by Alexey Karetnikov, Department of Molecular Genetics, University of Toronto
Published in: Frontiers in Public Health, 7 August 2015 (doi:10.3389/fpubh.2015.00193)
A commentary on
Questioning the HIV-AIDS hypothesis: 30 years of dissent
by Goodson P. Front Public Health (2014) 2:154. doi: 10.3389/fpubh.2014.00154
A recent Opinion article by Dr. Goodson (1) expresses pseudoscientific views typical of HIV/AIDS denialism (2–13) and ignores the overwhelming evidence that HIV is a causative agent of AIDS, the evidence accumulated during more than 30 years of research.
Fulfilling the Koch’s Postulate 1: HIV is Invariably Epidemiologically Associated with AIDS
The overwhelming evidence suggests an invariable epidemiological association of HIV with AIDS. AIDS occurs exclusively in HIV-infected people (16). HIV can be detected in all AIDS patients (17). High levels of HIV in the organism predict progression to AIDS (18–23). Many children born to HIV-infected mothers have developed AIDS and died (24). AIDS-related conditions, such as Pneumocystis pneumonia and disseminated Mycobacterium avium complex disease, have become much more common after the start of the HIV epidemic (25). Death rates are much higher in HIV-seropositive treatment-naïve than in seronegative individuals (26–34).
An HIV-triggered decrease in CD4+ T-lymphocyte count is a specific feature of HIV infection, and is extraordinarily rare in the absence of HIV (16, 35–37). The HIV-caused CD4+ T-lymphocyte depletion occurs through at least two mechanisms. (1) Direct killing of infected CD4+ T-lymphocytes. Dr. Goodson seems unfamiliar with the fact that HIV-1, HIV-2, and other representatives of the genus Lentivirus (e.g., Simian immunodeficiency virus), as well as some other retroviruses (e.g., Feline leukemia virus and members of the Avian leukosis virus group), exert a cytopathic effect in infected cells (38). (2) HIV directly kills Th17 CD4+ T-lymphocytes in the intestinal submucosa, triggering the damage of the mucosal integrity, translocation of microbial products from the intestine to the blood and chronic immune activation, resulting in further massive loss of CD4+ T-lymphocytes (39, 40).
Dr. Goodson claims that recreational drug use, clotting factor VIII, or receptive anal intercourse, but not HIV, are causes of AIDS. However, all of these claims have long ago been rejected by overwhelming scientific evidence (16, 35–37, 41–45).
Fulfilling the Koch’s Postulate 2: HIV has been Isolated from Patients at all Stages of the Infection
Contrary to Dr. Goodson’s claims, HIV has been isolated from patients at all stages of HIV infection, including AIDS, and propagated in cell culture (17, 46–54). Various protocols for HIV-1 isolation (without “contaminants” claimed by Dr. Goodson) have been developed, and each of these protocols can be considered “standard” (55–62). Detailed images of HIV-1 virions, revealing morphology typical of the genus Lentivirus, have been obtained using transmission electron microscopy (46–48, 53, 63) and electron cryotomography (64, 65). A combination of immunofluorescent and electron microscopy has allowed visualization of intracellular trafficking of individual HIV-1 particles toward the nucleus of the infected cell (66). The process of cell-to-cell transfer of HIV-1 between T-lymphocytes has been visualized using high-speed three-dimensional video microscopy (67).
Fulfilling the Koch’s Postulate 3: Accidental HIV Transmission in Humans
Dr. Goodson ignores several tragic cases of accidental HIV transmission to laboratory workers who worked with purified HIV-1, became infected after a needle-stick or mucosal exposure and developed AIDS-like symptoms. HIV has been isolated from their blood, and DNA sequencing confirmed that the HIV variant isolated was identical to the one they were working with (15, 68–70). Other well-documented cases include HIV transmission from a dentist in the USA to several patients (15, 71), and HIV transmission through blood transfusion to 11 children in the USA (72) and 75 children in the former Soviet Union (73).
