Human Immunodeficiency Virus - Essay Example

Human Immunodeficiency Virus (HIV) 1. Introduction: Human immunodeficiency virus more commonly known as HIV is a retrovirus that is responsible for acquired immunodeficiency syndrome (AIDS). The initial recognition of AIDS took place in 1981 in Los Angeles, USA, when an illness in previously healthy young homosexual men was reported that was characterized by unusual opportunistic infections, certain malignant tumours and immunodeficiency. HIV is believed to have its origins in Central Africa, starting in the 1950s and reaching the United States, Europe and the rest of the world via its spread to the Caribbean Nester, Anderson, Roberts, Pearsall & Nester, 2004). Within the short span of its believed existence, the evidence of its impact is dramatic. By 2002 there were forty-two million people living with HIV infection around the world and it cause more than twenty million deaths around the globe. HIV recognizes no territorial boundaries, nor does it show any preference for colour cast or creed. In spite of billions of dollars spent on research, there is no cure or vaccine as yet and so HIV continues to be a feared infection around the world (Joshi, 2005). 2. Aetiology: HIV belongs to the class Retroviruses and family lentivirinae. HIV stores its genetic information as ribonucleic acid (RNA). Two types of HIV are known namely HIV-1 and HIV -2. Around the world the predominant virus is HIV-1. This has led to the practice that when HIV is referred to without specifying the type, the reference is to HIV-1. In comparison HIV-2 is relatively uncommon, being concentrated in West Africa and hardly seen in other parts of the world. HIV-2 is less easily transmitted and has a longer incubation period. HIV-1 has three groups the “major” group M, the “outlier” group O and the “new” group N. Ninety percent of HIV-1 infections are caused by HIV-1 group M. HIV- 1 group O is restricted to west-central Africa and HIV-1 group N, which is extremely rare was newly discovered in 1998 in Cameroon (Baveja, 2005). HIVs are enveloped single strand RNA viruses, which encode reverse transcriptase that copies the genome into double-stranded DNA and becomes integrated into the host cell genome. The HIV virion contains three virus-specific proteins that are critical to the viral replication. These three proteins are reverse transcriptase, protease and integrase. The group-specific antigen (gag) gene encodes the structural proteins of the virus. The polymerase (pol) gene is responsible for encoding reverse transcriptase and the function of the envelope gene (env) is to encode the two membrane glycoproteins found in the viral envelope. It is the surface protein, which in the case of HIV -1 is gp120 that is responsible for the host range of the virus and its antigenicity (Drew, 2001). The viral DNA integrates into the host cell DNA as a latent provirus, through a viral endonuclease. Should the infection take place latently no infection develops, but if actively infected the proviral DNA gets transcribed and translated, leading to production of viral proteins and RNA. The viral proteins collect and bud through the host cell plasma as new virions. The dissemination of the virus is through budding or by cell-to-cell transfer (Drew, 2001). 3. Transmission: The geographic distribution of the disease by the year 2004 can be seen in Table -1 of the Appendix. The table shows that the region with the highest prevalence of HIV is Sub-Saharan Africa, which is followed by the Caribbean, probably a reflection of the believed origin and route of spread of the virus. East Asia, Western Europe, the Middle-East and North Africa are the regions that have the minimal incidence of HIV (Bartlett, 2005). The spread of the HIV virus is essentially through the exposure to contaminated fluids of the human body. Though the HIV virus has been isolated in blood, semen, vaginal secretions, saliva, cerebro-spinal fluid, breast milk, amniotic fluid, cervical cells and bronchioalveolar lavage fluid, evidence from studies suggest that nearly seventy percent of HIV infections result from sexual intercourse, twenty-seven percent from sharing of needles from during intravenous drug use, three percent from blood transfusions and almost one