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  1. Article ; Online: Ongoing HIV-1 evolution and reservoir reseeding in two elite controllers with genetically diverse peripheral proviral quasispecies.

    de Azevedo, Suwellen Sardinha Dias / Côrtes, Fernanda Heloise / Villela, Larissa M / Hoagland, Brenda / Grinsztejn, Beatriz / Veloso, Valdilea Gonçalvez / Morgado, Mariza G / Bello, Gonzalo

    Memorias do Instituto Oswaldo Cruz

    2023  Volume 118, Page(s) e230066

    Abstract: Background: Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small ... ...

    Abstract Background: Elite controllers (EC) are human immunodeficiency virus (HIV)-positive individuals who can maintain low viral loads for extended periods without antiretroviral therapy due to multifactorial and individual characteristics. Most have a small HIV-1 reservoir composed of identical proviral sequences maintained by clonal expansion of infected CD4+ T cells. However, some have a more diverse peripheral blood mononuclear cell (PBMC)-associated HIV-1 reservoir with unique sequences.
    Objectives: To understand the turnover dynamics of the PBMC-associated viral quasispecies in ECs with relatively diverse circulating proviral reservoirs.
    Methods: We performed single genome amplification of the env gene at three time points during six years in two EC with high intra-host HIV DNA diversity.
    Findings: Both EC displayed quite diverse PBMCs-associated viral quasispecies (mean env diversity = 1.9-4.1%) across all time-points comprising both identical proviruses that are probably clonally expanded and unique proviruses with evidence of ongoing evolution. HIV-1 env glycosylation pattern suggests that ancestral and evolving proviruses may display different phenotypes of resistance to broadly neutralising antibodies consistent with persistent immune pressure. Evolving viruses may progressively replace the ancestral ones or may remain as minor variants in the circulating proviral population.
    Main conclusions: These findings support that the high intra-host HIV-1 diversity of some EC resulted from long-term persistence of archival proviruses combined with the continuous reservoir's reseeding and low, but measurable, viral evolution despite undetectable viremia.
    MeSH term(s) Humans ; Proviruses/genetics ; HIV-1/genetics ; Quasispecies/genetics ; Leukocytes, Mononuclear ; HIV Infections ; Viral Load ; CD4-Positive T-Lymphocytes
    Language English
    Publishing date 2023-06-05
    Publishing country Brazil
    Document type Journal Article
    ZDB-ID 953293-6
    ISSN 1678-8060 ; 0074-0276
    ISSN (online) 1678-8060
    ISSN 0074-0276
    DOI 10.1590/0074-02760230066
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  2. Article ; Online: Comparative HIV-1 Proviral Dynamics in Two Individuals That Maintained Viral Replication Control with or without Antiretroviral Therapy following Superinfection.

    de Azevedo, Suwellen Sardinha Dias / Côrtes, Fernanda H / Villela, Larissa M / Hoagland, Brenda / Grinsztejn, Beatriz / Veloso, Valdilea G / Morgado, Mariza G / Bello, Gonzalo

    Viruses

    2022  Volume 14, Issue 12

    Abstract: The analysis of the HIV-1 proviral dynamics after superinfection in the context of both natural and antiretroviral therapy (ART)-mediated suppression could yield unique insights into understanding the persistence of viral variants that seeded the ... ...

    Abstract The analysis of the HIV-1 proviral dynamics after superinfection in the context of both natural and antiretroviral therapy (ART)-mediated suppression could yield unique insights into understanding the persistence of viral variants that seeded the infected cells at different times. In this study, we performed a longitudinal analysis of the env diversity of PBMC-associated HIV DNA quasispecies in two HIV controllers (EEC09 and VC32) that were superinfected with subtype F1 viruses several years after primoinfection with subtype B viruses. Patient EEC09 started ART soon after superinfection, while patient VC32 maintained a natural control of virus replication for at least six years following the superinfection. Our analysis revealed no significant temporal changes in the overall proportion of primo-infecting and superinfecting proviral variants over 2-3 years after superinfection in both HIV controllers. Upon the introduction of ART, individual EEC09 displayed no evidence of HIV-infected cell turnover or viral evolution, while subject VC32 displayed some level of HIV-infected cell reseeding and detectable evolution (divergence) of both viral variants. These results confirm that proviral variants that seeded the reservoir at different times throughout infection could persist for long periods under fully suppressive ART or natural viremic control, but the HIV-1 proviral dynamics could be different in both settings.
    MeSH term(s) Humans ; Proviruses/genetics ; HIV-1/genetics ; Superinfection ; Leukocytes, Mononuclear ; Virus Replication ; HIV Infections ; HIV Seropositivity ; Viral Load
    Language English
    Publishing date 2022-12-15
    Publishing country Switzerland
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2516098-9
    ISSN 1999-4915 ; 1999-4915
    ISSN (online) 1999-4915
    ISSN 1999-4915
    DOI 10.3390/v14122802
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Possible risk compensation, attitudes, and beliefs among Brazilian individuals potentially eligible for pre-exposure prophylaxis.

