Authors:
Aubin Joseph Nanfack
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.
Date:
2022-11-30
