HIV/AIDS Global Epidemic

  • Phyllis J. KankiEmail author


The HIV/AIDS epidemic is now in its third decade since the discovery of the virus responsible for the disease in 1981. While the first cases of AIDS were first recognized in young men who have sex with men in the United States and Europe in the 1980s, it soon became clear that the virus could be spread through contaminated blood products and heterosexual sex. At the time of its discovery, acquired immunodeficiency syndrome (AIDS) was a new disease with high mortality, and the discovery of a new human virus as its cause in 1983 created new challenges for prevention, treatment, and vaccine efforts, many of which remain unmet today. Human immunodeficiency virus type 1 (HIV-1), as the causative agent of AIDS, has been the subject of intense research over the past three decades, in an effort to understand the biological properties of this new virus, its relatedness to other known retroviruses, characterize its epidemiology, and discover drugs and vaccines to control the epidemic.


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Acquired immunodeficiency syndrome (AIDS)

A clinical syndrome caused by the human immunodeficiency virus (HIV). Its pathogenesis is related to a qualitative and quantitative impairment of the immune system, particularly a reduction of the CD4+ helper T lymphocyte cell count (surrogate marker of the disease). After an average of 10 years, if untreated, HIV + individuals can develop opportunistic diseases (i.e., infections and cancers rarely detected in people with normal immune systems). The natural history of the disease can be dramatically modified with administration of combination therapy composed of antiretroviral (ARV) drugs.


A cell membrane protein expressed on several cell types including peripheral blood-derived dendritic cells, CD34+ hematopoietic progenitor cells, and certain activated/memory Th1 lymphocytes. This receptor is well defined as a major coreceptor in conjunction with CD4+, implicated in susceptibility to HIV-1 infection.


A large glycoprotein that is found on the surface of helper T lymphocyte cells, regulatory T cells, monocytes, and dendritic cells. Its natural function is as a coreceptor that assists the T cell receptor (TCR) to activate its T cell following an interaction with an antigen-presenting cell. CD4+ is a primary receptor used by HIV-1 to gain entry into host T cells.

CD4+ T cell

An immune cell, lymphocyte (white blood cell) characterized by the CD4+ antigen (protein) on its surface. This is a T lymphocyte considered to have a “helper” function to enhance the cellular immune response. The CD4+ is the primary receptor for the HIV virus, and upon infection, the virus can destroy the CD4+ cell. In HIV-infected people, the drop in CD4+ T lymphocyte cells is a major determinant of the progression of HIV infection to AIDS.

Coreceptor (CCR-5 or CXCR-4)

Protein molecules on the surface of lymphocytes or monocytes that bind to the gp120 protein of HIV and facilitate, with CD4, binding, fusion, and entry of the virus into the susceptible cell.


An alpha-chemokine receptor specific for stromal-derived factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. This coreceptor is one of several chemokine receptors that HIV isolates can use to specifically infect CD4+ T cells.

DNA (deoxyribonucleic acid)

A nucleic acid that contains the molecular basis of heredity for all known living organisms and some viruses and is found in the nuclei and mitochondria of eukaryotes. Chemically, DNA consists of two polymer strands of units called nucleotides made up of one of four possible bases plus sugar and phosphate groups. The polymers are joined at the bases by hydrogen bonds to form a double helix structure.

Fusion of virus and cell membranes

A merging of cell and virus membranes that permits HIV proteins and nucleic acids to enter the host cell.

Fusion/entry inhibitors

A class of ART drugs that interferes with the virus’ ability to fuse with the target cell’s outer membrane, thereby blocking entry of the HIV into the host cell.


The major HIV envelope glycoprotein having a molecular weight of 120 that protrudes from the outer surface of the virion. This glycoprotein binds to a CD4+ receptor on a T cell to facilitate entry of the virus into the cell.

Human immunodeficiency virus (HIV)

The virus that causes acquired immunodeficiency syndrome (AIDS). It is a lentivirus belonging to Retroviridae family and was discovered in 1983 by Robert Gallo and Luc Montagnier. HIV infects and destroys helper T cells of the immune system causing a marked reduction in their numbers. Loss of CD4 cells leads to generalized failure of the immune system and susceptibility to life-threatening opportunistic infections. It is transmitted mainly through sexual intercourse, exchange of contaminated syringes among intravenous drug users, and contaminated blood transfusion. HIV-1 is the HIV type most frequently detected HIV worldwide and responsible for the global pandemic.

HIV-1 subtypes or clades

Genetically related HIV strains that are essentially phylogenetically equidistant, generating a starlike phylogeny. Subtypes A, B, C, D, F, G, H, J, and K are currently known subtypes A, B, C, and D are highly prevalent others have low prevalence and limited geographic distributions.


The second HIV virus discovered in West Africa in 1984, the virus is more closely related to the simian immunodeficiency virus of primates. Although HIV-2 can cause AIDS, it has a distinct epidemiology, lower rate of transmission, and slower progression to disease.


Rate describing the number of new cases of disease occurring within a given time period, expressed as new cases per person-time.


An enzyme found in retroviruses including HIV that permits the reverse transcribed viral DNA to be integrated into the infected cell’s DNA. Integrase is an enzyme encoded by the polymerase gene of HIV.

Integrase inhibitors

A class of ART drugs that blocks the viral integrase the enzyme HIV uses to integrate its genetic material into its target host cell DNA.


A membrane-enclosed central compartment of a cell that functions to contain the genomic DNA and to regulate gene expression.


Number of cases of disease in a defined population at a specific point in time it is often expressed as a percentage.


An enzyme that hydrolyzes or cleaves the polyproteins into proteins and is important in the final steps of HIV maturation. In HIV, the protease enzyme is encoded by the polymerase gene.

Protease inhibitors

A class of ART drugs that interferes with the viral protease enzyme of HIV by inhibiting the viral polyproteins from being cleaved, which would allow the individual viral proteins to produce infectious viral particles.

Reverse transcriptase

An enzyme found in HIV that creates double-stranded DNA using viral RNA as a template and host tRNA as primers. The reverse transcriptase enzyme is encoded by the polymerase gene of HIV.

Reverse transcriptase (RT) inhibitors

A class of ART drugs that interfere with the reverse transcription step during the HIV life cycle. During this step, the HIV enzyme RT converts HIV RNA to HIV DNA. There are two main classes of RT inhibitors that are used as ART drugs.

Nucleoside/nucleotide RT inhibitors (NRTI) are faulty DNA building blocks. When these faulty pieces are incorporated into the HIV DNA (during the process when HIV RNA is converted to HIV DNA), the DNA chain cannot be completed, thereby blocking HIV from replicating in a cell.

Nonnucleoside RT inhibitors (NNRTI) bind to RT, interfering with its ability to convert the HIV RNA into HIV DNA.

RNA (ribonucleic acid)

A universal form of genetic material typically transcribed from DNA, it differs from DNA in that it contains ribose and uracil as structural components. In retroviruses like HIV, RNA is their primary genetic material and is found in a mature virus particle.


A characteristic of a virus that infects and replicates in T lymphocytes, a type of immune cell. This was the descriptor of the human T cell leukemia virus (HTLV), a human retrovirus that causes T cell leukemia and lymphoma and is T-lymphotropic like HIV. HIV was originally called human T-lymphotropic virus type III (HTLV-III) by Gallo and colleagues.


