Recent Advancements in the Treatment of Human Immunodeficiency Virus

Amy House

One of the most common treatments for Human Immunodeficiency Virus (HIV) is highly active antiretroviral treatments, or HAART. HAART, when successful, suppresses the progression and replication of the virus. HAART is effective as a treatment for drastically prolonging the lives of patients with HIV, but it does has some flaws. In addition to the toxicity of HAART and the ineffectiveness of HAART against some resistant strains of HIV, perhaps the largest flaw of this treatment is that it doesn’t eradicate the virus – it simply lessens it’s effect and slows it down. While the reduction in HIV mortality due to HAART should not be undermined, newer treatments must be found that are more effective at ridding the body of HIV altogether. HAART is extremely successful in many cases, but new treatments still need to be sought out. The most promising new treatment for HIV, radioimmunotherapy (RIT) holds hopes to be a more successful therapy – and possibly a cure – to this destructive terminal illness.  Recent scientific breakthroughs might soon lead to the mainstream use of RIT as a treatment and cure for HIV. Research is also being done on HIV prevention and the use of antiretroviral drug HPTN 052 in preventing the spread of this deadly virus, which could potentially lead to eradication of HIV worldwide.

Highly active antiretroviral therapy can reduce the presence of the virus in the blood, reduce the probability of opportunistic infections, and prolong patient survival. When administered correctly, HAART can even lead to complete suppression of viral replication in sufferers of HIV. However, HAART treatments fail with failures in treatment administration, prior exposure to other drugs, counteractive drug interactions, and etcetera. Resistance to HAART can affect up to fifty percent of patients treated, and these drug-resistant HIV strands can be transmitted to others, rendering the treatments ineffective. Drug resistance is an extremely serious hindrance to the treatment of HIV. These resistant strains of HIV do not always show up on screening tests and, if present even in very small quantities, they reproduce rapidly when exposed to the new treatment. The microbes have evolved and developed resistance, and current treatments will become even less effective as the resistant strains grow and spread. Associated with this type of treatment is also a significant toxicity, in other words, a level of poisonousness to the human body. While HAART is extremely successful when it works, it simply does not always work. And, as mentioned above, even when this treatment is successful, it unfortunately provides only a temporary remedy and not a lifelong cure for HIV.  (Perrin et al.)

Such a permanent cure could possibly lie in radioimmunotherapy, a radiation treatment originally manufactured to treat cancer patients. RIT makes use of monoclonal antibodies (mAbs), which can stimulate “apoptosis-like cell death” and decrease microbial metabolic activity when radiolabeled with certain alpha and beta-emitters. Within the past ten years this treatment has been adapted to experimentally treat fungal, bacterial and viral infections, the most pressing of which is HIV. RIT would theoretically treat HIV by targeting the diseased cells and aiming an approach for eradicating reservoirs of cells and cellular factories of the virus.

Doctor Ekaterina Dadochova has been streamlining research for RIT as a treatment for HIV for about ten years. She performed a successful study on mice published in 2009, which had positive results. In the experiment, the RIT was successful in eliminating infected peripheral blood mononuclear cells (PBMCs) from the mice, establishing that RIT could effectively target and eliminate the effected PBMCs in HIV patients. Due to the highly specified application of the RIT, the toxicity was found to be minimal in comparison to that of HAART, and the benefits of the procedure most likely outweigh the long-term risk. RIT in addition to HAART could possibly provide a key impact on the treatment and elimination of HIV-infected cells. ( “RIT of Infectious Diseases”)

Radioimmunotherapy is a promising treatment for HIV and infectious disease, with many benefits over traditional HAART therapy. In fact, RIT might be better suited to treat infectious diseases such as HIV than it is to treat cancer. While strains of HIV have developed that are multi-resistant to HAART and other treatments, it is extremely unlikely that it would develop a resistance to RIT, as RIT damages microbes by multiple mechanisms. In addition, harmful prozone-like phenomena should not occur because the mAb levels administered are miniscule.  It is possible to use alpha or beta emitters paired with RIT, which are certain types of radiation emitters. This is similar to the radiation they use commonly in cancer treatment. RIT also has the power to kill cells that are harboring the HIV microbes – in addition to solely killing the active HIV cells. This is due to the crossfire effect, which is when radiation kills not only the specific infected cells but also the cells nearby that get ‘caught in the crossfire,’ so to speak. (“RIT of Infectious Diseases”)