HIV Laboratory Testing
Three types of assays are used for HIV detection: (1) ELISA – specificity 98.5–99.9% (75–77), (2) Western blot (77), and (3) PCR – specificity 98.3–100% (78–80). The probability that both ELISA and Western blot would give false-positive results is extremely low (<1/140,000) (77). Thus, contrary to Dr. Goodson’s claims, these tests are highly specific for HIV-1. Since the diagnosis is based on the combination of the three tests (77), HIV testing will produce similar conclusions irrespective of the country.
Contrary to Dr. Goodson’s claims, antiretroviral therapy (ART) has profoundly improved the prognosis for HIV-1-infected patients, suppressing their viral load, restoring CD4+ T-lymphocyte count, and reducing the risk of developing AIDS or dying (Figure 1A) (82–104). The success of ART has been determined by its high specificity for HIV-1-encoded proteins (105, 106). Along with therapeutic agents for many other diseases, ART does have side effects, but these are far outweighed by its benefits (106). New anti-HIV agents should help to mitigate side effects, overcome drug resistance, and ultimately cure HIV infection, e.g., through excising HIV proviral DNA from the chromosome (107–109).
Figure 1. Contrasting impacts of HIV/AIDS science versus HIV/AIDS denialism on public health. (A) Mortality and frequency of use of protease inhibitor-based combination antiretroviral therapy among HIV-infected patients with fewer than 100 CD4+ T-lymphocytes per cubic millimeter, in January 1994–June 1997. Reproduced from Ref. (91), with permission from Massachusetts Medical Society©. (B) Estimating the human costs of Mbeki’s AIDS policies implemented with the direct support of HIV/AIDS denialists. Reproduced from Ref. (12), with permission from the Author.
Dr. Goodson misrepresents the study by the ART Cohort Collaboration, which showed that ART is extremely beneficial for HIV-infected patients, but better clinical outcomes are observed when CD4+ T-lymphocyte counts at the start of ART are higher than 200 cells/μl (110). These conclusions have been corroborated by many other studies (111–117) and serve as a background to recommend starting ART early, when the HIV-triggered damage of the immune system is easier to restore (106).
Detrimental Impact of HIV/AIDS Denialism on Public Health
P. Duesberg, D. Rasnick, and some other HIV/AIDS denialists served on a controversial advisory panel of the South African president Thabo Mbeki. The policy of the South African government over HIV/AIDS during the period 2000–2005 is considered by a majority of scientists to have resulted in the death of at least 330,000 HIV-infected people (Figure 1B) (9, 12, 118). The Opinion article by Dr. Goodson (1) [as well as earlier published or publicly expressed opinions of P. Duesberg, K. Mullis, and other denialists, none of whom has ever worked with HIV/AIDS (2–5, 7–12)] is similarly harmful for public health, as it disseminates dangerous misinformation about HIV/AIDS that can affect prevention decisions made by uninfected people and treatment decisions made by HIV-infected people. Therefore, the following recommendations should be given to public health workers: (1) to learn and disseminate up-to-date knowledge on HIV/AIDS based on the most recent scientific literature, and (2) to be aware of HIV/AIDS denialism and be able to effectively counteract its detrimental impact on public health.
Conflict of Interest Statement
The author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
I would like to thank Dr. Nicoli Nattrass for providing an electronic file for Figure 1B, Raymond W. Wong for providing PDF files, and Andrew Reddin for critical reading of the manuscript.
2. Gallo RC. “A single disease with a single cause”, “About causes of disease (and, in particular, why HIV is the cause of AIDS)”. In: Gallo RC, editor. Virus Hunting. AIDS, Cancer and the Human Retroviruses: A Story of Scientific Discovery. New York: BasicBooks (1991). p. 127–62, 276–97.
17. Jackson JB, Kwok SY, Sninsky JJ, Hopsicker JS, Sannerud KJ, Rhame FS, et al. Human immunodeficiency virus type 1 detected in all seropositive symptomatic and asymptomatic individuals. J Clin Microbiol (1990) 28:16–9.
