EDCTP Alumni Network

Fostering excellence and collaboration in the next generation of researchers

Call Career Development Fellowship (CDF)
Programme EDCTP2
Start Date 2021-11-01
End Date 2023-05-03
Project Code TMA2020CDF-3228
Status Active

Title

Characterisation of Viral Reservoirs among HIV-1 non-B Vertically Infected Adolescents receiving Antiretroviral Therapy in Cameroon

Host Organisation

Institution Country

Current Organisation

Chantal Biya International Reference Centre (CIRCB)

Current Job Title

Researcher

Students Supervised

Type Name Title University Start Date End Date
full time Leslie Kenou MSc Protestant University of Central Africa, Yaounde, Cameroon 2022 2023
Full time Michelle Tsoptio MSc University of Dschang, Dschang, Cameroon 2022 2023

Memberships

Role Committee/board Start Date End Date

Education

Institution Degree Year
University of Rome Tor vergata, Italy PhD. 2015-04-09

Areas Of Specialisation

Human Immuno-deficiency Virus (HIV)

Grants

Publications

Authors:
Aubin Joseph Nanfack , Nanfack AJ, Ambada Ndzengue GE, Fokam J, Ka'e AC, Sonela N, Kenou L, Tsoptio M, Sagnia B, Elong E, Beloumou G, Perno CF, Colizzi V, Ndjolo A
Date:
2022-11-30
Journal:
Journal of Medical Internet Research Protocols
Content:

Background: Antiretroviral therapy (ART) can bring HIV-1 levels in blood plasma to the undetectable level and allow a

near-normal life expectancy for HIV-infected individuals. Unfortunately, ART is not curative and must be taken for life, because

within a few weeks of treatment cessation, HIV viremia rebounds in most patients except for rare elite or posttreatment controllers

of viremia. The primary source of this rebound is the highly stable reservoir of latent yet replication-competent HIV-1 proviruses

integrated into the genomic DNA of the resting memory cluster of differentiation 4 (CD4+) T cells. To achieve a cure for HIV,

understanding the cell reservoir environment is of paramount importance. The size and nature of the viral reservoir might vary

according to the timing of therapy, therapeutic response, ART duration, and immune response. The mechanisms of reservoir

maintenance generally depend on the levels/type of immune recognition; in addition, the dynamics of viral persistence are different

between pediatric and adult populations. This difference could become more evident as children grow toward adolescence.

Objective: We aim to characterize the HIV reservoirs and their variability as per the virological and immunological profiles of

HIV-1 non-B vertically infected adolescents receiving ART in Cameroon during the Adolescents' Viral Reservoirs study to

provide accurate and reliable data for HIV cure research.

Methods: This study will involve HIV-1 non-B vertically infected adolescents selected from an existing cohort in our institution.

Blood samples will be collected for analyzing immunological/virological profiles, including CD4/CD8 count, plasma viral load,

immune activation/inflammatory markers, genotyping, and quantification of HIV-1 viral reservoirs. We will equally recruit an

age-matched group of HIV-negative adolescents as control for immunological profiling.

Results: This study received funding in November 2021 and was approved by the national institutional review board in December

2021. Sample collection will start in November 2022, and the study will last for 18 months. The HIV-1 sequences generated will 

provide information on the circulating HIV-1 subtypes to guide the selection of the most appropriate ART for the participants.

The levels of immune biomarkers will help determine the immune profile and help identify factors driving persistent immune

activation/inflammation in HIV-infected adolescents compared to those in HIV-uninfected adolescents. Analysis of the virological

and immunological parameters in addition to the HIV-1 reservoir size will shed light on the characteristics of the viral reservoir

in adolescents with HIV-1 non-B infection.

Conclusions: Our findings will help in advancing the knowledge on HIV reservoirs, in terms of size and genetic variability in

adolescents living with HIV. Such evidence will also help in understanding the effects of ART timing and duration on the size

of the reservoirs among adolescents living with HIV—a unique population from whom the findings generated will largely

contribute to designing functional cure strategies.

Authors:
Aude Christelle Ka’e1,2*†, Aubin Joseph Nanfack1*†, Georgia Ambada1,3‡, Maria Mercedes Santoro2‡, Desire Takou1, Ezechiel Ngoufack Jagni Semengue1, Alex Durand Nka1, Marie Laure Mpouel Bala1,4, Orphelie Ndoh Endougou1,5, Elise Elong1, Grace Beloumou1, Sandrine Djupsa1, 11 Davy Hyacinthe Gouissi , Nadine Fainguem , Michel Carlos Tommo Tchouaket1,5, Samuel Martin Sosso1, Daniel Kesseng6, Francis Ateba Ndongo6,7,8, Nelson Sonela1, Arnaud Cedric Lacmago Kamta9,10, Hyppolite K. Tchidjou11, Therese Ndomgue1,4, Suzie Tetang Moyo Ndiang12, Anne Esther Njom Nlend13, Celine Nguefeu Nkenfou1, Carla Montesano2, Gregory Edie Halle-Ekane14, Giulia Cappelli1,15, Caroline T. Tiemessen16, Vittorio Colizzi1,2,17, Francesca Ceccherini-Silberstein2, Carlo-Federico Perno1,18 and Joseph Fokam1,4,14* , Ka’e AC, Nanfack AJ, Ambada G, Santoro MM, Takou D, Semengue ENJ, Nka AD, Bala MLM, Endougou ON, Elong E, Beloumou G, Djupsa S, Gouissi DH, Fainguem N, Tchouaket MCT, Sosso SM, Kesseng D, Ndongo FA, Sonela N, Kamta ACL, Tchidjou HK, Ndomgue T, Ndiang STM, Nlend AEN, Nkenfou CN, Montesano C, Halle-Ekane GE, Cappelli G, Tiemessen CT, Colizzi V, Ceccherini-Silberstein F, Perno C-F and Fokam J (2023) Inflammatory profile of vertically HIV-1 infected adolescents receiving ART in Cameroon: a contribution toward optimal pediatric HIV control strategies. Front. Immunol. 14:1239877. doi: 10.3389/fimmu.2023.1239877
Date:
2023-08-14
Journal:
Frontiers in Immunology
Content:

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 amongART-experiencedALPHIinYaoundé-Cameroon,HIV-1RNAwasmeasured 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, 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 inflammation- related 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 TNFa 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 TNFa cytokine was found to be an inflammatory marker of HIV infection; IFNg, IL-1b, 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.

Projects

Fellow:
Aubin Nanfack
Collaborators:
Name Country Institution
Aubin Nanfack Cameroon CIRCB
Objectives:
1- Determine HIV-1 genetic variability and drug resistance in cellular reservoirs;
2- Characterize immune activation/inflammation in adolescents vertically infected with HIV-1; 3- Evaluate the size of HIV reservoir; 
4- Evaluate the effect of antiretroviral therapy and immune response on the viral reservoir profile.
Sites:
Yaounde - Cameroon
Study Design:
We plan to conduct an observational and comparative study among adolescent living with HIV and receiving ART in Cameroon. Participants will be selected and enrolled from an existing cohort of close to 300 vertically infected adolescents recruited for the EDCTP-READY study.
Subjects:
HIV-1 non-B infected adolescents
Outcomes:
Our findings will help in advancing knowledge on HIV reservoir, in terms of size and genetic variability in adolescents living with HIV (ADLHIV). Such evidence will also help in understanding the effects of ART timing and duration on the size of reservoirs among ADLHIV, a unique population from whom findings generated will largely contribute in designing functional cure strategies in this vulnerable population. 
Start Date:
2021-11-01
End Date:
2023-10-31

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