Immune Surveillance of the HIV Reservoir: Mechanisms, Therapeutic Targeting and New Avenues for HIV CureSubmit Manuscript on this topic
HIV infection remains a global challenge with a total of 78 million infections recorded since the beginning of the pandemic. The introduction of anti-retroviral treatment (ART) has been a cornerstone in the control of HIV. However, lifelong-ART does not normalize the immune function of HIV-infected people and HIV persists in a quiescent form in the presence of this therapy. If ART is stopped, HIV replication is likely to recommence to pre-therapy levels in the majority of cases.
The current paradigm is that while ART is on-going, HIV remains transcriptionally silent and invisible to immune recognition. The persisting HIV reservoir is a significant limitation for curing patients and for effective remission strategies. However, the roles played by the different arms of the immune system during ART are not fully understood and whether these can be augmented or manipulated to target the reservoir remains elusive. There is increasing evidence that our definition of the HIV reservoir is too simplistic and recent data suggest that the reservoir may be more dynamic than previously thought. Questions that immediately follow from this aim to determine how a successful cure strategy may be developed. Recent data from animal models on ART suggest a role for CD8+ T-cells during therapy. Other players in the immune system may also be activated in the presence of therapy as indicated by treatment interruption studies invoking a role for NK cells and also for B cells following HIV rebound in the presence of Rituximab treatment.
Even if immunity is ineffective in the patient native state, promising technologies enable host immunity to be artificially augmented. For example, bi-specific antibodies, CAR T-cells and other T-cell redirecting immunotherapies have shown promising results in the field of clinical oncology. There are clear similarities between the ‘minimal residual disease’ model for cancer and persistent HIV infection. The question is whether these therapies could also be effective to target the HIV reservoir.
In this Research Topic, we aim to: (i) Review the data on current immune responses that control the HIV reservoir and (ii) Review on-going efforts in immune therapeutics that aim to develop strategies for curing HIV. We seek Reviews, Mini-Reviews and Original Research articles that cover, but are not limited to, the following topics:
1. Enhancing The Effectors – Immune Targeting of The Latent HIV Reservoir:
a. Cytotoxic Lymphocytes (CTLs).
b. NK cells.
c. B cells.
d. Other cell types including MAIT cells and cytotoxic CD4+ T cells.
2. Immune Therapeutics Targeting HIV Reservoirs:
a. Neutralizing antibodies.
b. Enhancing T-cell function (Bites/DARTs/CAR T-cells).
c. Reversing immune dysfunction (checkpoint blockade).