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Article ; Online: Editorial: Advances in T Cell Therapeutic Vaccines for HIV.

Macatangay, Bernard J C / Landay, Alan L / Garcia, Felipe / Rinaldo, Charles R

2022 Volume 13, Page(s) 905836

MeSH term(s)	AIDS Vaccines ; HIV Infections ; HIV-1 ; Humans ; T-Lymphocytes
Chemical Substances	AIDS Vaccines
Language	English
Publishing date	2022-04-27
Publishing country	Switzerland
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.905836
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Article ; Online: TIM-3 signaling contributes to the suppressive capacity of Tregs from people with HIV on antiretroviral therapy.

Nieves-Rosado, Hector M / Jacobs, Jana L / Naqvi, Asma / Mellors, John W / Macatangay, Bernard J C / Kane, Lawrence P

Journal of leukocyte biology

2023 Volume 114, Issue 4, Page(s) 368–372

Abstract: TIM-3 expression is increased on peripheral regulatory T cells (Tregs) of virally suppressed persons with HIV-1 on antiretroviral therapy (PWH-ART). However, the relevance of TIM-3 expression in this setting is unclear. We used flow cytometry to evaluate ...

Abstract	TIM-3 expression is increased on peripheral regulatory T cells (Tregs) of virally suppressed persons with HIV-1 on antiretroviral therapy (PWH-ART). However, the relevance of TIM-3 expression in this setting is unclear. We used flow cytometry to evaluate the suppressive phenotype and signaling pathways in peripheral TIM-3- vs TIM-3+ Tregs in PWH-ART. TIM-3+ Tregs showed increased expression of IL-10 compared with persons without HIV-1. In addition, TIM-3+ Tregs displayed elevated signaling and activation, relative to TIM-3- Tregs from the same PWH-ART. Dramatically, TIM-3 blockade restrained the in vitro suppressive capacity of peripheral Tregs. Therefore, our data demonstrate not only that TIM-3 expression by Tregs is associated with an immunosuppressive response among PWH-ART, but also that TIM-3 contributes directly to the enhanced suppressive activity of Tregs in this setting.
MeSH term(s)	Humans ; Hepatitis A Virus Cellular Receptor 2/metabolism ; T-Lymphocytes, Regulatory/metabolism ; HIV Infections/drug therapy ; HIV Infections/metabolism
Chemical Substances	Hepatitis A Virus Cellular Receptor 2
Language	English
Publishing date	2023-06-07
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1093/jleuko/qiad068
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Article: Safety and Immune Responses Following Anti-PD-1 Monoclonal Antibody Infusions in Healthy Persons With Human Immunodeficiency Virus on Antiretroviral Therapy.

Open forum infectious diseases

2024 Volume 11, Issue 3, Page(s) ofad694

Abstract: Background: T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific CD4: Methods: This was a phase 1/2, randomized (4:1), double-blind, placebo-controlled study in adults with suppressed HIV on ... ...

Abstract	Background: T cells in people with human immunodeficiency virus (HIV) demonstrate an exhausted phenotype, and HIV-specific CD4 Methods: This was a phase 1/2, randomized (4:1), double-blind, placebo-controlled study in adults with suppressed HIV on antiretroviral therapy with CD4 Results: Five men were enrolled (median CD4 Conclusions: One of 4 participants exhibited increased HIV-1
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Clinical Trial
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad694
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Article ; Online: Suppressed renoprotective purines in COVID-19 patients with acute kidney injury.

Jackson, Edwin K / Kitsios, Georgios D / Lu, Michael Y / Schaefer, Caitlin M / Kessinger, Cathy J / McVerry, Bryan J / Morris, Alison / Macatangay, Bernard J C

Scientific reports

2022 Volume 12, Issue 1, Page(s) 17353

Abstract: Acute kidney injury (AKI) is common in patients hospitalized for COVID-19, complicating their clinical course and contributing to worse outcomes. Animal studies show that adenosine, inosine and guanosine protect the kidney against some types of AKI. ... ...