18. Cao Y, Qin L, Zhang L, Safrit J, Ho DD. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med (1995) 332:201–8. doi:10.1056/NEJM199501263320401
19. Pantaleo G, Menzo S, Vaccarezza M, Graziosi C, Cohen OJ, Demarest JF, et al. Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med (1995) 332:209–16. doi:10.1056/NEJM199501263320402
20. Mellors JW, Muñoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, et al. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med (1997) 126:946–54. doi:10.7326/0003-4819-126-12-199706150-00003
21. Barker E, Mackewicz CE, Reyes-Terán G, Sato A, Stranford SA, Fujimura SH, et al. Virological and immunological features of long-term human immunodeficiency virus-infected individuals who have remained asymptomatic compared with those who have progressed to acquired immunodeficiency syndrome. Blood (1998) 92:3105–14.
22. Palumbo PE, Raskino C, Fiscus S, Pahwa S, Fowler MG, Spector SA, et al. Predictive value of quantitative plasma HIV RNA and CD4+ lymphocyte count in HIV-infected infants and children. JAMA (1998) 279:756–61. doi:10.1001/jama.279.10.756
23. Taha TE, Kumwenda NI, Hoover DR, Biggar RJ, Broadhead RL, Cassol S, et al. Association of HIV-1 load and CD4 lymphocyte count with mortality among untreated African children over one year of age. AIDS (2000) 14:453–9. doi:10.1097/00002030-200003100-00021
24. Ades AE, Newell ML, Peckham CS, Giaquinto C, Zacchello F, De Rossi A, et al. Children born to women with HIV-1 infection: natural history and risk of transmission. European Collaborative Study. Lancet (1991) 337:253–60. doi:10.1016/0140-6736(91)90866-N
25. Sax PE, Cohen CJ, Kuritzkes DR, Cunha BA, Kubiak DW. Prophylaxis and treatment of opportunistic infections. In: Sax PE, Cohen CJ, Kuritzkes DR, editors. HIV Essentials. 7th ed. Burlington, MA: Jones & Bartlett Learning (2014). p. 72–133.
26. Thea DM, St Louis ME, Atido U, Kanjinga K, Kembo B, Matondo M, et al. A prospective study of diarrhea and HIV-1 infection among 429 Zairian infants. N Engl J Med (1993) 329:1696–702. doi:10.1056/NEJM199312023292304
27. Ackah AN, Coulibaly D, Digbeu H, Diallo K, Vetter KM, Coulibaly IM, et al. Response to treatment, mortality, and CD4 lymphocyte counts in HIV-infected persons with tuberculosis in Abidjan, Côte d’Ivoire. Lancet (1995) 345:607–10. doi:10.1016/S0140-6736(95)90519-7
28. Borgdorff MW, Barongo LR, Klokke AH, Newell JN, Senkoro KP, Velema JP, et al. HIV-1 incidence and HIV-1 associated mortality in a cohort of urban factory workers in Tanzania. Genitourin Med (1995) 71:212–5.
29. Darby SC, Ewart DW, Giangrande PL, Dolin PJ, Spooner RJ, Rizza CR. Mortality before and after HIV infection in the complete UK population of haemophiliacs. UK Haemophilia Centre Directors’ Organisation. Nature (1995) 377:79–82. doi:10.1038/377079a0
30. Leroy V, Msellati P, Lepage P, Batungwanayo J, Hitimana DG, Taelman H, et al. Four years of natural history of HIV-1 infection in African women: a prospective cohort study in Kigali (Rwanda), 1988-1993. J Acquir Immune Defic Syndr Hum Retrovirol (1995) 9:415–21. doi:10.1097/00042560-199508000-00013
31. Nunn AJ, Mulder DW, Kamali A, Ruberantwari A, Kengeya-Kayondo JF, Whitworth J. Mortality associated with HIV-1 infection over five years in a rural Ugandan population: cohort study. BMJ (1997) 315:767–71. doi:10.1136/bmj.315.7111.767
32. Spira R, Lepage P, Msellati P, Van De Perre P, Leroy V, Simonon A, et al. Natural history of human immunodeficiency virus type 1 infection in children: a five-year prospective study in Rwanda. Mother-to-Child HIV-1 Transmission Study Group. Pediatrics (1999) 104(5):e56. doi:10.1542/peds.104.5.e56