The infectious disease caused by Mycobacterium tuberculosis. It usually involves the lungs (pulmonary tuberculosis) but can also affect other organs (i.e., kidneys, central nervous system, lymph nodes, bones, etc.; extrapulmonary tuberculosis). Pulmonary tuberculosis, which is the most frequent clinical form, can be classified as smear positive or smear negative according to the result of the sputum bacteriological examination. The former is a major public health problem being highly contagious. Only a few individuals develop tuberculosis after a mycobacterial infection, and most of them soon after infection: it is estimated that the lifetime risk is 5–10% in HIV negatives and 5–15% yearly in HIV positives.


A single and complete extracellular infective form of a virus that consists of an RNA or DNA core and in the case of HIV with a glycoprotein coat or “envelope.”


  1. 1.
  2. 2.
  3. 3.
    Gottlieb MS, Schroff R, Schanker HM, Weisman JD, Fan PT, Wolf RA, Saxon A (1981) Pneumocystis carinii pneumonia and mucosal candidiasis in previously healthy homosexual men: evidence of a new acquired cellular immunodeficiency. N Engl J Med 305:1425–1431PubMedCrossRefGoogle Scholar
  4. 4.
    Masur H, Michelis MA, Greene JB, Onorato I, Stouwe RA, Holzman RS, Brettman L, Lange M, Murray HW, Cunningham-Rundles S (1981) An outbreak of community-acquired Pneumocystis carinii pneumonia: initial manifestation of cellular immune dysfunction. New Eng J Med 305:1431–1438PubMedCrossRefGoogle Scholar
  5. 5.
    Siegal FP, Lopez C, Hammer GS, Brown AE, Kornfeld SJ, Gold J, Hassett J, Hirschman SZ, Cunningham-Rundles C, Adelsberg BR et al (1981) Severe acquired immunodeficiency in male homosexuals, manifested by chronic perianal ulcerative herpes simplex lesions. New Eng J Med 305:1439–1444PubMedCrossRefGoogle Scholar
  6. 6.
    Anonymous (1982) Epidemiologic aspects of the current outbreak of Kaposi’s sarcoma and opportunistic infections. New Eng J Med 306:248–252Google Scholar
  7. 7.
    Davis KC, Horsburgh CR Jr, Hasiba U, Schocket AL, Kirkpatrick CH (1983) Acquired immunodeficiency syndrome in a patient with hemophilia. Ann Int Med 98:284–286PubMedGoogle Scholar
  8. 8.
    Poon MC, Landay A, Prasthofer EF, Stagno S (1983) Acquired immunodeficiency syndrome with Pneumocystis carinii pneumonia and Mycobacterium avium-intracellulare infection in a previously healthy patient with classic hemophilia. Clinical, immunologic, and virologic findings. Ann Int Med 98:287–290PubMedGoogle Scholar
  9. 9.
    Elliott JL, Hoppes WL, Platt MS, Thomas JG, Patel IP, Gansar A (1983) The acquired immunodeficiency syndrome and Mycobacterium avium-intracellulare bacteremia in a patient with hemophilia. Ann Int Med 98:290–293PubMedGoogle Scholar
  10. 10.
    Curran JW, Lawrence DN, Jaffe H, Kaplan JE, Zyla LD, Chamberland M, Weinstein R, Lui KJ, Schonberger LB, Spira TJ et al (1984) Acquired immunodeficiency syndrome (AIDS) associated with transfusions. New Eng J Med 310:69–75PubMedCrossRefGoogle Scholar
  11. 11.
    Jaffe HW, Francis DP, McLane MF, Cabradilla C, Curran JW, Kilbourne BW, Lawrence DN, Haverkos HW, Spira TJ, Dodd RY, Gold J, Armstrong D, Ley A, Groopman J, Mullins JI, Lee TH, Essex M (1984) Transfusion-associated AIDS: serologic evidence of human T-cell leukemia virus infection of donors. Science 223:1309–1312PubMedCrossRefGoogle Scholar
  12. 12.
    Piot P, Quinn TC, Taelman H, Feinsod FM, Minlangu KB, Wobin O, Mbendi N, Mazebo P, Ndangi K, Stevens W (1984) Acquired immunodeficiency syndrome in a heterosexual population in Zaire. Lancet 2:65–69PubMedCrossRefGoogle Scholar
  13. 13.
    Van de Perre P, Rouvroy D, Lepage P, Bogaerts J, Kestelyn P, Kayihigi J, Hekker AC, Butzler JP, Clumeck N (1984) Acquired immunodeficiency syndrome in Rwanda. Lancet 2:62–65PubMedCrossRefGoogle Scholar
  14. 14.
    Clumeck N, Mascart-Lemone F, de Maubeuge J, Brenez D, Marcelis L (1983) Acquired immune deficiency syndrome in Black Africans (letter). Lancet 1:642PubMedCrossRefGoogle Scholar
  15. 15.
    Oleske J, Minnefor A, Cooper R et al (1983) Immune deficiency syndrome in children. J Am Med Assoc 249:2345–2349CrossRefGoogle Scholar
  16. 16.
    Scott GB, Buck BE, Leterman JG et al (1984) Acquired immunodeficiency syndrome in infants. New Eng J Med 310:76–81PubMedCrossRefGoogle Scholar
  17. 17.
    Francis DP, Curran JW, Essex M (1983) Epidemic acquired immune deficiency syndrome (AIDS): epidemiologic evidence for a transmitted agent. J Natl Cancer Inst 71:1–6PubMedGoogle Scholar
  18. 18.
    Essex M, McLane MF, Lee TH, Falk L, Howe CWS, Mullins J, Cabradilla C, Francis DP (1983) Antibodies to cell membrane antigens associated with human T-cell leukemia virus in patients with AIDS. Science 220:859–862PubMedCrossRefGoogle Scholar
  19. 19.
    Essex M, McLane MF, Lee TH, Tachibana N, Mullins JI, Kreiss J, Kasper CK, Poon M-C, Landay A, Stein SF, Francis DP, Cabradilla C, Lawrence DN, Evatt BL (1983) Antibodies to human T-cell leukemia virus membrane antigens (HTLV-MA) in hemophiliacs. Science 221:1061–1064PubMedCrossRefGoogle Scholar
  20. 20.
    Gelmann EP, Franchini G, Manzari V, Wong-Staal F, Gallo RC (1984) Molecular cloning of a unique human T-cell leukemia virus (HTLV-IIMo). Proc Natl Acad Sci USA 81:993–997PubMedCrossRefGoogle Scholar
  21. 21.
    Gallo RC, Sarin PS, Gelmann EP, Robert-Guroff M, Richardson E, Kalyanaraman VS, Mann D, Sidhu GD, Stahl RE, Zolla-Pazner S, Leibowitch J, Popovic M (1983) Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science 220:865–867PubMedCrossRefGoogle Scholar
  22. 22.
    Barre-Sinoussi F, Chermann J-C, Rey F, Nugeyre MT, Chamaret S, Gruest J, Dauguet C, Axler-Blin C, Vezinet-Brun F, Rouzioux C, Rozenbaum W, Montagnier L (1983) Isolation of T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220:868–870PubMedCrossRefGoogle Scholar
  23. 23.
    Poiesz BJ, Ruscetti FW, Reitz MS, Kalyanaraman VS, Gallo RC (1981) Isolation of a new type C retrovirus (HTLV) in primary uncultured cells of a patient with Sezary T-cell leukaemia. Nature 294:268–271PubMedCrossRefGoogle Scholar
