HIV/AIDS Epidemiology, pathogenesis, prevention, treatment and genomic medicine.

Alessandro Toso

Introduction: More than 38.6 million people live with human immunodeficiency virus (HIV) in the world. The Virus was identified and isolated in 1984.The identification of HIV allowed us to develop new strategies for HIV prevention and design efficient antiretroviral therapies . The Virus: On HIV-1 envelop there are two molecules,gp120 and gp41.After the interaction of these two glycoproteins with CD4+ cells, two co-receptors CCR5 and CXCR4 are essential for the entry of the virus core in the cells. The viral genome is reverse transcribed into DNA. Some mutation in genes like the delta32 deletion in CCR5 can give a HIV-resistant immune system. Therapies: The best therapy in the meantime is the use of antiretroviral drugs(ART),which helps to suppress the viral replication and to preserve the immunologic function. New gene therapies ,that involve the CCR5 gene, the TAT gene of HIV virus, can displace the ART therapies in the near future. Conclusions: Advances in genomics have led to mounting expectations in regard to their impact on health care and disease prevention. Humans show remarkable variation in vulnerability to infection by HIV-1 and specially in the clinical outcome . The studies about the CCR5 mutations, and the virus genome ,can soon free patient from a drug therapy.

the presence of other sexually transmitted disease .the bulletin of Center for Disease Control (CDC) . a rare infection. the causative agent named human immunodeficiency virus type 1 (HIV1) was identified . (figura 1) da lancet 2006. Although Southern Africa remains the epicentre of the pandemia. The causative relation between HIV 1and AIDS was accepted by the scientific and medical community in 1984 and in 1985 a blood test for HIV was available. The identification of HIV allowed us to eliminate HIV transmission through the transfusion of blood .Outside Africa HIV 1 infections are acquired also through injecting drug use. both Gallo’s laboratory and Montagnier’s laboratory tried to isolate in culture the AIDS virus. Occupational exposures of health care workers to HIV infected blood and body fluids through ipercutaneous inoculation is there's no region of the world untouched by this disease.(1) The case involved five young homosexual men affected by Pneumocystis Carinii pneumonia. Sexual relationships .and population mobility patterns increase the probability of HIV 1 acquisition. while about 25 million have died already. Nowadays the main problem is that an estimated 38. After many similar reports.partner change .6 million people live with HIV-1.368:489-504 Sexual transmission remains the dominant mode of transmission and accounts for about 85% of all HIV1 infections . when a report entitled “ Pneumocystis carinii Pneumonia-Los Angeles” appeared in the Morbidity and Mortality Weekly Report (MMWR) .sexual practices . occurring only in patients with underlying immune deficiency. . in the University of California at Los Angeles (UCLA) Medical create rational policies for prevention and desing efficient therapies.Introduction The AIDS epidemic began in June 1981. The collaboration among these groups of scientists and clinicians was essential to achieve the goal and only three years later.

Furthemore HIV is transmitted through blood from mother infected to infant. either CCR5 . because of the no proofreading activity of the reverse transcriptase.or CX chemiokine receptor 4(CXCR4). Viral variants can be generated during this process. Some Virus may exclusively use either CRC5 (virus type R5) or CXCR4 (virus type X4) or may use both ( virus dual-tropic). and are associated with the disease progression.which encode genetic structures from two or more subtypes. Human immunodeficiency virus 1 requires a second receptor. Pathogenesis of HIV The HIV 1 life cycle is complex. HIV-1 viruses has diversified into at least nine subtypes and many circulating recombinant forms . . Subsequent interactions between virus and chemokine coreceptors CCR5 and/or CXCR4 trigger irreversible conformational changes and by pore formation the virus core is released in the cytoplasm . During the entry process gp120 attaches to the cell membrane by first binding to the CD+4 receptor.HIV -1 viruses are divided into three different groups. On the HIV1 envelop the are two molecules : the external glycoprotein gp120 and the transmembrane protein gp41. and R5 virus is predominant early in the Infection. Most transmitted variants are R5.Than the viral genome is reverse transcribed into DNA by the virus’ own reverse transcriptase enzyme. Virus Characteristics Based on their genetic make-up .which in turn might facilitate viral replication .to enter CD4+ cells. The continuously evolving HIV1 viral diversity poses an immense challenge to the development of any preventive or therapeutic intervention. The HIV 1 in the early steps gains access to cell without causing immediate lethal damages but the entry process can stimulate intracellular signal cascades .CXCR4-tropic viruses appear in late stages of infection.

