinatally acquired HIV-1 infection.

show abstract

Section: Discussionmentioning

confidence: 94%

Clinical Correlates of Human Immunodeficiency Virus–1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years

Ransy

Hawkes

Annabi

et al. 2019

Clinical Infectious Diseases

Self Cite

View full text Add to dashboard Cite

show abstract

“…In the pediatric context, the model of early treatment showed a reduction of HIV viral reservoirs in isolated cases of post-treatment interruption of HIV viral control [105,106,107]. In line with this, we identified possible combined immune therapeutic interventions aiming at HIV-1 remission in perinatally HIV-1 infected children treated early after birth [108].…”

Section: Viral Modulation Of Dnam-1 and Its Ligandsmentioning

confidence: 95%

DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?

Cifaldi

Doria

Cotugno

et al. 2019

IJMS

Self Cite

View full text Add to dashboard Cite

Natural Killer (NK) cells play a critical role in host defense against viral infections. The mechanisms of recognition and killing of virus-infected cells mediated by NK cells are still only partially defined. Several viruses induce, on the surface of target cells, the expression of molecules that are specifically recognized by NK cell-activating receptors. The main NK cell-activating receptors involved in the recognition and killing of virus-infected cells are NKG2D and DNAM-1. In particular, ligands for DNAM-1 are nectin/nectin-like molecules involved also in mechanisms allowing viral infection. Viruses adopt several immune evasion strategies, including those affecting NK cell-mediated immune surveillance, causing persistent viral infection and the development of virus-associated diseases. The virus’s immune evasion efficacy depends on molecules differently expressed during the various phases of infection. In this review, we overview the molecular strategies adopted by viruses, specifically cytomegalovirus (CMV), human immunodeficiency virus (HIV-1), herpes virus (HSV), Epstein-Barr virus (EBV) and hepatitis C virus (HCV), aiming to evade NK cell-mediated surveillance, with a special focus on the modulation of DNAM-1 activating receptor and its ligands in various phases of the viral life cycle. The increasing understanding of mechanisms involved in the modulation of activating ligands, together with those mediating the viral immune evasion strategies, would provide critical tools leading to design novel NK cell-based immunotherapies aiming at viral infection control, thus improving cure strategies of virus-associated diseases.

show abstract

“…Specific antibody responses were measured with 20 μL of thawed plasma by enzyme immunoassay according to the manufacturer's instructions (Western blot [WB] kit 2.2, MP Diagnostics, Singapore), against 10 HIV viral proteins (gp160, gp120, p66, p55, p51, gp41, p39, p31, p24, and p17). Methods of analyzing the WB strips have been previously published ( 15 ). When the gray-scale value of each antigen was ≥50, 10–49, or 0–9% of those calculated in the strong positive control for the same antigen, the corresponding value was assigned a score 1, 0.5, or 0, respectively ( Figure 3C , left panel).…”

Section: Methodsmentioning

confidence: 99%

HIV Reservoir Decay and CD4 Recovery Associated With High CD8 Counts in Immune Restored Patients on Long-Term ART

et al. 2020

View full text Add to dashboard Cite

Background: Whether varying CD8 counts influence the human immunodeficiency virus (HIV) reservoir and CD4 restoration in patients with CD4 counts ≥ 500 cells/µL after long-term antiretroviral therapy (ART) remains unknown. In this study, we analyzed relationships between CD8 levels and viral reservoir decay or CD4 recovery in immune restored patients on long-term ART. Methods: Chronic HIV-infected patients who received 5 years of ART with CD4 counts ≥ 500 cells/µL were grouped according to CD8 counts: CD8 <500 (Group 1), 500-1,000 (Group 2), and ≥1,000 cells/µL (Group 3). CD4 recovery, viral decay, CD8 T-cell function, and their correlations were analyzed during ART among the three groups. Results: Dynamics of viral decay and CD4 recovery were different among the three groups. Both viral decay and CD4 recovery were higher in Group 3 than the other two groups after 5 years of ART, mainly during years 3-5 of ART. Higher expression levels of Ki67 while PD-1 levels were lower on CD8 T-cells in Group 3 compared with the other groups, and Group 3 showed stronger CD8 T-cells functional capacity after 3 years of ART. Reduced HIV DNA levels and increased CD4 counts between years 3 and 5 of ART were positively correlated with CD8 counts and function. Conclusions: High CD8 counts are beneficial for persistent viral decay and CD4 recovery in immune restored patients during long-term ART.

show abstract

Human Immunodeficiency Virus (HIV)-Antibody Repertoire Estimates Reservoir Size and Time of Antiretroviral Therapy Initiation in Virally Suppressed Perinatally HIV-Infected Children

Abstract: Western blot score can estimate HIV-DNA size and timing of ART initiation in long-term virally suppressed children. This rapid, inexpensive, and easily reproducible tool can provide useful information to identify potential candidates for HIV remission studies.

Cited by 28 publications

References 21 publications

Clinical Correlates of Human Immunodeficiency Virus–1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years

Clinical Correlates of Human Immunodeficiency Virus–1 (HIV-1) DNA and Inducible HIV-1 RNA Reservoirs in Peripheral Blood in Children With Perinatally Acquired HIV-1 Infection With Sustained Virologic Suppression for at Least 5 Years

DNAM-1 Activating Receptor and Its Ligands: How Do Viruses Affect the NK Cell-Mediated Immune Surveillance during the Various Phases of Infection?

HIV Reservoir Decay and CD4 Recovery Associated With High CD8 Counts in Immune Restored Patients on Long-Term ART

Contact Info

Product

Resources

About