Since its first identification and description in 1981, medical advances have offered effective therapies to keep the virus at bay, and in some cases even completely cure a patient of the human immunodeficiency virus, or HIV, and to prevent it from becoming the acquired immunodeficiency syndrome, or AIDS, which is often catastrophic to the patient. Unfortunately, as of 2021 per the World Health Organization (WHO), there are still over 38 million people living with HIV, with approximately 1.5 million new infections and 650,000 HIV-related deaths. Much of this has to do with lack of education or proper infrastructure and often obstacles to accessibility for treatment and prevention. I hope to explore HIV with you during this month of awareness so we can do our part to mitigate this persistent epidemic.
I was intrigued to find that there is a dedicated website to the American government strategy to combat HIV. Harold Phillips is the Director of the White House Office of National AIDS Policy (ONAP) and has set up a top five priorities list to tackle this epidemic:
- Achieving health equity with a focus on populations and jurisdictions with the greatest need.
- Increasing the uptake of PrEP among those who could benefit from this prevention method.
- Accelerating public/private partnerships to help reach communities most impacted by HIV.
- Increasing access to substance use disorder treatment and mental health services.
- Modernizing and repealing outdated HIV criminalization laws.
This priority list aligns with the National HIV/AIDS Strategy set up by the President with a goal of ending the HIV epidemic in the United States by the year 2030. The immediate goal is to prevent new HIV infections, to ensure everyone can get tested, knows their status with respect to the virus, receives treatment needed to maintain quality of life, and hopefully through education, reduce the prejudice against people living with the disease. This strategy acts in concert with academic institutions and biotech companies that develop the novel therapeutics to ensure that the patients in need will get the medicine they require.
There are also first-line antiretroviral treatments to prevent transmission of HIV. You’ve probably seen those commercials for pre-exposure prophylaxis (PrEP) and there is also post-exposure prophylaxis (PEP) for folks who are sexually active but might fear contracting HIV. PrEP is taken prior to HIV exposure, while PEP is taken as soon as possible after suspected HIV exposure. Another potential therapy, leronlimab, could also work as a pre-exposure preventative drug, and studies are underway to determine whether this drug could be continuously manufactured through gene therapy. While both PrEP and PEP are highly effective, neither will completely eliminate the risk of infection, so again, common sense needs to prevail.
There are various treatment strategies for patients living with HIV that keep the virus under control. Beyond small molecule inhibitors against the HIV protease or other viral proteins, many targeted therapies are based on broadly neutralizing monoclonal antibodies (bNAb) that are directed to HIV glycans or the co-receptor CCR5 that allows the virus to enter cells. 1, 2 There is a need to calibrate the dosage to achieve the level of viral control needed to maintain the patient’s health. 1
There is some evidence that extracellular vesicles (EVs) may be an effective therapeutic agent. By transporting HIV restriction factors to nearby cells, or by presenting viral antigens on their surface, EVs may be able to stimulate antiviral responses. However, EV transport of HIV and its molecules throughout the host could also reactivate HIV, so fine-tuning the pro-viral and anti-viral effects would be critical to the success of this treatment strategy. 6 Presenting antigen more efficiently, possibly through the host dendritic cells, could serve as a therapeutic vaccine against HIV infection as it could activate the host immune system naturally to target a stronger response against the virus. 7
Many people are leading normal, healthy lives while living with the virus (Magic Johnson comes to mind) but there have been sprinkles of success stories as new techniques and therapies are reported in which the person not only thrives but is essentially free of the HIV that once infected them. While many of these stories give us hope, the patients would need to be tracked long term to ensure that HIV is not just lying dormant to strike again.
Pharmaceutical specialty companies like ViiV Healthcare are working not only on better treatments, but eventually a cure for HIV. One of the challenges is that HIV tends to mask itself within the host cells and remains dormant in a “latent reservoir” where it can rest until antiretroviral treatments stop, at which point the HIV can re-emerge and propagate again. Through massive collaboration, the goal is to trick HIV into presenting viral proteins that can allow the virus to be tagged and subsequently recognized by the host immune system for destruction. 8
Combining multiple approaches, a group from Israel recently reported that they were able to edit B cells in live mice to begin secreting sufficient bNAbs to target HIV in their animal model. 9 Such a technique has yet to be tested in humans, but the initial results are encouraging and suggest that it could be applied to fight other types of diseases, including autoimmunity and cancer.
Of course, the holy grail of health science against any disease is a vaccine to prevent infection or illness before the virus can get a foothold. Recently, a Phase 1 clinical trial was published in Science Magazine that showed a safe and effective response in human patients in developing bNAbs against HIV antigens, hopefully paving the road to an eventual broadly administered vaccine to quell the epidemic once and for all!
With over 40 years of research and advancement, we are likely to see more of these success stories as scientists and medical professionals fine-tune and master their gene editing techniques. The obstacle is in the delivery method and in ensuring safety, but the promise is apparent. With government policies and continued individual vigilance, HIV may one day be eradicated just as we did with other major human diseases.
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