The ANRS Rhiviera consortium

What are the objectives of the Rhiviera consortium?

The objectives of ANRS Rhiviera are to :

1. understand the mechanisms underlying control of infection without treatment,
2. identify predictive markers of control or viral relapse after treatment interruption,
3. develop strategies allowing a large majority of HIV-infected patients to achieve HIV remission.

To fulfil these goals and objectives ANRS Rhiviera is conducting ambitious translational projects, through public and private partnerships, to gain knowledge on the establishment of cellular HIV reservoirs and body sanctuaries, to develop technologies and markers to identify and evaluate the reservoirs, as well as to characterize immune responses able to control or eliminate the infected cells. ANRS RHIVIERA focuses on the benefits achieved through early cART initiation, and also tries to identify optimal drug combinations ensuring optimal diffusion in tissues that may further limit the establishment and replenishment of the reservoir and preserve immune responses. These studies rely on the combination of basic and clinical research and the access to unique cohorts of HIV-infected individuals and equivalent models on non-human primates.

ANRS Rhiviera is now engaging in pre-clinical and clinical proof of principle studies to explore some of the potential clues arising from the overall research program.

Rhiviera: on the road to cure for people living with HIV

Watch the Rhiviera consortium presentation by Asier Saez-Cirion, Institut Pasteur, Paris

Latest project news

2025: Discovery of a post-transcriptional block in nucleocytoplasmic export of viral RNA in cellular reservoirs

Antiretroviral therapies (ART) can effectively block HIV-1 replication in individuals living with HIV. However, they are not curative and must be taken for life. The virus can remain latent in cellular reservoirs. It is replication-competent but transcriptionally silent. This is a major obstacle to eradication and to reaching cure.

While HIV-1 latency is well characterised at transcriptional level, little is known about post-transcriptional mechanisms and their contribution to reactivation. Key factors are able to control HIV-1 transcriptional inhibition and reactivation. The viral protein Rev in quiescent cells controls the nucleocytoplasmic export of spliced and unspliced messenger RNA. This is a potential target for therapies aimed at reactivating HIV-1 in order to purge reservoirs (the “shock and kill” approach).

ANRS MIE co-funded- work carried out by European researchers has identified a post-transcriptional regulation of unspliced HIV-1 RNA by host factors MATR3 and MTR4, and the viral protein Rev. This is a previously uncharacterised post-transcriptional block in nucleocytoplasmic export, which plays a crucial role in the latency and reactivation of HIV-1.

The team demonstrated nuclear retention of unspliced RNA in ex vivo cell cultures from 22 ART-treated people with HIV. These findings highlight a reversible post-transcriptional block to viral RNA nuclearcytoplasmic export that may be relevant to the design of curative interventions.

The Rhiviera consortium’s objectives achieved by 2024:

• Publication of the princeps manuscript of the primate-VISCONTI study showing the benefit of two years of ART initiated 4 weeks vs 6 months after infection in promoting post-treatment SIV control in SIVmac251 infected macaques  (Passaes et al Nat Com, 2024). To find out more, read the press release.
• Start of inclusion in the ANRS 176 RHIVIERA 02 trial in April 2024.

The Rhiviera consortium’s objectives achieved by 2023:

• Identification of a new family of broadly neutralizing antibodies in a post-treatment controller from the ANRS VISCONTI study (Molinos-Albert et al, Cell Host&Microbe 2023 ; Nat Com 2022).
• IInitiation of the ANRS 175 RHIVIERA 01 trial in March 2023: 16 participants have been enrolled ed. The primary objective of the trial is to evaluate the probability of control of HIV infection, defined as a viral load (VL) < 400 cp/mL, following an analytical interruption of antiretroviral treatment (IAT) in early-treated participants from the ANRS CO6 PRIMO cohort with the MHC B35/53 Bw4TTC2 genotype.
• Funding obtained for the project Development of an adjuvanted mRNA lipid nanoparticle (LNP) vaccine platform to induce effective anti-HIV immunity. The development of innovative approaches to combat HIV infection, including prophylactic and therapeutic vaccines, remains a priority if the HIV/AIDS pandemic is to be brought to an end. The mRNA lipid nanoparticle (LNP) platform shows very promising potential for vaccination. However, there is evidence that its immunogenicity and long-term efficacy need to be enhanced, which is usually achieved through the effects of adjuvants. The aim here is to develop and evaluate the reactogenicity and potential for inducing effective HIV/SIV-specific immunity of a vaccine platform combining mRNA-LNP and a STING agonist as adjuvant (principal investigator: Victor Appay) (ANRS MIE funding evaluated by CSS11 “Basic research on HIV/AIDS: from virus to host”).

Find out more about Rhiviera Read the press release on the p-VISCONTI study