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? Human immunodeficiency virus
Stylized rendering of a cross section of the human immunodeficiency virus
Virus classification
Group: Group VI (ssRNA-RT) Family: Retroviridae Genus: Lentivirus Species: Human immunodeficiency virus 1 Species: Human immunodeficiency virus 2

Human immunodeficiency virus, commonly called HIV, is a retrovirus that primarily infects vital components of the human immune system such as CD4+ T cells, macrophages and dendritic cells. It also directly and indirectly destroys CD4+ T cells. As CD4+ T cells are required for the proper functioning of the immune system, when enough CD4+ T cells have been destroyed by HIV, the immune system barely works, leading to AIDS. HIV also directly attacks organs, such as the kidneys, the heart and the brain leading to acute renal failure, cardiomyopathy, dementia and encephalopathy. Many of the problems faced by people infected with HIV results from the failure of the immune system to protect them from opportunistic infections and cancers.

HIV is transmitted through direct contact of a mucous membrane with a bodily fluid such as blood, semen, vaginal fluid or breast milk. This transmission can come in the form of: penetrative (anal or vaginal) sex; oral sex; blood transfusion; contaminated needles; exchange between mother and infant during pregnancy, childbirth, or breastfeeding; or other exposure to one of the above bodily fluids.

AIDS is thought to have originated in sub-Saharan Africa during the twentieth century and it is now a global epidemic. At the end of 2004, UNAIDS estimated that nearly 40 million people were currently living with HIV. The World Health Organization estimated that the AIDS epidemic had claimed more than 3 million people and that 5 million people had acquired HIV in the same year. Currently it is estimated that 28 million people have died and that it is set to infect 90 million Africans alone, resulting in a minimum estimate of 18 million orphans in the African continent alone.

Contents 1 Introduction 2 Transmission 3 The clinical course of HIV-1 infection 3.1 Primary Infection 3.2 Clinical Latency 3.3 The declaration of AIDS 4 HIV structure and genome 5 HIV tropism 6 Life cycle of HIV 6.1 Viral entry to the cell 6.2 Viral replication and transcription 6.3 Viral assembly and release 7 Genetic variability of HIV 8 Treatment 9 Epidemiology 10 Other viewpoints 11 References 12 See also 13 External links 14 AIDS News

Introduction

In 1983, scientists led by Luc Montagnier at the Pasteur Institute in France first discovered the virus that causes AIDS (Barré-Sinoussi et al., 1983). They called it lymphadenopathy-associated virus (LAV). A year later, Robert Gallo and Marvin Reitz of the United States confirmed the discovery of the virus, and they named it human T lymphotropic virus type III (HTLV-III) (Popovic et al., 1984). In 1986, both names were dropped in favour of the term human immunodeficiency virus (HIV) (Coffin, 1986).

HIV is a member of the genus lentivirus (ICTVdb, 61.0.6), part of the family of retroviridae (ICTVdb, 61). Lentiviruses have many common morphologies and biological properties. Many species are infected by lentiviruses, which are characteristically responsible for long duration illnesses associated with a long period of incubation (Lévy, 1993). Lentiviruses are transmitted as single-stranded, positive-sense, enveloped RNA viruses. Upon infection of the target-cell, the viral RNA genome is converted to double-stranded DNA by a virally encoded reverse transcriptase which is present in the virus particle. This viral DNA is then integrated into the cellular DNA for replication using cellular machinery. Once the virus enters the cell, two pathways are possible: either the virus becomes latent and the infected cell continues to function or the virus becomes active, replicates and a large number of virus particles are liberated which can infect other cells.

Two species of HIV infect humans: HIV-1 and HIV-2. HIV-1 is the more virulent and easily transmitted, and is the source of the majority of HIV infections throughout the world; HIV-2 is largely confined to west Africa (Reeves and Doms, 2002). Both species originated in west and central Africa, jumping from primates to humans in a process known as zoonosis. HIV-1 has evolved from a simian immunodeficiency virus (SIVcpz) found in the chimpanzee subspecies, Pan troglodytes troglodytes (Gao et al., 1999). HIV-2 crossed species from a different strain of SIV, found in sooty mangabey monkeys in Guinea-Bissau (Reeves and Doms, 2002).

Transmission

Since the beginning of the epidemic, three main transmission routes of HIV have been identified:

• Sexual route. The majority of HIV infections are acquired through unprotected sexual relations. Sexual transmission occurs when there is contact between sexual secretions of one partner with the rectal, genital or mouth mucous membranes of another. The probability of transmission per act is between 1 in 53 to 1 in 10,000 for the case of receptive vaginal sex (Pilcher et al., 2004), 1 in 8000 in the case of insertive vaginal sex, 1 in 1000 in the case of insertive anal sex, and between 1 in 100 to 1 in 30 in the case of receptive anal sex [1].

