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