Abstract	Acute kidney injury (AKI) is common in patients hospitalized for COVID-19, complicating their clinical course and contributing to worse outcomes. Animal studies show that adenosine, inosine and guanosine protect the kidney against some types of AKI. However, until now there was no evidence in patients supporting the possibility that abnormally low kidney levels of adenosine, inosine and guanosine contribute to AKI. Here, we addressed the question as to whether these renoprotective purines are altered in the urine of COVID-19 patients with AKI. Purines were measured by employing ultra-high-performance liquid chromatography-tandem mass spectrometry with stable-isotope-labeled internal standards for each purine of interest. Compared with COVID-19 patients without AKI (n = 23), COVID-19 patients with AKI (n = 20) had significantly lower urine levels of adenosine (P < 0.0001), inosine (P = 0.0008), and guanosine (P = 0.0008) (medians reduced by 85%, 48% and 61%, respectively) and lower levels (P = 0.0003; median reduced by 67%) of the 2nd messenger for A
MeSH term(s)	Acute Kidney Injury ; Adenosine ; Adenosine Monophosphate ; Animals ; COVID-19 ; Guanosine/metabolism ; Guanosine Monophosphate ; Inosine/metabolism ; Purines/metabolism
Chemical Substances	Purines ; Guanosine (12133JR80S) ; Adenosine Monophosphate (415SHH325A) ; Inosine (5A614L51CT) ; Guanosine Monophosphate (85-32-5) ; Adenosine (K72T3FS567) ; purine (W60KTZ3IZY)
Language	English
Publishing date	2022-10-17
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-022-22349-z
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Article ; Online: Preserving HIV-specific T cell responses: does timing of antiretroviral therapy help?

Macatangay, Bernard J C / Rinaldo, Charles R

Current opinion in HIV and AIDS

2015 Volume 10, Issue 1, Page(s) 55–60

Abstract: Purpose of review: HIV-specific T cell responses are likely to have an important role in HIV cure strategies that aim for long-lasting viral control without antiretroviral therapy (ART). An important issue in enhancing virus-specific T cell responses is ...

Abstract	Purpose of review: HIV-specific T cell responses are likely to have an important role in HIV cure strategies that aim for long-lasting viral control without antiretroviral therapy (ART). An important issue in enhancing virus-specific T cell responses is whether timing of ART can influence their magnitude and breadth. Recent findings: Early ART is associated with lower T cell activation, preservation of T cell numbers, smaller DNA and RNA reservoir size, and, in a single study (VISCONTI), control of plasma viremia after treatment interruption. The prevention of T cell destruction by early ART is associated with relatively low anti-HIV CD8⁺ T cell responses but stronger CD4⁺ T helper function. The relatively lower CD8⁺T cell response, which is presumably due to rapid lowering of HIV antigen burden after early ART, appears sufficient to control residual viral replication as well as viral rebound upon treatment interruption. Summary: Available evidence of starting ART during acute or early HIV infection has shown benefit in both virologic and immunologic parameters despite the lower HIV-specific CD8⁺ T cell responses observed. Encouraging as this is, more extensive data are necessary to evaluate its role in combination with immunotherapeutic and latency activation strategies that are being assessed in various HIV cure-related studies.
MeSH term(s)	Anti-Retroviral Agents/administration & dosage ; Anti-Retroviral Agents/pharmacology ; CD4-CD8 Ratio ; CD8-Positive T-Lymphocytes/drug effects ; CD8-Positive T-Lymphocytes/immunology ; HIV Infections/drug therapy ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/immunology ; Humans
Chemical Substances	Anti-Retroviral Agents
Language	English
Publishing date	2015-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	2502511-9
ISSN	1746-6318 ; 1746-630X
ISSN (online)	1746-6318
ISSN	1746-630X
DOI	10.1097/COH.0000000000000124
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Article: Partial Normalization of Biomarkers of Inflammation and Immune Activation Among Virally Suppressed Men With HIV Infection and High ART Adherence.

Castillo-Mancilla, Jose R / Brown, Todd T / Palella, Frank J / Macatangay, Bernard J C / Breen, Elizabeth C / Jacobson, Lisa P / Wada, Nikolas I

Open forum infectious diseases

2020 Volume 7, Issue 4, Page(s) ofaa099

Abstract: Background: The objective of this study was to investigate whether 100% antiretroviral therapy (ART) adherence in men with HIV (MWH) is associated with normalization of concentrations of biomarkers of inflammation and immune activation compared with HIV- ...

