Elite controllers as a model of functional cure

Current Opinion in HIV and AIDS

Volumn 6, Issue 3, 2011, Pages 181-187

  Autran, Brigitte ^a,b   Descours, Benjamin ^a   Avettand Fenoel, Véronique ^c,d   Rouzioux, Christine ^c,d  

^a SORBONNE UNIVERSITÉ   (France)

^b PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d HÔPITAL NECKER ENFANTS MALADES   (France)

Author keywords

elite controllers; genetic markers; HIV cure; HIV reservoirs

Indexed keywords

ANTIRETROVIRUS AGENT;

ARTICLE; CELLULAR IMMUNITY; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS INFECTED PATIENT; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE DEFICIENCY; PRIORITY JOURNAL; VIRUS REPLICATION; VIRUS TRANSMISSION;

AIDS VACCINES; ANTI-HIV AGENTS; HIV INFECTIONS; HIV LONG-TERM SURVIVORS; HIV-1; HUMANS; TREATMENT OUTCOME; VIREMIA;

EID: 79955480538     PISSN: 1746630X     EISSN: 17466318     Source Type: Journal    
DOI: 10.1097/COH.0b013e328345a328     Document Type: Article

References (71)

1. Hutter G, Nowak D, Mossner M, et al. Long-term control of HIV by CCR5 Delta32/Delta32 stem-cell transplantation. N Engl J Med 2009; 360:692-698.
2. Rerks-Ngarm S, Pitisuttithum P, Nitayaphan S, et al. Vaccination with ALVAC and AIDSVAX to prevent HIV-1 infection in Thailand. N Engl J Med 2009; 361:2209-2220.
3. Blankson JN. Control of HIV-1 replication in elite suppressors. Discov Med 2010; 9:261-266.
4. Blankson JN. Effector mechanisms in HIV-1 infected elite controllers: highly active immune responses? Antiviral Res 2010; 85:295-302.
5. Lambotte O, Boufassa F, Madec Y, et al. HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication. Clin Infect Dis 2005; 41:1053-1056. (Pubitemid 41368233)
6. Lefrere JJ, Mariotti M, Morand-Joubert L, et al. Plasma human immunodeficiency virus RNA below 40 copies/mL is rare in untreated persons even in the first years of infection. J Infect Dis 1999; 180:526-529. (Pubitemid 30256341)
7. Deeks SG, Walker BD. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 2007; 27:406-416. (Pubitemid 47418678)
8. Allers K, Hutter G, Hofmann J, et al. Evidence for the cure of HIV infection by CCR5{Delta}32/{Delta}32 stem cell transplantation. Blood 2010; 117: 2791-2798.
9. El-Sadr WM, Lundgren JD, Neaton JD, et al. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 2006; 355:2283-2296. (Pubitemid 44837777)
10. Joos B, Fischer M, Kuster H, et al. HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc Natl Acad Sci USA 2008; 105:16725-16730.
11. Murphy RL, Autran B, Katlama C, et al. A step ahead on the HIV collaboratory. Science 2009; 324:1264-1265.
12. Richman DD, Margolis DM, Delaney M, et al. The challenge of finding a cure for HIV infection. Science 2009; 323:1304-1307.
13. Trono D, Van Lint C, Rouzioux C, et al. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 2010; 329:174-180.
14. Hocqueloux L, Prazuck T, Avettand-Fenoel V, et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS 2010; 24:1598-1601.
15. Grabar S, Selinger-Leneman H, Abgrall S, et al. Prevalence and comparative characteristics of long-term nonprogressors and HIV controller patients in the French Hospital Database on HIV. AIDS 2009; 23:1163-1169.
16. Hubert JB, Burgard M, Dussaix E, et al. Natural history of serum HIV-1 RNA levels in 330 patients with a known date of infection. The SEROCO Study Group. AIDS 2000; 14:123-131. (Pubitemid 30116437)
