By: Hadas Goshen and Prof. Shimon Pollack, Director of the Institute of Immunology, Allergies and AIDS, Rambam Health Care Campus
AIDS, or Acquired Immune Deficiency Syndrome, is a disease caused by the HIV virus, which belongs to the family of retroviruses (the genetic material of which is RNA). HIV penetrates into the body through the genital mucosa or directly into the bloodstream, and infects the white blood cells, especially the T lymphocytes. The infected lymphocytes present a receptor, called CD4, on their outer surface. The virus uses this receptor and another one, the CCR5, to penetrate into the cell and to enslave the genetic material in the cellular nucleus for the production and multiplication of multiple viruses. Having destroyed the host cell, these viruses are released into the bloodstream, infecting other cells, in which the virus multiplies again, repeating the cycle. Destruction of the immunological white blood cells leads to suppression of the immune system and development of severe infectious and malignant diseases.

History and Epidemiology
The first cases of AIDS in the western world were described in 1981, with simultaneous reports coming from various places in the US regarding seven young men suffering from a rare type of pneumonia (PCP) that is observed only in patients with immuno-suppression. The rapid spread of the virus turned into a worldwide epidemic, and the current number of carriers worldwide is over 40 million.

Prof. Shimon Pollack, Director of the Institute of Immunology, Allergy and AIDS, Rambam Health Care Campus, states, surprisingly: "Although it is customary to think that the epidemic began in the 1980s, data from analysis of the viral nuclear material, including traces found in simian feces, as well as epidemiological data, indicates that AIDS has existed in Africa for 75 years, since the 1930s! In the 1960s, probably a million people were infected with AIDS in Africa, but the medical–scientific community was not aware of this until the outbreak in the US."  
Initially, thousands of viral infection cases occurred mainly by direct contact with HIV-contaminated blood (such as by blood transfusion or by sharing needles during drug injection), or by homosexual intercourse. However, over the years, heterosexual intercourse has become the most common method of infection, and the prevalence of HIV infection among men and women has become almost equal. By the way, the current percentage of homosexuals and drug users among HIV carriers does not exceed 20% of the entire carrier population.
The major focus of the epidemic is in Africa, south of the Sahara, and the severity increases, the further south we go. Prof. Pollack says, "In some regions of South Africa, every second or third resident above the age of 15 is infected with HIV!"
Another especially tragic aspect is that about 3.5 million affected children, most of them in Africa, are infected by their carrier mothers during passage through the birth canal.
The treatment of AIDS – a cat and mouse game
During its replication, numerous mutations occur in the AIDS virus (genetic changes), due to the lack of a system for correcting these replication errors. These rapid changes enable the virus to escape from both the immune system and the medication, thus developing resistance to them both.
The initial assumption was that intervention at one stage of infection would be sufficient to stop the virus. However, it soon became clear that the AIDS virus is aggressive and capable of rapid adaptation, and will not give up when it is blocked at one stage. Therefore, in order to inhibit the virus, several of its life stages have to be attacked simultaneously. Several families of drugs are now available, each of which is targeted against a certain stage in the life cycle of the virus, and a combination of drugs from each family is the "cocktail" that enables successful treatment.
Due to continuous and intensive research and development, the drugs comprising the current cocktail are more effective and cause fewer side effects.
"There is a constant war between the carrier receiving medication therapy and the virus," says Prof. Pollack. "The chance of the virus developing resistance increases, the longer the duration of the treatment, thus requiring replacement of the drugs used with new ones. However, the virus develops resistance to the new drugs as well, requiring development of even newer drugs. Furthermore, resistance to one drug may result in abandoning the use of all the remaining drugs of the same family that operate with the same mechanism. Thus, drugs that operate with new mechanisms have to be developed continuously."
Taking the drugs correctly and without any interruption, even for a single day, decreases the capacity of the virus to develop resistance, because mutations develop during replication, and the treatment is aimed at suppression of viral replication. Incidentally, about 25 drugs and drug combinations against AIDS have been developed up to now.

Vaccines – not what you thought
For many years we have heard, and read in media reports, about the hope for the magic solution of a vaccine against AIDS, but the results obtained up to date have been disappointing. Prof. Pollack emphasizes, "The breakthrough in the development of the AIDS vaccine requires a radical change in the traditional approach to vaccine development." 
In contrast to all the other viruses that attack humans, HIV is the only virus that directly attacks the system that is supposed to fight against it."
The vaccine should stimulate the immune response, which is stimulated anyway, but it is not effective: during the initial stages of the disease, prior to immune system suppression, enormous quantities of antibodies are created, but they are incapable of neutralizing the virus. Even the destructive cytotoxic lymphocytes, which directly attack the virus, act for a while and are then suppressed.
The mutation rate of the virus is tremendous. At present, several hundred aggressive sub strains exist, and their number is increasing. One of the factors causing this increase is the use of numerous drugs, leading to the formation of resistant strains. No efficient vaccine will be found until a common denominator for all these sub strains is discovered. Although common components were previously discovered, they were not critical for the existence of the virus.
A recent report described a new approach to vaccination, which was successful in apes. According to this approach, the vaccine contains a live, sterilized virus, following removal of all the genes that encode its aggressive properties. Several years will pass before this approach can be implemented in humans.

Medicine of the future
a. An intracellular targeted missile
The student, Tomer Bronstein, completed his Ph.D. project under the guidance of Prof. Marcelle Machluf at the Faculty of Biotechnology and Food Engineering, the Technion, and Prof. Pollack. The project focused on targeted therapy against HIV. "If we succeed in targeting only the treatment against the affected cells, we will be able to increase the doses of the drugs to levels that may completely destroy the virus, rather than just inhibiting its replication," says Prof. Pollack.
Such treatment requires development of a Trojan Horse, which will carry the drug and insert it into the infected cells. The scientists created in the laboratory a liposome, which is a microscopic bag composed of lipid vesicles, carrying the drug inside it and coated with viral proteins. The liposome penetrates into the CD4+ cell and releases the drug inside it.
This was followed by examination of the possibility of adding antibodies against HIV to the liposome membrane, in order to enable treatment targeted against the infected CD4+ cells. This treatment is intended to protect the intact cells of the immune system against damage.

b. Experiment using natural immunity
The virus needs two "keys" in order to enter the cell ─ the CD4 receptor and the CCR5 receptor. There is a rare condition of natural immunity, which was originally discovered in African prostitutes who were not infected with AIDS, despite having had very frequent sexual intercourse, mainly with HIV carriers. It turned out that their CCR5 receptor was blocked, thus protecting them from infection.
About 1%-2% of people in the western world carry a genetic defect, causing deficiency of the CCR5 receptor. These people are naturally immune to HIV infection via sexual intercourse.
A recent report described an AIDS patient with blood cancer, who underwent a bone marrow transplant from a donor with CCR5 receptor deficiency. This patient received treatment for both his diseases simultaneously – he received healthy blood cells, including immunological cells, and the virus disappeared from his blood within several months. Some people claim that this is the first AIDS patient who was apparently cured.