  24. 24.
    Ammann AJ, Abrams D, Conant M, Chudwin D, Cowan M, Volberding P, Lewis B, Casavant C (1983) Acquired immune dysfunction in homosexual men: immunologic profiles. Clin Immunol Immunopathol 27:315–325PubMedCrossRefGoogle Scholar
  25. 25.
    Fahey JL, Prince H, Weaver M, Groopman J, Visscher B, Schwartz K, Detels R (1984) Quantitative changes in T helper or T suppressor/cytotoxic lymphocyte subsets that distinguish acquired immune deficiency syndrome from other immune subset disorders. Amer J Med 6:95–100CrossRefGoogle Scholar
  26. 26.
    Lane HC, Masur H, Gelmann EP, Longo DL, Steis RG, Chused T, Whalen G, Edgar LC, Fauci AS (1985) Correlation between immunologic function and clinical subpopulations of patients with the acquired immune deficiency syndrome. Am J Med 78:417–422PubMedCrossRefGoogle Scholar
  27. 27.
    Kalyanaraman VS, Sarngadharan MG, Robert-Guroff M, Miyoshi I, Golde D, Gallo RC (1982) A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science 218:571–573PubMedCrossRefGoogle Scholar
  28. 28.
    Gelmann EP, Popovic M, Blayney D, Masur H, Sidhu G, Stahl RE, Gallo RC (1983) Proviral DNA of a retrovirus, human T-cell leukemia virus, in two patients with AIDS. Science 220:862–865PubMedCrossRefGoogle Scholar
  29. 29.
    Popovic M, Sarin PS, Robert GM, Kalyanaraman VS, Mann D, Minowada J, Gallo RC (1983) Isolation and transmission of human retrovirus (human T-cell leukemia virus). Science 219:856–859PubMedCrossRefGoogle Scholar
  30. 30.
    Schupbach J, Popovic M, Gilden RV, Gonda MA, Sarngadharan MG, Gallo RC (1984) Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Science 224:503–505PubMedCrossRefGoogle Scholar
  31. 31.
    Sarngadharan MG, Popovic M, Bruch L, Schupbach J, Gallo RC (1984) Antibodies reactive with human T-lymphotropic retroviruses (HTLV-III) in the serum of patients with AIDS. Science 224:506–508PubMedCrossRefGoogle Scholar
  32. 32.
    Barin F, M'Boup S, Denis F, Kanki P, Allan JS, Lee TH, Essex M (1985) Serological evidence for virus related to simian T-lymphotropic retrovirus III in residents of west Africa. Lancet 2:1387–1389PubMedCrossRefGoogle Scholar
  33. 33.
    Kanki P, Barin F, Mboup S, Allan JS, Romet-Lemonne JL, Marlink R, McLane MF, Lee TH, Arbeille B, Denis F, Essex M (1986) New human T-Lymphotropic retrovirus related to simian T-lymphotropic virus type III (STLV-IIIAGM). Science 232:238–243PubMedCrossRefGoogle Scholar
  34. 34.
    Gao F, Bailes E, Robertson DL, Chen Y, Rodenburg CM, Michael SF, Cummins LB, Arthur LO, Peeters M, Shaw GM, Sharp PM, Hahn BH (1999) Origin of HIV-1 in the chimpanzee Pan troglodytes troglodytes (see comments). Nature 397:436–441PubMedCrossRefGoogle Scholar
  35. 35.
    Hirsch VM, Olmsted RA, Murphey Corb M, Purcell RH, Johnson PR (1989) An African primate lentivirus (SIVsm) closely related to HIV-2. Nature 339:389–392PubMedCrossRefGoogle Scholar
  36. 36.
    Marlink R, Kanki P, Thior I, Travers K, Eisen G, Siby T, Traore I, Hsieh SS, Dia MC, Gueye EH, Hellinger J, Gueye NA, Sankalé JL, Ndoye I, Mboup S, Essex M (1994) Reduced rate of disease development with HIV-2 compared to HIV-1. Science 265:1587–1590PubMedCrossRefGoogle Scholar
  37. 37.
    Kanki PJ, De Cock KM (1994) Epidemiology and natural history of HIV-2. AIDS 8:S1–S9Google Scholar
  38. 38.
    Kanki P, Peeters M, Gueye-NDiaye A (1997) Virology of HIV-1 and HIV-2. AIDS 2(Suppl B):S33–S42Google Scholar
  39. 39.
    Kanki P (1989) HIV-2 infection in West Africa. In: Volberding P, Jacobson M (eds) 1988 AIDS clinical reviews. Marcel Dekker, New York, pp 95–108Google Scholar
  40. 40.
    Kanki P, Meloni S (2009) Biology and variation in HIV-2 and HIV-1. In: Marlink RG, Teitelman S (eds) From the ground up: building comprehensive HIV/AIDS care programs in resource-limited settings. Elizabeth Glaser Pediatric AIDS Foundation, Washington, DC, pp 1–24Google Scholar
  41. 41.
    Katzourakis A, Tristem M, Pybus OG, Gifford RJ (2007) Discovery and analysis of the first endogenous lentivirus. Proc Natl Acad Sci USA 104:6261–6265PubMedCrossRefGoogle Scholar
  42. 42.
    Wong-Staal F (1990) Human immunodeficiency viruses and their replication. In: Fields DM et al (eds) Virology. Raven, New York, pp 1529–1540Google Scholar
  43. 43.
  44. 44.
    Jiang S (1997) HIV-1–co-receptors binding (letter; comment) (published erratum appears in Nat Med 1997 Aug; 3(8):817). Nat Med 3:367–368PubMedCrossRefGoogle Scholar
  45. 45.
    Feng Y, Broder CC, Kennedy PE, Berger EA (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane G protein-coupled receptor. Science 272:872–877PubMedCrossRefGoogle Scholar
  46. 46.
    Deng H, Liu R, Ellmeier W, Choe S, Unutmaz D, Burkhart M, Di Marzio P, Marmon S, Sutton RE, Hill CM, Davis CB, Peiper SC, Schall TJ, Littman DR, Landau NR (1996) Identification of a major co-receptor for primary isolates of HIV-1. Nature 381:661–666PubMedCrossRefGoogle Scholar
  47. 47.
    Cocchi F, DeVico AL, Garzino-Demo A, Cara A, Gallo RC, Lusso P (1996) The V3 domain of the HIV-1 gp120 envelope glycoprotein is critical for chemokine-mediated blockade of infection. Nat Med 2:1244–1247PubMedCrossRefGoogle Scholar
  48. 48.
    Dittmar M, McNight A, Simmons G, Clapham P, Weiss R (1997) HIV-1 tropism and co-receptor use. Nature 385:495–496PubMedCrossRefGoogle Scholar
  49. 49.
    Moore PS, Boshoff C, Weiss RA, Chang Y (1996) Molecular mimicry of human cytokine and cytokine response pathway genes by KSHV. Science 274:1739–1744PubMedCrossRefGoogle Scholar
  50. 50.
    Cooper DA, Imrie AA, Penny R (1987) Antibody response to human immunodeficiency virus after primary infection. J Infect Dis 155:1113–1118PubMedCrossRefGoogle Scholar
  51. 51.
    Loes S, de Saussure P, Saurat JH, Stalder H, Hirschel B, Perrin LH (1993) Symptomatic primary infection due to human immunodeficiency virus type 1: review of 31 Cases. Clin Infect Dis 17:59–65CrossRefGoogle Scholar
  52. 52.