17. Okulicz JF,MarconiVC, LandrumML, et al. Clinical outcomes of elite controllers, viremic controllers, and long-term nonprogressors in the US Department of Defense HIV natural history study. J Infect Dis 2009; 200:1714-1723.
18. Martinez V, Costagliola D, Bonduelle O, et al. Combination of HIV-1-specific CD4 Th1 cell responses and IgG2 antibodies is the best predictor for persistence of long-term nonprogression. J Infect Dis 2005; 191:2053-2063. (Pubitemid 40800576)
19. Rouzioux C, Hubert JB, Burgard M, et al. Early levels of HIV-1 DNA in peripheral blood mononuclear cells are predictive of disease progression independently of HIV-1 RNA levels and CD4+ T cell counts. J Infect Dis 2005; 192:46-55. (Pubitemid 40863856)
20. Bailey JR, Williams TM, Siliciano RF, Blankson JN. Maintenance of viral suppression in HIV-1-infected HLA-B*57+ elite suppressors despite CTL escape mutations. J Exp Med 2006; 203:1357-1369. (Pubitemid 43736603)
21. Madec Y, Boufassa F, Avettand-Fenoel V, et al. Early control of HIV-1 infection in long-term nonprogressors followed since diagnosis in the ANRS SEROCO/ HEMOCO cohort. J Acquir Immune Defic Syndr 2009; 50:19-26.
22. Julg B, Pereyra F, Buzon MJ, et al. Infrequent recovery of HIV from but robust exogenous infection of activated CD4(+) T cells in HIV elite controllers. Clin Infect Dis 2010; 51:233-238.
23. Wang B, Mikhail M, Dyer WB, et al. First demonstration of a lack of viral sequence evolution in a nonprogressor, defining replication-incompetent HIV-1 infection. Virology 2003; 312:135-150. (Pubitemid 36918466)
24. Hatano H, Delwart EL, Norris PJ, et al. Evidence for persistent low-level viremia in individuals who control human immunodeficiency virus in the absence of antiretroviral therapy. J Virol 2009; 83:329-335.
25. Pereyra F, Palmer S, Miura T, et al. Persistent low-level viremia in HIV-1 elite controllers and relationship to immunologic parameters. J Infect Dis 2009; 200:984-990.
26. Blankson JN, Bailey JR, Thayil S, et al. Isolation and characterization of replication-competent human immunodeficiency virus type 1 from a subset of elite suppressors. J Virol 2007; 81:2508-2518.
27. Candotti D, Costagliola D, Joberty C, et al. Status of long-term asymptomatic HIV-1 infection correlates with viral load but not with virus replication properties and cell tropism. French ALT Study Group. J Med Virol 1999; 58:256-263. (Pubitemid 29278028)
28. Cao Y, Qin L, Zhang L, et al. Virologic and immunologic characterization of long-term survivors of human immunodeficiency virus type 1 infection. N Engl J Med 1995; 332:201-208.
29. Mens H, Kearney M, Wiegand A, et al. HIV-1 continues to replicate and evolve in patients with natural control of HIV infection. J Virol 2010; 84:12971-12981.
30. Miura T, Brockman MA, Brumme CJ, et al. Genetic characterization of human immunodeficiency virus type 1 in elite controllers: lack of gross genetic defects or common amino acid changes. J Virol 2008; 82:8422-8430.
31. O'Connell KA, Brennan TP, Bailey JR, et al. Control of HIV-1 in elite suppressors despite ongoing replication and evolution in plasma virus. J Virol 2010; 84:7018-7028.
32. Navis M, Schellens I, van Baarle D, et al. Viral replication capacity as a correlate of HLA B57/B5801-associated nonprogressive HIV-1 infection. J Immunol 2007; 179:3133-3143.
33. Lassen KG, Lobritz MA, Bailey JR, et al. Elite suppressor-derived HIV-1 envelope glycoproteins exhibit reduced entry efficiency and kinetics. PLoS Pathog 2009; 5:e1000377.