Abstract	Background: The objective of this study was to investigate whether 100% antiretroviral therapy (ART) adherence in men with HIV (MWH) is associated with normalization of concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men. Methods: We analyzed person-visits with available biomarker data from the Multicenter AIDS Cohort Study (MACS) among MWH receiving ART with HIV RNA <50 copies/mL and among HIV-uninfected men. Self-reported adherence was classified as 100% if no missed ART doses in the past 4 days were reported. We evaluated associations between ART adherence and concentrations of 24 serum biomarkers compared with HIV-uninfected visits using a generalized gamma model, adjusting for potential confounders. Results: Person-visits (2565 from MWH reporting 100% ART adherence and 1588 from HIV-uninfected men) from a total of 1469 men were included in the analysis. Serum concentrations of interleukin-6 (IL-6), soluble interleukin-6 receptor (sIL-6R), IL-1β, interferon-γ (IFN-γ), chemokine C-C motif ligand 2 (CCL2), and CCL14 from person-visits among MWH who reported 100% adherence were similar to HIV-uninfected person-visits. Comparatively higher concentrations of 11 biomarkers and lower concentrations of 7 biomarkers were observed in person-visits from MWH who reported 100% ART adherence, compared with HIV-uninfected person-visits. Conclusions: Although MWH with virologic suppression who reported 100% ART adherence exhibited overall higher concentrations of biomarkers of inflammation and immune activation compared with HIV-uninfected men, some biomarker concentrations were similar in both groups. These findings suggest that optimal ART adherence could have clinical implications beyond achieving and sustaining viral suppression.
Language	English
Publishing date	2020-03-23
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofaa099
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Article: Rapid Emergence of Potentially Transmissible Severe Acute Respiratory Syndrome Coronavirus 2 With Resistance to Combination Monoclonal Antibody Therapy.

Open forum infectious diseases

2023 Volume 10, Issue 5, Page(s) ofad278

Abstract: Prolonged coronavirus disease 2019 may generate new viral variants. We report an immunocompromised patient treated with monoclonal antibodies who experienced rebound of viral RNA and emergence of an antibody-resistant (>1000-fold) variant containing 5 ... ...

Abstract	Prolonged coronavirus disease 2019 may generate new viral variants. We report an immunocompromised patient treated with monoclonal antibodies who experienced rebound of viral RNA and emergence of an antibody-resistant (>1000-fold) variant containing 5 mutations in the spike gene. The mutant virus was isolated from respiratory secretions, suggesting the potential for secondary transmission.
Language	English
Publishing date	2023-05-17
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad278
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Article ; Online: Antiretroviral Therapy Intensification for Neurocognitive Impairment in Human Immunodeficiency Virus.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America

2023 Volume 77, Issue 6, Page(s) 866–874

Abstract: Background: Neurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system.: Methods: A5324 was a randomized, double-blind, placebo- ... ...

Abstract	Background: Neurocognitive impairment (NCI) in people with HIV (PWH) on antiretroviral therapy (ART) is common and may result from persistent HIV replication in the central nervous system. Methods: A5324 was a randomized, double-blind, placebo-controlled, 96-week trial of ART intensification with dolutegravir (DTG) + MVC, DTG + Placebo, or Dual - Placebo in PWH with plasma HIV RNA <50 copies/mL on ART and NCI. The primary outcome was the change on the normalized total z score (ie, the mean of individual NC test z scores) at week 48. Results: Of 357 screened, 191 enrolled: 71% male, 51% Black race, 22% Hispanic ethnicity; mean age 52 years; mean CD4+ T-cells 681 cells/µL. Most (65%) had symptomatic HIV-associated NC disorder. Study drug was discontinued due to an adverse event in 15 (8%) and did not differ between arms (P = .17). Total z score, depressive symptoms, and daily functioning improved over time in all arms with no significant differences between them at week 48 or later. Adjusting for age, sex, race, study site, efavirenz use, or baseline z score did not alter the results. Body mass index modestly increased over 96 weeks (mean increase 0.32 kg/m2, P = .006) and did not differ between arms (P > .10). Conclusions: This is the largest, randomized, placebo-controlled trial of ART intensification for NCI in PWH. The findings do not support empiric ART intensification as a treatment for NCI in PWH on suppressive ART. They also do not support that DTG adversely affects cognition, mood, or weight.
MeSH term(s)	Humans ; Male ; Middle Aged ; Female ; Antiretroviral Therapy, Highly Active/methods ; HIV-1/genetics ; HIV Infections/complications ; HIV Infections/drug therapy ; Anti-HIV Agents/therapeutic use ; CD4-Positive T-Lymphocytes ; Viral Load
Chemical Substances	Anti-HIV Agents
Language	English
Publishing date	2023-05-15
Publishing country	United States
Document type	Randomized Controlled Trial ; Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1099781-7
ISSN	1537-6591 ; 1058-4838
ISSN (online)	1537-6591
ISSN	1058-4838
DOI	10.1093/cid/ciad265
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Article ; Online: MDSC: a new player in HIV immunopathogenesis.

