A highly intensified ART regimen induces long-term viral suppression and restriction of the viral reservoir in a simian AIDS model

PLoS Pathogens

Volumn 8, Issue 6, 2012, Pages

  Shytaj, Iart Luca ^a   Norelli, Sandro ^a   Chirullo, Barbara ^a   Della Corte, Alessandro ^a   Collins, Matt ^b   Yalley Ogunro, Jake ^b   Greenhouse, Jack ^b   Iraci, Nunzio ^c   Acosta, Edward P ^d   Barreca, Maria Letizia ^c   Lewis, Mark G ^b   Savarino, Andrea ^a  

^a ISTITUTO SUPERIORE DI SANITÀ   (Italy)

^b BIOQUAL INC   (United States)

^c UNIVERSITY OF PERUGIA   (Italy)

^d UNIVERSITY OF ALABAMA AT BIRMINGHAM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

DARUNAVIR PLUS RITONAVIR; EMTRICITABINE; MARAVIROC; RALTEGRAVIR; TENOFOVIR; 2 PYRROLIDONE DERIVATIVE; ADENINE; ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; CYCLOHEXANE DERIVATIVE; DARUNAVIR; DEOXYCYTIDINE; DRUG DERIVATIVE; PHOSPHONIC ACID DERIVATIVE; RITONAVIR; SULFONAMIDE; TRIAZOLE DERIVATIVE;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DRUG EFFECT; DRUG EFFICACY; NONHUMAN; RHESUS MONKEY; TREATMENT OUTCOME; VIREMIA; VIRUS INHIBITION; VIRUS LOAD; ANIMAL; DRUG COMBINATION; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; METHODOLOGY; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; T LYMPHOCYTE SUBPOPULATION;

ANIMALIA; MACACA; MACACA MULATTA; SIMIAE;

ADENINE; ANIMALS; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CYCLOHEXANES; DEOXYCYTIDINE; DRUG THERAPY, COMBINATION; FLOW CYTOMETRY; FLUORESCENT ANTIBODY TECHNIQUE; MACACA MULATTA; PHOSPHONIC ACIDS; PYRROLIDINONES; RITONAVIR; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; SULFONAMIDES; T-LYMPHOCYTE SUBSETS; TRIAZOLES; VIRAL LOAD; VIREMIA;

EID: 84864051807     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1002774     Document Type: Article

References (49)

