HIV

Template:Taxobox begin Template:Taxobox image Template:Taxobox begin placement virus Template:Taxobox group vi entry Template:Taxobox familia entry Template:Taxobox genus entry Template:Taxobox species entry Template:Taxobox species entry Template:Taxobox end placement Template:Taxobox end The 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+ cells have been destroyed by HIV, the immune system barely works, leading to AIDS. HIV also directly attacks certain human 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 certain opportunistic infections and cancers.

HIV is transmitted through penetrative (anal or vaginal) and oral sex; blood transfusion; the sharing of contaminated needles in health care settings and through drug injection; and, between mother and infant, during pregnancy, childbirth and breastfeeding.

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 ^[1]. 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.

Introduction

In 1983, scientists in France led by Luc Montagnier, first discovered the virus that causes AIDS ^[2]. They called it lymphadenopathy-associated virus (LAV). A year later, Robert Gallo of the United States, confirmed the discovery of the virus, and they named it human T lymphotropic virus type III (HTLV-III) ^[3]. In 1986, both names were dropped in favour of the term human immunodeficiency virus (HIV) ^[4].

HIV is a member of the genus lentivirus ^[5], part of the family of retroviridae ^[6]. 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 ^[7]. Lentiviruses are transmitted as single-stranded negatively-sensed 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 ^[8]. 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 troglodyte troglodyte ^[9]. HIV-2 crossed species from a different strain of SIV, found in sooty mangabeys, an old world monkey of Guinea-Bissau ^[10].

The clinical course of HIV-1 infection

Figure 1. Graph showing HIV virus and CD4+ levels over the course of an untreated 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 ^[11].

Primary Infection

Primary, or acute infection is a period of rapid viral replication that immediately follows the individuals 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 ^[12]. 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 defence, 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. In 1990, the World Health Organization (WHO) grouped these infections and conditions together by introduced a staging system for patients infected with HIV-1. 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.

Further information: WHO Disease Staging System for HIV Infection and Disease

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.

Further information: CDC Classification System for HIV Infection

Many factors such as host susceptibility and immune function ^[13][14][15], health care and co-infections ^[16][17][18], as well as factors relating to the viral strain ^[19][20] may affect the rate of progression to AIDS. Thus, following infection with HIV-1, the rate of clinical disease progression varies enormously between individuals.

Further information: HIV Disease Progression Rates

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 ^[21].

HIV can also infect dendritic cells ^[22].

Life cycle of HIV

Figure 5. The HIV replication cycle

Figure 6. The immature and mature forms of HIV

Viral entry to the cell

The interaction between the gp120, coreceptor and CD4 provokes conformational changes in gp120 that exposes a previously buried portion of the transmembrane glycoprotein, gp41, and allows access of the V3 loop of gp120 to the coreceptor. 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 ^[23][24].

Once HIV has bound to the CD4+ T-cell a viral protein known as gp41 penetrates the cell membrane and 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 5). 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 ^[25].

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 ^[26]. 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 ^[27]. This step can be inhibited by drugs. The virus is then able to infect another cell. There are two forms of the virus:

Immature form

When the virus leaves the cell it is not infectious and the inner part of the virus particle contains a spherical core (stains dark on electron micrographs). There are spikes on the outer membrane that are the Env proteins (gp120 and gp41) (Figure 6). Sometimes a virus can be seen during the process of budding, when it looks like a dark arc sitting under the cell membrane. The Env proteins link together in groups of three (trimers).

Mature form

Once the virus protease has cleaved the gag proteins, the core rearranges into a truncated cone (like a traffic cone sliced at an angle across the top). Some reports also show a small filament linking the core to the membrane. The envelope spikes are often much rarer on mature particles, because they are easily dislodged. It is the mature conical core that makes HIV easily identifiable.

Genetic variability of HIV

Figure 7. The phylogenetic tree of the SIV and HIV viruses (click on image for a detailed description).