    Villela, Larissa M / Veloso, Valdiléa G / Hoagland, Brenda / Fernandes, Nilo M / Kallas, Esper G / Madruga, Jose V / Moreira, Ronaldo I / Grinsztejn, Beatriz / De Boni, Raquel B

    International journal of STD & AIDS

    2021  Volume 32, Issue 9, Page(s) 806–815

    Abstract: Pre-exposure prophylaxis (PrEP) prevents HIV infection among men who have sex with men (MSM) and transgender women (TGW) who are the groups that presents the high incidence risk in Brazil. This cross-sectional secondary analysis describes possible risk ... ...

    Abstract Pre-exposure prophylaxis (PrEP) prevents HIV infection among men who have sex with men (MSM) and transgender women (TGW) who are the groups that presents the high incidence risk in Brazil. This cross-sectional secondary analysis describes possible risk compensation, attitudes, and beliefs regarding the use of PrEP among 723 MSM and TGW evaluated in the
    MeSH term(s) Anti-HIV Agents/therapeutic use ; Attitude ; Brazil ; Cross-Sectional Studies ; Female ; HIV Infections/drug therapy ; HIV Infections/prevention & control ; Homosexuality, Male ; Humans ; Male ; Pre-Exposure Prophylaxis ; Sexual and Gender Minorities ; Transgender Persons
    Chemical Substances Anti-HIV Agents
    Language English
    Publishing date 2021-02-20
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 1018089-8
    ISSN 1758-1052 ; 0956-4624
    ISSN (online) 1758-1052
    ISSN 0956-4624
    DOI 10.1177/0956462421992157
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 2829: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: HIV-1 elite controllers present a high frequency of activated regulatory T and Th17 cells.

    Caetano, Diogo G / de Paula, Hury H S / Bello, Gonzalo / Hoagland, Brenda / Villela, Larissa M / Grinsztejn, Beatriz / Veloso, Valdilea G / Morgado, Mariza G / Guimarães, Monick L / Côrtes, Fernanda H

    PloS one

    2020  Volume 15, Issue 2, Page(s) e0228745

    Abstract: HIV-1 infection is characterized by generalized deregulation of the immune system, resulting in increased chronic immune activation. However, some individuals called HIV controllers (HICs) present spontaneous control of viral replication and have a more ... ...

    Abstract HIV-1 infection is characterized by generalized deregulation of the immune system, resulting in increased chronic immune activation. However, some individuals called HIV controllers (HICs) present spontaneous control of viral replication and have a more preserved immune system. Among HICs, discordant results have been observed regarding immune activation and the frequency of different T cell subsets, including Treg and Th17 cells. We evaluated T cell immune activation, differentiation and regulatory profiles in two groups of HICs-elite controllers (ECs) and viremic controllers (VCs)-and compared them to those of cART-treated individuals (cART) and HIV-1-negative (HIV-neg) individuals. ECs demonstrated similar levels of activated CD4+ and CD8+ T cells in comparison to HIV-neg, while cART and VCs showed elevated T cell activation. CD4+ T cell subset analyses showed differences only for transitional memory T cell frequency between the EC and HIV-neg groups. However, VC individuals showed higher frequencies of terminally differentiated, naïve, and stem cell memory T cells and lower frequencies of transitional memory and central memory T cells compared to the HIV-neg group. Among CD8+ T cell subsets, ECs presented higher frequencies of stem cell memory T cells, while VCs presented higher frequencies of terminally differentiated T cells compared to the HIV-neg group. HICs showed lower frequencies of total Treg cells compared to the HIV-neg and cART groups. ECs also presented higher frequencies of activated and a lower frequency of resting Treg cells than the HIV-neg and cART groups. Furthermore, we observed a high frequency of Th17 cells in ECs and high Th17/Treg ratios in both HIC groups. Our data showed that ECs had low levels of activated T cells and a high frequency of activated Treg and Th17 cells, which could restrict chronic immune activation and be indicative of a preserved mucosal response in these individuals.
    MeSH term(s) Adult ; Female ; HIV Infections/immunology ; HIV-1/physiology ; Humans ; Lymphocyte Activation ; Lymphocyte Count ; Male ; Middle Aged ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/cytology ; Th17 Cells/immunology
    Language English
    Publishing date 2020-02-05
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0228745
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Infusion Reactions After Receiving the Broadly Neutralizing Antibody VRC01 or Placebo to Reduce HIV-1 Acquisition: Results From the Phase 2b Antibody-Mediated Prevention Randomized Trials.