percent from perinatal transmission. Thus the virus is mainly spread through promiscuity and multiple sex partners and the in intravenous drug abuse (Faia, Bakri, Kim & Moinfar, 2007). According to the World Health Organization (WHO) estimates in 2007, nearly forty million people in the world are currently living with HIV infection. The same estimates suggest that four million more people were infected with AIDS in 2006 and nearly three million of the deaths in 2006 could be attributed to HIV infections. Sub-Saharan Africa accounts for two-thirds of the global burden of HIV, which is followed by twenty-five percent of the global burden of HIV in Asia, primarily India and to a lesser extent in China. There is a sharp contrast in the incidence and growth rates of HIV infection in the developed world and the developing world. The lower growth rates and incidence levels of HIV infection in the developed world may be a reflection of the HIV prevention programmes of the developed world (Tapper, 2007). 4. Pathogenesis: Subsequent to exposure to HIV there is an incubation period of two to six weeks. before the onset of symptoms. Employing the standard ELISSA and Western blot methods it is not often possible to determine whether an individual is in the window period prior to the production of IgG antibody. Several other serological essays like the HIV specific IgM antibody, p24 antigen levels, HIV-1 DNA RNA levels, and viral isolation by culture, when employed may be more useful. Typically the time interval between infection and detection of anti-bodies by ELISSA is one to two months (Russell & Sepkowitz, 1998). The HIV virus exists in its extra cellular form as a lipid-coated cylindrical nucleocapsid, which has inserted within its lipid envelope glycoproteins. It is the glycoprotein 120 that provides the binding region for attachment to the CD4 receptor of the host cells consisting of T-lymphocyte helper cells, activated monocytes and macrophages and glial cells. Subsequent to the fusion with the cell membrane of the host cells the, the virus gives up its envelope. The next step is reverse transcription of RNA to DNA. The viral DNA integrates itself with the host cell DNA as a latent provirus viral endonnuclease. In latent infection of the host cell there is no development of infection. Active infection is a frequent occurrence. In active infection of the host cell the proviral DNA is transcribed and translated leading to the production of viral proteins and RNA. The viral proteins group and bud in a process called reverse endocytosis, through the host cell plasma membrane as new virions. The viral infection spreads by budding or cell-to-cell transfer. (Faia, Bakri, Kim & Moinfar, 2007). The natural course of HIV infection differs from one individual to another. Yet, three phases have been identified in the transition from HIV infection to auto immune deficiency syndrome (AIDS). These three phases are the primary HIV infection (PHI), clinically latent phase (chronic illness and the phase of advanced disease (AIDS). The PHI phase refers to the time span between the entry of the virus till an effective immune response sets in and usually ranges from a few weeks to a couple of months. During this stage the HIV and the HIV infected cells reach the lymph nodes and other lymphoid tissues, where there is the active immune response to viral antigen and the same time intense replication of the virus occurs in the T-cells. During the chronic illness stage the symptoms of the acute disease disappear and the stage is also marked by the down regulation of viraemia and the stabilization of the viral level at a particular set point. However, active and continuous viral replication continues at the lymph nodes and lymphoid tissues. The advanced stage of the infection is marked by increase in all the virological parameters in the peripheral blood and the lymph nodes. There is complete destruction of the architecture of the lymphoid tissue, which results in severe immune deficiency exposing the individual to high risk of developing life threatening opportunistic infections and malignant diseases (Baveja, 2005). The severe immune deficiency that is characteristic of the severity of the progress of the HIV infection is the result of the