File:Subtype.png Figure 8. 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 ^[28](Figure 7). Group M is the most prevalent and is subdivided into eight subtypes, based on the whole genome, that are each geographically distinct ^[29]. 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 8); these subtypes form branches in the phylogenetic tree representing the lineage of the M group of HIV-1 (Figure 7). Coinfection with distinct subtypes gives rise to circulating recombinant forms (CRFs).

The first CRFs to be isolated were the AG recombinant from west and central Africa, the AGI recombinant from Cyprus and Greece, the AB recombinant from Russia, and the AE virus from Southeast Asia. However, the parent subtype E of CRF01_AE has not yet been identified and its status as a recombinant is in dispute.

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 ^[30] (Figure 8). 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.

Further information: Antiretroviral drug

Transmission

HIV is transmitted through penetrative and oral sex whether vaginal or anal, blood transfusion, the sharing of contaminated needles through drug injection and in health care settings, and between mother and infant during pregnancy, childbirth and breastfeeding ^[31]. The use of physical barriers such as the latex condom is widely advocated to reduce the sexual transmission of HIV.

At the end of 2004 there were between 36 and 44 million people living with HIV, of whom 25 million were in sub-Saharan Africa. Global estimates for new HIV infection in 2004 were 4.3-6.4 million. ^[32].

