HIV/AIDS: Why is it so difficult to treat or cure?

Human Immunodeficiency Virus (HIV) is a viral infection that affects the human immune system, leading to acquired immunodeficiency syndrome (AIDS). HIV is characterized by its ability to establish a latent infection in host cells, which makes it difficult to cure. HIV latency refers to the period when the virus remains dormant within infected cells, during which it is not actively replicating, but can reactivate later.

HIV latency is one of the biggest challenges in the development of a cure for HIV. In this article, we will discuss the mechanism of HIV latency, its impact on HIV treatment, and potential strategies to eliminate latent HIV.

 

Mechanism of HIV latency:

The replication cycle of HIV involves several steps, including binding to a host cell, fusion, reverse transcription, integration, transcription, translation, and assembly of new virions. After integration, HIV can either start replicating immediately or become latent.

The HIV genome integrates into the host chromosome, where it is maintained as a provirus. The provirus remains silent because its gene expression is suppressed by multiple mechanisms, including the absence of essential transcription factors, chromatin remodeling, and epigenetic modifications. The infected cell continues to divide and produce new daughter cells, which carry the provirus. This process results in the establishment of a stable reservoir of latent HIV.

 

Impact of HIV latency on treatment:

Latent HIV poses a significant obstacle to HIV treatment because it is not affected by current antiretroviral therapy (ART). ART works by inhibiting the active replication of HIV, but it cannot target latent HIV. Therefore, even with prolonged ART, latent HIV persists in the body and can reactivate when ART is discontinued. This results in the rebound of viremia and the progression of HIV disease.

 

Potential strategies to eliminate latent HIV:

Several strategies are being investigated to eliminate latent HIV, including the use of latency-reversing agents (LRAs), gene editing, and immunotherapy.

LRAs are drugs that can reactivate latent HIV by disrupting the mechanisms that suppress viral gene expression. This results in the production of viral proteins that can trigger the immune system to recognize and eliminate infected cells. However, the use of LRAs alone has not been successful in reducing the latent reservoir size.

Gene editing involves the use of engineered nucleases, such as CRISPR/Cas9, to cut the HIV provirus out of the host chromosome. This approach has shown promising results in preclinical studies, but it still faces many technical and safety challenges before it can be used in human trials.

Immunotherapy aims to boost the immune system’s ability to recognize and eliminate infected cells. This can be achieved by using therapeutic vaccines, adoptive T-cell therapy, or monoclonal antibodies. However, the efficacy of immunotherapy against latent HIV remains to be determined.

HIV latency poses a significant challenge to HIV treatment. Although several strategies are being investigated to eliminate latent HIV, a cure for HIV remains elusive. Continued research is needed to understand the mechanisms of HIV latency and to develop safe and effective interventions that can lead to a cure.

If you are struggling to get to the bottom of your health concerns and are ready for a root cause approach to finally feel your best, contact The Functional Medicine Center for Personalized Care, LLC (www.FxMedCenters.com) at 201-880-8247 or Specialized Therapy Associates at 201-488-6678 for our Integrative Mind-Body Health services and set up an appointment with our experts.

 

References:

Archin NM, Sung JM, Garrido C, Soriano-Sarabia N, Margolis DM. Eradicating HIV-1 infection: seeking to clear a persistent pathogen. Nat Rev Microbiol. 2014 Nov;12(11):750-64.

Deeks SG. HIV: Shock and kill. Nature. 2012 May 3;485(7397):S60-1.

Khalili K, Kaminski R, Gordon J, Cosentino L, Hu W, Huang Y, et al. Stem Cell-Based Gene Therapy for HIV Cure. Front Microbiol. 2019 Nov 22.

Karn J. The molecular biology of HIV/AIDS  latency: breaking and restoring the Tat-dependent transcriptional circuit. Curr Opin HIV AIDS. 2011 Jan;6(1):4-11. doi: 10.1097/COH.0b013e328340ffbb. PMID: 21242887; PMCID: PMC3032057.