    Takuva, Simbarashe / Karuna, Shelly T / Juraska, Michal / Rudnicki, Erika / Edupuganti, Srilatha / Anderson, Maija / De La Grecca, Robert / Gaudinski, Martin R / Sehurutshi, Alice / Orrell, Catherine / Naidoo, Logashvari / Valencia, Javier / Villela, Larissa M / Walsh, Stephen R / Andrew, Philip / Karg, Carissa / Randhawa, April / Hural, John / Gomez Lorenzo, Margarita M /
    Burns, David N / Ledgerwood, Julie / Mascola, John R / Cohen, Myron / Corey, Lawrence / Mngadi, Kathy / Mgodi, Nyaradzo M

    Journal of acquired immune deficiency syndromes (1999)

    2021  Volume 89, Issue 4, Page(s) 405–413

    Abstract: Background: The antibody-mediated prevention (AMP) studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. ... ...

    Abstract Background: The antibody-mediated prevention (AMP) studies (HVTN 703/HPTN 081 and HVTN 704/HPTN 085) are harmonized phase 2b trials to assess HIV prevention efficacy and safety of intravenous infusion of anti-gp120 broadly neutralizing antibody VRC01. Antibodies for other indications can elicit infusion-related reactions (IRRs), often requiring premedication and limiting their application. We report on AMP study IRRs.
    Methods: From 2016 to 2018, 2699 HIV-uninfected, at-risk men and transgender adults in the Americas and Switzerland (704/085) and 1924 at-risk heterosexual women in sub-Saharan Africa (703/081) were randomized 1:1:1 to VRC01 10 mg/kg, 30 mg/kg, or placebo. Participants received infusions every 8 weeks (n = 10/participant) over 72 weeks, with 104 weeks of follow-up. Safety assessments were conducted before and after infusion and at noninfusion visits. A total of 40,674 infusions were administered.
    Results: Forty-seven participants (1.7%) experienced 49 IRRs in 704/085; 93 (4.8%) experienced 111 IRRs in 703/081 (P < 0.001). IRRs occurred more frequently in VRC01 than placebo recipients in 703/081 (P < 0.001). IRRs were associated with atopic history (P = 0.046) and with younger age (P = 0.023) in 703/081. Four clinical phenotypes of IRRs were observed: urticaria, dyspnea, dyspnea with rash, and "other." Urticaria was most prevalent, occurring in 25 (0.9%) participants in 704/085 and 41 (2.1%) participants in 703/081. Most IRRs occurred with the initial infusion and incidence diminished through the last infusion. All reactions were managed successfully without sequelae.
    Conclusions: IRRs in the AMP studies were uncommon, typically mild or moderate, successfully managed at the research clinic, and resolved without sequelae. Analysis is ongoing to explore potential IRR mechanisms.
    MeSH term(s) Antibodies, Monoclonal/therapeutic use ; Antibodies, Neutralizing ; Broadly Neutralizing Antibodies ; Female ; HIV Antibodies ; HIV Infections/drug therapy ; HIV-1 ; Humans ; Male ; Randomized Controlled Trials as Topic
    Chemical Substances Antibodies, Monoclonal ; Antibodies, Neutralizing ; Broadly Neutralizing Antibodies ; HIV Antibodies
    Language English
    Publishing date 2021-12-27
    Publishing country United States
    Document type Clinical Trial, Phase II ; 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.0000000000002892
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2442: Show issues Location:
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