UpToDate
Official reprint from UpToDate®
www.uptodate.com ©2016 UpToDate®

Factors affecting HIV progression

Author
John G Bartlett, MD
Section Editor
Martin S Hirsch, MD
Deputy Editor
Jennifer Mitty, MD, MPH

INTRODUCTION

As of 2009, the World Health Organization (WHO) estimated that approximately 33 million people are living with HIV/AIDS [1]. From early in the HIV epidemic, it was clear that some patients rapidly progressed to AIDS, while others experienced relative immunologic stability.

Laboratory measurements, such as numbers of CD4 cells and levels of plasma HIV RNA, are helpful in determining the stage of infection and may serve as prognostic markers. Other factors may also influence outcome. This topic covers the demographic, viral, and host factors that may play a role in disease progression as well as describing the important impact antiretroviral therapy has had over the past decade.

The relative stages of HIV infection are discussed elsewhere. (See "The natural history and clinical features of HIV infection in adults and adolescents".)

LABORATORY MARKERS OF PROGRESSION

Two important laboratory determinants of the rate of progression are the CD4 cell count and the plasma viral load [2,3]. (See "Techniques and interpretation of measurement of the CD4 cell count in HIV-infected patients" and "Techniques and interpretation of HIV-1 RNA quantitation".)

CD4 counts and levels of HIV RNA — The average rate of decline of CD4 cells ("CD4 slope") is about 50/mm3 per year and the average viral burden (without therapy) is 30,000 to 50,000 copies/mL. The CD4 cell count and the viral load are independent predictors of progression [2-4]. This is illustrated by the following natural history studies prior to the era of HAART [4,5]:

                              

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Nov 2016. | This topic last updated: Fri Nov 13 00:00:00 GMT+00:00 2015.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2016 UpToDate, Inc.
References
Top
  1. http://www.unaids.org/en/aboutunaids/.
  2. Mellors JW, Rinaldo CR Jr, Gupta P, et al. Prognosis in HIV-1 infection predicted by the quantity of virus in plasma. Science 1996; 272:1167.
  3. Mellors JW, Muñoz A, Giorgi JV, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 1997; 126:946.
  4. Vlahov D, Graham N, Hoover D, et al. Prognostic indicators for AIDS and infectious disease death in HIV-infected injection drug users: plasma viral load and CD4+ cell count. JAMA 1998; 279:35.
  5. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. www.aidsinfo.nih.gov/guidelines/adult/AA_040705.pdf (Accessed on April 07, 2005).
  6. Rodríguez B, Sethi AK, Cheruvu VK, et al. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA 2006; 296:1498.
  7. Giorgi JV, Liu Z, Hultin LE, et al. Elevated levels of CD38+ CD8+ T cells in HIV infection add to the prognostic value of low CD4+ T cell levels: results of 6 years of follow-up. The Los Angeles Center, Multicenter AIDS Cohort Study. J Acquir Immune Defic Syndr 1993; 6:904.
  8. Egger M, May M, Chêne G, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 2002; 360:119.
  9. Gebo KA, Gallant JE, Keruly JC, Moore RD. Absolute CD4 vs. CD4 percentage for predicting the risk of opportunistic illness in HIV infection. J Acquir Immune Defic Syndr 2004; 36:1028.
  10. Goicoechea M, Haubrich R. CD4 lymphocyte percentage versus absolute CD4 lymphocyte count in predicting HIV disease progression: an old debate revisited. J Infect Dis 2005; 192:945.
  11. Moore DM, Hogg RS, Yip B, et al. CD4 percentage is an independent predictor of survival in patients starting antiretroviral therapy with absolute CD4 cell counts between 200 and 350 cells/microL. HIV Med 2006; 7:383.
  12. Hulgan T, Shepherd BE, Raffanti SP, et al. Absolute count and percentage of CD4+ lymphocytes are independent predictors of disease progression in HIV-infected persons initiating highly active antiretroviral therapy. J Infect Dis 2007; 195:425.