• Blood or blood product route. This transmission route is particularly important for intravenous drug users, hemophiliacs and recipients of blood transfusions and blood products. It is also of concern for persons receiving medical care in regions where there is prevalent substandard hygiene in the use of injection equipment (e.g. reused needles in Third World settings). Health care workers (nurses, laboratory workers, doctors, etc) are also directly concerned, although more rarely. Also concerned by this route are people who give and receive tattoos and piercings, i.e. "scarification" procedures.

• Mother-to-child route. The transmission of the virus from the mother to the child can occur in utero during the last weeks of pregnancy and at childbirth. Breast feeding also presents a risk of infection for the baby. In the absence of treatment, the transmission rate between the mother and child was 20%. However, where treatment is available, combined with the availability of Cesarian section, this has been reduced to 1%.

HIV has been found at low concentrations in the saliva, tears and urine of infected individuals, but the risk of transmission by these secretions is considered to be negligible.

The use of physical barriers such as the latex condom is widely advocated to reduce the sexual transmission of HIV. Recently, it has been proposed that male circumcision may reduce the risk of HIV transmission (Siegfried et al., 2005), but many experts believe that it is premature to recommend male circumcision as part of HIV prevention programs (WHO, 2005).

For more details on this topic, see AIDS prevention

The clinical course of HIV-1 infection

Infection with HIV-1 is associated with a progressive loss of CD4+ T-cells. This rate of loss can be measured and is used to determine the stage of infection. The loss of CD4+ T-cells is linked with an increase in viral load. The clinical course of HIV-infection generally includes three stages: primary infection, clinical latency and AIDS (Figure 1). HIV plasma levels during all stages of infection range from just 50 to 11 million virions per ml (Piatak et al., 1993).

Primary Infection

Primary, or acute infection is a period of rapid viral replication that immediately follows the individual's exposure to HIV. During primary HIV infection, most individuals (80 to 90 %) develop an acute syndrome characterised by flu-like symptoms of fever, malaise, lymphadenopathy, pharyngitis, headache, myalgia, and sometimes a rash (Kahn and Walker, 1998). Within an average of three weeks after transmission of HIV-1, a broad HIV-1 specific immune response occurs that includes seroconversion. Because of the nonspecific nature of these illnesses, it is often not recognized as a sign of HIV infection. Even if patients go to their doctors or a hospital, they will often be misdiagnosed as having one of the more common infectious diseases with the same symptoms. Since not all patients develop it, and since the same symptoms can be caused by many other common diseases, it cannot be used as an indicator of HIV infection. However, recognizing the syndrome is important because the patient is much more infectious during this period

Clinical Latency

As a result of the strong immune defense, the number of viral particles in the blood stream declines and the patient enters clinical latency (Figure 1). Clinical latency is variable in length and can vary between two weeks and 20 years. During this phase HIV is active within lymphoid organs where large amounts of virus become trapped in the follicular dendritic cells (FDC) network early in HIV infection. The surrounding tissues that are rich in CD4+ T-cells also become infected, and viral particles accumulate both in infected cells and as free virus. Individuals who have entered into this phase are still infectious.

The declaration of AIDS

AIDS is the most severe manifestation of infection with HIV. Acute HIV infection progresses over time to clinical latent HIV infection and then to early symptomatic HIV infection and later, to AIDS, which is identified on the basis of certain infections.

For more details on this topic, see AIDS symptomology.

HIV structure and genome

Main article: HIV structure and genome

HIV is different in structure from previously described retroviruses. It is around 120 nm in diameter (120 billionths of a meter; around 60 times smaller than a red blood cell) and roughly spherical.

HIV-1 is composed of two copies of single-stranded RNA enclosed by a conical capsid, which is in turn surrounded by a plasma membrane that is formed from part of the host-cell membrane. Other enzymes contained within the virion particle include reverse transcriptase, integrase, and protease.

HIV has several major genes coding for structural proteins that are found in all retroviruses, and several nonstructural ("accessory") genes that are unique to HIV. The gag gene provides the physical infrastructure of the virus; pol provides the basic enzymes by which retroviruses reproduce; the env gene supplies the proteins essential for viral attachment and entry into a target cell. The accessory proteins tat, rev, nef, vif, vpr, and vpu enhance virus production. Although called accessory proteins, tat and rev are essential for virus replication. In some strains of HIV, a mutation causes the production of an alternate accessory protein, Tev, from the fusion of tat, rev, and env.