    Fauci AS, Pantaleo G, Stanley S, Weissman D (1996) Immunopathogenic mechanisms of HIV infection. Ann Intern Med 124:654–663PubMedGoogle Scholar
  53. 53.
    Pantaleo G, Graziosi C, Demarest JF, Butini L, Montroni M, Fox CH, Orenstein JM, Kotler DP, Fauci AS (1993) HIV infection is active and progressive in lymphoid tissue during the clinically latent stage of disease. Nature 362:355–358PubMedCrossRefGoogle Scholar
  54. 54.
    Cavarelli M, Scarlatti G (2011) Human immunodeficiency virus type 1 mother-to-child transmission and prevention: successes and controversies. J Intern Med 270(6):561–579Google Scholar
  55. 55.
    Bongaarts J, Sinding S (2011) Population policy in transition in the developing world. Science 333:574–576PubMedCrossRefGoogle Scholar
  56. 56.
    Bongaarts J, Pelletier F, Gerland P (2010) How many more AIDS deaths? Lancet 375:103–104Google Scholar
  57. 57.
    Root R (2010) Situating experiences of HIV-related stigma in Swaziland. Glob Public Health 5:523–538PubMedCrossRefGoogle Scholar
  58. 58.
    Wu Z, Sullivan SG, Wang Y, Rotheram-Borus MJ, Detels R (2007) Evolution of China’s response to HIV/AIDS. Lancet 369:679–690PubMedCrossRefGoogle Scholar
  59. 59.
    Wang L (2007) Overview of the HIV/AIDS epidemic, scientific research and government responses in China. AIDS 21(Suppl 8):S3–7PubMedCrossRefGoogle Scholar
  60. 60.
    UNAIDS (2010) Global report Europe and Central Asia.
  61. 61.
    Guillard EM, Eustache L (2007) Estimation de la séroprevalence du VIH en Haiti en 2007 selon le milieu de residence urbain et rural pour chacun des 10 départments. United States Agency for International Development, Washington, DCGoogle Scholar
  62. 62.
    Anonymous (2008) US Virgin Islands and Caribbean HIV epidemic need more attention, researchers say. HIV infection rate is high among sex workers. AIDS Alert 23:42–44Google Scholar
  63. 63.
    Bezemer D, de Wolf F, Boerlijst MC, van Sighem A, Hollingsworth TD, Prins M, Geskus RB, Gras L, Coutinho RA, Fraser C (2008) A resurgent HIV-1 epidemic among men who have sex with men in the era of potent antiretroviral therapy. AIDS 22:1071–1077PubMedCrossRefGoogle Scholar
  64. 64.
    Mathers BM, Degenhardt L, Ali H, Wiessing L, Hickman M, Mattick RP, Myers B, Ambekar A, Strathdee SA (2010) HIV prevention, treatment, and care services for people who inject drugs: a systematic review of global, regional, and national coverage. Lancet 375:1014–1028PubMedCrossRefGoogle Scholar
  65. 65.
    Strathdee SA, Hallett TB, Bobrova N, Rhodes T, Booth R, Abdool R, Hankins CA (2010) HIV and risk environment for injecting drug users: the past, present, and future. Lancet 376:268–284PubMedCrossRefGoogle Scholar
  66. 66.
    Stockman JK, Strathdee SA (2010) HIV among people who use drugs: a global perspective of populations at risk. J Acquir Immune Def Syn 55(Suppl 1):S17–22CrossRefGoogle Scholar
  67. 67.
    de Felipe B, Perez-Romero P, Abad-Fernandez M, Fernandez-Cuenca F, Martinez-Fernandez FJ, Trastoy M, Mata Rdel C, Lopez-Cortes LF, Leal M, Viciana P, Vallejo A (2011) Prevalence and resistance mutations of non-B HIV-1 subtypes among immigrants in Southern Spain along the decade 2000–2010. Virol J 8:416PubMedCrossRefGoogle Scholar
  68. 68.
    Ryan CE, Gare J, Crowe SM, Wilson K, Reeder JC, Oelrichs RB (2007) The heterosexual HIV type 1 epidemic in Papua New Guinea is dominated by subtype C. AIDS Res Hum Retroviruses 23:941–944PubMedCrossRefGoogle Scholar
  69. 69.
    Centers for Disease Control and Prevention (2011) High-impact HIV prevention – CDC’s approach to reducing HIV infections in the United States. CDC, AtlantaGoogle Scholar
  70. 70.
    Katoff L, Dunne R (1988) Supporting people with AIDS: the Gay Men’s health crisis model. J Palliat Care 4:88–95PubMedGoogle Scholar
  71. 71.
    Laga M, Galavotti C, Sundararaman S, Moodie R (2010) The importance of sex-worker interventions: the case of Avahan in India. Sex Transm Infect 86(Suppl 1):i6–7PubMedCrossRefGoogle Scholar
  72. 72.
    Verma R, Shekhar A, Khobragade S, Adhikary R, George B, Ramesh BM, Ranebennur V, Mondal S, Patra RK, Srinivasan S, Vijayaraman A, Paul SR, Bohidar N (2010) Scale-up and coverage of Avahan: a large-scale HIV-prevention programme among female sex workers and men who have sex with men in four Indian states. Sex Transm Infect 86(Suppl 1):i76–i82PubMedCrossRefGoogle Scholar
  73. 73.
    Tobian AA, Gray RH (2011) The medical benefits of male circumcision. J Am Med Assoc 306:1479–1480CrossRefGoogle Scholar
  74. 74.
    Kreiss JK, Hopkins SG (1993) The association between circumcision status and human immunodeficiency virus infection among homosexual men. J Infect Dis 168:1404–1408PubMedCrossRefGoogle Scholar
  75. 75.
    Weiss HA, Quigley MA, Hayes RJ (2000) Male circumcision and risk of HIV infection in sub-Saharan Africa: a systematic review and meta-analysis. AIDS 14:2361–2370PubMedCrossRefGoogle Scholar
  76. 76.
    Siegfried N, Muller M, Deeks JJ, Volmink J (2009) Male circumcision for prevention of heterosexual acquisition of HIV in men. Cochrane Database Syst Rev: CD003362Google Scholar
  77. 77.
    Weiss HA, Hankins CA, Dickson K (2009) Male circumcision and risk of HIV infection in women: a systematic review and meta-analysis. Lancet Infect Dis 9:669–677PubMedCrossRefGoogle Scholar
  78. 78.
    Auvert B, Taljaard D, Lagarde E, Sobngwi-Tambekou J, Sitta R, Puren A (2005) Randomized, controlled intervention trial of male circumcision for reduction of HIV infection risk: the ANRS 1265 Trial. PLoS Med 2:e298PubMedCrossRefGoogle Scholar
  79. 79.
    Gray RH, Kigozi G, Serwadda D, Makumbi F, Watya S, Nalugoda F, Kiwanuka N, Moulton LH, Chaudhary MA, Chen MZ, Sewankambo NK, Wabwire-Mangen F, Bacon MC, Williams CF, Opendi P, Reynolds SJ, Laeyendecker O, Quinn TC, Wawer MJ (2007) Male circumcision for HIV prevention in men in Rakai, Uganda: a randomised trial. Lancet 369:657–666PubMedCrossRefGoogle Scholar
  80. 80.