  13. Hulgan T, Raffanti S, Kheshti A, et al. CD4 lymphocyte percentage predicts disease progression in HIV-infected patients initiating highly active antiretroviral therapy with CD4 lymphocyte counts >350 lymphocytes/mm3. J Infect Dis 2005; 192:950.
  14. 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR Recomm Rep 1992; 41:1.
  15. McGovern BH, Golan Y, Lopez M, et al. The impact of cirrhosis on CD4+ T cell counts in HIV-seronegative patients. Clin Infect Dis 2007; 44:431.
  16. Gandhi RT. Cirrhosis is associated with low CD4+ T cell counts: implications for HIV-infected patients with liver disease. Clin Infect Dis 2007; 44:438.
  17. Rutherford GW, Lifson AR, Hessol NA, et al. Course of HIV-I infection in a cohort of homosexual and bisexual men: an 11 year follow up study. BMJ 1990; 301:1183.
  18. Centers for Disease Control (CDC). Revision of the CDC surveillance case definition for acquired immunodeficiency syndrome. Council of State and Territorial Epidemiologists; AIDS Program, Center for Infectious Diseases. MMWR Suppl 1987; 36:1S.
  19. Osmond D, Charlebois E, Lang W, et al. Changes in AIDS survival time in two San Francisco cohorts of homosexual men, 1983 to 1993. JAMA 1994; 271:1083.
  20. Walsh MB, Calabrese LH. Rapid progression of HIV-1 infection to AIDS. Cleve Clin J Med 1992; 59:637.
  21. Time from HIV-1 seroconversion to AIDS and death before widespread use of highly-active antiretroviral therapy: a collaborative re-analysis. Collaborative Group on AIDS Incubation and HIV Survival including the CASCADE EU Concerted Action. Concerted Action on SeroConversion to AIDS and Death in Europe. Lancet 2000; 355:1131.
  22. Altisent C, Montoro JB, Ruiz I, Lorenzo JI. Long-term survivors and progression of human immunodeficiency virus infection. N Engl J Med 1996; 334:1065.
  23. Darby SC, Ewart DW, Giangrande PL, et al. Importance of age at infection with HIV-1 for survival and development of AIDS in UK haemophilia population. UK Haemophilia Centre Directors' Organisation. Lancet 1996; 347:1573.
  24. Mariotto AB, Mariotti S, Pezzotti P, et al. Estimation of the acquired immunodeficiency syndrome incubation period in intravenous drug users: a comparison with male homosexuals. Am J Epidemiol 1992; 135:428.
  25. Galai N, Vlahov D, Margolick JB, et al. Changes in markers of disease progression in HIV-1 seroconverters: a comparison between cohorts of injecting drug users and homosexual men. J Acquir Immune Defic Syndr Hum Retrovirol 1995; 8:66.
  26. Margolick JB, Muñoz A, Vlahov D, et al. Direct comparison of the relationship between clinical outcome and change in CD4+ lymphocytes in human immunodeficiency virus-positive homosexual men and injecting drug users. Arch Intern Med 1994; 154:869.
  27. Melnick SL, Sherer R, Louis TA, et al. Survival and disease progression according to gender of patients with HIV infection. The Terry Beirn Community Programs for Clinical Research on AIDS. JAMA 1994; 272:1915.
  28. Vella S, Giuliano M, Floridia M, et al. Effect of sex, age and transmission category on the progression to AIDS and survival of zidovudine-treated symptomatic patients. AIDS 1995; 9:51.
  29. Chaisson RE, Keruly JC, Moore RD. Race, sex, drug use, and progression of human immunodeficiency virus disease. N Engl J Med 1995; 333:751.
  30. Alcabes P, Muñoz A, Vlahov D, Friedland GH. Incubation period of human immunodeficiency virus. Epidemiol Rev 1993; 15:303.
  31. Tai JH, Udoji MA, Barkanic G, et al. Pregnancy and HIV disease progression during the era of highly active antiretroviral therapy. J Infect Dis 2007; 196:1044.
