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

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 Yaounde-Cameroon, HIV-1 RNA wasmeasured 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 13HIV-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 (3.174.66) RNA Log10 (copies)/mL and median CD4 count was 326 (201-654) cells/ mm3. As compared to HIV-negative adolescents, TNFa was highly expressed among ALPHI (p<0.01). Following a virological response, inflammatory cytokines (IFNg and IL-12), anti-inflammatory cytokines (IL-4 and IL-10) and inflammationrelated cytokines (IL-6 and IL-1b) 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 TNF alpha was highly expressed in those that are immunocompetent (CD4 >= 500 cell/mm(3)) vs. immunocompromised (CD4<500 cell/mm(3)), 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 TNFa cytokine was found to be an inflammatory marker of HIV infection; IFN gamma, IL-1 beta, 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.