Although RIT is an extremely promising revelation to the world of HIV treatment, there are some downsides to this promising therapy. One such setback is the high cost of RIT as opposed to the traditional therapies. This is a result of the manufacturing costs (the antibodies must be produced in a living donor or cell culture), intravenous administration, and specificity of diagnosis needed for the treatment to take place (“RIT of Infectious Diseases”). Although the risks and toxicity are lower than those of conventional therapy, they must be brought to our awareness. Some of these risks include radiation-induced mutations and possible toxicity to the liver and spleen (“Antibodies as Delivery Vehicles”).

Dadachova has continued her research on RIT for HIV and infectious disease, and very recently publicized her findings that RIT might be able to eradicate all HIV-infected cells and cease the replication without causing harm to the non-infected cells, meaning that it might just be the long awaited cure for HIV. In tests performed on the blood samples of fifteen HIV positive patients, Dadachova’s team found that the treatment had the ability to exclusively target and kill HAART-treated lymphocytes and to condense the HIV infection to untraceable concentrations in most of the samples. They also found that RIT could target HIV in the brain and central nervous system without damaging other important structures, something previously unfounded with other treatment options. The next step of the currently pre-clinical research is to perform clinical trials on live patients and see what the results bring forth. (Branley)

Another recent revelation in a May 2011 trial found that a specific antiretroviral drug, HPTN 052, can act as not only a treatment for HIV but as a preventative mechanism to halt the transmission of HIV in 96 percent of heterosexual couples by reducing the presence of HIV in the blood and bodily fluids and therefore making it less transmissible. Because of the nearly 100 percent efficacy this “treatment as prevention” method could halt the AIDS epidemic in whole countries and, eventually, world-wide. Unfortunately this treatment is also difficult and costly, and must be taken long-term. Because of these difficulties and logistics, this treatment will not be performed on a grand scale in the near future, but it holds great promise and has intensified the search for a cure for HIV/AIDS. (Cohen)

HIV is a destructive disease that has taken many lives in recent years. While the currently practiced HAART treatments are quite often very successful at immobilizing viral replication, decreasing severity and prolonging the lives of HIV sufferers, a permanent cure for this viral disease has not yet been discovered. Radioimmunotherapy and HPTN o52 treatment as prevention both have turned up very favorable results in drug trials within the past few years. The ultimate goal is to live in a world completely eradicated of HIV/AIDS, and this permanent solution for ending HIV might lie in one or both of these progressive new drug treatments.

Works Cited

Branley, Deirdre, ed. “Albert Einstein College of Medicine at Yeshiva University.” Targeting HIV with Radioimmunotherapy: Radioimmunotherapy Could Potentially Eradicate Lingering HIV Infection. N.p., 03 Dec 2013. Web. 26 Jan 2014. <http://www.einstein.yu.edu/news/releases/957/radioimmunotherapy- could-potentially-eradicate-lingering-hiv-infection/>.

Cohen , Jon. “BREAKTHROUGH OF THE YEAR: HIV Treatment as Prevention.” Science Magazine. 334.6063 (2011): n. page. Web. 26 Jan. 2014. <http://www.sciencemag.org/content/334/6063/1628.full>.

Dadachova, Ekaterina, and Arturo Casadevall. “Antibodies as Delivery Vehicles for Radioimmunotherapy of Infectious Diseases.” Expert Opinion on Drug Delivery. 1075.84 (2005): 1075-1084. Web. 26 Jan. 2014.  <http://informahealthcare.com/doi/pdf/10.1517/17425247.2.6.1075>.

Dadachova, Ekaterina, and Arturo Casadevall. “Radioimmunotherapy of Infectious Diseases.” Seminars in Nuclear Medicine. 39.2 (2009): n. page. Web. 26 Jan.   2014. <http://www.sciencedirect.com/science/article/pii/S0001299808001244>.

Perrin, Luc, and Amalio Telenti. “HIV Treatment Failure: Testing for HIV Resistance in Clinical Practice.” Science Magazine. 280.5371 (1998): n. page. Web. 28 Jan.   2014. <http://www.sciencemag.org/content/280/5371/1871.full>.