abnormalities that are caused to almost all the components of the human immune response system. However, the most marked impact seen in the impairment of the cell-mediated (T-cell) immunity. The HIV attaches itself directly to the CD4 receptor of the T helper cell that causes a progressive reduction in the population of the T helper cell with the resultant consequence of the limited activation of the B cells to mount a cytotoxic response to the presence of the virus, and reducing the efficiency of the immune system to not just the virus, but the efficiency of the human immune response system on the whole with additional consequences of the reduced ability to form delayed-type hypersensitivity reactions and the reduced capability to process foreign substances challenging the immune system. The HIV has also been seen to infect monocytes and macrophages. Thus the advanced stage of the disease is characterized by severe impairment of the humoral immune system in a majority of the patients. (Faia, Bakri, Kim & Moinfar, 2007). The more frequently seen symptoms in the PHI phase are fever, night sweats, arthralgia, myalgia, malaise, headache, nausea, vomiting, diarrhoea, and anorexia. The frequently seen signs include pharyngitis, rash, weight loss, lymphadenopathy, leucopoenia, thrombocytopenia, meningitis, neuropathy and encephalopathy (Russell & Sepkowitz, 1998). The advanced phase of AIDS as result of the HIV infection is reflected in respiratory diseases, neurological diseases, GI tract diseases, dermatological diseases, cardiovascular diseases, genito-urinary diseases, ophthalmologic disease, endocrine diseases, musculoskeletal diseases and the like (Duggal & Duggal, 2005). An analysis of host factors shows that HIV infection in adults’ progresses more rapidly with advance in age, however age cannot be taken as a single independent predictor of the progress of the disease, as its significance in prediction of the progress of the disease has still not been confirmed. The factor of gender does not appear to have any significant influence on the progress of the disease. Though ethnicity and race are not significant factors, host genotype may exert some influence. Lower socio-economic groups have an increased tendency to the infection, but this may be the result of high risk behaviour (Rewari & Nag). The presence of HIV infection results in strong humoral and cellular immune responses in the infected individual. An effective immune response in the PHI phase is normally successful in down regulating the viraemia. In the humoral immune response antibodies of different classes and isotypes directed against products of gag, pol and env genes and the regulatory proteins of HIV are produced. The cellular immune response is made up of two types of cells called the HIV (1) antigen-specific effector cells and the non-specific effecter cells. However these immune responses are not able to eliminate HIV completely and progress to the chronic phase of the disease is inevitable (Baveja, 2005). 5. Diagnosis: The diagnosis includes evaluation of the predisposing factors of sexual activity with an infected person, injection drug use, blood product transfusion, perinatal exposure to an infected mother and percutaneous occupational exposure. The second step in the diagnosis is doing an evaluation for the key signs and symptoms of the infection in the patient. The final process in the diagnosis is the laboratory evaluation blood serum for the presence of HIV antibodies, which confirm the diagnosis of HIV infection (Zavasky, Gerberding & Sande, 2001). The Enzyme-Linked ImmunoSorbent Assay (ELISA) is the initial laboratory test conducted for HIV, using a sample of blood taken from the vein of the patient. In the case of a positive ELISA test, a second test called the Western Blot is employed to confirm the positive finding of the ELISA test, using the same sample of blood. The Western Blot test is considered more confirmatory, as it detects antibodies to several different components of the virus. When the initial ELISA test is negative there is no, no further tests are done, except when the findings are inconclusive, which call for additional testing. These HIV antibody tests have their limitations in that the incubation period for virus can extend up to three months. During this window of time testing for HIV antibodies will fail. (How HIV is Diagnosed). HIV is highly infectious and this makes identifying people who have recently acquired the disease important in the combat curb the spread of the deadly virus. Identifying groups of individuals like those who have a recent history of sexually transmitted disease or ethnic groups more prone to HIV and offering HIV testing as a more routine practice could lead to early detection and reduce the spread of HIV. (Schwarz, et al, 2007). 