Further information: AIDS_pandemic

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
• ^ Bentwich, Z., Kalinkovich., A. and Weisman, Z. (1995) Immune activation is a dominant factor in the pathogenesis of African AIDS. Immunol. Today 16, 187-191 PMID 7734046
• ^ Bukrinsky M, Adzhubei A. (1999) Viral protein R of HIV-1. Rev Med Virol 9, 39-49 PMID 10371671
• ^ Campbell GR, Pasquier E, Watkins J, Bourgarel-Rey V, Peyrot V, Esquieu D, Barbier P, de Mareuil J, Braguer D, Kaleebu P, Yirrell DL, Loret EP. (2004) The glutamine-rich region of the HIV-1 Tat protein is involved in T-cell apoptosis. J. Biol. Chem. 279, 48197-48204 PMID 15331610
• ^ Campbell GR, Watkins JD, Esquieu D, Pasquier E, Loret EP and Spector SA (2005) The C-terminus of HIV-1 Tat modulates the extent of CD178 mediated apoptosis of T cells. J. Biol. Chem. In Press. PMID 16155003
• ^ 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
• ^ Clerici, M., Balotta, C., Meroni, L., Ferrario, E., Riva, C., Trabattoni, D., Ridolfo, A., Villa, M., Shearer, G.M., Moroni, M. and Galli, M. (1996) Type 1 cytokine production and low prevalence of viral isolation correlate with long-term non progression in HIV infection. AIDS Res. Hum. Retroviruses. 12, 1053-1060 PMID 8827221
• ^ 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.
• ^ DHHS (2005) Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents April 7, 2005
• ^ DHHS (2005) Guidelines for the Use of Antiretroviral Agents in Pediatric HIV Infection March 24, 2005
• ^ Dybul, M., Fauci, A. S., Bartlett, J. G., Kaplan, J. E., Pau, A. K., and the Panel on Clinical Practices for Treatment of HIV. (2002) Guidelines for using antiretroviral agents among HIV-infected adults and adolescents. Ann Intern Med 137, 381-433 PMID 12617573.
• ^ 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.
• ^ Jeang, K. T. (1996) In: Human Retroviruses and AIDS: A Compilation and Analysis of Nucleic Acid and Amino Acid Sequences. Los Alamos National Laboratory (Ed.) pp. III-3–III-18
• ^ Kahn, J. O. and Walker, B. D. (1998) Acute Human Immunodeficiency Virus type 1 infection. N Engl J Med 331, 33-39 PMID 9647878.
• ^ Kim JB, Sharp PA. (2001) Positive transcription elongation factor B phosphorylates hSPT5 and RNA polymerase II carboxyl-terminal domain independently of cyclin-dependent kinase-activating kinase. J. Biol. Chem. 276, 12317-12323 PMID 11145967
• ^ Knight, S. C., Macatonia, S. E. and Patterson, S. (1990) HIV I infection of dendritic cells. Int Rev Immunol. 6,163-75 PMID 2152500
• ^ Learmont JC, Geczy AF, Mills J, Ashton LJ, Raynes-Greenow CH, Garsia RJ, Dyer WB, McIntyre L, Oelrichs RB, Rhodes DI, Deacon NJ, Sullivan JS. (1999) Immunologic and virologic status after 14 to 18 years of infection with an attenuated strain of HIV-1. A report from the Sydney Blood Bank Cohort. N Engl J Med 340, 1715-1722 PMID 10352163
• ^ Lévy, J. A. (1993) HIV pathogenesis and long-term survival. AIDS 7, 1401-1410 PMID 8280406
• ^ Morgan, D., Mahe, C., Mayanja, B. and Whitworth, J. A. (2002a) Progression to symptomatic disease in people infected with HIV-1 in rural Uganda: prospective cohort study. BMJ 324, 193-196 PMID 11809639
• ^ Morgan, D., Mahe, C., Mayanja, B., Okongo, J. M., Lubega, R. and Whitworth, J. A. (2002b) HIV-1 infection in rural Africa: is there a difference in median time to AIDS and survival compared with that in industrialized countries? AIDS 16, 597-6032 PMID 11873003
• ^ MMWR weekly (2005) Antiretroviral Postexposure Prophylaxis After Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV in the United States January 21, 54 (RR02), 1-20
• ^ 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
• ^ 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
• ^ Quiñones-Mateu, M. E., Mas, A., Lain de Lera, T., Soriano, V., Alcamí, J., Lederman, M. M. and Domingo, E. (1998) LTR and tat variability of HIV-1 isolates from patients with divergent rates of disease progression. Virus Research 57, 11-20 PMID 9833881
• ^ 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
• ^ Strebel, K (2003) Virus-host interactions: role of HIV proteins Vif, Tat, and Rev. AIDS 17 Suppl 4, S25-S34 PMID 15080177
• ^ 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
• ^ Thomson, M. M., Perez-Alvarez, L. and Najera, R. (2002) Molecular epidemiology of HIV-1 genetic forms and its significance for vaccine development and therapy. Lancet Infect Dis. 2, 461-71 PMID 12150845
• ^ UNAIDS How can HIV be transmitted]
• ^ UNAIDS (2004) AIDS epidemic update December 2004
• ^ Xiao, H., Neuveut, C., Tiffany, H. L., Benkirane, M., Rich, E. A., Murphy, P. M. and Jeang, K. T. (2000) Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1. Proc. Natl. Acad. Sci. U. S. A. 97, 11466-11471 PMID 11027346
• ^ WHO (2001) WHO/AFRO Press Release from the 51st Session of the WHO regional committee for Africa.
• ^ WHO (2003) Scaling up retroviral therapy in resource limited settings
• ^ WHO (2005) 26 July WHO/UNAIDS statement on South African trial findings regarding male circumcision and HIV
• ^ Wyatt, R. and Sodroski, J. (1998) The HIV-1 envelope glycoproteins: fusogens, antigens, and immunogens. Science 280, 1884-1888 PMID 9632381
• ^ Zheng, Y. H., Lovsin, N. and Peterlin, B. M. (2005) Newly identified host factors modulate HIV replication. Immunol Lett. 97, 225-234 PMID 15752562

See also

• Criminal Transmission of HIV
• HIV positive people
• HIV test
• List of HIV-positive people
• Post-exposure prophylaxis

External links

• AIDS.ORG: Educating - Raising HIV Awareness - Building Community
• AIDS/HIV Education
• Continuing medical education about HIV for healthcare providers
• Declaration of Commitment on HIV/AIDS UN 2001
• FightAIDS@Home
• HIV/AIDS Treatment Information Service
• Genome (HIV-1)
• Genome (HIV-2)
• Genome at sc.edu
• 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