33. Taha TE, Kumwenda NI, Broadhead RL, Hoover DR, Graham SM, Van Der Hoven L, et al. Mortality after the first year of life among human immunodeficiency virus type 1-infected and uninfected children. Pediatr Infect Dis J (1999) 18:689–94. doi:10.1097/00006454-199908000-00007
34. Madhi SA, Petersen K, Madhi A, Khoosal M, Klugman KP. Increased disease burden and antibiotic resistance of bacteria causing severe community-acquired lower respiratory tract infections in human immunodeficiency virus type 1-infected children. Clin Infect Dis (2000) 31:170–6. doi:10.1086/313925
35. Donegan E, Stuart M, Niland JC, Sacks HS, Azen SP, Dietrich SL, et al. Infection with human immunodeficiency virus type 1 (HIV-1) among recipients of antibody-positive blood donations. Ann Intern Med (1990) 113:733–9. doi:10.7326/0003-4819-113-10-733
38. Goff SP. Retroviridae: the retroviruses and their replication. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, Roizman B, et al., editors. Fields’ Virology. 5th ed. Philadelphia, PA: Wolters Kluwer/Lippincott Williams & Wilkins (2007). p. 1999–2069.
41. Aledort LM, Operskalski EA, Dietrich SL, Koerper MA, Gjerset GF, Lusher JM, et al. Low CD4+ counts in a study of transfusion safety. The Transfusion Safety Study Group. N Engl J Med (1993) 328:441–2. doi:10.1056/NEJM199302113280614
42. Hassett J, Gjerset GF, Mosley JW, Fletcher MA, Donegan E, Parker JW, et al. Effect on lymphocyte subsets of clotting factor therapy in human immunodeficiency virus-1-negative congenital clotting disorders. The Transfusion Safety Study Group. Blood (1993) 82:1351–7.
44. Sabin CA, Pasi KJ, Phillips AN, Lilley P, Bofill M, Lee CA. Comparison of immunodeficiency and AIDS defining conditions in HIV negative and HIV positive men with haemophilia A. BMJ (1996) 312:207–10. doi:10.1136/bmj.312.7025.207
45. Chao C, Jacobson LP, Tashkin D, Martínez-Maza O, Roth MD, Margolick JB, et al. Recreational drug use and T lymphocyte subpopulations in HIV-uninfected and HIV-infected men. Drug Alcohol Depend (2008) 94:165–71. doi:10.1016/j.drugalcdep.2007.11.010
46. Barré-Sinoussi F, Chermann JC, Rey F, Nugeyre MT, Chamaret S, Gruest J, et al. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science (1983) 220:868–71. doi:10.1126/science.6189183
47. Gallo RC, Salahuddin SZ, Popovic M, Shearer GM, Kaplan M, Haynes BF, et al. Frequent detection and isolation of cytopathic retroviruses (HTLV-III) from patients with AIDS and at risk for AIDS. Science (1984) 224:500–3. doi:10.1126/science.6200936
48. Levy JA, Hoffman AD, Kramer SM, Landis JA, Shimabukuro JM, Oshiro LS. Isolation of lymphocytopathic retroviruses from San Francisco patients with AIDS. Science (1984) 225:840–2. doi:10.1126/science.6206563
49. Albert J, Gaines H, Sönnerborg A, Nyström G, Pehrson PO, Chiodi F, et al. Isolation of human immunodeficiency virus (HIV) from plasma during primary HIV infection. J Med Virol (1987) 23:67–73. doi:10.1002/jmv.1890230108
50. Chiodi F, Albert J, Olausson E, Norkrans G, Hagberg L, Sönnerborg A, et al. Isolation frequency of human immunodeficiency virus from cerebrospinal fluid and blood of patients with varying severity of HIV infection. AIDS Res Hum Retroviruses (1988) 4:351–8. doi:10.1089/aid.1988.4.351
52. Evans LA, Moreau J, Odehouri K, Seto D, Thomson-Honnebier G, Legg H, et al. Simultaneous isolation of HIV-1 and HIV-2 from an AIDS patient. Lancet (1988) 2:1389–91. doi:10.1016/S0140-6736(88)90586-7
53. Eilbott DJ, Peress N, Burger H, LaNeve D, Orenstein J, Gendelman HE, et al. Human immunodeficiency virus type 1 in spinal cords of acquired immunodeficiency syndrome patients with myelopathy: expression and replication in macrophages. Proc Natl Acad Sci U S A (1989) 86:3337–41. doi:10.1073/pnas.86.9.3337