6. Treatment: Given the severity of the disease in the advanced stage and the diminished state of the immune system in an individual at this stage of the disease the objective in the treatment of HIV is to reduce viral burden at the early stage of the disease and thereby try and hinder the progress of the disease to the advanced stage and achieve a stable stage of the disease prior to the advanced stage. Antiretroviral therapy is the early treatment strategy with the view to diminish the spread of the virus, while the immune system is still functionally intact (Russell & Sepkowitz, 1998). Most of the antiretroviral drugs in use today target the viral enzymes of reverse transcriptase or protease. A recent introduction to the drugs targeting viral enzymes is raltegavir, which inhibits the viral integrase enzyme. The problem with all these antiviral drugs is that they possess limited cytotoxicity, since they are highly specific to viral enzymes and not cellular enzymes and HIV has a high mutation rate that allows it scope for easily developing resistance to these antiretroviral drugs. Besides this aspect adverse side effects are seen in many patients with these drugs. Yet the focus on drug development remains on the viral enzymes, as their structures and functions are clearly understood. (Rice & Sutton, 2007). This means that the challenge in the treatment of HIV lies in the development of new drugs to combat it. The cellular cofactors present another area for the potential development of a new class of drugs against the virus. HIV relies on cellular cofactors for mediation to several aspects in its replication and this makes the cellular cofactors present themselves as targets for the development of effective drugs to combat the virus. The initial success in this direction has been achieved with the development of the new antiretroviral drug maraviroc, which binds to the CCR5 molecule on the surface of cells and stops HIV from using it as a coreceptor to enter into the cells. (Rice & Sutton, 2007). 7. Prevention & Control: The high mutation rate of HIV reducing the efficiency of the presently available drugs in the treatment of HIV makes prevention and control significant factors in the battle against HIV. Creating awareness of HIV infection and its risks along with several preventive and control practices like screening of individuals in high risk groups for HIV infection, the use of condom during sexual intercourse, circumcision, reduction in multiple partner sex, have had an impact on reducing the incidence rates of HIV particularly in the Western world. Yet a lot more needs to be done as the worldwide rate of incidence of HIV has not yet reduced. The understanding of the manner in which HIV spreads allows for the identification of groups of individuals that have a high risk for contracting HIV infection and targeting them for awareness and prevention and control efforts has yielded efforts. This can be seen in the identification of gays in the western world, young women in Uganda, young men in Thailand, and drug users in Spain and Brazil as groups of individuals at high risk to contract HIV infection, and targeting prevention and control measures at them have resulted in reduced incidence of HIV in these groups of individuals. However both the size and scope of these efforts are limited to reduce the incidence rates for HIV worldwide, taking into consideration the incidence and ramifications of HIV all round the world. This means that there is the immediate requirement for widening the scope size and scope of such prevention and control measures to nearly every part of the world for a meaningful dent to be made in the incidence of HIV worldwide. (Intensifying HIV Prevention). However