HIV/AIDS Global Epidemic
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.
KeywordsMale Circumcision Intravenous Drug User Contaminate Blood Product International Donor Community United Nations Millennium Summit
- 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.UNAIDS (2007) AIDS epidemic update. http://data.unaids.org/pub/epislides/2007/2007_epiupdate_en.pdf
- 2.UNAIDS (2009) AIDS epidemic update. http://data.unaids.org/pub/Report/2009/JCI700/EpiUpdate2009en.pdf
- 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.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.Anonymous (1982) Epidemiologic aspects of the current outbreak of Kaposi’s sarcoma and opportunistic infections. New Eng J Med 306:248–252Google Scholar
- 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
- 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
- 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
- 37.Kanki PJ, De Cock KM (1994) Epidemiology and natural history of HIV-2. AIDS 8:S1–S9Google Scholar
- 38.Kanki P, Peeters M, Gueye-NDiaye A (1997) Virology of HIV-1 and HIV-2. AIDS 2(Suppl B):S33–S42Google Scholar
- 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.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
- 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.NIAID (2011) HIV Replication cycle. http://www.niaid.nih.gov/topics/HIVAIDS/Understanding/Biology/Pages/hivReplicationCycle.aspx
- 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
- 56.Bongaarts J, Pelletier F, Gerland P (2010) How many more AIDS deaths? Lancet 375:103–104Google Scholar
- 60.UNAIDS (2010) Global report Europe and Central Asia. http://www.unaids.org/en/regionscountries/regions/easterneuropeandcentralasia/
- 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.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
- 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
- 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
- 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
- 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
- 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.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.WHO/UNAIDS (2007) Announce recommendations about male circumcision as HIV prevention. Strategy should be employed with care. AIDS Alert 22:66–67Google Scholar
- 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.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.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
- 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.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
- 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.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.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
- 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.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
- 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
- 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
- 110.Louwagie J, McCutchan F, Mascola J (1993) Genetic subtypes of HIV-1. AIDS Res Hum Retroviruses 9(Suppl 1):147s–150sGoogle Scholar
- 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
- 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.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
- 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
- 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
- 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
- 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
- 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
- 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.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.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.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.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
- 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.United Nations (2001) Secretary-general urges united states business leaders to take concerted action against “Unparalleled Nightmare” of AIDS, U.N. DocumentGoogle Scholar
- 144.UNAIDS (2003) AIDS epidemic. data.unaids.org/publications/inc-pub06/jc943.epiupdate2003_en_pdf
- 145.PEPFAR (2011) United States President’s emergency plan for AIDS relief. http://www.pepfar.gov/about/index.html
- 146.GFATM (2002) Global fund to fight AIDS, Tuberculosis and Malaria. http://www.theglobalfund.org/en/
- 147.BMGF (2011) Bill & Melinda Gates Foundation Global Health http://www.gatesfoundation.org/global-health/Pages/overview.aspx
- 148.CHAI (2011) Clinton Health Access Initiative. http://www.clintonfoundation.org/what-we-do/clinton-health-access-initiative
- 149.MAP (2011) World Bank Multi-Country HIV/AIDS Program (MAP). http://web.worldbank.org/WBSITE/EXTERNAL/COUNTRIES/AFRICAEXT/EXTAFRHEANUTPOP/EXTAFRREGTOPHIVAIDS/0,,contentMDK:20415735∼menuPK:1001234∼pagePK:34004173∼piPK:34003707∼theSitePK:717148,00.html
- 150.MSF (2011) Medecins sans Frontieres. http://www.msf.org/msf/about-msf/about-msf_home.cfm
- 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
- 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
- 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.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
- 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
- 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.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.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.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
- 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
- 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.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.Kresge KJ (2009) Raft of results energizes researchers. IAVI Rep 13:4–5, 7–13, 17Google Scholar
- 177.World Health Organization (2010) Antiretroviral therapy for HIV infection in adults and adolescents: recommendations for a public health approach. 2010 Revision, GenevaGoogle Scholar