  32. Dorrucci M, Rezza G, Porter K, et al. Temporal trends in postseroconversion CD4 cell count and HIV load: the Concerted Action on Seroconversion to AIDS and Death in Europe Collaboration, 1985-2002. J Infect Dis 2007; 195:525.
  33. Ariën KK, Vanham G, Arts EJ. Is HIV-1 evolving to a less virulent form in humans? Nat Rev Microbiol 2007; 5:141.
  34. Learmont JC, Geczy AF, Mills J, et al. 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 1999; 340:1715.
  35. Barbour JD, Hecht FM, Wrin T, et al. Higher CD4+ T cell counts associated with low viral pol replication capacity among treatment-naive adults in early HIV-1 infection. J Infect Dis 2004; 190:251.
  36. Daar ES, Kesler KL, Wrin T, et al. HIV-1 pol replication capacity predicts disease progression. AIDS 2005; 19:871.
  37. Simon F, Mauclère P, Roques P, et al. Identification of a new human immunodeficiency virus type 1 distinct from group M and group O. Nat Med 1998; 4:1032.
  38. Kanki PJ, Hamel DJ, Sankalé JL, et al. Human immunodeficiency virus type 1 subtypes differ in disease progression. J Infect Dis 1999; 179:68.
  39. Vasan A, Renjifo B, Hertzmark E, et al. Different rates of disease progression of HIV type 1 infection in Tanzania based on infecting subtype. Clin Infect Dis 2006; 42:843.
  40. Baeten JM, Chohan B, Lavreys L, et al. HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads. J Infect Dis 2007; 195:1177.
  41. Kiwanuka N, Laeyendecker O, Robb M, et al. Effect of human immunodeficiency virus Type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection. J Infect Dis 2008; 197:707.
  42. Poveda E, Briz V, Quiñones-Mateu M, Soriano V. HIV tropism: diagnostic tools and implications for disease progression and treatment with entry inhibitors. AIDS 2006; 20:1359.
  43. Pope M, Haase AT. Transmission, acute HIV-1 infection and the quest for strategies to prevent infection. Nat Med 2003; 9:847.
  44. Shepherd JC, Jacobson LP, Qiao W, et al. Emergence and persistence of CXCR4-tropic HIV-1 in a population of men from the multicenter AIDS cohort study. J Infect Dis 2008; 198:1104.
  45. Goetz MB, Leduc R, Kostman JR, et al. Relationship between HIV coreceptor tropism and disease progression in persons with untreated chronic HIV infection. J Acquir Immune Defic Syndr 2009; 50:259.
  46. Hunt PW, Harrigan PR, Huang W, et al. Prevalence of CXCR4 tropism among antiretroviral-treated HIV-1-infected patients with detectable viremia. J Infect Dis 2006; 194:926.
  47. Wilkin T, Su Z, Kuritzkes D, et al. Presented at the 13th annual Conference on Retroviruses and Opportunistic Infections, Denver, CO, February 5-8th, 2006; abstract #283.
  48. Wilkin TJ, Su Z, Kuritzkes DR, et al. HIV type 1 chemokine coreceptor use among antiretroviral-experienced patients screened for a clinical trial of a CCR5 inhibitor: AIDS Clinical Trial Group A5211. Clin Infect Dis 2007; 44:591.
  49. Roy AM, Schweighardt B, Eckstein LA, et al. Enhanced replication of R5 HIV-1 over X4 HIV-1 in CD4(+)CCR5(+)CXCR4(+) T cells. J Acquir Immune Defic Syndr 2005; 40:267.
  50. Zaitseva MB, Lee S, Rabin RL, et al. CXCR4 and CCR5 on human thymocytes: biological function and role in HIV-1 infection. J Immunol 1998; 161:3103.
  51. Lin YL, Mettling C, Portalès P, et al. The efficiency of R5 HIV-1 infection is determined by CD4 T-cell surface CCR5 density through G alpha i-protein signalling. AIDS 2006; 20:1369.
