New Study Reveals Stem Cell Transplant Can Lower HIV Reservoir
Much like its predecessor—Tuberculosis—HIV’s initial introduction into the public sphere was marked by an onslaught of misinformation and social stigma. While the nightly news was steadfast in covering the various dangers associated with the virus, the entertainment industry struggled to produce story lines and music that accurately depicted the epidemic that would eventually shape the national conversation of the 1980s. Fortunately, the taboo has gradually dissipated since its early years and our understanding of HIV has only improved.
HIV stands for human immunodeficiency virus. HIV is indeed a virus, just like the common cold or flu. A virus is an infective agent that can replicate itself and essentially act as a set of instructions for making new viruses. However, a virus can’t perform without living cells, similar to a brain without a body. In order to spread from host to host, a virus must first infect a cell. Once infected, a host cell is forced to generate thousands of identical copies of the original virus at an astounding rate.
HIV mostly infects CD4 cells, also known as T cells, or T-helper cells. These are white blood cells that coordinate the immune system to fight disease. Once inside the cell, HIV starts producing millions of microscopic viruses, which eventually kill the cell and then rapidly start infecting other cells. Drugs marketed to treat HIV work by obstructing this process.
Contrary to popular belief, HIV cannot survive outside the body, which means it cannot spread through the air, from touching, or from using toilet seats or shared cutlery. HIV can only be transmitted through certain bodily fluids. This includes:
- Open-mouth kissing if both partners have sores or bleeding gums and blood from the HIV-positive partner enters the bloodstream of the HIV-negative partner
- Unprotected sexual intercourse (vaginal or anal), and oral sex with an HIV-positive person
- Transfusion of contaminated blood
- Sharing of contaminated needles, syringes, or other sharp instruments
- HIV-positive mother and her infant during pregnancy, childbirth, or breastfeeding
Without treatment, HIV progresses in stages, worsening over time. Once the virus fully takes hold, it stays in the body for life. At that point, the body is vulnerable to a wide range of infections and can’t effectively fight them off. Thus, HIV will weaken and ultimately damage the immune system and cause acquired immunodeficiency syndrome (AIDS).
According to the Mayo Clinic, the majority of people with HIV who don’t get treatment develop AIDS within 10 years. WHO and UNAIDS estimate that 36.7 million people were living with HIV globally at the end of 2016. That same year, some 1.8 million people became newly infected, and one million died of HIV-related causes.
Introduction of Antiretroviral Therapy
In a breakthrough that would forever alter the HIV/AIDS treatment landscape, the FDA approved an open label study of saquinavir in June 1995. Saquinavir is a unique drug that effectively targets a cell’s protease, which is a protein needed by HIV to replicate itself.
Six months later in December 1995, saquinavir was officially approved for use in combination with other nucleoside analogue medications, clearing the pathway for combination therapy. The scientific community collectively regarded the use of drugs (typically two) in combination with a protease inhibitor as the “AIDS cocktail,” HAART, or antiretroviral therapy. Antiretroviral therapy became widely accessible to people living with HIV/AIDS in 1996, with AIDS morbidity and mortality declining almost immediately in the industrialized world.
More than 20 years later, antiretroviral therapy is still widely viewed as an effective tool that allows those afflicted with the virus to lead normal or near-normal lives. There are also cases in which HIV-positive women can safely conceive and give birth without the looming fear of transmitting the virus to their offspring. However, despite its success, antiretroviral therapy has never been able to eliminate the virus entirely because of a dormant reservoir of HIV that remains in every patient.
In fact, only one HIV-positive patient has ever experienced a complete “cure.” The so-called Berlin patient, as he is regarded in medical literature, is completely void of HIV after being diagnosed with leukemia and undergoing two stem-cell transplants from the same donor more than 10 years ago. Others infected with HIV who have had stem-cell transplants have not been able to achieve complete removal of the virus, although there is evidence that suggests that these procedures can significantly reduce the levels of HIV reservoir residing in the body.
Newest Development: IciStem Project
Recently, a team of researchers based in Barcelona, Spain, conducted a study called the IciStem project to determine what factors may be considered in the significant reduction of these HIV reservoirs as a pathway to the ability to completely eradicate HIV from the body.
In the study, six HIV-positive male participants who were undergoing antiretroviral therapy and who also needed stem-cell transplants due to hematologic diseases such as leukemia, were closely monitored. Following their stem-cell transplants, five out of the six patients had imperceptible viral reservoirs and one of them no longer had any HIV antibodies in his blood.
The scientists discovered that immune-compatible donors who have a particular gene mutation called CCR5 are an important factor, even though such donors are fairly rare. Their findings have also revealed that graft vs. host disease may actually enable the degeneration of HIV reservoir. Graft vs. host disease is a common complication of stem-cell transplants that takes place when the new donor’s immune cells attack certain cells in the host.
“We believe this reactivity [between donor cells and host cells] might eventually help to sweep away any leftover infected cell[s] from the recipient that might still be circulating in the body, thus contributing to the clearance of the viral reservoir,” Javier Martinez-Picado, PhD, a research professor at the IrsiCaixa AIDS Research Institute in Barcelona and co-author of the study, said in an interview with Contagion®.
Full chimerism, otherwise known as the amount of time it takes for all of the donor cells to be present in the host could be another factor. Based on the results of this study, the longer it takes to achieve full chimerism, the more problematic it may be. The single participant who didn’t witness a full eradication of his HIV reservoir took more than a year to achieve full chimerism after his transplant, in contrast to the other subjects, one of whom achieved full chimerism within a month of the transplant.
A third possible factor in the eradication of the HIV reservoir is pre-transplant conditioning.
“Pre-transplant conditioning [such as] chemotherapy and sometimes radiotherapy…helps to reduce the viral reservoir, as it eliminates recipient hematological cells which will be replaced by the new cells from the donor—although some studies show that the influence of conditioning in the viral outcome after transplant is limited,” Dr. Martinez-Picado said.
Due to the complex nature of stem-cell transplants, they are not recommended as a way for someone living with HIV to try to rid himself or herself of the virus.
“This is a high-risk medical procedure,” Dr. Martinez-Picardo warned. “At the moment, this strategy is not scalable, but it allows researchers to understand more about viral reservoirs, and how and where to look for latent viruses. In addition, alternative more scalable interventions are being investigated.”