The global effort to combat HIV is seeing progress through innovative prevention strategies and potential curative therapies, yet challenges persist in managing this complex virus.
Challenges in HIV Management
HIV, a retrovirus integrating into host genomes, poses significant treatment challenges. Untreated HIV leads to AIDS, characterized by a CD4 cell count below 200 cells per cubic millimeter or opportunistic infections, with a typical survival of around three years without intervention. Combined antiretroviral therapy (cART) is the standard treatment, suppressing viral replication but failing to eradicate latent reservoirs, necessitating lifelong therapy and potentially leading to toxicity and drug resistance.
Dr. Emmanuel Ho, a professor at the University of Waterloo, explains, "HIV can establish latent reservoirs within our body...hide within cells...and lay dormant for a long period of time...Once they become active, they can immediately replicate and infect other immune cells." He further notes HIV's ability to evade the immune system and develop drug resistance.
Global disparities in treatment access persist, with approximately 10 million people living with HIV lacking antiretroviral therapy. A 2023 UNAIDS report indicates only 43% of children with HIV have access to life-saving medicine. Sub-Saharan Africa bears a disproportionate burden, with women accounting for 63% of new infections in the region in 2022. Stigma, discrimination, and healthcare access issues further exacerbate these challenges, as highlighted by Dr. Jamie Mann, senior lecturer in vaccinology and immunotherapy at the University of Bristol.
Novel Prevention Strategies
Dr. Emmanuel Ho's research focuses on innovative drug delivery strategies, including nanomedicines, for HIV prevention. His team developed a novel nanomedicine loaded with small interfering RNAs (siRNAs) to combat HIV by reducing the expression of CCR5, a gene encoding a protein crucial for HIV entry into host cells. The nanomedicine also releases a second siRNA to reduce the expression of Nef, a protein produced by HIV to inhibit autophagy, thereby reactivating autophagy to eliminate the virus.
"siRNAs will play an important role in the development of novel HIV therapeutics," said Ho. "If we can identify a ‘target’ (e.g., gene) in our body that promotes or enhances HIV infection...we can easily design siRNAs to bind and knockdown the expression of that target."
The nanomedicine is designed for intravaginal delivery to prevent sexual transmission of HIV. Encapsulating siRNAs in PEG-PLGA polymer nanoparticles addresses challenges associated with naked siRNA degradation and inefficient mucosal uptake. The team aims to optimize the nanoparticle system for 100% protection against infection.
Potential Cures on the Horizon
Dr. Jamie Mann is focusing on developing therapeutic and prophylactic vaccines against HIV to address the lack of a cure. Mann co-led an international study demonstrating the ability of an HIV-virus-like particle (HLP) therapeutic to reactivate dormant HIV, rendering it susceptible to cART and the immune system. The study, using blood samples from 32 participants living with chronic HIV on stable cART, showed that HLP specifically targets immune cells containing latent HIV reservoirs and purges these cells of HIV.
"Our data shows that divergent strains of HIV are also susceptible to the same HLP treatment, suggesting that the HLP could have global applications as a therapy," said Mann.
HLPs are engineered to resemble HIV but lack a viral genome, making them incapable of causing infection or replicating. Mann and the team plan to transition this work to clinical trials to rigorously evaluate the effectiveness of this strategy in a controlled setting, bringing them closer to making a cure a reality.