    Wawer MJ, Makumbi F, Kigozi G, Serwadda D, Watya S, Nalugoda F, Buwembo D, Ssempijja V, Kiwanuka N, Moulton LH, Sewankambo NK, Reynolds SJ, Quinn TC, Opendi P, Iga B, Ridzon R, Laeyendecker O, Gray RH (2009) Circumcision in HIV-infected men and its effect on HIV transmission to female partners in Rakai, Uganda: a randomised controlled trial. Lancet 374:229–237PubMedCrossRefGoogle Scholar
  81. 81.
    WHO/UNAIDS (2007) Announce recommendations about male circumcision as HIV prevention. Strategy should be employed with care. AIDS Alert 22:66–67Google Scholar
  82. 82.
    Shapiro RL, Hughes MD, Ogwu A, Kitch D, Lockman S, Moffat C, Makhema J, Moyo S, Thior I, McIntosh K, van Widenfelt E, Leidner J, Powis K, Asmelash A, Tumbare E, Zwerski S, Sharma U, Handelsman E, Mburu K, Jayeoba O, Moko E, Souda S, Lubega E, Akhtar M, Wester C, Tuomola R, Snowden W, Martinez-Tristani M, Mazhani L, Essex M (2010) Antiretroviral regimens in pregnancy and breast-feeding in Botswana. N Engl J Med 362:2282–2294PubMedCrossRefGoogle Scholar
  83. 83.
    Chasela CS, Hudgens MG, Jamieson DJ, Kayira D, Hosseinipour MC, Kourtis AP, Martinson F, Tegha G, Knight RJ, Ahmed YI, Kamwendo DD, Hoffman IF, Ellington SR, Kacheche Z, Soko A, Wiener JB, Fiscus SA, Kazembe P, Mofolo IA, Chigwenembe M, Sichali DS, van der Horst CM (2010) Maternal or infant antiretroviral drugs to reduce HIV-1 transmission. N Engl J Med 362:2271–2281PubMedCrossRefGoogle Scholar
  84. 84.
    World Health Organization (2010) Antiretroviral drugs for treating pregnant woman and preventing HIV infections in infants, Recommendations for a public health approach. 2010 revision.Google Scholar
  85. 85.
    Youle M, Wainberg MA (2003) Pre-exposure chemoprophylaxis (PREP) as an HIV prevention strategy. J Int Assoc Physicians AIDS Care (Chic) 2:102–105CrossRefGoogle Scholar
  86. 86.
    Young TN, Arens FJ, Kennedy GE, Laurie JW, Rutherford G (2007) Antiretroviral post-exposure prophylaxis (PEP) for occupational HIV exposure. Cochrane Database Syst Rev:CD002835Google Scholar
  87. 87.
    Karim QA, Kharsany AB, Frohlich JA, Baxter C, Yende N, Mansoor LE, Mlisana KP, Maarschalk S, Arulappan N, Grobler A, Sibeko S, Omar Z, Gengiah TN, Mlotshwa M, Samsunder N, Karim SS (2011) Recruitment of high risk women for HIV prevention trials: baseline HIV prevalence and sexual behavior in the CAPRISA 004 tenofovir gel trial. Trials 12:67PubMedCrossRefGoogle Scholar
  88. 88.
    Karim QA, Kharsany AB, Naidoo K, Yende N, Gengiah T, Omar Z, Arulappan N, Mlisana KP, Luthuli LR, Karim SS (2011) Co-enrollment in multiple HIV prevention trials – experiences from the CAPRISA 004 Tenofovir gel trial. Contemp Clin Trials 32:333–338PubMedCrossRefGoogle Scholar
  89. 89.
    Abdool Karim Q, Abdool Karim SS, Frohlich JA, Grobler AC, Baxter C, Mansoor LE, Kharsany AB, Sibeko S, Mlisana KP, Omar Z, Gengiah TN, Maarschalk S, Arulappan N, Mlotshwa M, Morris L, Taylor D (2010) Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women. Science 329:1168–1174PubMedCrossRefGoogle Scholar
  90. 90.
    Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, Goicochea P, Casapia M, Guanira-Carranza JV, Ramirez-Cardich ME, Montoya-Herrera O, Fernandez T, Veloso VG, Buchbinder SP, Chariyalertsak S, Schechter M, Bekker LG, Mayer KH, Kallas EG, Amico KR, Mulligan K, Bushman LR, Hance RJ, Ganoza C, Defechereux P, Postle B, Wang F, McConnell JJ, Zheng JH, Lee J, Rooney JF, Jaffe HS, Martinez AI, Burns DN, Glidden DV (2010) Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med 363:2587–2599PubMedCrossRefGoogle Scholar
  91. 91.
    Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, Hakim JG, Kumwenda J, Grinsztejn B, Pilotto JH, Godbole SV, Mehendale S, Chariyalertsak S, Santos BR, Mayer KH, Hoffman IF, Eshleman SH, Piwowar-Manning E, Wang L, Makhema J, Mills LA, de Bruyn G, Sanne I, Eron J, Gallant J, Havlir D, Swindells S, Ribaudo H, Elharrar V, Burns D, Taha TE, Nielsen-Saines K, Celentano D, Essex M, Fleming TR (2011) Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365:493–505PubMedCrossRefGoogle Scholar
  92. 92.
    Vissers DC, Voeten HA, Nagelkerke NJ, Habbema JD, de Vlas SJ (2008) The impact of pre-exposure prophylaxis (PrEP) on HIV epidemics in Africa and India: a simulation study. PLoS One 3:e2077PubMedCrossRefGoogle Scholar
  93. 93.
    Veronese F, Anton P, Fletcher CV, DeGruttola V, McGowan I, Becker S, Zwerski S, Burns D (2011) Implications of HIV PrEP trials results. AIDS Res Hum Retroviruses 27:81–90PubMedCrossRefGoogle Scholar
  94. 94.
    Alizon M, Wain-Hobson S, Montagnier L, Sonigo P (1986) Genetic variability of the AIDS virus: nucleotide sequence analysis of two isolates from African patients. Cell 46:63–74PubMedCrossRefGoogle Scholar
  95. 95.
    Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH, Saag MS, Shaw GM (1995) Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373:117–122PubMedCrossRefGoogle Scholar
  96. 96.
    Ho DD, Nuemann AU, Perelson AS, Chen W, Leonard JM, Markovitz M (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373:123–126PubMedCrossRefGoogle Scholar
  97. 97.
    Starcich BR, Hahn BH, Shaw GM, McNeely PD, Modrow S, Wolf H, Parks ES, Parks WP, Josephs SF, Gallo RC, Wong-Staal F (1986) Identification and characterization of conserved and variable regions in the envelope gene of HTLV-III/LAV, the retrovirus of AIDS. Cell 45:637–648PubMedCrossRefGoogle Scholar
  98. 98.
    Wong-Staal F, Gallo RC (1985) Human T-lymphotropic retroviruses. Nature 317:395–403PubMedCrossRefGoogle Scholar
  99. 99.
    Myers G, Pavlakis GN (1992) Evolutionary potential of complex retroviruses. In: Levy JA (ed) The retroviridae. Plenum, New York, pp 1–37Google Scholar
  100. 100.
    Goodenow M, Huet TH, Saurin W, Kowk S, Sninsky J, Wain-Hobson S (1989) HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Def Syn 2:344–352Google Scholar
  101. 101.
    Wolfs TFW, deJong JJ, van den Berg H, Tijnagel JMGH, Krone WJA, Goudsmit J (1990) Evolution of sequences encoding the principal neutralization epitope of human immunodeficiency virus type 1 is host dependent, rapid, and continuous. Proc Natl Acad Sci USA 87:9938–9942PubMedCrossRefGoogle Scholar