Humans show remarkable variation in vulnerability to infection by HIV1 and in the clinical outcome after infection. Therapies Since 1987 at least 20 antiretroviral compounds have been approved for clinical use. .Infections with two o more genetically distinct viruses could lead to new recombinant viruses.bp deletion in a chemokine receptor gene CCR5. In sub-Saharan Africa. The most relevant genetic variants include those of major histocompatibility complex (MCH) genes. as well as others variants. The goal of treatment is to decrease the morbidity and mortality of the infection. The therapy helps to increase disease-free survival through maximal suppression of viral replication and preservation of immunologic function. in the chemokine receptors CCR5 CCR2.progressors and highly exposed persistently seronegative individuals have been studied to identify innate and acquired protective determinants. Persons who are homozygous for this deletion are almost completely resistant to infection whit HIV1 and those who are heterozygous for the deletion have slower progression from infection to AIDS. Human genomics and infectious diseases The epidemiology.genetic factor that delay HIV disease progression will likely become enriched in the population whereas those which promote rapid progression to AIDS will decline.These effects arise because CCR5 is an important part of the mechanism by which HIV enters the cell. numerous associations between human genetic variants and antiretroviral treatment (ART) responses have been reported. Two groups of long. Most of antiretroviral drugs approved by US Food and drug Administration. pathogenesis and therapeutics of HIV-1 infection are certainly influenced by human genomics.term non. target the viral reverse transcriptase or protease. where HIV is highly endemic . One example of this is a 32.

He loaded the genes into CD34 stem cells and reinjected into patients.and what doses. In fact the practice of medicine has now entered an era in which the individual patient’s genome will help determine the optimal approach to care it is preventive. which. which can distrupt any gene you choose. In Germany a man had been cured of HIV through a bone marrow transplant. diagnostic or therapeutic. The modified cells replicate faster and live longer than the infected one. the CCR5 genes are sabotaged. and stops its replication. . The donor was known to have two copies of a delta32 mutation in CCR5 gene. Ronald Mitsuyasu extracted CD34 from 74 people. Adding a harmless virus that encode for ZFN in CD4+ cells taken from blood samples of 12 patient. snips up the tat gene in any HIV that enters the cell. The HIV-resistant cells took over the man’s immune system. and the other half with a virus that carries a gene for a ribozyme. which means that CD4+ can’t make a protein on their surface that HIV virus uses to invade cells. its interactions with the environment and implications for patient care.Pharmacogenomic assay oh both human and viral genomes may ultimately be used to determine when therapy should be initiated . when expressed.(3) Philp Gregory is studying in California a new gene therapy for HIV. Conclusions All physicians will soon need to understand the concept of genetic variability. John Rossi is studying a third gene therapy. which uses three genes to defend patient’s blood cells from HIV: one prevents production of CCR5. and treated half of the cells with a placebo. ”curing” him from HIV. in this case the CCR5 gene.which drugs . He makes artificial version of zinc finger nucleases(ZFN). New therapies are studied in order to free patient from a lifetime of drugs. and the modified CD4+ cells are re-injected into patients.the other two to sabotage HIV. Another gene therapy can be made with CD34 steam cells. and become the dominant CD4+.

NewScientist 2009 .Mossner M et al “Long-term control of HIV by CCR5 Delta32/delta32 atem cell transplantation” N Engl J Med 2009. could be free from drugs.344:1788-90 2)Simon V. the various gene therapies and the bone marrow transplant success show how in the future patient infected by HIV.360:692-8. BIBLIOGRAPHY 1)Gottlieb MS “ AIDS past and future” N Engl J Med 2001. “ HIV/AIDS epidemiology.Nowak D. 4)Andy Coghlan ” One shot to rid body of HIV”.and treatment.Although the ART is still the best therapy for HIV.prevention.21:8-9 .Abdool Karim Quarrisha et al.368:489-504 3)Hutter Gero.pathogenesis.” Lancet 2006.

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