1. Norelli S, El Daker S, D'Ostilio D, Mele F, Mancini F, et al. (2008) Response of feline immunodeficiency virus (FIV) to tipranavir may provide new clues for development of broad-based inhibitors of retroviral proteases acting on drug-resistant HIV-1 Curr. HIV Res 6: 306-17.
2. Witvrouw M, Pannecouque C, Switzer WM, Folks TM, De Clercq E, et al. (2004) Susceptibility of HIV-2, SIV and SHIV to various anti-HIV-1 compounds: implications for treatment and post exposure prophylaxis. Antivir Ther 9: 57-65.
3. Deere JD, Schinazi RF, North TW, (2011) Simian immunodeficiency virus macaque models of HIV latency. Curr Opin HIV AIDS 6: 57-61.
4. Dinoso JB, Rabi SA, Blankson JN, Gama L, Mankowski JL, et al. (2009) A simian immunodeficiency virus-infected macaque model to study viral reservoirs that persist during highly active antiretroviral therapy. J Virol 83: 9247-9257.
5. Lewis MG, Norelli S, Collins M, Barreca ML, Iraci N, et al. (2010) Response of a simian immunodeficiency virus (SIVmac251) to raltegravir: a basis for a new treatment for simian AIDS and an animal model for studying lentiviral persistence during antiretroviral therapy. Retrovirology 7: 21.
6. Vahey MT, Ockenhouse CF, Wang Z, Yalley-Ogunro J, Greenhouse J, et al. (2007) Impact of antiretroviral treatment on gene expression in peripheral blood mononuclear cells from SIVmac251-infected macaques. J Infect Dis 196: 384-393.
7. Lewis MG, Dafonseca S, Chomont N, Palamara AT, Tardugno M, et al. (2011) Gold drug auranofin restricts the viral reservoir in the monkey AIDS model and induces containment of viral load following ART suspension. AIDS 25: 1347-56.
8. Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, et al. (2009) HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 15: 893-900.
9. Chomont N, DaFonseca S, Vandergeeten C, Ancuta P, Sékaly RP, (2011) Maintenance of CD4+ T-cell memory and HIV persistence: keeping memory, keeping HIV. Curr Opin HIV AIDS 6: 30-6 Review.
10. Paiardini M, Cervasi B, Reyes-Aviles E, Micci L, Ortiz AM, et al. (2011) Low levels of SIV infection in sooty mangabey central memory CD4+ T cells are associated with limited CCR5 expression. Nat Med 17: 830-6.
11. Fultz PN, Stricker RB, McClure HM, Anderson DC, Switzer WM, et al. (1990) Humoral response to SIV/SMM infection in macaque and mangabey monkeys. J Acquir Immune Defic Syndr 3: 319-29.
12. Lifson J, (2012) The Role of Non-human Primate Models in the Evaluation of ARV Suppression, Residual Virus, and Viral Eradication Strategies in AIDS Virus Infection [Abstract 107]. In: Proceedings of the 19th Conference on Retroviruses and Opportunistic Infections; 5-8 March 2012, Seattle, Washington, United States. CROI 2012, Available: http://www.retroconference.org/2012b/Abstracts/45277.htm. Accessed 14 May 2012.
13. Bensi T, Mele F, Ferretti M, Norelli S, El Daker S, et al. (2009) Evaluation of the antiretroviral effects of a PEG-conjugated peptide derived from human CD38. Expert Opin Ther Targets 13: 141-52.
14. Kovalevsky AY, Louis JM, Aniana A, Ghosh AK, Weber IT, (2008) Structural evidence for effectiveness of darunavir and two related antiviral inhibitors against HIV-2 protease. J Mol Biol 384: 178-92.
15. Muzammil S, Armstrong AA, Kang LW, Jakalian A, Bonneau PR, et al. (2007) Unique thermodynamic response of tipranavir to human immunodeficiency virus type 1 protease drug resistance mutations. J Virol 81: 5144-54.
16. Chen Z, Zhou P, Ho DD, Landau NR, Marx PA, (1997) Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry. J Virol 71: 2705-14.
17. Veazey RS, Klasse PJ, Ketas TJ, Reeves JD, Piatak M Jr, et al. (2003) Use of a small molecule CCR5 inhibitor in macaques to treat simian immunodeficiency virus infection or prevent simian-human immunodeficiency virus infection. J Exp Med 198: 1551-62.
18. Palmer S, Maldarelli F, Wiegand A, Bernstein B, Hanna GJ, et al. (2008) Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A 105: 3879-84.
19. Smith CJ, Staszewski S, Sabin CA, Nelson M, Dauer B, et al. (2004) Use of viral load measured after 4 weeks of highly active antiretroviral therapy to predict virologic outcome at 24 weeks for HIV-1-positive individuals. J Acquir Immune Defic Syndr 37: 1155-9.
20. Mira JA, Macías J, Nogales C, Fernández-Rivera J, García-García JA, et al. (2002) Transient rebounds of low-level viraemia among HIV-infected patients under HAART are not associated with virological or immunological failure. Antivir Ther 7: 251-6.
21. Ellis RJ, Gamst AC, Capparelli E, Spector SA, Hsia K, et al. (2000) Cerebrospinal fluid HIV RNA originates from both local CNS and systemic sources. Neurology 54: 927-36.
22. Kim RB, Fromm MF, Wandel C, Leake B, Wood AJ, et al. (1998) The drug transporter P-glycoprotein limits oral absorption and brain entry of HIV-1 protease inhibitors. J Clin Invest 101: 289-294.
23. Savarino A, Lucia MB, Rastrelli E, Rutella S, Golotta C, et al. (2004) Anti-HIV effects of chloroquine: inhibition of viral particle glycosylation and synergism with proteaseinhibitors. J Acquir Immune Defic Syndr 35: 223-32.
24. Bourry O, Mannioui A, Sellier P, Roucairol C, Durand-Gasselin L, et al. (2010) Effect of a short-term HAART on SIV load in macaque tissues is dependent on time of initiation and antiviral diffusion. Retrovirology 7: 78.
