PMID- 36449339
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20221217
IS  - 1929-0748 (Print)
IS  - 1929-0748 (Electronic)
IS  - 1929-0748 (Linking)
VI  - 11
IP  - 11
DP  - 2022 Nov 30
TI  - Characterization of the Viral Reservoirs Among HIV-1 Non-B Vertically Infected 
      Adolescents Receiving Antiretroviral Therapy: Protocol for an Observational and 
      Comparative Study in Cameroon.
PG  - e41473
LID - 10.2196/41473 [doi]
LID - e41473
AB  - 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. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): 
      PRR1-10.2196/41473.
CI  - (c)Aubin Joseph Nanfack, Georgia Elna Ambada Ndzengue, Joseph Fokam, Aude 
      Christelle Ka'e, Nelson Sonela, Leslie Kenou, Michelle Tsoptio, Bertrand Sagnia, 
      Elise Elong, Carlo Federico Perno, Vittorio Colizzi, Alexis Ndjolo. Originally 
      published in JMIR Research Protocols (https://www.researchprotocols.org), 
      30.11.2022.
FAU - Nanfack, Aubin Joseph
AU  - Nanfack AJ
AUID- ORCID: 0000-0003-2896-0508
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
FAU - Ambada Ndzengue, Georgia Elna
AU  - Ambada Ndzengue GE
AUID- ORCID: 0000-0003-4342-5538
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
AD  - Department of Animal Biology and Physiology, University of Yaounde, Yaounde, 
      Cameroon.
FAU - Fokam, Joseph
AU  - Fokam J
AUID- ORCID: 0000-0002-1501-2763
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
AD  - Faculty of Health Science, University of Buea, Buea, Cameroon.
AD  - Faculty of Medicine and Biomedical Sciences, University of Yaounde, Yaounde, 
      Cameroon.
FAU - Ka'e, Aude Christelle
AU  - Ka'e AC
AUID- ORCID: 0000-0002-2381-4299
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
AD  - Department of Immunology, University of Rome Tor Vergata, Rome, Italy.
FAU - Sonela, Nelson
AU  - Sonela N
AUID- ORCID: 0000-0001-7137-1130
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
AD  - Medical School, University of KwaZulu-Natal, Durban, South Africa.
FAU - Kenou, Leslie
AU  - Kenou L
AUID- ORCID: 0000-0001-9881-4704
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
AD  - Department of Microbiology and Parasitology, Protestant University of Central 
      Africa, Yaounde, Cameroon.
FAU - Tsoptio, Michelle
AU  - Tsoptio M
AUID- ORCID: 0000-0001-8773-8638
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
AD  - Faculty of Medicine and Biomedical Science, University of Dschang, Dschang, 
      Cameroon.
FAU - Sagnia, Bertrand
AU  - Sagnia B
AUID- ORCID: 0000-0002-6707-8473
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
FAU - Elong, Elise
AU  - Elong E
AUID- ORCID: 0000-0002-3558-6748
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
FAU - Beloumou, Grace
AU  - Beloumou G
AUID- ORCID: 0000-0002-6870-7366
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
FAU - Perno, Carlo Federico
AU  - Perno CF
AUID- ORCID: 0000-0002-0825-5388
AD  - Bambino Gesu Children's Hospital, Rome, Italy.
FAU - Colizzi, Vittorio
AU  - Colizzi V
AUID- ORCID: 0000-0003-0007-8580
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
AD  - Department of Immunology, University of Rome Tor Vergata, Rome, Italy.
FAU - Ndjolo, Alexis
AU  - Ndjolo A
AUID- ORCID: 0000-0002-4951-9271
AD  - International Reference Center Chantal Biya, Yaounde, Cameroon.
LA  - eng
PT  - Journal Article
DEP - 20221130
PL  - Canada
TA  - JMIR Res Protoc
JT  - JMIR research protocols
JID - 101599504
PMC - PMC9752448
OTO - NOTNLM
OT  - Cameroon
OT  - HIV
OT  - adolescents
OT  - vertical infection
OT  - viral reservoirs
COIS- Conflicts of Interest: None declared.
EDAT- 2022/12/01 06:00
MHDA- 2022/12/01 06:01
PMCR- 2022/11/30
CRDT- 2022/11/30 11:53
PHST- 2022/07/27 00:00 [received]
PHST- 2022/08/19 00:00 [accepted]
PHST- 2022/11/30 11:53 [entrez]
PHST- 2022/12/01 06:00 [pubmed]
PHST- 2022/12/01 06:01 [medline]
PHST- 2022/11/30 00:00 [pmc-release]
AID - v11i11e41473 [pii]
AID - 10.2196/41473 [doi]
PST - epublish
SO  - JMIR Res Protoc. 2022 Nov 30;11(11):e41473. doi: 10.2196/41473.