54. Brown BK, Darden JM, Tovanabutra S, Oblander T, Frost J, Sanders-Buell E, et al. Biologic and genetic characterization of a panel of 60 human immunodeficiency virus type 1 isolates, representing clades A, B, C, D, CRF01_AE, and CRF02_AG, for the development and assessment of candidate vaccines. J Virol (2005) 79:6089–101. doi:10.1128/JVI.79.10.6089-6101.2005
55. Gorantla S, Che M, Gendelman HE. Isolation, propagation, and HIV-1 infection of monocyte-derived macrophages and recovery of virus from brain and cerebrospinal fluid. Methods Mol Biol (2005) 304:35–48. doi:10.1385/1-59259-907-9:035
58. Schuitemaker H, Kootstra NA. Isolation, propagation, and titration of human immunodeficiency virus type 1 from peripheral blood of infected individuals. Methods Mol Biol (2005) 304:17–24. doi:10.1385/1-59259-907-9:017
62. Dispinseri S, Saba E, Vicenzi E, Kootstra NA, Schuitemaker H, Scarlatti G. HIV-1 isolation from infected peripheral blood mononuclear cells. Methods Mol Biol (2014) 1087:187–96. doi:10.1007/978-1-62703-670-2_15
63. Achilli G, Barbarini G, Cattaneo E, Cecchini A, Concia E, De Rocco L, et al. AIDS nosography. In: Rondanelli EG, editor. AIDS: Clinical and Laboratory Atlas. Pavia: Edizione Medico-Scientifiche (1989). p. 10–40.
64. Schur FK, Hagen WJ, Rumlová M, Ruml T, Müller B, Kräusslich HG, et al. Structure of the immature HIV-1 capsid in intact virus particles at 8.8 Å resolution. Nature (2015) 517:505–8. doi:10.1038/nature13838
66. McDonald D, Vodicka MA, Lucero G, Svitkina TM, Borisy GG, Emerman M, et al. Visualization of the intracellular behavior of HIV in living cells. J Cell Biol (2002) 159:441–52. doi:10.1083/jcb.200203150
67. Hübner W, McNerney GP, Chen P, Dale BM, Gordon RE, Chuang FY, et al. Quantitative 3D video microscopy of HIV transfer across T cell virological synapses. Science (2009) 323:1743–7. doi:10.1126/science.1167525
69. Sipsas NV, Kalams SA, Trocha A, He S, Blattner WA, Walker BD, et al. Identification of type-specific cytotoxic T lymphocyte responses to homologous viral proteins in laboratory workers accidentally infected with HIV-1. J Clin Invest (1997) 99:752–62. doi:10.1172/JCI119221
71. Ciesielski CA, Marianos DW, Schochetman G, Witte JJ, Jaffe HW. The 1990 Florida dental investigation. The press and the science. Ann Intern Med (1994) 121:886–8. doi:10.7326/0003-4819-121-11-199412010-00011
72. van den Berg H, Gerritsen EJ, van Tol MJ, Dooren LJ, Vossen JM. Ten years after acquiring an HIV-1 infection: a study in a cohort of eleven neonates infected by aliquots from a single plasma donation. Acta Paediatr (1994) 83:173–8. doi:10.1111/j.1651-2227.1994.tb13045.x
75. Weber B, Gürtler L, Thorstensson R, Michl U, Mühlbacher A, Bürgisser P, et al. Multicenter evaluation of a new automated fourth-generation human immunodeficiency virus screening assay with a sensitive antigen detection module and high specificity. J Clin Microbiol (2002) 40:1938–46. doi:10.1128/JCM.40.6.1938-1946.2002
76. Sickinger E, Stieler M, Kaufman B, Kapprell HP, West D, Sandridge A, et al. Multicenter evaluation of a new, automated enzyme-linked immunoassay for detection of human immunodeficiency virus-specific antibodies and antigen. J Clin Microbiol (2004) 42:21–9. doi:10.1128/JCM.42.1.21-29.2004
77. Sax PE, Cohen CJ, Kuritzkes DR, Cunha BA, Kubiak DW. Diagnosis and evaluation of HIV infection. In: Sax PE, Cohen CJ, Kuritzkes DR, editors. HIV Essentials. 7th ed. Burlington, MA: Jones & Bartlett Learning (2014). p. 6–18.