34. Brumme ZL, Li C, Miura T, et al. Reduced replication capacity of NL4-3 recombinant viruses encoding reverse transcriptase-integrase sequences from HIV-1 elite controllers. J Acquir Immune Defic Syndr 2011; 56:100-108.
35. Miura T, Brumme ZL, Brockman MA, et al. Impaired replication capacity of acute/early viruses in persons who become HIV controllers. J Virol 2010; 84:7581-7591.
36. Bailey JR, O'Connell K, Yang HC, et al. Transmission of human immunodeficiency virus type 1 from a patient who developed AIDS to an elite suppressor. J Virol 2008; 82:7395-7410. (Pubitemid 352031208)
37. Carrington M, Nelson GW, Martin MP, et al. HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 1999; 283:1748-1752.
38. Kaslow RA, Carrington M, Apple R, et al. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat Med 1996; 2:405-411. (Pubitemid 26193012)
39. Magierowska M, Theodorou I, Debre 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; 93:936-941. (Pubitemid 29067859)
40. Pereyra F, Jia X, McLaren PJ, et al. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 2010; 330:1551-1557.
41. Rabi SA, O'Connell KA, Nikolaeva D, et al. Unstimulated primary CD4+ T cells from HIV-1-positive elite suppressors are fully susceptible to HIV-1 entry and productive infection. J Virol 2011; 85:979-986.
42. Migueles SA, Sabbaghian MS, Shupert WL, et al. HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-infected long term nonprogressors. Proc Natl Acad Sci USA 2000; 97:2709-2714. (Pubitemid 30159236)
43. Dalmasso C, Carpentier W, Meyer L, et al. Distinct genetic loci control plasma HIV-RNA and cellular HIV-DNA levels in HIV-1 infection: the ANRS Genome Wide Association 01 study. PLoS One 2008; 3:e3907.
44. Fellay J, Shianna KV, Ge D, et al. A whole-genome association study of major determinants for host control of HIV-1. Science 2007; 317:944-947. (Pubitemid 47301321)
45. Almeida JR, Price DA, Papagno L, et al. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 2007; 204:2473-2485. (Pubitemid 47529331)
46. Saez-Cirion A, Lacabaratz C, Lambotte O, et al. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc Natl Acad Sci USA 2007; 104:6776-6781. (Pubitemid 47175577)
47. Xie J, Lu W, Samri A, et al. Distinct differentiation profiles of HIV-Gag and Nefspecific central memory CD8+ T cells associated with HLA-B57/5801 and virus control. AIDS 2010; 24:2323-2329.
48. Migueles SA, Osborne CM, Royce C, et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity 2008; 29:1009-1021.
49. Almeida JR, Sauce D, Price DA, et al. Antigen sensitivity is a major determinant of CD8+ T-cell polyfunctionality and HIV-suppressive activity. Blood 2009; 113:6351-6360.
50. Papagno L, Alter G, Assoumou L, et al. Comprehensive analysis of virusspecific T-cells provides clues for the failure of therapeutic immunization with ALVAC-HIV vaccine. AIDS 2011; 25:27-36.
51. Vingert B, Perez-Patrigeon S, Jeannin P, et al. HIV controller CD4+ T cells respond to minimal amounts of Gag antigen due to high TCR avidity. PLoS Pathog 2010; 6:e1000780.
52. Ferre AL, Hunt PW,McConnell DH, et al. HIV controllers with HLA-DRB1*13 and HLA-DQB1*06 alleles have strong, polyfunctional mucosal CD4+ T-cell responses. J Virol 2010; 84:11020-11029.
53. Saez-Cirion A, Sinet M, Shin SY, et al. Heterogeneity in HIV suppression by CD8 T cells from HIV controllers: association with Gag-specific CD8 T cell responses. J Immunol 2009; 182:7828-7837.
