Frontiers in Immunology (Aug 2023)

Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in Cameroon: a contribution toward optimal pediatric HIV control strategies

  • Aude Christelle Ka’e,
  • Aude Christelle Ka’e,
  • Aubin Joseph Nanfack,
  • Georgia Ambada,
  • Georgia Ambada,
  • Maria Mercedes Santoro,
  • Desire Takou,
  • Ezechiel Ngoufack Jagni Semengue,
  • Alex Durand Nka,
  • Marie Laure Mpouel Bala,
  • Marie Laure Mpouel Bala,
  • Orphelie Ndoh Endougou,
  • Orphelie Ndoh Endougou,
  • Elise Elong,
  • Grace Beloumou,
  • Sandrine Djupsa,
  • Davy Hyacinthe Gouissi,
  • Nadine Fainguem,
  • Michel Carlos Tommo Tchouaket,
  • Michel Carlos Tommo Tchouaket,
  • Samuel Martin Sosso,
  • Daniel Kesseng,
  • Francis Ateba Ndongo,
  • Francis Ateba Ndongo,
  • Francis Ateba Ndongo,
  • Nelson Sonela,
  • Arnaud Cedric Lacmago Kamta,
  • Arnaud Cedric Lacmago Kamta,
  • Hyppolite K. Tchidjou,
  • Therese Ndomgue,
  • Therese Ndomgue,
  • Suzie Tetang Moyo Ndiang,
  • Anne Esther Njom Nlend,
  • Celine Nguefeu Nkenfou,
  • Carla Montesano,
  • Gregory Edie Halle-Ekane,
  • Giulia Cappelli,
  • Giulia Cappelli,
  • Caroline T. Tiemessen,
  • Vittorio Colizzi,
  • Vittorio Colizzi,
  • Vittorio Colizzi,
  • Francesca Ceccherini-Silberstein,
  • Carlo-Federico Perno,
  • Carlo-Federico Perno,
  • Joseph Fokam,
  • Joseph Fokam,
  • Joseph Fokam

DOI
https://doi.org/10.3389/fimmu.2023.1239877
Journal volume & issue
Vol. 14

Abstract

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Antiretroviral therapy (ART) has improved the lifespan of people living with HIV. However, their immune system remains in a state of sustained activation/inflammation, which favors viral replication and depletion of helper T-cells with varying profiles according to ART-response. We herein sought to ascertain the inflammatory profile of adolescents living with perinatal HIV-1 infection (ALPHI) receiving ART in an African context. In this cross-sectional and comparative study among ART-experienced ALPHI in Yaoundé-Cameroon, HIV-1 RNA was measured by Abbott Real-time PCR; CD4 cells were enumerated using flow cytometry; serum cytokines were measured by ELISA; HIV-1 proviral DNA was genotyped by Sanger-sequencing; and archived drug resistance mutations (ADRMs) were interpreted using Stanford HIVdb.v9.0.1. Overall, 73 adolescents were enrolled (60 ALPHI and 13 HIV-1 negative peers) aged 15 (13-18) years; 60.00% were female. ART median duration was 92 (46-123) months; median viral load was 3.99 (3.17-4.66) RNA Log10 (copies)/mL and median CD4 count was 326 (201-654) cells/mm3. As compared to HIV-negative adolescents, TNFα was highly expressed among ALPHI (p<0.01). Following a virological response, inflammatory cytokines (IFNγ and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammation-related cytokines (IL-6 and IL-1β) were highly expressed with viral suppression (VS) vs. virological failure (VF), while the chemokine CCL3 was highly expressed with VF (p<0.01). Regarding the immune response, the inflammatory cytokine TNFα was highly expressed in those that are immunocompetent (CD4≥500 cell/mm3) vs. immunocompromised (CD4<500 cell/mm3), p ≤ 0.01; while chemokine CCL2 was highly expressed in the immunocompromised (p<0.05). In the presence of ADRMs, IL-4 and CCL3 were highly expressed (p=0.027 and p=0.043 respectively). Among ART-experienced ALPHI in Cameroon, the TNFα cytokine was found to be an inflammatory marker of HIV infection; IFNγ, IL-1β, IL-6, and IL-12 are potential immunological markers of VS and targeting these cytokines in addition to antiretroviral drugs may improve management. Moreover, CCL3 and CCL2 are possible predictors of VF and/or being immunocompromised and could serve as surrogates of poor ART response.

Keywords