Human Immunodeficiency Virus (HIV, AIDS) (cont.)
Eric S. Daar, MD
Eric S. Daar, MD
Dr. Daar received his undergraduate degree from UCLA and medical degree from Georgetown University School of Medicine. He completed an internship and residency in internal medicine at Cedars-Sinai Medical Center and his clinical and research fellowship in infectious diseases at Cedars-Sinai Medical Center and UCLA.
In this Article
What is the future for HIV-infected individuals with regards to treatment simplification and cure research?
Trends continue toward simplifying drug regimens to improve adherence and decrease side effects. In addition, the availability of multiple new drugs in new classes has made it possible to suppress viral load to undetectable levels even in many of the most treatment-experienced patients. With such great success in treatment, the field has increasingly considered strategies that may someday allow patients to control viral replication without the use of antiretrovirals. This could be in the form of a true cure with complete eradication of HIV from the body or a functional cure where the virus persists but is unable to replicated, a situation analogous to what happens when patients are on effective antiretroviral therapy. Research is in the very earliest stages with regards to development of strategies for viral eradication. Studies to control viral replication in the absence of antiretroviral therapy are actively being pursued, although thus far with limited success. One strategy has been to use immune-based therapies to boost the natural immune response to HIV and allow for complete or partial control. Another area of research is to purge infected cells, so-called "latent reservoir," with various agents to facilitate eradication from the body. While research in these areas is under way, it has met with limited success.
The recent report of the so called "Berlin patient" has stimulated a great deal of interest. This man had leukemia, which was treated with a bone marrow transplant. His doctors were able to identify a tissue-matched donor who happened to be one of the rare individuals who carried a genetic defect resulting in the lack of CCR5 on the surface of their cells. CCR5 is required for certain types of HIV to enter the cells, and these unique individuals are relatively resistant to infection. After the bone marrow transplant, the patient was able to stop antiretroviral therapy and for years has not had detectable HIV in his body. While only time will tell as to how long this will last, it provides evidence that a person whose blood cells can be replaced with those without the CCR5 molecule might be able to stop HIV therapy without viral rebound. It is also worth noting that this individual experienced far more than the engraftment of unique bone marrow. He underwent intensive chemotherapy and radiation treatment to destroy most immune cells in the body, as well as graft-versus-host disease which could also further destroy residual HIV-infected cells. Together these events could have markedly reduced the reservoir of virus that persists in the body of all infected individuals, which could have facilitated the purported "cure" or set the stage for the ultimate success associated with the engraftment of the unique bone marrow. The experience with the Berlin patient has not yet been replicated and, even if it is, will not be an option for most people. First, bone marrow transplants are associated with very high risk of illness and death, and second, very few patients who need a bone marrow transplant for any reason are likely to find a tissue-matched donor who carries this rare genetic mutation. However, research is pursuing the potential role each part of this individual's treatment may have had on the successful control of HIV off therapy, as well as working on ways to genetically engineer an individual's own blood CD4 cells or stem cells to not have the CCR5 molecule. While this research is in the very early stages of development, it certainly provides hope for the future of research related to HIV eradication and/or cure.
Another recent report of a "cured baby" is also being actively investigated to gain further insight into what might be needed to allow patients with HIV infection to be followed off antivirals without viral rebound, so-called "functional cure." This baby was born to an HIV-infected mother who was unaware of her infection status until in labor. Since she did not receive prenatal antiviral therapy, the decision was made to treat the baby with full doses of a three-drug regimen that is normally reserved for those actually infected, as opposed to what is traditionally recommended for exposed newborns to simply prevent infection. The baby was quickly found to meet criteria for having been infected and was maintained on treatment until lost to follow-up. Upon the mother returning the baby for care, it was determined that treatment had been stopped for months and the baby had no evidence of virus in the body. Based upon this, it was declared that the baby had at a minimum a functional cure, and research is under way to better understand what actually happened in this case and whether this baby was indeed infected and cured.
Reviewed by Jay W. Marks, MD on 4/3/2013
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