real and effective prevention and control of HIV is possible only through the development of efficient vaccines against HIV. Several factors have impeded the efforts to find a safe and effective vaccine against. These factors include the lack of a suitable animal model for HIV infection, the incomplete understanding of protective immune response to this infection and the best most suited strategy for the large-scale testing of promising candidate vaccines (Davey, 1990). Recent advances in the direction of developing a vaccine against HIV do present hopers for such a reality. The first advances have been the ongoing studies using nonhuman primate viruses, which are known, which are known to cause simian immunodeficiency viruses on Asian macaques to provide an understanding of the immunopathogenesis in these animals and through that the possibility of identifying candidate vaccines in humans. Traditional designs to the development of vaccines have not held out promise in the case of a vaccine against HIV. This has led to the second advance in the form of novel designs for the development of vaccines against HIV. The designs include the use of plasmid DNA immunogens, live recombinant vectors like the gene-deleted adenovirus and single-strand RNA alphaviruses and the pox viruses that have yielded a modified vaccinia Ankara (Letvin, 2002). Finally moving on to the appropriate strategies for the last scale testing of vaccines developed, a joint venture strategy between the vaccine manufacturers, health authorities and the people has emerged. Efforts utilising this strategy of a joint effort between the vaccine manufacturers, health authorities and the people have started, as can be seen from the example of activities in Thailand. Such activities have led to the development of candidate HIV vaccines matching the strains of HIV prevalent in the country and phase I and phase II clinical trials to demonstrate the safety and immunogenecity of these candidate vaccines were initiated in 1999. Such developments give hope that it s not far away when vaccines against HIV infection will be available (Rerks-Ngarm, et al, 2006). 8. Conclusions and Future Outlook: The growth in incidence of HIV infections has been dramatic and so is its impact on humanity, with little chance of escaping the severe consequences of the infection. The versatility of the virus has made combating it all the more difficult. However there are signs that the corner is being turned, as the creation of awareness of the severity of the risks combined with preventive and control measures have seen a decline in the growth rate of HIV infections in the developed world. Identifying of high risk groups and targeting these groups for the prevention and control measures holds out promise as the best means to implement prevention and control measures. Widening of the size and scope of such activities will have the impact of reducing the incidence of HIV worldwide. Better understanding of HIV and its pathogenesis has led to identifying possible targets against which drugs can be developed. Such widening of the target range against the several cofactors associated with the virus gives hope that more effective treatment measures will be available soon, through more efficient drugs. Vigorous efforts are on to develop vaccines capable of preventing HIV infections, yielding limited success and the appropriate strategy for the large scale testing of these candidate vaccines has been identified and being employed. These factors suggest that the future outlook on HIV is not bleak for humankind as more effective and efficient prevention and control strategies will reduce the incidence of HIV and the development of more effective drugs to combat HIV would give hope to those infected with the virus already. The trump card in the fight against HIV that will emerge is a vaccine or a combination of vaccines to provide protection and immunity to HIV. Literary References Bartlett, G. John, 2005, ‘Global Perspectives: HIV Epidemiology and Prevention’, Medscape Today [Online] Available at: http://www.medscape.com/viewarticle/511545 (Accessed January 23, 2008). Baveja, K. Usha. 2005, ‘The Human Immunodeficiency Viruses’, in Diagnosis and Management of HIV/AIDS: A Clinician’s Perspective, eds. Usha K. Baveja & B. B. Rewari, Anshan Limited, Kent, pp. 1-15. Baveja, K. Usha. 2005, ‘Immunopathogenesis of HIV/ADS’, in Diagnosis and Management of HIV/AIDS: A Clinician’s Perspective, eds. Usha K. Baveja & B. B. Rewari, Anshan Limited, Kent, pp. 30-48. Baveja, K. Usha. 2005, ‘Immune Response to HIV Infection’, in Diagnosis and Management of HIV/AIDS: A Clinician’s Perspective, eds. Usha K. Baveja & B. B. Rewari, Anshan Limited, Kent, pp. 49-62. Davey, R. T. 1990, ‘Current issues in the development of a vaccine against HIV infection’, Ear, nose, & throat journal, vol. 69, no. 7, pp. 497-505. Drew, W. Lawrence. 