The gp120 and gp41 proteins, both encoded by the env gene, enable the virus to attach to and fuse with target cells to initiate the infectious cycle. Both, especially gp120, have been considered as targets of future treatments or vaccines against HIV.

HIV tropism

The term viral tropism refers to the cell type that the virus infects and replicates in. HIV can infect a variety of cells such as CD4+ helper T-cells and macrophages that express the CD4 molecule on its surface. HIV-1 entry to macrophages and T helper cells is mediated not only through interaction of the virion envelope glycoproteins (gp120) with the CD4 molecule on the target cells but also with its chemokine coreceptors. Macrophage (M-tropic) strains of HIV-1, or non-syncitia-inducing strains (NSI) use the beta-chemokine receptor CCR5 for entry and are thus able to replicate in macrophages and CD4+ T-cells. The normal ligands for this receptor, RANTES, macrophage inflammatory protein (MIP)-1-beta and MIP-1-alpha, are able to suppress HIV-1 infection in vitro. This CCR5 coreceptor is used by almost all primary HIV-1 isolates regardless of viral genetic subtype. Indeed, macrophages play a key role in several critical aspects of HIV disease. They appear to be the first cells infected by HIV and perhaps the very source of HIV production when CD4+ cells are markedly depleted in the patient. Macrophages and microglial cells are the cells infected by HIV in the central nervous system. In tonsils and adenoids of HIV-infected patients, macrophages fuse into multinucleated giant cells that produce copious amounts of virus. T-tropic isolates, or syncitia-inducing (SI) strains replicate in primary CD4+ T-cells as well as in macrophages and use the alpha-chemokine receptor, CXCR4, for entry. The alpha-chemokine, SDF-1, a ligand for CXCR4, suppresses replication of T-tropic HIV-1 isolates. It does this by down regulating the expression of CXCR4 on the surface of these cells. Viruses that use only the CCR5 receptor are termed R5, those that only use CXCR4 are termed X4, and those that use both, X4R5. However, the use of coreceptor alone does not explain viral tropism, as not all R5 viruses are able to use CCR5 on macrophages for a productive infection (Coakley et al., 2005).

HIV can also infect a subtype of dendritic cells (Knight et al., 1990), MDC-1, which probably constitute a major reservoir that maintains infection when T helper cell numbers have declined to extremely low levels.

Life cycle of HIV

Figure 2. The HIV replication cycle

Figure 3. The immature and mature forms of HIV

Viral entry to the cell

The interaction between the glycoprotein gp120 on the HIV virion and its receptor, CD4 on the target cell, provokes conformational changes in gp120. This exposes a region of gp120, the V3 loop, which binds to a cytokine receptor on the target cell, such as CCR5 or CXCR4 depending on the strain of HIV. Without a coreceptor, fusion does not take place, explaining why HIV favors some types of CD4+ cells over others.

The change in gp120's shape also exposes a portion of the gp41 glycoprotein, which was previously buried in the viral membrane and loosely bound to gp120. A fusion peptide within gp41 causes the fusion of the viral envelope and the host-cell envelope, allowing the capsid to enter the target cell. The exact mechanism by which gp41 causes the fusion is still largely unknown (Chan and Kim, 1998; Wyatt and Sodroski, 1998).

Once HIV has bound to the target cell, the HIV RNA and various enzymes, including but not limited to reverse transcriptase, integrase and protease, are injected into the cell.

Viral replication and transcription

Once the viral capsid has entered the cell, an enzyme called reverse transcriptase liberates the single-stranded (+)RNA from the attached viral proteins and copies it into a negatively sensed viral complementary DNA of 9 kb pairs (cDNA) (Figure 2). This process of reverse transcription is extremely error prone and it is during this step that mutations (such as drug resistance) are likely to arise. The reverse transcriptase then makes a complementary DNA strand to form a double-stranded viral DNA intermediate (vDNA). This new vDNA is then transported into the nucleus. The integration of the proviral DNA into the host genome is carried out by another viral enzyme called integrase. This is called the latent stage of HIV infection (Zheng et al., 2005).

To actively produce virus, certain transcription factors need to be present in the cell. The most important is called NF-kB (NF Kappa B) and is present once the T cells becomes activated. This means that those cells most likely to be killed by HIV are in fact those currently fighting infection.