  52. Markowitz M, Mohri H, Mehandru S, et al. Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report. Lancet 2005; 365:1031.
  53. Richman DD, Bozzette SA. The impact of the syncytium-inducing phenotype of human immunodeficiency virus on disease progression. J Infect Dis 1994; 169:968.
  54. Weiser B, Philpott S, Klimkait T, et al. HIV-1 coreceptor usage and CXCR4-specific viral load predict clinical disease progression during combination antiretroviral therapy. AIDS 2008; 22:469.
  55. Waters L, Mandalia S, Randell P, et al. The impact of HIV tropism on decreases in CD4 cell count, clinical progression, and subsequent response to a first antiretroviral therapy regimen. Clin Infect Dis 2008; 46:1617.
  56. Daar ES, Kesler KL, Petropoulos CJ, et al. Baseline HIV type 1 coreceptor tropism predicts disease progression. Clin Infect Dis 2007; 45:643.
  57. Vasilescu A, Terashima Y, Enomoto M, et al. A haplotype of the human CXCR1 gene protective against rapid disease progression in HIV-1+ patients. Proc Natl Acad Sci U S A 2007; 104:3354.
  58. Dean M, Carrington M, Winkler C, et al. Genetic restriction of HIV-1 infection and progression to AIDS by a deletion allele of the CKR5 structural gene. Hemophilia Growth and Development Study, Multicenter AIDS Cohort Study, Multicenter Hemophilia Cohort Study, San Francisco City Cohort, ALIVE Study. Science 1996; 273:1856.
  59. Dragic T, Litwin V, Allaway GP, et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 1996; 381:667.
  60. McDermott DH, Zimmerman PA, Guignard F, et al. CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS). Lancet 1998; 352:866.
  61. Ioannidis JP, Rosenberg PS, Goedert JJ, et al. Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. Ann Intern Med 2001; 135:782.
  62. Lederman MM, Penn-Nicholson A, Cho M, Mosier D. Biology of CCR5 and its role in HIV infection and treatment. JAMA 2006; 296:815.
  63. Hütter G, Nowak D, Mossner M, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 2009; 360:692.
  64. Allers K, Hütter G, Hofmann J, et al. Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation. Blood 2011; 117:2791.
  65. Tebas P, Stein D, Tang WW, et al. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 2014; 370:901.
  66. Schuitemaker H, Koot M, Kootstra NA, et al. Biological phenotype of human immunodeficiency virus type 1 clones at different stages of infection: progression of disease is associated with a shift from monocytotropic to T-cell-tropic virus population. J Virol 1992; 66:1354.
  67. Koot M, Keet IP, Vos AH, et al. Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med 1993; 118:681.
  68. Daar ES, Lynn HS, Donfield SM, et al. Stromal cell-derived factor-1 genotype, coreceptor tropism, and HIV type 1 disease progression. J Infect Dis 2005; 192:1597.
  69. Kemal KS, Beattie T, Dong T, et al. Transition from long-term nonprogression to HIV-1 disease associated with escape from cellular immune control. J Acquir Immune Defic Syndr 2008; 48:119.
  70. Bochud PY, Hersberger M, Taffé P, et al. Polymorphisms in Toll-like receptor 9 influence the clinical course of HIV-1 infection. AIDS 2007; 21:441.
  71. An P, Johnson R, Phair J, et al. APOBEC3B deletion and risk of HIV-1 acquisition. J Infect Dis 2009; 200:1054.
  72. Kidd JM, Newman TL, Tuzun E, et al. Population stratification of a common APOBEC gene deletion polymorphism. PLoS Genet 2007; 3:e63.
  73. Brumme ZL, Brumme CJ, Chui C, et al. Effects of human leukocyte antigen class I genetic parameters on clinical outcomes and survival after initiation of highly active antiretroviral therapy. J Infect Dis 2007; 195:1694.
  74. Carrington M, O'Brien SJ. The influence of HLA genotype on AIDS. Annu Rev Med 2003; 54:535.
  75. Hogan CM, Hammer SM. Host determinants in HIV infection and disease. Part 2: genetic factors and implications for antiretroviral therapeutics. Ann Intern Med 2001; 134:978.