2001, ‘HIV & Other Retroviruses, in CURRENT Diagnosis & Treatment in INFECTIOUS DISEASES, eds. Walter R. Wilson & Merle A. Sande, Lange Medical Books/McGraw-Hill Medical Publishing Company, New York, 442-447. Duggal, Lalith & Duggal, Nandini. 2005, ‘Clinical Manifestations of HIV Infections’, in Diagnosis and Management of HIV/AIDS: A Clinician’s Perspective, eds. Usha K. Baveja & B. B. Rewari, Anshan Limited, Kent, pp. 63-88. Faia, J. Lisa, Bakri, S., Kim, B. DooHoo & Moinfar, Nader. 2007, ‘HIV’, emedicine from WebMD, [Online] Available at: http://www.emedicine.com/oph/TOPIC417.HTM (Accessed January 23, 2008). ‘How HIV is Diagnosed’, 2007, HIVInfoSourc, from, NYU Medical Center [Online] Available at: http://www.hivinfosource.org/hivis/hivbasics/diagnosis/ (Accessed January 23, 2008). ‘Intensifying HIV prevention’. 2005, UNAIDS policy position paper, from, UNAIDS [Online] Available at: http://data.unaids.org/publications/irc-pub06/jc1165-intensif_hiv-newstyle_en.pdf (Accessed January 23, 2008). Joshi, P. L. 2005, ‘An Overview of HIV/AIDS Epidemic in India’, in Diagnosis and Management of HIV/AIDS: A Clinician’s Perspective, eds. Usha K. Baveja & B. B. Rewari, Anshan Limited, Kent, pp. 16-30. Letvin, N. L. 2002, ‘Strategies for an HIV vaccine’, Journal of Clinical Investigation, vol. 110, no. 1, pp. 15-27. Nester, E. W., Anderson, D. G., Roberts, E. C., Pearsall, N. N. & Nester, M. T. 2004, MICROBIOLOGY: A HUMAN PERSPECTIVE, Fourth Edition, McGraw-Hill Higher Education, Boston. Rewari, B. B. & Nag, N. 2005. ‘Natural History of HIV/AIDS’, in Diagnosis and Management of HIV/AIDS: A Clinician’s Perspective, eds. Usha K. Baveja & B. B. Rewari, Anshan Limited, Kent, pp. 53-62. Rerks-Ngarm, S., Brown, A. E., Chirasak, K., Thongcharoen, P. & Kunasol, P. 2006, ‘HIV/AIDS Preventive Vaccine 'Prime-Boost' Phase III Trial: Foundations and Initial Lessons Learned From Thailand’, AIDS, vol. 20, no. 11, pp. 1471-1479. Rice, A. P. & Sutton, R. E. 2007, ‘Targeting Protein-protein Interactions for HIV Therapeutics’, Future HIV Therapy, vol. 1, no. 3, pp. 369-385. Russell, D. Nina & Sepkowitz, A. Kent.1998, ‘Primary HIV Infection: Clinical, Immunologic, and Virologic Predictors of Progression’, The AIDS Reader, vol. 8, no. 4, pp. 164-172. Schwarz, S., Weinstock, H., Louie, B., Kellogg, T., Douglas, J., Lalota, M., Dickenson, G., Torian, L., Wendell, D., Paul, S., Goza, G., Ruiz, J., Boyett, B., McMormick, L & Bennett, D. 2007, Journal of acquired immune deficiency syndromes, vol. 44, no. 1, pp. 112-115. Tapper, L. Michael. 2007. ‘Update on Epidemiology of HIV, Hepatitis, and STDs - CROI 2007’, Fourteenth Conference on Retroviruses and Opportunistic Infections, Medscape Today, [Online] Available at: http://www.medscape.com/viewarticle/554182 (Accessed January 23, 2008). Zavasky, D., Gerberding, J. L. & Sande, M. A. 2001, ‘Patients with AIDS’, in CURRENT Diagnosis & Treatment in INFECTIOUS DISEASES, eds. Walter R. Wilson & Merle A. Sande, Lange Medical Books/McGraw-Hill Medical Publishing Company, New York, 315-327. Appendix Table – 1 HIV Incidence and Prevalence 2004 Region Living With HIV New Infections Adult Prevalence Deaths Sub-Saharan 25.4 million 3.1 million 7.4% 2.3 million N. Africa, Middle East 540,000 92,000 0.3% 28,000 South and Southeast Asia 7.1 million 890,000 0.6% 490,000 East Asia 1.1 million 290,000 0.1% 51,000 Latin America 1.7 million 240,000 0.6% 95,000 Caribbean 440,000 53,000 2.3% 36,000 East Europe 1.4 million 210,000 0.8% 60,000 Western/Central Europe 610,000 21,000 0.3% 6500 North America 1.0 million 44,000 0.6% 16,000 Total 39.4 million 4.9 million 1.1% 3.1 million (Bartlett, 2005). Read More