78. Salminen MO, Koch C, Sanders-Buell E, Ehrenberg PK, Michael NL, Carr JK, et al. Recovery of virtually full-length HIV-1 provirus of diverse subtypes from primary virus cultures using the polymerase chain reaction. Virology (1995) 213:80–6. doi:10.1006/viro.1995.1548
79. Young NL, Shaffer N, Chaowanachan T, Chotpitayasunondh T, Vanparapar N, Mock PA, et al. Early diagnosis of HIV-1-infected infants in Thailand using RNA and DNA PCR assays sensitive to non-B subtypes. J Acquir Immune Defic Syndr (2000) 24:401–7. doi:10.1097/00126334-200008150-00001
80. Beck IA, Drennan KD, Melvin AJ, Mohan KM, Herz AM, Alarcón J, et al. Simple, sensitive, and specific detection of human immunodeficiency virus type 1 subtype B DNA in dried blood samples for diagnosis in infants in the field. J Clin Microbiol (2001) 39:29–33. doi:10.1128/JCM.39.1.29-33.2001
81. Rodríguez B, Sethi AK, Cheruvu VK, Mackay W, Bosch RJ, Kitahata M, et al. Predictive value of plasma HIV RNA level on rate of CD4 T-cell decline in untreated HIV infection. JAMA (2006) 296:1498–506. doi:10.1001/jama.296.12.1498
82. Collier AC, Coombs RW, Schoenfeld DA, Bassett RL, Timpone J, Baruch A, et al. Treatment of human immunodeficiency virus infection with saquinavir, zidovudine, and zalcitabine. AIDS Clinical Trials Group. N Engl J Med (1996) 334:1011–7. doi:10.1056/NEJM199604183341602
83. Katzenstein DA, Hammer SM, Hughes MD, Gundacker H, Jackson JB, Fiscus S, et al. The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team. N Engl J Med (1996) 335:1091–8. doi:10.1056/NEJM199610103351502
84. O’Brien WA, Hartigan PM, Martin D, Esinhart J, Hill A, Benoit S, et al. Changes in plasma HIV-1 RNA and CD4+ lymphocyte counts and the risk of progression to AIDS. Veterans Affairs Cooperative Study Group on AIDS. N Engl J Med (1996) 334:426–31. doi:10.1056/NEJM199602153340703
85. Hammer SM, Squires KE, Hughes MD, Grimes JM, Demeter LM, Currier JS, et al. A controlled trial of two nucleoside analogues plus indinavir in persons with human immunodeficiency virus infection and CD4 cell counts of 200 per cubic millimeter or less. AIDS Clinical Trials Group 320 Study Team. N Engl J Med (1997) 337:725–33. doi:10.1056/NEJM199709113371101
86. Cameron DW, Heath-Chiozzi M, Danner S, Cohen C, Kravcik S, Maurath C, et al. Randomised placebo-controlled trial of ritonavir in advanced HIV-1 disease. The Advanced HIV Disease Ritonavir Study Group. Lancet (1998) 351:543–9. doi:10.1016/S0140-6736(97)04161-5
87. Detels R, Muñoz A, McFarlane G, Kingsley LA, Margolick JB, Giorgi J, et al. Effectiveness of potent antiretroviral therapy on time to AIDS and death in men with known HIV infection duration. Multicenter AIDS Cohort Study Investigators. JAMA (1998) 280:1497–503. doi:10.1001/jama.280.17.1497
88. Marschner IC, Collier AC, Coombs RW, D’Aquila RT, DeGruttola V, Fischl MA, et al. Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy. J Infect Dis (1998) 177:40–7. doi:10.1086/513823
89. Mocroft A, Vella S, Benfield TL, Chiesi A, Miller V, Gargalianos P, et al. Changing patterns of mortality across Europe in patients infected with HIV-1. EuroSIDA Study Group. Lancet (1998) 352:1725–30. doi:10.1016/S0140-6736(98)03201-2
90. Montaner JS, DeMasi R, Hill AM. The effects of lamivudine treatment on HIV-1 disease progression are highly correlated with plasma HIV-1 RNA and CD4 cell count. AIDS (1998) 12:F23–8. doi:10.1097/00002030-199805000-00003
91. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med (1998) 338:853–60. doi:10.1056/NEJM199803263381301
92. Hogg RS, Yip B, Kully C, Craib KJ, O’Shaughnessy MV, Schechter MT, et al. Improved survival among HIV-infected patients after initiation of triple-drug antiretroviral regimens. CMAJ (1999) 160:659–65.