  76. Limou S, Le Clerc S, Coulonges C, et al. Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02). J Infect Dis 2009; 199:419.
  77. Le Clerc S, Limou S, Coulonges C, et al. Genomewide association study of a rapid progression cohort identifies new susceptibility alleles for AIDS (ANRS Genomewide Association Study 03). J Infect Dis 2009; 200:1194.
  78. Magierowska M, Theodorou I, Debré P, et al. Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals. Blood 1999; 93:936.
  79. Fellay J, Shianna KV, Ge D, et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007; 317:944.
  80. Navis M, Schellens IM, van Swieten P, et al. A nonprogressive clinical course in HIV-infected individuals expressing human leukocyte antigen B57/5801 is associated with preserved CD8+ T lymphocyte responsiveness to the HW9 epitope in Nef. J Infect Dis 2008; 197:871.
  81. Jackson JB, Erice A, Englund JA, et al. Prevalence of cytomegalovirus antibody in hemophiliacs and homosexuals infected with human immunodeficiency virus type 1. Transfusion 1988; 28:187.
  82. Alkhatib G, Combadiere C, Broder CC, et al. CC CKR5: a RANTES, MIP-1alpha, MIP-1beta receptor as a fusion cofactor for macrophage-tropic HIV-1. Science 1996; 272:1955.
  83. Vidal F, Peraire J, Domingo P, et al. Polymorphism of RANTES chemokine gene promoter is not associated with long-term nonprogressive HIV-1 infection of more than 16 years. J Acquir Immune Defic Syndr 2006; 41:17.
  84. Liu H, Hwangbo Y, Holte S, et al. Analysis of genetic polymorphisms in CCR5, CCR2, stromal cell-derived factor-1, RANTES, and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin in seronegative individuals repeatedly exposed to HIV-1. J Infect Dis 2004; 190:1055.
  85. Martin MP, Qi Y, Goedert JJ, et al. IL28B polymorphism does not determine outcomes of hepatitis B virus or HIV infection. J Infect Dis 2010; 202:1749.
  86. Schwarze-Zander C, Blackard JT, Zheng H, et al. GB virus C (GBV-C) infection in hepatitis C virus (HCV)/HIV-coinfected patients receiving HCV treatment: importance of the GBV-C genotype. J Infect Dis 2006; 194:410.
  87. Schacker T, Zeh J, Hu H, et al. Changes in plasma human immunodeficiency virus type 1 RNA associated with herpes simplex virus reactivation and suppression. J Infect Dis 2002; 186:1718.
  88. Buchacz K, Patel P, Taylor M, et al. Syphilis increases HIV viral load and decreases CD4 cell counts in HIV-infected patients with new syphilis infections. AIDS 2004; 18:2075.
  89. Podlekareva D, Mocroft A, Kirk O, et al. Fungal infection as a risk factor for HIV disease progression among patients with a CD4 count above 200/microl in the era of cART. Scand J Infect Dis 2008; 40:908.
  90. Webster A, Lee CA, Cook DG, et al. Cytomegalovirus infection and progression towards AIDS in haemophiliacs with human immunodeficiency virus infection. Lancet 1989; 2:63.
  91. Rugman FP, Mannion PT, Hay CR, et al. Cytomegalovirus, serum beta 2 microglobulin, and progression to AIDS in HIV-seropositive haemophiliacs. Lancet 1989; 2:631.
  92. Becherer PR, Smiley ML, Matthews TJ, et al. Human immunodeficiency virus-1 disease progression in hemophiliacs. Am J Hematol 1990; 34:204.
  93. Deayton JR, Prof Sabin CA, Johnson MA, et al. Importance of cytomegalovirus viraemia in risk of disease progression and death in HIV-infected patients receiving highly active antiretroviral therapy. Lancet 2004; 363:2116.
  94. Sheng WH, Hung CC, Wu RJ, et al. Clinical impact of GB virus C viremia on patients with HIV type 1 infection in the era of highly active antiretroviral therapy. Clin Infect Dis 2007; 44:584.