The production of the virus is regulated, like that of many viruses. Initially the integrated provirus is copied to mRNA which is then spliced into smaller chunks. These small chunks produce the regulatory proteins Tat (which encourages new virus production) and Rev. As Rev accumulates it gradually starts to inhibit mRNA splicing (Pollard and Malim, 1998). At this stage the structural proteins Gag and Env are produced from the full-length mRNA. Additionally the full-length RNA is actually the virus genome, so it binds to the Gag protein and is packaged into new virus particles.

Interestingly, HIV-1 and HIV-2 appear to package their RNA differently; HIV-1 will bind to any appropriate RNA whereas HIV-2 will preferentially bind to the mRNA which was used to create the Gag protein itself. This may mean that HIV-1 is better able to mutate (HIV-1 causes AIDS faster than HIV-2 and is the majority species of the virus).

Viral assembly and release

The final step of the viral cycle is the assembly of new HIV-1 virions, begins at the plasma membrane of the host cell. The Env polyprotein (gp160) goes through the endoplasmic reticulum and is transported to the Golgi complex where it is cleaved by protease and processed into the two HIV envelope glycoproteins gp41 and gp120. These are transported to the plasma membrane of the host cell where gp41 anchors the gp120 to the membrane of the infected cell. The Gag (p55) and Gag-Pol (p160) polyproteins also associate with the inner surface of the plasma membrane along with the HIV genomic RNA as the forming virion begins to bud from the host cell. Maturation either occurs in the forming bud or in the immature virion after it buds from the host cell. During maturation, HIV proteases (proteinases) cleave the polyproteins into individual functional HIV proteins and enzymes. The various structural components then assemble to produce a mature HIV virion (Gelderblom, 1997). This step can be inhibited by drugs. The virus is then able to infect another cell.

Genetic variability of HIV

Figure 4. The phylogenetic tree of the SIV and HIV viruses (click on image for a detailed description).

Figure 5. Map showing HIV-1 subtype prevalence. The bigger the pie chart, the more infections are present.

One of the major characteristics of HIV is its high genetic variability as a result of its fast replication cycle and the high error rate and recombinogenic properties of reverse transcriptase. This means that different genomic combinations may be generated within an individual who is infected by genetically different HIV strains. Recombination results when a cell is simultaneously infected by two different strains of HIV and one RNA transcript from two different viral strains are encapsidated into the same virion particle. This virion then infects a new cell where it undergoes replication. During this phase, the reverse transcriptase, by jumping back and forth between the two different RNA templates, will generate a newly synthesized retroviral DNA sequence that is a recombinant between the two parental genomes. This recombination is most obvious when it occurs between subtypes.

Three groups of HIV-1 have been identified on the basis of differences in env: M, N and O (Thomson et al., 2002) (Figure 4). Group M is the most prevalent and is subdivided into eight subtypes, based on the whole genome, that are each geographically distinct (Carr et al., 1998). The most prevalent are subtypes B (found predominantly in North America and Europe), A and D (found predominantly in Africa), and C (found predominantly in Africa and Asia) (Figure 5); these subtypes form branches in the phylogenetic tree representing the lineage of the M group of HIV-1 (Figure 4). Coinfection with distinct subtypes gives rise to circulating recombinant forms (CRFs).

In 2000, the last year in which an analysis of global subtype prevalence was made, 47.2% of infections worldwide were of subtype C, 26.7% were of subtype A/CRF02_AG, 12.3% were of subtype B, 5.3% were of subtype D, 3.2% were of CRF_AE, and the remaining 5.3% were composed of other subtypes and CRFs (Osmanov et al., 2000) (Figure 5). Almost 95% of all HIV research currently taking place is focused on subtype B, while a few laboratories focus on other subtypes.

Treatment

HIV infection is a chronic infectious disease that can be treated, but not yet cured. There are effective means of preventing complications and delaying, but not preventing, progression to AIDS. At the present time, not all persons infected with HIV have progressed to AIDS, but it is generally believed that the majority will. People with HIV infection need to receive education about the disease and treatment so that they can be active partners in decision making with their health care provider.

A combination of several antiretroviral agents, termed Highly Active Anti-Retroviral Therapy HAART, has been highly effective in reducing the number of HIV particles in the blood stream (as measured by a blood test called the viral load). This can improve T-cell counts. This is not a cure for HIV, and people on HAART with suppressed levels of HIV can still transmit the virus to others through sex or sharing of needles. There is good evidence that if the levels of HIV remain suppressed and the CD4 count remains greater than 200, then the quality and length of life can be significantly improved and prolonged. Improved antiretroviral inhibitors against proteins such as Reverse transcriptase, Integrase and Tat are being researched and developed. One of the most promising new therapies is a new class of drugs called fusion or entry inhibitors.