93. Ledergerber B, Egger M, Opravil M, Telenti A, Hirschel B, Battegay M, et al. Clinical progression and virological failure on highly active antiretroviral therapy in HIV-1 patients: a prospective cohort study. Swiss HIV Cohort Study. Lancet (1999) 353:863–8. doi:10.1016/S0140-6736(99)01122-8
94. McNaghten AD, Hanson DL, Jones JL, Dworkin MS, Ward JW. Effects of antiretroviral therapy and opportunistic illness primary chemoprophylaxis on survival after AIDS diagnosis. Adult/Adolescent Spectrum of Disease Group. AIDS (1999) 13:1687–95. doi:10.1097/00002030-199909100-00012
95. Vittinghoff E, Scheer S, O’Malley P, Colfax G, Holmberg SD, Buchbinder SP. Combination antiretroviral therapy and recent declines in AIDS incidence and mortality. J Infect Dis (1999) 179:717–20. doi:10.1086/314623
96. Porter K. Survival after introduction of HAART in people with known duration of HIV-1 infection. The CASCADE Collaboration. Concerted Action on SeroConversion to AIDS and Death in Europe. Lancet (2000) 355:1158–9. doi:10.1016/S0140-6736(00)02069-9
97. de Martino M, Tovo PA, Balducci M, Galli L, Gabiano C, Rezza G, et al. Reduction in mortality with availability of antiretroviral therapy for children with perinatal HIV-1 infection. Italian Register for HIV Infection in Children and the Italian National AIDS Registry. JAMA (2000) 284:190–7. doi:10.1001/jama.284.2.190
98. Kaplan JE, Hanson D, Dworkin MS, Frederick T, Bertolli J, Lindegren ML, et al. Epidemiology of human immunodeficiency virus-associated opportunistic infections in the United States in the era of highly active antiretroviral therapy. Clin Infect Dis (2000) 30(Suppl 1):S5–14. doi:10.1086/313843
100. Schwarcz SK, Hsu LC, Vittinghoff E, Katz MH. Impact of protease inhibitors and other antiretroviral treatments on acquired immunodeficiency syndrome survival in San Francisco, California, 1987-1996. Am J Epidemiol (2000) 152:178–85. doi:10.1093/aje/152.2.178
101. Schneider MF, Gange SJ, Williams CM, Anastos K, Greenblatt RM, Kingsley L, et al. Patterns of the hazard of death after AIDS through the evolution of antiretroviral therapy: 1984-2004. AIDS (2005) 19:2009–18. doi:10.1097/01.aids.0000189864.90053.22
102. Holkmann Olsen C, Mocroft A, Kirk O, Vella S, Blaxhult A, Clumeck N, et al. Interruption of combination antiretroviral therapy and risk of clinical disease progression to AIDS or death. HIV Med (2007) 8:96–104. doi:10.1111/j.1468-1293.2007.00436.x
104. Lima VD, Lourenço L, Yip B, Hogg RS, Phillips P, Montaner JS. Trends in AIDS incidence and AIDS-related mortality in British Columbia between 1981 and 2013. Lancet HIV (2015) 2(3):e92–7. doi:10.1016/S2352-3018(15)00017-X
106. Sax PE, Cohen CJ, Kuritzkes DR, Cunha BA, Kubiak DW. Treatment of HIV infection. In: Sax PE, Cohen CJ, Kuritzkes DR, editors. HIV Essentials. 7th ed. Burlington, MA: Jones & Bartlett Learning (2014). p. 19–54.