  95. Vahidnia F, Petersen M, Stapleton JT, et al. Acquisition of GB virus type C and lower mortality in patients with advanced HIV disease. Clin Infect Dis 2012; 55:1012.
  96. Maidana-Giret MT, Silva TM, Sauer MM, et al. GB virus type C infection modulates T-cell activation independently of HIV-1 viral load. AIDS 2009; 23:2277.
  97. Beilke MA, Theall KP, O'Brien M, et al. Clinical outcomes and disease progression among patients coinfected with HIV and human T lymphotropic virus types 1 and 2. Clin Infect Dis 2004; 39:256.
  98. Bassani S, López M, Toro C, et al. Influence of human T cell lymphotropic virus type 2 coinfection on virological and immunological parameters in HIV type 1-infected patients. Clin Infect Dis 2007; 44:105.
  99. Turci M, Pilotti E, Ronzi P, et al. Coinfection with HIV-1 and human T-Cell lymphotropic virus type II in intravenous drug users is associated with delayed progression to AIDS. J Acquir Immune Defic Syndr 2006; 41:100.
  100. Walson JL, Herrin BR, John-Stewart G. Deworming helminth co-infected individuals for delaying HIV disease progression. Cochrane Database Syst Rev 2009; :CD006419.
  101. Kallestrup P, Zinyama R, Gomo E, et al. Schistosomiasis and HIV-1 infection in rural Zimbabwe: effect of treatment of schistosomiasis on CD4 cell count and plasma HIV-1 RNA load. J Infect Dis 2005; 192:1956.
  102. Nielsen NO, Simonsen PE, Dalgaard P, et al. Effect of diethylcarbamazine on HIV load, CD4%, and CD4/CD8 ratio in HIV-infected adult Tanzanians with or without lymphatic filariasis: randomized double-blind and placebo-controlled cross-over trial. Am J Trop Med Hyg 2007; 77:507.
  103. Walson JL, Otieno PA, Mbuchi M, et al. Albendazole treatment of HIV-1 and helminth co-infection: a randomized, double-blind, placebo-controlled trial. AIDS 2008; 22:1601.
  104. Wheeler DA. Weight loss and disease progression in HIV infection. AIDS Read 1999; 9:347.
  105. Fawzi WW, Msamanga GI, Spiegelman D, et al. A randomized trial of multivitamin supplements and HIV disease progression and mortality. N Engl J Med 2004; 351:23.
  106. Marston B, De Cock KM. Multivitamins, nutrition, and antiretroviral therapy for HIV disease in Africa. N Engl J Med 2004; 351:78.
  107. Kaiser JD, Campa AM, Ondercin JP, et al. Micronutrient supplementation increases CD4 count in HIV-infected individuals on highly active antiretroviral therapy: a prospective, double-blinded, placebo-controlled trial. J Acquir Immune Defic Syndr 2006; 42:523.
  108. Baum MK, Shor-Posner G, Bonvehi P, et al. Influence of HIV infection on vitamin status and requirements. Ann N Y Acad Sci 1992; 669:165.
  109. Isanaka S, Mugusi F, Hawkins C, et al. Effect of high-dose vs standard-dose multivitamin supplementation at the initiation of HAART on HIV disease progression and mortality in Tanzania: a randomized controlled trial. JAMA 2012; 308:1535.
  110. Peterson PK, Sharp BM, Gekker G, et al. Morphine promotes the growth of HIV-1 in human peripheral blood mononuclear cell cocultures. AIDS 1990; 4:869.
  111. Mientjes GH, Miedema F, van Ameijden EJ, et al. Frequent injecting impairs lymphocyte reactivity in HIV-positive and HIV-negative drug users. AIDS 1991; 5:35.
  112. Celentano DD, Galai N, Sethi AK, et al. Time to initiating highly active antiretroviral therapy among HIV-infected injection drug users. AIDS 2001; 15:1707.