For more details on this topic, see Antiretroviral drug.

Post-exposure prophylaxis (PEP) with a course of antiviral drugs is also thought to reduce the risk of seroconversion after high risk exposure (unprotected anal or vaginal sex) to HIV. To be effective, it must be started as soon as possible after exposure and no later than 72 hours. The treatment for HIV lasts four weeks. While there is compelling data to suggest that PEP after HIV exposure is extremely effective, there have been cases where it has failed.

As yet, no vaccine has been developed to prevent HIV infection or disease in people who are not yet infected with HIV, but the potential worldwide public health benefits of such a preventive vaccine are vast. Researchers in many countries are seeking to produce such a vaccine, including through the International AIDS vaccine initiative.

Epidemiology

Figure 6. The adult HIV prevalence at the end of 2004

UNAIDS and the WHO estimated that between 36 and 44 million people around the world were living with HIV in December 2004 [2]. It was estimated that during 2004, between 4.3 and 6.4 million people were newly infected with HIV and between 2.8 and 3.5 million people with AIDS died (UNAIDS, 2004). Sub-Saharan Africa remains by far the worst-affected region, with 23.4 million to 28.4 million people living with HIV at the end of 2004. Just under two thirds (64%) of all people living with HIV are in sub-Saharan Africa, as are more than three quarters (76%) of all women living with HIV. [3] South & South East Asia are second most affected with 15%. AIDS accounts for the deaths of 500,000 children.

The epidemic is not homogeneous within regions with some countries more afflicted than others (Figure 6). Even at the country level there are wide variations in infection levels between different areas. The number of people living with HIV continues to rise in all parts of the world, despite strenuous prevention strategies.

For more details on this topic, see AIDS pandemic.

Other viewpoints

A small minority of scientists, such as Peter Duesberg and 1993 chemistry nobel prize winner Kary Mullis, express doubts over the HIV-AIDS link, and others, such as Eleni Papadopulos-Eleopulos, a medical physicist based at Royal Perth Hospital in Australia, deny the existence of HIV altogether. However, these claims have been refuted by the scientific community for almost 20 years now.

For more details on this topic, see AIDS reappraisal.

