By Samuel Belmont

Human Immunodeficiency Virus (HIV) has been a subject of intense scientific research and debate since the western world became acquainted with the virus in the 1980s. The HIV and Acquired Immunodeficiency Syndrome (AIDS) epidemic began in illness, fear and death as the world faced this new and unknown virus. However, scientific advances, such as the development of antiretroviral treatment (ART) drugs, have enabled people with access to treatment to live long and healthy lives with HIV. ART restricts viral infection by stalling various steps of the viral life cycle, effectively transforming HIV infection into a chronic treatable disease. ART, however, is not a permanent cure as the HIV virus persists latently as integrated copies of proviral DNA within the host genome in infected tissues. As ART cessation results in viral reactivation and disease progression to AIDS, the inability of ART to eliminate virus in these tissues remains the major obstacle towards a disease cure1.

However, with recent advances in gene-editing technology, there is optimism that there will soon be a way of controlling or eradicating the virus without the need for further HIV treatment. For the past few years eager researchers have been employing new gene-editing technologies in their quests for curing various genetic diseases. At the forefront of the gene-editing revolution is the CRISPR-Cas9 system, which since its debut in 2012 has held the most promise of curing the over 6,000 known genetic diseases. My first encounter with CRISPR (pronounced “Crisper”) was when my 10th-grade biology teacher waxed poetic about the potential world-changing applications of this freshly minted technology. CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats) utilizes enzymes to act as “scissors” to cut DNA in a very specific way. Theoretically, it seems that this technology could cure HIV by removing certain genes that assists the HIV virus in replicating or by removing latent HIV genes completely from infected cells.

Putting theory into practice, Dash et al. at the University of Nebraska Medical Center and Temple University employed a two-pronged strategy consisting of both gene-editing CRISPR technology and a highly potent long-lasting, slow-releasing form of the normal ART meds to try to cure mice of HIV2. They demonstrated a successful cure in five out of 13 transgenic mice, suggesting that this dual-punch approach that combines gene editing with targeted drugs could be the trick we need. What’s more, the team reported no “off-target” effects.  While that doesn’t exactly prove that this method of treatment is completely safe, this adds to the promising outlook.

If we could apply the same approach to people, it would create the potential for abandoning daily retroviral medication and the variety of uncomfortable side effects the drugs come with. It should go without saying how impactful this development might be. According to UNAIDS, it is estimated that more than 36.7 million people worldwide are infected with HIV and more than 5000 individuals worldwide are newly infected each day3. In short, if it comes to fruition that this is a viable method for curing HIV, it would be world-changing.

Of course, we are perhaps years away from seeing this reality. Trials on primates are needed before we consider CRISPR as a method for HIV treatment, as even mice engineered to mimic our bodies are no substitute for actual humans. Demonstrating to regulators that the technique is safe enough will be a major obstacle to overcome. Moreover, providing this cure to the millions around the globe who are already denied access to standard HIV medication may not ever be economically feasible. While each subsequent step towards a cure should be cause for celebration, for now, time will tell if this is the one we’ve been hoping for.

References

1. Chun TW, Davey Jr. RT, Engel D, Lane HC, Fauci AS. Re-emergence of HIV after stopping therapy. Nature. 1999;401:874-875.
2. Dash PK, Kaminski R, Bella R, Su H, Mathews S, Ahooyi TM, Chen C, Mancuso P, Sariyer R, Ferrante P, Donadoni M, Robinson JA, Sillman B, Lin Z, Hilaire JR, Banoub M, Elango M, Gautam N, Mosley RL, Poluektova LY, McMillan J, Bade AN, Gorantla S, Sariyer IK, Burdo TH, Young WB, Amini S, Gordon J, Jacobson JM, Edagwa B, Khalili K, Gendelman HE. Sequential LASER ART and CRISPR Treatments Eliminate HIV-1 in a Subset of Infected Humanized Mice. Nature Communications. 2019;10(1):2753.
3. HIV infection and AIDS. Annual epidemiological report for 2017. Stockholm: European Centre for Disease Prevention and Control (ECDC); 2019 ((https://ecdc.europa.eu/sites/portal/files/documents/AER_for_2017-hiv-infection-aids_1.pdf, accessed 7 July 2019).