The current antiretroviral therapy (ART) has significantly improved the prognosis for those living with HIV. Although the treatment suppresses viral replication, the virus can survive in different viral reservoirs throughout the body, where it is protected against the immune system and medical interventions. Most people living with HIV must therefore be on treatment for the rest of their lives. To develop new strategies for an HIV cure, it is essential to understand how the viral reservoirs are maintained and which mechanisms regulate HIV infection, virus latency and reactivation.
Mechanisms of HIV latency and reactivation
Epigenetic regulation of both the virus and the host cell plays a key role in maintaining HIV latency and reactivation of the virus. In addition to regulation by proteins and DNA, gene expression is regulated by chemical modifications of messenger RNA (mRNA). Such modifications can affect mRNA function, subcellular localisation and their translation into protein.
Our hypothesis is that methylation of HIV-RNA and mRNA from infected host cells contribute to the regulation of HIV replication. We investigate methylation levels in viral RNA and host cell mRNA, and the mechanisms regulating these modifications. Our goal is to increase the understanding of how HIV infection and virus latency is maintained, and how the virus may be reactivated.
HIV remission after stem cell transplantation : The Oslo patient
The Oslo patient is part of the international research on long term HIV remission after allogeneic stem cell transplantation. The study covers a person who achieved sustained HIV remission after stem cell transplantation from a donor who was homozygous for the CCR5Δ32 mutation. This mutation results in the lack of a functional CCR5 coreceptor on the cell surface, making the immune cells resistant to HIV variants depending on this coreceptor to infect cells.
Through extensive analysis of blood and intestinal tissue, we investigate whether HIV reservoirs are still present after transplantation. Using methods such as droplet digital PCR (ddPCR), analysis of intact proviral HIV DNA, and quantitative viral outgrowth analyses, we investigate the levels of HIV DNA and replication competent virus. The study provides important insight into mechanisms behind long term HIV remission, and contributes to understanding potentially relevant strategies for a future cure for HIV.
Immunological reconstitution in HIV : immunological responders (IR) and non-responders (NR)
Even with effective antiretroviral therapy, not all people living with HIV achieve satisfactory immune reconstitution. Immunological non-responders (INR) have persistently low CD4⁺ T-cell counts despite successful viral repression, while immunological responders (IR) achieve adequate immune reconstitution during treatment.
We compare IRs and INRs to investigate differences in immune function, inflammation and the integrity of the intestinal barrier. By combining analyses of blood and intestinal tissue we study immune cell composition and function, markers for intestinal damage and inflammation, and the links between intestinal immune environment and HIV reservoirs. Our goal is to identify the mechanisms contributing to sustained immunodeficiency despite effective treatment, and to uncover biomarkers and potential therapeutic targets that could lead to improved immune reconstitution in those who do not achieve sufficient CD4⁺ T-cell counts.