Genetic testing of predispositions to resistance to the HIV virus (possibility of HIV infection, prognosis, survival, therapy)
The bogeyman in the guise of the HIV virus appeared at the beginning of the 1980s. Specifically, in the year 1981 a new disease was described and was soon named Acquired Immune Deficiency Syndrome, AIDS for short. Many laboratories worldwide tried to uncover what caused this disease. In 1983, the teams of Doctor Gallo in the USA and Doctor Montagnier in France independently discovered the causal agent of AIDS. This is a virus that was called HIV - Human Immunodeficiency Virus, which causes the loss of immune defences in humans. The virus is transmitted only by sexual intercourse or blood, any transmission via contaminated objects (crockery, hairbrush, doorknob), kissing, handshakes or mosquitoes is practically impossible.
The first drug for the treatment of AIDS began production worldwide, including the then Czechoslovakia, several years after the discovery of the virus. Today, physicians have at their disposal a great range of drugs that affect viral replication on several levels. Drugs to which resistance develops progressively may be switched and patient lives may thus be prolonged.
The HIV virus is very insidious. If it infects a person, it is capable of rapidly changing so that the immune system is forced to continually endeavour to liquidate the virus. It is no secret that HIV positive persons may be further infected by another HIV person. An HIV person may actually become infected from an HIV person whom he/she has recently infected. The virus mutates so rapidly that it becomes as if another organism and thus an HIV positive person may become infected several times. The prognosis of multiple infections is naturally worse.
Scientists all over the world are striving to discover a drug that would cure HIV positive persons. It is a very difficult task as the HIV virus belongs to the so-called RNA viruses that have the annoying ability to incorporate themselves into the genetic information of the host organism. The infected person thus has the genetic information of the HIV virus incorporated in his/her DNA. All the drugs used currently focus on suppressing viral replication and are thus unable to “kill” the virus. The only possibility in the near future of truly curing HIV positive persons lies in the application of resources of molecular biology. The only concrete hope for the battle against this insidious virus is so-called gene therapy.
During their research of the HIV virus, scientists have uncovered a very interesting finding. Certain persons who very frequently come into contact with HIV positive blood either did not develop AIDS or even did not become HIV positive. This led the scientists to study the genetic differences between HIV positive persons and persons who though they could have, did not become HIV positive. The scientists actually discovered several genes whose certain variants protect human beings against infection with the HIV virus or which in the event of infection with this virus strikingly prolong that person’s life. For entry into a cell, the virus requires the presence of receptors that enable its entry into the cell interior. These receptors include on the one hand CD4, as well as necessary co-receptors – e.g. CCR5 or CXCR4. As has been discovered recently, mutation of the CCR5 co-receptor leads to resistance to HIV or to superior prognosis following infection with the HIV virus.
In the Czech population, we studied overall 719 person, of which 383 were men and 336 women. We found that the frequency of the gene coding CCR5 was 0.13 in men and 0.11 in women. In the whole population, the frequency of the mutated allele was 0.12. These results show that approximately every fourth man and every fifth woman of Czech nationality carries a mutant allele, and thus a certain degree of resistance to HIV. This does not mean that if a person discovers that he/she carries a mutation of the gene coding CCR5 then he/she is protected against HIV infection. Such a person only has a smaller probability of being infected. The incidence and prevalence of HIV infection in the Czech Republic is low overall, and this is probably associated with the relatively high incidence of CCR5 gene mutations in the Czech population.
HIV positivity
In 2006, a total of 819 812 tests for the presence of HIV infection were conducted in the Czech Republic. Ninety three new cases of HIV positivity were discovered. In 2006, there were a total of 920 HIV positive persons in the Czech Republic, of which 209 had AIDS and of these 123 died. Fifty four HIV positive persons in 2006 were intravenous drug users.