25. Turner L, Ward SG, Sansom D, Westwick J, (1996) A role for RANTES in T lymphocyte proliferation. Biochem Soc Trans 24: 93S.
26. Gutiérrez C, Díaz L, Vallejo A, Hernández-Novoa B, Abad M, et al. (2011) Intensification of antiretroviral therapy with a CCR5 antagonist in patients with chronic HIV-1 infection: effect on T cells latently infected. PLoS One 6: e27864.
27. Funderburg N, Kalinowska M, Eason J, Goodrich J, Heera J, et al. (2010) Effects of maraviroc and efavirenz on markers of immune activation and inflammation and associations with CD4+ cell rises in HIV-infected patients. PLoS One 5: e13188.
28. d'Ettorre G, Paiardini M, Zaffiri L, Andreotti M, Ceccarelli G, et al. (2011) HIV persistence in the gut mucosa of HIV-infected subjects undergoing antiretroviral therapy correlates with immune activation and increased levels of LPS. Curr HIV Res 9: 148-53.
29. Hocqueloux L, Prazuck T, Avettand-Fenoel V, Lafeuillade A, Cardon B, et al. (2010) Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS 24: 1598-601.
30. Benlhassan-Chahour K, Penit C, Dioszeghy V, Vasseur F, Janvier G, et al. (2003) Kinetics of lymphocyte proliferation during primary immune response in macaques infected with pathogenic simian immunodeficiency virus SIVmac251: preliminary report of the effect of early antiviral therapy. J Virol 77: 12479-93.
31. Lori F, Lewis MG, Xu J, Varga G, Zinn DE Jr, et al. (2000) Control of SIV rebound through structured treatment interruptions during early infection. Science 290: 1591-3.
32. Lewin SR, Rouzioux C, (2011) HIV cure and eradication: how will we get from the laboratory to effective clinical trials? AIDS 25: 885-97.
33. Johnston R, Barre-Sinoussi F, (2012) Controversies in HIV cure research. J Int AIDS Soc 15: 16.
34. Mudd PA, Ericsen AJ, Burwitz BJ, Wilson NA, O'Connor DH, et al. (2012) Escape from CD8+ T Cell Responses in Mamu-B*00801+ Macaques Differentiates Progressors from Elite Controllers. J Immunol 188: 3364-70.
35. Ortiz AM, Klatt NR, Li B, Yi Y, Tabb B, et al. (2011) Depletion of CD4+T cells abrogates post-peak decline of viremia in SIV-infected rhesus macaques. J Clin Invest 121: 4433-45.
36. Gordon SN, Weissman AR, Cecchinato V, Fenizia C, Ma ZM, et al. (2010) Preexisting infection with human T-cell lymphotropic virus type 2 neither exacerbates nor attenuates simian immunodeficiency virus SIVmac251 infection in macaques. J Virol 84: 3043-58.
37. Yeh WW, Jaru-Ampornpan P, Nevidomskyte D, Asmal M, Rao SS, et al. (2009) Partial protection of Simian immunodeficiency virus (SIV)-infected rhesus monkeys against superinfection with a heterologous SIV isolate. J Virol 83: 2686-96.
38. Reimann KA, Parker RA, Seaman MS, Beaudry K, Beddall M, et al. (2005) Pathogenicity of simian-human immunodeficiency virus SHIV-89.6P and SIVmac is attenuated in cynomolgus macaques and associated with early T-lymphocyte responses. J Virol 79: 8878-85.
39. Schacker T, Stevenson M, Fletcher C, (2011) Anatomic HIV Reservoirs [Abstract 35]. In: Final Program and Abstracts of the 5th International Workshop on HIV Persistence during Therapy; St Maarten, West Indies, 6-9 December, 2011. Global Antiviral J 7: 28-29.
40. Rong L, Perelson AS, (2009) Modeling latently infected cell activation: viral and latent reservoir persistence, and viral blips in HIV-infected patients on potent therapy. PLoS Comput Biol 5: e1000533.
41. Chen HY, Di Mascio M, Perelson AS, Ho DD, Zhang L, (2007) Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques. Proc Natl Acad Sci U S A 104: 19079-84.
42. Ananworanich J, Schuetz A, Vandergeeten C, Sereti I, de Souza M, et al. (2012) Impact of Multi-Targeted Antiretroviral Treatment on Gut T Cell Depletion and HIV Reservoir Seeding during Acute HIV Infection. PLoS One 7: e33948.
43. Groot F, van Capel TM, Schuitemaker J, Berkhout B, de Jong EC, (2006) Differential susceptibility of naïve, central memory and effector memory T cells to dendritic cell-mediated HIV-1 transmission. Retrovirology 3: 52.
44. Bostik P, Noble ES, Mayne AE, Gargano L, Villinger F, et al. (2006) Central memory CD4 T cells are the predominant cell subset resistant to anergy in SIV disease resistant sooty mangabeys. AIDS 20: 181-8.
45. Zhang ZQ, Fu TM, Casimiro DR, Davies ME, Liang X, et al. (2002) Mamu-A*01 allele-mediated attenuation of disease progression in simian-human immunodeficiency virus infection. J Virol 76: 12845-54.
46. Yant LJ, Friedrich TC, Johnson RC, May GE, Maness NJ, et al. (2006) The high-frequency major histocompatibility complex class I allele Mamu-B*17 is associated with control of simian immunodeficiency virus SIVmac239 replication. J Virol 80: 5074-7.
47. Loffredo JT, Maxwell J, Qi Y, Glidden CE, Borchardt GJ, et al. (2007) Mamu-B*08-positive macaques control simian immunodeficiency virus replication. J Virol 81 (16): 8827-32.
48. Boyer JD, Kumar S, Robinson T, Parkinson R, Wu L, et al. (2006) Initiation of antiretroviral therapy during chronic SIV infection leads to rapid reduction in viral loads and the level of T-cell immune response. J Med Primatol 35: 202-9.
49. Bacchetti P, Deeks SG, McCune JM, (2011) Breaking free of sample size dogma to perform innovative translational research. Sci Transl Med 3: 87.