  102. 102.
    Balfe P, Simmonds P, Ludlam CA, Bishop JO, Brown AJ (1990) Concurrent evolution of human immunodeficiency virus type 1 in patients infected from the same source: rate of sequence change and low frequency of inactivating mutations. J Virol 64:6221–6233PubMedGoogle Scholar
  103. 103.
    Essex M, Kanki P (1997) Human immunodeficiency virus type 2 (HIV-2). In: Merigan T, Bartlett J, Bologenesi D (eds) Textbook of AIDS medicine, 2nd edn. Williams & Wilkins, Baltimore, pp 873–886Google Scholar
  104. 104.
    Sharp PM, Bailes E, Chaudhuri RR, Rodenburg CM, Santiago MO, Hahn BH (2001) The origins of acquired immune deficiency syndrome viruses: where and when? Philos Trans R Soc Lond B Biol Sci 356:867–876PubMedCrossRefGoogle Scholar
  105. 105.
    Gurtler LG, Hauser PH, Eberle J, von Brunn A, Knapp S, Zekeng L, Tsague JM, Kaptue L (1994) A new subtype of human immunodeficiency virus type 1 (MVP-5180) from Cameroon. J Virol 68:1581–1585PubMedGoogle Scholar
  106. 106.
    Simon F, Mauclére P, Roques P, Loussert-Ajaka I, Muller-Trutwin MC, Saragosti S, Georges-Courbot MC, Barre-Sinoussi F, Brun-Vezinet F (1998) Identification of a new human immunodeficiency virus type 1 distinct from group M and group O. Nat Med 4:1032–1037PubMedCrossRefGoogle Scholar
  107. 107.
    Plantier JC, Leoz M, Dickerson JE, De Oliveira F, Cordonnier F, Lemee V, Damond F, Robertson DL, Simon F (2009) A new human immunodeficiency virus derived from gorillas. Nat Med 15:871–872PubMedCrossRefGoogle Scholar
  108. 108.
    Keele BF, Van Heuverswyn F, Li Y, Bailes E, Takehisa J, Santiago ML, Bibollet-Ruche F, Chen Y, Wain LV, Liegeois F, Loul S, Ngole EM, Bienvenue Y, Delaporte E, Brookfield JF, Sharp PM, Shaw GM, Peeters M, Hahn BH (2006) Chimpanzee reservoirs of pandemic and nonpandemic HIV-1. Science 313:523–526PubMedCrossRefGoogle Scholar
  109. 109.
    Hemelaar J, Gouws E, Ghys PD, Osmanov S (2011) Global trends in molecular epidemiology of HIV-1 during 2000–2007. AIDS 25:679–689PubMedCrossRefGoogle Scholar
  110. 110.
    Louwagie J, McCutchan F, Mascola J (1993) Genetic subtypes of HIV-1. AIDS Res Hum Retroviruses 9(Suppl 1):147s–150sGoogle Scholar
  111. 111.
    Louwagie J, McCutchan F, Peeters M (1993) Phylogenetic analysis of gag genes from 70 international HIV-1 isolates provides evidence for multiple genotypes. AIDS 7:769–780PubMedCrossRefGoogle Scholar
  112. 112.
    McCutchan F, Salimen MO, Carr JK, Burke DS (1996) HIV-1 genetic diversity. AIDS 10:S13–S20PubMedCrossRefGoogle Scholar
  113. 113.
    Burke D, McCutchan F (1997) Global distribution of human immunodeficiency virus-1 clades. In: Vincent T, DeVita J, Hellman S, Rosenberg S (eds) AIDS: biology, diagnosis, treatment and preventions, 4th edn. Lippincott-Raven, Philadelphia, pp 119–126Google Scholar
  114. 114.
    Weniger BG, Takebe Y, Ou C-Y, Yamazaki S (1994) The molecular epidemiology of HIV in Asia. AIDS 8:13s–28sCrossRefGoogle Scholar
  115. 115.
    Korber B, Brander C, Moore J, D’Souza P, Walker B, Koup R, Moore J, Haynes B, Myers G (eds) (1996) HIV molecular immunology database 1996. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los AlamosGoogle Scholar
  116. 116.
    Robertson D, Gao F, Hahn B, Sharp PM (1997) Intersubtype recombinant HIV-1 sequences. In: Korber B, Hahn B, Foley B, Mellors JW, Leitner T, Myers G, McCutchan F, Kuiken C (eds) Human retroviruses and AIDS 1997. Theoretical Biology and Biophysics Group, Los Alamos National Laboratory, Los Alamos, pp III-25-III30Google Scholar
  117. 117.
    Jain MK, John TJ, Keusch GT (1994) Epidemiology of HIV and AIDS in India. AIDS 8:S61–75PubMedGoogle Scholar
  118. 118.
    Soto-Ramirez LE, Renjifo B, McLane MF, Marlink R, O’Hara C, Sutthent R, Wasi C, Vithayasai P, Vithayasai V, Apichartpiyakul C, Auewarakul P, Pena Cruz V, Chui DS, Osathanondh R, Mayer K, Lee TH, Essex M (1996) HIV-1 Langerhans’ cell tropism associated with heterosexual transmission of HIV. Science 271:1291–1293PubMedCrossRefGoogle Scholar
  119. 119.
    Taylor BS, Sobieszczyk ME, McCutchan FE, Hammer SM (2008) The challenge of HIV-1 subtype diversity. N Engl J Med 358:1590–1602PubMedCrossRefGoogle Scholar
  120. 120.
    Vanharmelen J, Wood R, Lambrick M, Rybicki EP, Williamson AL, Williamson C (1997) An association between HIV-1 subtypes and mode of transmission in Capetown, South Africa. AIDS 11:81–87CrossRefGoogle Scholar
  121. 121.
    Liitsola K, Holmstrom P, Laukkanen T, Brummer-Korvenkontio H, Leinikki P, Salminen MO (2000) Analysis of HIV-1 genetic subtypes in Finland reveals good correlation between molecular and epidemiological data. Scand J Infect Dis 32:475–480PubMedCrossRefGoogle Scholar
  122. 122.
    Kalish ML, Korber BT, Pillai S, Robbins KE, Leo YS, Saekhou A, Verghese I, Gerrish P, Goh CL, Lupo D (2002) The sequential introduction of HIV-1 subtype B and CRF01 in Singapore by sexual transmission: accelerated V3 region evolution in a subpopulation of Asian CRF01 viruses. Virology 304:311–329PubMedCrossRefGoogle Scholar
  123. 123.
    Ou CY, Takebe Y, Weniger BG, Luo CC, Kalish ML, Auwanit W, Yamazaki S, Gayle HD, Young NL, Schochetman G (1993) Independent introduction of two major HIV-1 genotypes into distinct high-risk populations in Thailand. Lancet 341:1171–1174PubMedCrossRefGoogle Scholar
  124. 124.
    Herring BL, Ge YC, Wang B, Ratnamohan M, Zheng F, Cunningham AL, Saksena NK, Dwyer DE (2003) Segregation of human immunodeficiency virus type 1 subtypes by risk factor in Australia. J Clin Microbiol 41:4600–4604PubMedCrossRefGoogle Scholar
  125. 125.
    Renjifo B, Fawzi W, Mwakagile D, Hunter D, Msamanga G, Spiegelman D, Garland M, Kagoma C, Kim A, Chaplin B, Hertzmark E, Essex M (2001) Differences in perinatal transmission among human immunodeficiency virus type 1 genotypes. J Hum Virol 4:16–25PubMedGoogle Scholar
  126. 126.
    Renjifo B, Gilbert P, Chaplin B, Vannberg F, Mwakagile D, Msamanga G, Hunter D, Fawzi W, Essex M (1999) Emerging recombinant human immunodeficiency viruses: uneven representation of the envelope V3 region. AIDS 13:1613–1621PubMedCrossRefGoogle Scholar