  113. Wood E, Hogg RS, Lima VD, et al. Highly active antiretroviral therapy and survival in HIV-infected injection drug users. JAMA 2008; 300:550.
  114. Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: a collaborative analysis of 14 cohort studies. Lancet 2008; 372:293.
  115. Lucas GM, Griswold M, Gebo KA, et al. Illicit drug use and HIV-1 disease progression: a longitudinal study in the era of highly active antiretroviral therapy. Am J Epidemiol 2006; 163:412.
  116. Samet JH, Cheng DM, Libman H, et al. Alcohol consumption and HIV disease progression. J Acquir Immune Defic Syndr 2007; 46:194.
  117. Pol S, Artru P, Thépot V, et al. Improvement of the CD4 cell count after alcohol withdrawal in HIV-positive alcoholic patients. AIDS 1996; 10:1293.
  118. Fischl MA, Dickinson GM, La Voie L. Safety and efficacy of sulfamethoxazole and trimethoprim chemoprophylaxis for Pneumocystis carinii pneumonia in AIDS. JAMA 1988; 259:1185.
  119. Pierce M, Crampton S, Henry D, et al. A randomized trial of clarithromycin as prophylaxis against disseminated Mycobacterium avium complex infection in patients with advanced acquired immunodeficiency syndrome. N Engl J Med 1996; 335:384.
  120. Kitahata MM, Koepsell TD, Deyo RA, et al. Physicians' experience with the acquired immunodeficiency syndrome as a factor in patients' survival. N Engl J Med 1996; 334:701.
  121. Kitahata MM, Van Rompaey SE, Shields AW. Physician experience in the care of HIV-infected persons is associated with earlier adoption of new antiretroviral therapy. J Acquir Immune Defic Syndr 2000; 24:106.
  122. Brosgart CL, Mitchell TF, Coleman RL, et al. Clinical experience and choice of drug therapy for human immunodeficiency virus disease. Clin Infect Dis 1999; 28:14.
  123. Cunningham WE, Tisnado DM, Lui HH, et al. The effect of hospital experience on mortality among patients hospitalized with acquired immunodeficiency syndrome in California. Am J Med 1999; 107:137.
  124. Detels R, Tarwater P, Phair JP, et al. Effectiveness of potent antiretroviral therapies on the incidence of opportunistic infections before and after AIDS diagnosis. AIDS 2001; 15:347.
  125. Jaggy C, von Overbeck J, Ledergerber B, et al. Mortality in the Swiss HIV Cohort Study (SHCS) and the Swiss general population. Lancet 2003; 362:877.
  126. Centers for Disease Control and Prevention. HIV-AIDS Surveillance Report 1985-2002, United States. www.cdc.gov/hiv/dhap.htm (Accessed on March 09, 2005).
  127. Jordan R, Gold L, Cummins C, Hyde C. Systematic review and meta-analysis of evidence for increasing numbers of drugs in antiretroviral combination therapy. BMJ 2002; 324:757.
  128. Tassie JM, Grabar S, Lancar R, et al. Time to AIDS from 1992 to 1999 in HIV-1-infected subjects with known date of infection. J Acquir Immune Defic Syndr 2002; 30:81.
  129. Lee LM, Karon JM, Selik R, et al. Survival after AIDS diagnosis in adolescents and adults during the treatment era, United States, 1984-1997. JAMA 2001; 285:1308.
  130. Mocroft A, Katlama C, Johnson AM, et al. AIDS across Europe, 1994-98: the EuroSIDA study. Lancet 2000; 356:291.
  131. Severe P, Leger P, Charles M, et al. Antiretroviral therapy in a thousand patients with AIDS in Haiti. N Engl J Med 2005; 353:2325.
  132. Ferradini L, Jeannin A, Pinoges L, et al. Scaling up of highly active antiretroviral therapy in a rural district of Malawi: an effectiveness assessment. Lancet 2006; 367:1335.
  133. Lima VD, Hogg RS, Harrigan PR, et al. Continued improvement in survival among HIV-infected individuals with newer forms of highly active antiretroviral therapy. AIDS 2007; 21:685.