Symptoms
Shortly after infection, at 3 to 8 weeks, approximately 50% of those infected develop symptoms of the first acute HIV infection, which usually is in the form of an influenza-like illness, increased fatigue, often with a transitory rash. After this phase, the patient enters a period of latency that is variably long. During this period, the infected person usually has no symptoms. Sometimes, transitory or permanent enlargement of lymph nodes occurs. During the asymptomatic HIV-carrier period, there are progressive changes in the immune system, though, most noticeably a significant decrease in CD4 lymphocyte counts. The first symptoms that signal decreased efficiency of the immune system regularly occur when CD4 lymphocyte counts fall below 500/mm3, when the patient crosses from clinical category A- asymptomatic HIV infection- into category B- symptomatic phase of HIV infection. The symptomatic phase of HIV infection is characterised by recurrent fungal infections of the skin, fungal infections of the vagina, herpes zoster and often general symptoms such as fatigue, fever, diarrhoea and weight loss. In the course of the symptomatic stage, one must expect the onset of so-called major opportunistic infections whose incidence indicates that the patient should be classified in clinical category C- i.e. full blown AIDS, characterised by the incidence of so-called major opportunistic infections, certain cancers and other manifestations.
Causes
The cause of HIV positivity is the transmission of the HIV virus into the host body in such a dose so as to induce HIV positivity. The HIV virus has a diameter of 110 nanometres and its genetic information consists of two identical strands of ribonucleic acid (RNA). Apart from these basic structures, the viral particle contains certain enzymes, especially reverse transcriptase, which enable the virus to replicate inside the host cell. Similarly to other retroviruses, HIV is characterised by the ability to incorporate its genetic information in the genome of the host cell and thus induce its chronic lifelong infection. To date, we have no means of eliminating the viral genetic material from cells. HIV mainly assails cells of the immune system, especially T lymphocytes with the CD4 receptor. It may also infect a number of other cells.
Prevention
The HIV virus is found in body fluids, especially blood, sperm, vaginal secretions and maternal milk. For a person to be infected, a certain amount of the HIV virus must penetrate to body, we speak thus of a so-called infectious dose. Only three routes of HIV transmission are known. The highest risk of transmission involves unprotected sex, administration of infected blood or the use of infected needles, and the transmission from mother to child during pregnancy, delivery and lactation. The basic preventive measures are based on these facts and include limiting anonymous sexual intercourse, the use of condoms, the use of safe blood derivatives and of sterile (unused) needles, and the testing of pregnant mothers for HIV.
Treatment
Antiviral therapy forms the basis of treatment along with prophylaxis and timely treatment of opportunistic infections. The goal of antiviral therapy is to slow down viral replication and to prevent the collapse of the immune system. The final goal of antiviral therapy- elimination of the virus from the organism- has not as yet been resolved. All the antiviral drugs available only slow down viral replication in the organism, more or less successfully, by targeting the viral replication cycle. There exists a whole range of anti-retroviral preparations that act in various phases of viral replication. by combining these agents, it is possible to achieve greater efficacy and to restrict the incidence of resistant variants of HIV. Azidothymidine (AZT) remains the basic drug of choice. In pregnant women, administration of AZT during pregnancy decreases the possible transmission of the infection to the newborn.
GenScan
GenScan analysis does not in any way test for the presence of the virus in the organism. GenScan is not an HIV test. On contrary, GenScan provides clients with the possibility of having themselves tested for resistance to the HIV virus that is for the resistance of their organism to infection with the HIV virus. Apart from analysis of the CCR5 gene, clients are offered a panel that tests all known polymorphisms and mutations of genes that lead to resistance to the HIV virus. A result of this test indicating a decreased risk of HIV infection may partially reassure persons who e.g. in the course of their job are frequently exposed to the risk of HIV infection. This test may also help physicians treating HIV positive persons determine the prognosis of the disease and recommend the most suitable therapeutic approach. A decreased risk of HIV infection does not mean, though, in any way, that the tested person cannot be infected with the HIV virus. Such a person merely has a greater probability that on contact with the virus he/she will remain HIV negative.