  127. 127.
    Hudgens MG, Longini IM Jr, Vanichseni S, Hu DJ, Kitayaporn D, Mock PA, Halloran ME, Satten GA, Choopanya K, Mastro TD (2002) Subtype-specific transmission probabilities for human immunodeficiency virus type 1 among injecting drug users in Bangkok, Thailand. Am J Epidemiol 155:159–168PubMedCrossRefGoogle Scholar
  128. 128.
    Kanki PJ, Hamel DJ, Sankalé JL, Hsieh CC, Thior I, Barin F, Woodcock SA, Guèye-NDiaye A, Zhang E, Montano M, NDoye I, Essex ME, MBoup S (1999) Human immunodeficiency virus type 1 subtypes differ in disease progression. J Infect Dis 179:68–73PubMedCrossRefGoogle Scholar
  129. 129.
    Kaleebu P, French N, Mahe C, Yirrell D, Watera C, Lyagoba F, Nakiyingi J, Rutebemberwa A, Morgan D, Weber J, Gilks C, Whitworth J (2002) Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda. J Infect Dis 185:1244–1250PubMedCrossRefGoogle Scholar
  130. 130.
    Kaleebu P, Ross A, Morgan D, Yirrell D, Oram J, Rutebemberwa A, Lyagoba F, Hamilton L, Biryahwaho B, Whitworth J (2001) Relationship between HIV-1 env subtypes A and D and disease progression in a rural Ugandan cohort. AIDS 15:293–299PubMedCrossRefGoogle Scholar
  131. 131.
    Neilson JR, John GC, Carr JK, Lewis P, Kreiss JK, Jackson S, Nduati RW, Mbori-Ngacha D, Panteleeff DD, Bodrug S, Giachetti C, Bott MA, Richardson BA, Bwayo J, Ndinya-Achola J, Overbaugh J (1999) Subtypes of human immunodeficiency virus type 1and disease stage among women in Nairobi, Kenya. J Virol 73:4393–4403PubMedGoogle Scholar
  132. 132.
    Hu DJ, Vanichseni S, Mastro TD, Raktham S, Young NL, Mock PA, Subbarao S, Parekh BS, Srisuwanvilai L, Sutthent R, Wasi C, Heneine W, Choopanya K (2001) Viral load differences in early infection with two HIV-1 subtypes. AIDS 15:683–691PubMedCrossRefGoogle Scholar
  133. 133.
    Sarr AD, Eisen G, Gueye-Ndiaye A, Mullins C, Traore I, Dia MC, Sankale JL, Faye D, Mboup S, Kanki P (2005) Viral dynamics of primary HIV-1 infection in Senegal, West Africa. J Infect Dis 191:1460–1467PubMedCrossRefGoogle Scholar
  134. 134.
    Sagar M, Lavreys L, Baeten JM, Richardson BA, Mandaliya K, Chohan BH, Kreiss JK, Overbaugh J (2003) Infection with multiple human immunodeficiency virus type 1 variants is associated with faster disease progression. J Virol 77:12921–12926PubMedCrossRefGoogle Scholar
  135. 135.
    Zhang M, Foley B, Schultz AK, Macke JP, Bulla I, Stanke M, Morgenstern B, Korber B, Leitner T (2010) The role of recombination in the emergence of a complex and dynamic HIV epidemic. Retrovirology 7:25–40PubMedCrossRefGoogle Scholar
  136. 136.
    Ellenberger DL, Li B, Lupo LD, Owen SM, Nkengasong J, Kadio-Morokro MS, Smith J, Robinson H, Ackers M, Greenberg A, Folks T, Butera S (2002) Generation of a consensus sequence from prevalent and incident HIV-1 infections in West Africa to guide AIDS vaccine development. Virology 302:156–163CrossRefGoogle Scholar
  137. 137.
    Essex M (2009) The impact of HIV variation on prevention and treatment. In: Kanki PM, Marlink RG (eds) A line drawn in the sand. Harvard University Press, Cambridge, MA, pp 231–242Google Scholar
  138. 138.
    Siegfried N, Uthman OA, Rutherford GW (2010) Optimal time for initiation of antiretroviral therapy in asymptomatic, HIV-infected, treatment-naive adults. Cochrane Database Syst Rev:CD008272Google Scholar
  139. 139.
    Spaulding A, Rutherford GW, Siegfried N (2010) Tenofovir or zidovudine in three-drug combination therapy with one nucleoside reverse transcriptase inhibitor and one non-nucleoside reverse transcriptase inhibitor for initial treatment of HIV infection in antiretroviral-naive individuals. Cochrane Database Syst Rev:CD008740Google Scholar
  140. 140.
    Spaulding A, Rutherford GW, Siegfried N (2010) Stavudine or zidovudine in three-drug combination therapy for initial treatment of HIV infection in antiretroviral-naive individuals. Cochrane Database Syst Rev:CD008651Google Scholar
  141. 141.
    Coffin JM (1996) HIV viral dynamics. AIDS 10:S75–84PubMedCrossRefGoogle Scholar
  142. 142.
    Kanki P, Marlink RG (2009) A line drawn in the sand: responses to the AIDS treatment crisis in Africa. Harvard University Press, Cambridge, MAGoogle Scholar
  143. 143.
    United Nations (2001) Secretary-general urges united states business leaders to take concerted action against “Unparalleled Nightmare” of AIDS, U.N. DocumentGoogle Scholar
  144. 144.
  145. 145.
    PEPFAR (2011) United States President’s emergency plan for AIDS relief.
  146. 146.
    GFATM (2002) Global fund to fight AIDS, Tuberculosis and Malaria.
  147. 147.
    BMGF (2011) Bill & Melinda Gates Foundation Global Health
  148. 148.
  149. 149.
  150. 150.
    MSF (2011) Medecins sans Frontieres.
  151. 151.
    Holmes C, Coggin W, Jamieson D, Mihm H, Savio P, Hope M, Ryan C, Moloney-Kitts M, Dybul M (2009) Measuring progress in reducing the costs of ARV drugs purchased by the president’s emergency plan for AIDS relief, 2005–2007. In: Conference on retroviruses and opportunistic infections. Montreal, CanadaGoogle Scholar
  152. 152.
    Shearer G, Clerici M (2010) Historical perspective on HIV-exposed seronegative individuals: has nature done the experiment for us? J Infect Dis 202(Suppl 3):S329–332PubMedCrossRefGoogle Scholar
  153. 153.
    O'Brien SJ, Nelson GW (2004) Human genes that limit AIDS. Nat Genet 36:565–574PubMedCrossRefGoogle Scholar
  154. 154.
    Wu X, Yang ZY, Li Y, Hogerkorp CM, Schief WR, Seaman MS, Zhou T, Schmidt SD, Wu L, Xu L, Longo NS, McKee K, O’Dell S, Louder MK, Wycuff DL, Feng Y, Nason M, Doria-Rose N, Connors M, Kwong PD, Roederer M, Wyatt RT, Nabel GJ, Mascola JR (2010) Rational design of envelope identifies broadly neutralizing human monoclonal antibodies to HIV-1. Science 329:856–861PubMedCrossRefGoogle Scholar
  155. 155.
    Koup RA, Graham BS, Douek DC (2011) The quest for a T cell-based immune correlate of protection against HIV: a story of trials and errors. Nat Rev Immunol 11:65–70PubMedCrossRefGoogle Scholar