Macatangay, Bernard J C / Landay, Alan L / Rinaldo, Charles R

AIDS (London, England)

2012 Volume 26, Issue 12, Page(s) 1567–1569

MeSH term(s)	Animals ; Biomarkers ; HIV Infections/immunology ; HIV Seropositivity ; HIV-1/immunology ; Humans ; Mice ; Myeloid Cells/immunology ; Neoplasms/immunology ; Precursor Cells, B-Lymphoid/immunology
Chemical Substances	Biomarkers
Language	English
Publishing date	2012-07-19
Publishing country	England
Document type	Editorial
ZDB-ID	639076-6
ISSN	1473-5571 ; 0269-9370 ; 1350-2840
ISSN (online)	1473-5571
ISSN	0269-9370 ; 1350-2840
DOI	10.1097/QAD.0b013e328355e682
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Article ; Online: Brief Report: Dipyridamole Decreases Gut Mucosal Regulatory T-Cell Frequencies Among People With HIV on Antiretroviral Therapy.

Mallarino-Haeger, Christina / Abebe, Kaleab Z / Jackson, Edwin K / Zyhowski, Ashley / Klamar-Blain, Cynthia / Cyktor, Joshua C / Comer, Diane / Brand, Rhonda M / Gillespie, Delbert G / Holleran, Kyle / Mellors, John W / McGowan, Ian / Riddler, Sharon A / Macatangay, Bernard J C

Journal of acquired immune deficiency syndromes (1999)

2021 Volume 85, Issue 5, Page(s) 665–669

Abstract: Background: We had previously conducted a double-blind, randomized placebo-controlled, partial cross-over trial showing that 12 weeks of dipyridamole decreased CD8 T-cell activation among treated HIV(+) individuals by increasing extracellular adenosine ... ...

Abstract	Background: We had previously conducted a double-blind, randomized placebo-controlled, partial cross-over trial showing that 12 weeks of dipyridamole decreased CD8 T-cell activation among treated HIV(+) individuals by increasing extracellular adenosine levels. Methods: In this substudy, rectosigmoid biopsies were obtained from 18 participants (9 per arm), to determine whether 12 weeks of dipyridamole affects mucosal immune cells. Participants randomized to placebo were then switched to dipyridamole for 12 weeks while the treatment arm continued dipyridamole for another 12 weeks. We evaluated T-cell frequencies and plasma markers of microbial translocation and intestinal epithelial integrity. Linear regression models on log-transformed outcomes were used for the primary 12-week analysis. Results: Participants receiving dipyridamole had a median 70.2% decrease from baseline in regulatory T cells (P = 0.007) and an 11.3% increase in CD8 T cells (P = 0.05). There was a nonsignificant 10.80% decrease in plasma intestinal fatty acid binding protein levels in the dipyridamole arm compared with a 9.51% increase in the placebo arm. There were no significant differences in plasma levels of β-D-glucan. In pooled analyses, there continued to be a significant decrease in regulatory T cells (-44%; P = 0.004). There was also a trend for decreased CD4 and CD8 T-cell activation. Conclusion: Increasing extracellular adenosine levels using dipyridamole in virally suppressed HIV (+) individuals on antiretroviral therapy can affect regulation of gut mucosal immunity.
MeSH term(s)	Adenosine/metabolism ; Anti-HIV Agents/therapeutic use ; Biopsy ; CD8-Positive T-Lymphocytes/drug effects ; Cross-Over Studies ; Dipyridamole/pharmacology ; Female ; Flow Cytometry ; HIV Infections/drug therapy ; Humans ; Intestinal Mucosa/drug effects ; Intestinal Mucosa/immunology ; Intestinal Mucosa/metabolism ; Intestinal Mucosa/pathology ; Lymphocyte Activation/drug effects ; Male ; Middle Aged ; T-Lymphocytes, Regulatory/drug effects
Chemical Substances	Anti-HIV Agents ; Dipyridamole (64ALC7F90C) ; Adenosine (K72T3FS567)
Language	English
Publishing date	2021-01-13
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
ZDB-ID	645053-2
ISSN	1944-7884 ; 1077-9450 ; 0897-5965 ; 0894-9255 ; 1525-4135
ISSN (online)	1944-7884 ; 1077-9450
ISSN	0897-5965 ; 0894-9255 ; 1525-4135
DOI	10.1097/QAI.0000000000002488
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