References

• Barré-Sinoussi, F., Chermann, J. C., Rey, F., Nugeyre, M. T., Chamaret, S., Gruest, J., Dauguet, C., Axler-Blin, C., Vezinet-Brun, F., Rouzioux, C., Rozenbaum, W. and Montagnier, L. (1983) Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS) Science 220, 868-871 PMID 6189183
• Carr, J. K., Foley, B. T., Leitner, T., Salminen, M., Korber, B. and McCutchan, F. (1998) Reference Sequences Representing the Principal Genetic Diversity of HIV-1 in the Pandemic. In: Los Alamos National Laboratory (Ed) HIV Sequence Compendium, pp. 10-19
• Chan, D. C. and Kim, P. S. (1998) HIV entry and its inhibition. Cell 93, 681-684 PMID 9630213
• Coakley, E., Petropoulos, C. J. and Whitcomb, J. M. (2005) Assessing chemokine co-receptor usage in HIV. Curr Opin Infect Dis. 18, 9-15. PMID 15647694
• Coffin, J., Haase, A., Levy, J. A., Montagnier, L., Oroszlan, S., Teich, N., Temin, H., Toyoshima, K., Varmus, H., Vogt, P. and Weiss, R. A. (1986) What to call the AIDS virus? Nature 321, 10. PMID 3010128.
• Gao, F., Bailes, E., Robertson, D. L., Chen, Y., Rodenburg, C. M., Michael, S. F., Cummins, L. B., Arthur, L. O., Peeters, M., Shaw, G. M., Sharp, P. M. and Hahn, B. H. (1999) Origin of HIV-1 in the chimpanzee Pantroglodytes troglodytes. Nature 397, 436-441 PMID 9989410
• Gelderblom, H. R. (1997) Fine structure of HIV and SIV. In: Los Alamos National Laboratory (Ed) HIV Sequence Compendium, 31-44.
• Gendelman, H. E., Phelps, W., Feigenbaum, L., Ostrove, J. M., Adachi, A., Howley, P. M., Khoury, G., Ginsberg, H. S. and Martin, M. A. (1986) Transactivation of the human immunodeficiency virus long terminal repeat sequences by DNA viruses. Proc. Natl. Acad. Sci. U. S. A. 83, 9759-9763 PMID 2432602
• ICTVdB Descriptions. 61.0.6. Lentiviruses.
• ICTVdB Descriptions. 61. Retroviridae.
• Kahn, J. O. and Walker, B. D. (1998) Acute Human Immunodeficiency Virus type 1 infection. N Engl J Med 331, 33-39 PMID 9647878.
• Knight, S. C., Macatonia, S. E. and Patterson, S. (1990) HIV I infection of dendritic cells. Int Rev Immunol. 6,163-75 PMID 2152500
• Lévy, J. A. (1993) HIV pathogenesis and long-term survival. AIDS 7, 1401-1410 PMID 8280406
• Osmanov, S., Pattou, C., Walker, N., Schwardlander, B., Esparza, J. and the WHO-UNAIDS Network for HIV Isolation and Characterization. (2002) Estimated global distribution and regional spread of HIV-1 genetic subtypes in the year 2000. J. Acquir. Immune. Defic. Syndr. 29, 184-190 PMID 11832690
• Piatak, M., Jr, Saag, M. S., Yang, L. C., Clark, S. J., Kappes, J. C., Luk, K. C., Hahn, B. H., Shaw, G. M. and Lifson, J.D. (1993) High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science 259, 1749-1754 PMID 8096089
• Pilcher CD, Tien HC, Eron JJ Jr, Vernazza PL, Leu SY, Stewart PW, Goh LE, Cohen MS; Quest Study; Duke-UNC-Emory Acute HIV Consortium. (2004) Brief but efficient: acute HIV infection and the sexual transmission of HIV J Infect Dis. 189, 1785-1792 PMID 15122514
• Pollard, V. W. and Malim, M. H. (1998) The HIV-1 Rev protein. Annu Rev Microbiol. 52, 491-532 PMID 9891806
• Popovic, M., Sarngadharan, M. G., Read, E. and Gallo, R. C. (1984) Detection, isolation, and continuous production of cytopathic retroviruses (HTLV-III) from patients with AIDS and pre-AIDS. Science 224, 497-500 PMID 6200935
• Reeves, J. D. and Doms, R. W. (2002) Human immunodeficiency virus type 2. J. Gen. Virol. 83, 1253-1265 PMID 12029140
• Siegfried N, Muller M, Deeks J, Volmink J, Egger M, Low N, Walker S, Williamson P. (2005) HIV and male circumcision--a systematic review with assessment of the quality of studies. Lancet Infect Dis 5, 165-173 PMID 15766651
• Tang, J. and Kaslow, R. A. (2003) The impact of host genetics on HIV infection and disease progression in the era of highly active antiretroviral therapy. AIDS 17, S51-S60 PMID 15080180
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• UNAIDS How can HIV be transmitted
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• WHO (2005) 26 July WHO/UNAIDS statement on South African trial findings regarding male circumcision and HIV
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See also

HIV/AIDS

HIV | AIDS

WHO Disease Staging System for HIV Infection and Disease | CDC Classification System for HIV Infection

HIV structure and genome | HIV Disease Progression Rates

HIV test | Antiretroviral drug | HIV vaccine

AIDS origin | AIDS pandemic | List of countries by HIV/AIDS adult prevalence rate

AIDS in Sub-Saharan Africa| | AIDS in the United States

Treatment Action Campaign | International AIDS Conferences | International AIDS Society| UNAIDS

World AIDS Day | List of AIDS-related topics | Timeline of AIDS

Common misconceptions about HIV and AIDS| OPV AIDS hypothesis

Reappraisal of HIV-AIDS Hypothesis | Duesberg hypothesis

NAMES Project AIDS Memorial Quilt | List of HIV-positive individuals

People With AIDS Self-Empowerment Movement | AIDS Museum | HIV-positive fictional characters

• Criminal Transmission of HIV
• Post-exposure prophylaxis

External links

• AIDS.ORG: Educating - Raising HIV Awareness - Building Community
• AIDS/HIV Education
• Watch an animated tutorial on the life cycle of HIV
• Continuing medical education about HIV for healthcare providers
• FightAIDS@Home
• HIV/AIDS Treatment Information Service
• HIV/AIDS Education in Teacher Preparation Programs
• HIV InSite
• How Aids Works (with animation)
• Medecins Sans Frontieres/Doctors Without Borders HIV/AIDS Pages
• NIH/NIAD/DAIDS
• "The Molecules of HIV" information resource
• Unsafe Health Care and the HIV/AIDS Pandemic 2003
• HIV/AIDS: global trends, global funds and delivery bottlenecks
• UNAIDS document regarding three scenarios for HIV/AIDS in Africa for the year 2025 (Large PDF file)
• UNAIDS - Joint United Nations Programme on HIV/AIDS webpage
• KNOW - HIV leads to AIDS