54. Lambotte O, Ferrari G, Moog C, et al. Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers. AIDS 2009; 23:897-906.
55. Bailey JR, Lassen KG, Yang HC, et al. Neutralizing antibodies do not mediate suppression of human immunodeficiency virus type 1 in elite suppressors or selection of plasma virus variants in patients on highly active antiretroviral therapy. J Virol 2006; 80:4758-4770.
56. Pereyra F, Addo MM, Kaufmann DE, et al. Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. J Infect Dis 2008; 197:563-571. (Pubitemid 351321534)
57. Braibant M, Brunet S, Costagliola D, et al. Antibodies to conserved epitopes of the HIV-1 envelope in sera from long-term nonprogressors: prevalence and association with neutralizing activity. AIDS 2006; 20:1923-1930. (Pubitemid 44427609)
58. Ngo-Giang-Huong N, Candotti D, Goubar A, et al. HIV type 1-specific IgG2 antibodies: markers of helper T cell type 1 response and prognostic marker of long-term nonprogression. AIDS Res Hum Retroviruses 2001; 17:1435-1446. (Pubitemid 33042811)
59. Scheid JF, Mouquet H, Feldhahn N, et al. Broad diversity of neutralizing antibodies isolated from memory B cells in HIV-infected individuals. Nature 2009; 458:636-640.
60. Doria-Rose NA, Klein RM, Manion MM, et al. Frequency and phenotype of human immunodeficiency virus envelope-specific B cells from patients with broadly cross-neutralizing antibodies. J Virol 2009; 83:188-199.
61. Alter G, Martin MP, Teigen N, et al. Differential natural killer cell-mediated inhibition of HIV-1 replication based on distinct KIR/HLA subtypes. J Exp Med 2007; 204:3027-3036. (Pubitemid 350179568)
62. Alter G, Rihn S, Walter K, et al. HLA class I subtype-dependent expansion of KIR3DS1+ and KIR3DL1+ NK cells during acute human immunodeficiency virus type 1 infection. J Virol 2009; 83:6798-6805.
63. Martin MP, Qi Y, Gao X, et al. Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nat Genet 2007; 39:733-740. (Pubitemid 46848586)
64. Vieillard V, Costagliola D, Simon A, Debre P. Specific adaptive humoral response against a gp41 motif inhibits CD4 T-cell sensitivity to NK lysis during HIV-1 infection. AIDS 2006; 20:1795-1804. (Pubitemid 44358897)
65. Chun TW, Carruth L, Finzi D, et al. Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 1997; 387:183-188. (Pubitemid 27209433)
66. Chun TW, Nickle DC, Justement JS, et al. Persistence of HIV in gutassociated lymphoid tissue despite long-term antiretroviral therapy. J Infect Dis 2008; 197:714-720. (Pubitemid 351364472)
67. Avettand-Fenoel V, Prazuck T, Hocqueloux L, et al. HIV-DNA in rectal cells is well correlated with HIV-DNA in blood in different groups of patients, including long-term nonprogressors. AIDS 2008; 22:1880-1882.
68. Chomont N, El-Far M, Ancuta P, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 2009; 15:893-900.
69. Hunt PW, Brenchley J, Sinclair E, et al. Relationship between T cell activation and CD4+ T cell count in HIV-seropositive individuals with undetectable plasma HIV RNA levels in the absence of therapy. J Infect Dis 2008; 197:126-133. (Pubitemid 351263476)
70. Okulicz JF, Grandits GA, Weintrob AC, et al. CD4 T cell count reconstitution in HIV controllers after highly active antiretroviral therapy. Clin Infect Dis 2010; 50:1187-1191.
71. Sedaghat AR, Rastegar DA, O'Connell KA, et al. T cell dynamics and the response to HAART in a cohort of HIV-1-infected elite suppressors. Clin Infect Dis 2009; 49:1763-1766.