108. Hu W, Kaminski R, Yang F, Zhang Y, Cosentino L, Li F, et al. RNA-directed gene editing specifically eradicates latent and prevents new HIV-1 infection. Proc Natl Acad Sci U S A (2014) 111:11461–6. doi:10.1073/pnas.1405186111
110. May MT, Sterne JA, Costagliola D, Sabin CA, Phillips AN, Justice AC, et al. HIV treatment response and prognosis in Europe and North America in the first decade of highly active antiretroviral therapy: a collaborative analysis. Lancet (2006) 368:451–8. doi:10.1016/S0140-6736(06)69152-6
111. Egger M, May M, Chêne G, Phillips AN, Ledergerber B, Dabis F, et al. Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet (2002) 360:119–29. doi:10.1016/S0140-6736(02)09411-4
112. 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) 372:293–9. doi:10.1016/S0140-6736(08)61113-7
113. Antiretroviral Therapy Cohort Collaboration; Zwahlen M, Harris R, May M, Hogg R, Costagliola D, et al. Mortality of HIV-infected patients starting potent antiretroviral therapy: comparison with the general population in nine industrialized countries. Int J Epidemiol (2009) 38:1624–33. doi:10.1093/ije/dyp306
114. HIV-CAUSAL Collaboration; Ray M, Logan R, Sterne JA, Hernández-Díaz S, Robins JM, et al. The effect of combined antiretroviral therapy on the overall mortality of HIV-infected individuals. AIDS (2010) 24:123–37. doi:10.1097/QAD.0b013e3283324283
115. Opportunistic Infections Project Team of the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord; Young J, Psichogiou M, Meyer L, Ayayi S, Grabar S, et al. CD4 cell count and the risk of AIDS or death in HIV-Infected adults on combination antiretroviral therapy with a suppressed viral load: a longitudinal cohort study from COHERE. PLoS Med (2012) 9(3):e1001194. doi:10.1371/journal.pmed.1001194
116. May MT, Ingle SM, Costagliola D, Justice AC, de Wolf F, Cavassini M, et al. Cohort profile: antiretroviral therapy cohort collaboration (ART-CC). Int J Epidemiol (2014) 43:691–702. doi:10.1093/ije/dyt010
117. Zhu H, Napravnik S, Eron JJ, Cole SR, Ma Y, Wohl DA, et al. Decreasing excess mortality of HIV-infected patients initiating antiretroviral therapy: comparison with mortality in general population in China, 2003-2009. J Acquir Immune Defic Syndr (2013) 63(5):e150–7. doi:10.1097/QAI.0b013e3182948d82
118. Chigwedere P, Seage GR III, Gruskin S, Lee TH, Essex M. Estimating the lost benefits of antiretroviral drug use in South Africa. J Acquir Immune Defic Syndr (2008) 49:410–5. doi:10.1097/QAI.0b013e31818a6cd5
Keywords: HIV, AIDS, antiretroviral therapy, AIDS denialism, pseudoscience, public health
Citation: Karetnikov A (2015) Commentary: Questioning the HIV-AIDS hypothesis: 30 years of dissent. Front. Public Health 3:193. doi: 10.3389/fpubh.2015.00193
Received: 30 April 2015; Accepted: 23 July 2015;
Published: 07 August 2015
Edited by: Philippe C. G. Adam, The University of New South Wales, Australia
John B. F. De Wit, The University of New South Wales, Australia
Seth Kalichman, University of Connecticut, USA
Copyright: © 2015 Karetnikov. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).