AIDS News

• Nov 2005 - Progress in HIV vaccine research -- Recorded interview with Prof. Robert Gallo (HIV discoverer)

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AIDS is an acronym for Acquired Immunodeficiency Syndrome or Acquired Immune Deficiency Syndrome and is defined as a collection of symptoms and infections resulting from the depletion of the immune system caused by infection with the human immunodeficiency virus, commonly called HIV (Marx et al., 1982). Although treatments for both AIDS and HIV exist to slow the virus' progression in a human patient, there is no known cure. The rate of clinical disease progression varies widely between individuals and has been shown to be affected by many factors such as host susceptibility (Clerici et al., 1996; Morgan et al., 2002a; Tang et al., 2003), health care and co-infections (Morgan et al., 2002b; Lawn et al., 2004), and peculiarities of the viral strain (Campbell et al., 2004; Campbell et al., 2005; Senkaali et al., 2005). AIDS is thought to have originated in sub-Saharan Africa (Gao et al., 1999) during the twentieth century and is now a global epidemic. UNAIDS and the WHO estimate that AIDS has killed more than 25 million people since it was first recognized in 1981, making it one of the most destructive epidemics in recorded history. In 2005 alone, AIDS claimed an estimated 3.1 million (between 2.8 and 3.6 million) of which more than half a million (570,000) were children (UNAIDS, 2005).

In countries where there is access to antiretroviral treatment, both mortality and morbidity of HIV infection have been reduced (Palella et al., 1998). However, side-effects of these antiretrovirals have also caused problem such as lipodystrophy, dyslipidaemia, insulin resistance and an increase in cardiovascular risks (Montessori et al., 2004), or viral escape and resistance linked to non-observance of the antiretroviral regimen (Becker et al., 2002).

Contents 1 Symptomology 1.1 AIDS and HIV case definitions 1.1.1 WHO Disease Staging System for HIV Infection and Disease 1.1.2 CDC Classification System for HIV Infection 1.2 Clinical symptoms of AIDS 1.2.1 The major pulmonary illnesses 1.2.1.1 Pneumocystis jiroveci pneumonia 1.2.1.2 Tuberculosis 1.2.2 The major gastro-intestinal illnesses 1.2.2.1 Esophagitis 1.2.2.2 Unexplained chronic diarrhea 1.2.3 The major neurological illnesses 1.2.3.1 Toxoplasmosis 1.2.3.2 Progressive multifocal leukoencephalopathy 1.2.3.3 HIV-associated dementia 2 Transmission 3 Prevention 3.1 Prevention of sexual transmission of HIV 3.1.1 Underlying science 3.1.2 Prevention strategies 3.1.3 Governmental programs 3.1.4 Circumcision 3.2 Prevention of blood or blood product route of HIV transmission 3.2.1 Underlying science 3.2.2 Prevention strategies 3.3 Mother to child transmission 3.3.1 Underlying science 3.3.2 Prevention strategies 4 Treatment 4.1 Alternative medicine 5 HIV test 6 Epidemiology 7 Origin of HIV/AIDS 8 Alternative theories 9 References 10 External links 11 AIDS News

Symptomology

The symptoms of AIDS are primarily the result of conditions that do not normally develop in individuals with healthy immune systems. Most of these conditions are infections caused by bacteria, viruses, fungi, parasites, and other organisms. Opportunistic infections are common in people with AIDS (Holmes et al., 2003). Nearly every organ system is affected. People with AIDS also have an increased risk to develop various cancers such as Kaposi sarcoma, cervical cancer and cancers of the immune system known as lymphomas. Common symptoms are fevers, sweats (particularly at night), swollen glands, chills, weakness, and weight loss (Guss, 1994a; 1994b). After the diagnosis of AIDS is made, the current average survival time with antiretroviral therapy is estimated to be between 4 to 5 years (Schneider et al., 2005). Without this therapy, progression to death normally occurs within a year (Morgan et al., 2002b). Most patients die from opportunistic infections or malignancies associated with the progressive failure of the immune system (Lawn et al., 2004).

AIDS and HIV case definitions

Since 1982, many different definitions have been developed for epidemiological surveillance such as the Bangui definition and the 1994 expanded World Health Organization AIDS case definition. However, these were never intended to be used for clinical staging of patients, for which they are neither sensitive nor specific. The World Health Organizations (WHO) staging system for HIV infection and disease, using clinical and laboratory data, can be used in developing countries and the Centers for Disease Control (CDC) Classification System can be used in developed nations.

