Abstract :
[en] The human immunodeficiency virus (HIV), the causative agent of acquired
immunodeficiency syndrome (AIDS), remains a significant public health challenge. In
Belgium, 1 to 2 new cases are diagnosed daily. Since the introduction of antiretroviral
therapy (ART) in 1996, the life expectancy and quality of life of people with HIV (PWH)
have improved. However, a curative treatment for HIV continues to be elusive, as
lifelong adherence to ART is required to prevent a rebound of viremia upon treatment
interruption. One of the main obstacles to curing HIV is the presence of residual
viremia. This presence is attributed to two mechanisms: the ability of the virus to
remain latent in certain infected cells and the potential for ongoing viral replication
despite ART, particularly in tissues where antiretroviral drug concentrations may be
insufficient to achieve full viral suppression. Clinical studies that investigated the
effects of adding antiretroviral drugs to the existing regimen (ART intensification) on
virological markers have yielded mixed results. Some studies suggested that residual
viral replication may persist in certain individuals, while others reported no detectable
effect. Understanding these mechanisms and developing strategies to address them
are essential steps towards achieving an HIV cure.
This dissertation presents two clinical studies conducted at the University Hospital of
Liège to investigate the impact of ART intensification and simplification on HIV
persistence. The first study examined whether intensifying treatment by doubling the
dolutegravir dosage could further suppress viral replication and reduce HIV reservoirs.
The second study evaluated the effects of switching from a triple therapy (dolutegravir,
abacavir, lamivudine) to a dual therapy (dolutegravir, lamivudine) on viral reservoirs,
residual viremia, immune activation and inflammation. This study aimed to determine
whether treatment simplification might have consequences on these parameters. A
secondary objective of both studies was to investigate the associations between HIV
persistence, inflammatory markers, immune cell populations, and clinical parameters,
providing insights into interplay between viral reservoirs and immune responses.
Together, these studies offer a comprehensive evaluation of the dynamics of HIV
persistence under different ART regimens and contribute to the ongoing debate on
the existence of residual viral replication despite effective treatment.