  156. 156.
    Bradac J, Dieffenbach CW (2009) HIV vaccine development: lessons from the past, informing the future. IDrugs 12:435–439PubMedGoogle Scholar
  157. 157.
    Girard MP, Osmanov S, Assossou OM, Kieny MP (2011) Human immunodeficiency virus (HIV) immunopathogenesis and vaccine development: a review. Vaccine 29:6191–6218PubMedCrossRefGoogle Scholar
  158. 158.
    Fauci AS, Johnston MI, Dieffenbach CW, Burton DR, Hammer SM, Hoxie JA, Martin M, Overbaugh J, Watkins DI, Mahmoud A, Greene WC (2008) HIV vaccine research: the way forward. Science 321:530–532PubMedCrossRefGoogle Scholar
  159. 159.
    Corey L, McElrath MJ (2010) HIV vaccines: mosaic approach to virus diversity. Nat Med 16:268–270PubMedCrossRefGoogle Scholar
  160. 160.
    Caputo A, Gavioli R, Bellino S, Longo O, Tripiciano A, Francavilla V, Sgadari C, Paniccia G, Titti F, Cafaro A, Ferrantelli F, Monini P, Ensoli F, Ensoli B (2009) HIV-1 Tat-based vaccines: an overview and perspectives in the field of HIV/AIDS vaccine development. Int Rev Immunol 28:285–334PubMedCrossRefGoogle Scholar
  161. 161.
    MacGregor RR, Boyer JD, Ugen KE, Lacy KE, Gluckman SJ, Bagarazzi ML, Chattergoon MA, Baine Y, Higgins TJ, Ciccarelli RB, Coney LR, Ginsberg RS, Weiner DB (1998) First human trial of a DNA-based vaccine for treatment of human immunodeficiency virus type 1 infection: safety and host response. J Infect Dis 178:92–100PubMedCrossRefGoogle Scholar
  162. 162.
    Pantaleo G, Esteban M, Jacobs B, Tartaglia J (2010) Poxvirus vector-based HIV vaccines. Curr Opin HIV AIDS 5:391–396PubMedCrossRefGoogle Scholar
  163. 163.
    Graham BS, Koup RA, Roederer M, Bailer RT, Enama ME, Moodie Z, Martin JE, McCluskey MM, Chakrabarti BK, Lamoreaux L, Andrews CA, Gomez PL, Mascola JR, Nabel GJ (2006) Phase 1 safety and immunogenicity evaluation of a multiclade HIV-1 DNA candidate vaccine. J Infect Dis 194:1650–1660PubMedCrossRefGoogle Scholar
  164. 164.
    Flynn NM, Forthal DN, Harro CD, Judson FN, Mayer KH, Para MF (2005) Placebo-controlled phase 3 trial of a recombinant glycoprotein 120 vaccine to prevent HIV-1 infection. J Infect Dis 191:654–665PubMedCrossRefGoogle Scholar
  165. 165.
    Gilbert PB, Peterson ML, Follmann D, Hudgens MG, Francis DP, Gurwith M, Heyward WL, Jobes DV, Popovic V, Self SG, Sinangil F, Burke D, Berman PW (2005) Correlation between immunologic responses to a recombinant glycoprotein 120 vaccine and incidence of HIV-1 infection in a phase 3 HIV-1 preventive vaccine trial. J Infect Dis 191:666–677PubMedCrossRefGoogle Scholar
  166. 166.
    Gilbert PB, Ackers ML, Berman PW, Francis DP, Popovic V, Hu DJ, Heyward WL, Sinangil F, Shepherd BE, Gurwith M (2005) HIV-1 virologic and immunologic progression and initiation of antiretroviral therapy among HIV-1-infected subjects in a trial of the efficacy of recombinant glycoprotein 120 vaccine. J Infect Dis 192:974–983PubMedCrossRefGoogle Scholar
  167. 167.
    Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN (2008) Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372:1881–1893PubMedCrossRefGoogle Scholar
  168. 168.
    McElrath MJ, De Rosa SC, Moodie Z, Dubey S, Kierstead L, Janes H, Defawe OD, Carter DK, Hural J, Akondy R, Buchbinder SP, Robertson MN, Mehrotra DV, Self SG, Corey L, Shiver JW, Casimiro DR (2008) HIV-1 vaccine-induced immunity in the test-of-concept step study: a case-cohort analysis. Lancet 372:1894–1905PubMedCrossRefGoogle Scholar
  169. 169.
    Gray G, Buchbinder S, Duerr A (2010) Overview of STEP and Phambili trial results: two phase IIb test-of-concept studies investigating the efficacy of MRK adenovirus type 5 gag/pol/nef subtype B HIV vaccine. Curr Opin HIV AIDS 5:357–361PubMedCrossRefGoogle Scholar
  170. 170.
    Nicholson O, Dicandilo F, Kublin J, Sun X, Quirk E, Miller M, Gray G, Pape J, Robertson MN, Mehrotra DV, Self S, Turner K, Sanchez J, Pitisuttithum P, Duerr A, Dubey S, Kierstead L, Casimiro D, Hammer SM (2010) Safety and immunogenicity of the MRKAd5 gag HIV type 1 vaccine in a worldwide phase 1 study of healthy adults. AIDS Res Hum Retroviruses 27(5):557–567Google Scholar
  171. 171.
    Voronin Y, Manrique A, Bernstein A (2010) The future of HIV vaccine research and the role of the Global HIV Vaccine Enterprise. Curr Opin HIV AIDS 5:414–420PubMedCrossRefGoogle Scholar
  172. 172.
    Voronin Y, Phogat S (2010) HIV/AIDS: vaccines and alternate strategies for treatment and prevention. Ann NY Acad Sci 1205(Suppl 1):E1–9PubMedCrossRefGoogle Scholar
  173. 173.
    Nitayaphan S, Pitisuttithum P, Karnasuta C, Eamsila C, de Souza M, Morgan P, Polonis V, Benenson M, VanCott T, Ratto-Kim S, Kim J, Thapinta D, Garner R, Bussaratid V, Singharaj P, El-Habib R, Gurunathan S, Heyward W, Birx D, McNeil J, Brown AE (2004) Safety and immunogenicity of an HIV subtype B and E prime-boost vaccine combination in HIV-negative Thai adults. J Infect Dis 190:702–706PubMedCrossRefGoogle Scholar
  174. 174.
    Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, Kaewkungwal J, Chiu J, Paris R, Premsri N, Namwat C, de Souza M, Adams E, Benenson M, Gurunathan S, Tartaglia J, McNeil JG, Francis DP, Stablein D, Birx DL, Chunsuttiwat S, Khamboonruang C, Thongcharoen P, Robb ML, Michael NL, Kunasol P, Kim JH (2009) Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 361:2209–2220PubMedCrossRefGoogle Scholar
  175. 175.
    Kresge KJ (2009) Raft of results energizes researchers. IAVI Rep 13:4–5, 7–13, 17Google Scholar
  176. 176.
    Dieffenbach CW, Fauci AS (2011) Thirty years of HIV and AIDS: future challenges and opportunities. Ann Intern Med 154:766–771PubMedGoogle Scholar
  177. 177.
    World Health Organization (2010) Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2010 Revision, GenevaGoogle Scholar

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© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of Immunology and Infectious DiseasesHarvard School of Public HealthBostonUSA

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