WHO Disease Staging System for HIV Infection and Disease

In 1990, the World Health Organization (WHO) grouped these infections and conditions together by introducing a staging system for patients infected with HIV-1 (WHO, 1990). This was updated in September 2005. Most of these conditions are opportunistic infections that can be easily treated in healthy people.

• Stage I: HIV disease is asymptomatic and not categorized as AIDS
• Stage II: include minor mucocutaneous manifestations and recurrent upper respiratory tract infections
• Stage III: includes unexplained chronic diarrhea for longer than a month, severe bacterial infections and pulmonary tuberculosis or
• Stage IV includes toxoplasmosis of the brain, candidiasis of the esophagus, trachea, bronchi or lungs and Kaposi's sarcoma; these diseases are used as indicators of AIDS.

For more details on this topic, see WHO Disease Staging System for HIV Infection and Disease.

CDC Classification System for HIV Infection

In the USA, the definition of AIDS is goverened by the Centers for Disease Control and Prevention (CDC). In 1993, the CDC expanded their definition of AIDS to include healthy HIV positive people with a CD4 positive T cell count of less than 200 per µl of blood. The majority of new AIDS cases in the United States are reported on the basis of a low T cell count in the presence of HIV infection (MMWR, 1992).

For more details on this topic, see CDC Classification System for HIV Infection.

Clinical symptoms of AIDS

The major pulmonary illnesses

Pneumocystis jiroveci pneumonia

Pneumocystis jiroveci pneumonia (originally known as Pneumocystis carinii pneumonia, often abbreviated PCP) is relatively rare in normal, immunocompetent people but common among HIV-infected individuals. Before the advent of effective treatment and diagnosis in Western countries it was a common immediate cause of death. In developing countries, it is still one of the first indications of AIDS in untested individuals, although it does not generally occur unless the CD4 count is less than 200 per µl (Feldman, 2005).

Tuberculosis

Among infections associated with HIV, tuberculosis (TB) is unique in that it may be transmitted to immunocompetent persons via the respiratory route, is easily treatable once identified, may occur in early-stage HIV disease, and is preventable with drug therapy. However, multi-drug resistance is a potentially serious problem. Even though its incidence has declined because of the use of directly observed therapy and other improved practices in Western countries, this is not the case in developing countries where HIV is most prevalent. In early-stage HIV infection (CD4 count >300 cells per µl), TB typically presents as a pulmonary disease. In advanced HIV infection, TB may present atypically and extrapulmonary TB is common infecting bone marrow, bone, urinary and gastrointestinal tracts, liver, regional lymph nodes, and the central nervous system (Decker and Lazarus, 2000).

The major gastro-intestinal illnesses

Esophagitis

Esophagitis is an inflammation of the lining of the lower end of the esophagus (gullet or swallowing tube leading to the stomach). In HIV infected individuals, this could be due to fungus (candidiasis), virus (herpes simplex-1 or cytomegalovirus). In rare cases, it could be due to mycobacteria (Zaidi and Cervia, 2002).

Unexplained chronic diarrhea

In HIV infection, there are many possible causes of diarrhea, including common bacterial (Salmonella, Shigella, Listeria, Campylobacter, or Escherichia coli) and parasitic infections, and uncommon opportunistic infections such as cryptosporidiosis, microsporidiosis, Mycobacterium avium complex (MAC) and cytomegalovirus (CMV) colitis. Diarrhea may follow a course of antibiotics (common for Clostridium difficile). It may also be a side effect of several drugs used to treat HIV, or it may simply accompany HIV infection, particularly during primary HIV infection. In the later stages of HIV infection, diarrhea is thought to be a reflection of changes in the way the intestinal tract absorbs nutrients, and may be an important component of HIV-related wasting (Guerrant et al., 1990).

The major neurological illnesses

Toxoplasmosis

Toxoplasmosis is a disease caused by the single-celled parasite called Toxoplasma gondii. T. gondii usually infects the brain causing toxoplasma encephalitis. It can also infect and cause disease in the eyes and lungs (Luft and Chua, 2000).

Progressive multifocal leukoencephalopathy

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disease, in which the myelin sheath covering the axons of nerve cells is gradually destroyed, impairing the transmission of nerve impulses. It is caused by a virus called JC virus which occurs in 70% of the population in latent form, causing disease only when the immune system has been severly weakened, as is the case for AIDS patients. It progresses rapidly, usually causing death within months of diagnosis (Sadler and Nelson, 1997).