  134. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med 2007; 146:87.
  135. Bhaskaran K, Hamouda O, Sannes M, et al. Changes in the risk of death after HIV seroconversion compared with mortality in the general population. JAMA 2008; 300:51.
  136. Sackoff JE, Hanna DB, Pfeiffer MR, Torian LV. Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City. Ann Intern Med 2006; 145:397.
  137. Walensky RP, Paltiel AD, Losina E, et al. The survival benefits of AIDS treatment in the United States. J Infect Dis 2006; 194:11.
  138. Schackman BR, Gebo KA, Walensky RP, et al. The lifetime cost of current human immunodeficiency virus care in the United States. Med Care 2006; 44:990.
  139. Sabine C, Antiretroviral Therapy (ART) Cohort Collaboration. AIDS events among individuals initiating HAART: do some patients experience a greater benefit from HAART than others? AIDS 2005; 19:1995.
  140. Braitstein P, Brinkhof MW, Dabis F, et al. Mortality of HIV-1-infected patients in the first year of antiretroviral therapy: comparison between low-income and high-income countries. Lancet 2006; 367:817.
  141. Pakker NG, Notermans DW, de Boer RJ, et al. Biphasic kinetics of peripheral blood T cells after triple combination therapy in HIV-1 infection: a composite of redistribution and proliferation. Nat Med 1998; 4:208.
  142. Mocroft A, Phillips AN, Gatell J, et al. Normalisation of CD4 counts in patients with HIV-1 infection and maximum virological suppression who are taking combination antiretroviral therapy: an observational cohort study. Lancet 2007; 370:407.
  143. Gandhi RT, Spritzler J, Chan E, et al. Effect of baseline- and treatment-related factors on immunologic recovery after initiation of antiretroviral therapy in HIV-1-positive subjects: results from ACTG 384. J Acquir Immune Defic Syndr 2006; 42:426.
  144. Moore RD, Keruly JC. CD4+ cell count 6 years after commencement of highly active antiretroviral therapy in persons with sustained virologic suppression. Clin Infect Dis 2007; 44:441.
  145. Poles MA, Boscardin WJ, Elliott J, et al. Lack of decay of HIV-1 in gut-associated lymphoid tissue reservoirs in maximally suppressed individuals. J Acquir Immune Defic Syndr 2006; 43:65.
  146. Siliciano JD, Kajdas J, Finzi D, et al. Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 2003; 9:727.
  147. Kieffer TL, Finucane MM, Nettles RE, et al. Genotypic analysis of HIV-1 drug resistance at the limit of detection: virus production without evolution in treated adults with undetectable HIV loads. J Infect Dis 2004; 189:1452.
  148. Finzi D, Hermankova M, Pierson T, et al. Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 1997; 278:1295.
  149. Wong JK, Hezareh M, Günthard HF, et al. Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 1997; 278:1291.
  150. Persaud D, Pierson T, Ruff C, et al. A stable latent reservoir for HIV-1 in resting CD4(+) T lymphocytes in infected children. J Clin Invest 2000; 105:995.
  151. García F, Plana M, Vidal C, et al. Dynamics of viral load rebound and immunological changes after stopping effective antiretroviral therapy. AIDS 1999; 13:F79.
  152. Zhang L, Ramratnam B, Tenner-Racz K, et al. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med 1999; 340:1605.
  153. Wirden M, Delaugerre C, Marcelin AG, et al. Comparison of the dynamics of resistance-associated mutations to nucleoside reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, and protease inhibitors after cessation of antiretroviral combination therapy. Antimicrob Agents Chemother 2004; 48:644.
  154. Lehrman G, Hogue IB, Palmer S, et al. Depletion of latent HIV-1 infection in vivo: a proof-of-concept study. Lancet 2005; 366:549.
  155. Siliciano JD, Lai J, Callender M, et al. Stability of the latent reservoir for HIV-1 in patients receiving valproic acid. J Infect Dis 2007; 195:833.