Persistent HIV-1 replication during antiretroviral therapy

Current Opinion in HIV and AIDS

Volumn 11, Issue 4, 2016, Pages 417-423

  Martinez Picado, Javier ^a,b,c   Deeks, Steven G ^d  

^a UNIVERSITAT AUTÒNOMA DE BARCELONA   (Spain)

^b UNIVERSITY OF VIC CENTRAL UNIVERSITY OF CATALONIA   (Spain)

^c INSTITUCIÓ CATALANA DE RECERCA I ESTUDIS AVANÇATS ICREA   (Spain)

^d UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

abnormal levels of immune activation and inflammation; cell to cell infection; HIV residual replication during ART; limited drug penetration within tissues; presence of immune sanctuaries

Indexed keywords

ANTIRETROVIRUS AGENT; RALTEGRAVIR;

CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; DNA INTEGRATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; INFLAMMATION; LONG TERMINAL REPEAT; LYMPHOID TISSUE; PRIORITY JOURNAL; REVIEW; T LYMPHOCYTE ACTIVATION; VIRUS REPLICATION; VIRUS TRANSMISSION; HIV INFECTIONS; PHYSIOLOGY; VIROLOGY;

ANTI-RETROVIRAL AGENTS; HIV INFECTIONS; HIV-1; HUMANS; LYMPHOID TISSUE; VIRUS REPLICATION;

EID: 84963526778     PISSN: 1746630X     EISSN: 17466318     Source Type: Journal    
DOI: 10.1097/COH.0000000000000287     Document Type: Review

References (70)

1. Hockett RD, Kilby JM, et al. Constant mean viral copy number per infected cell in tissues regardless of high, low, or undetectable plasma HIV RNA. J Exp Med 1999; 189:1545-1554.
2. Hatano H, Delwart EL, 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.
3. Mens H, Kearney M, et al. HIV-1 continues to replicate and evolve in patients with natural control of HIV infection. J Virol 2010; 84:12971-12981.
4. Chun TW, Shawn Justement J, et al. Effect of antiretroviral therapy on HIV reservoirs in elite controllers. J Infect Dis 2013; 208:1443-1447.
5. Hatano H, Yukl SA, et al. Prospective antiretroviral treatment of asymptomatic, HIV-1 infected controllers. PLoS Pathog 2013; 9:e1003691.
6. Maldarelli F, Palmer S, et al. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog 2007; 3:e46.
7. Palmer S, Maldarelli F, et al. Low-level viremia persists for at least 7 years in patients on suppressive antiretroviral therapy. Proc Natl Acad Sci U S A 2008; 105:3879-3884.
8. Joos B, Fischer M, et al. HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc Natl Acad Sci U S A 2008; 105:16725-16730.
9. Evering TH, Mehandru S, et al. Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection. PLoS Pathog 2012; 8:e1002506.
10. Josefsson L, von Stockenstrom S, et al. The HIV-1 reservoir in eight patients on long-term suppressive antiretroviral therapy is stable with few genetic changes over time. Proc Natl Acad Sci U S A 2013; 110:E4987-E4996.
11. Kearney MF, Spindler J, et al. Lack of detectable HIV-1 molecular evolution during suppressive antiretroviral therapy. PLoS Pathog 2014; 10:e1004010
12. Kearney MF, Wiegand A, et al. Origin of rebound plasma HIV includes cells with identical proviruses that are transcriptionally active before stopping of antiretroviral therapy. J Virol 2015; 90:1369-1376
13. Lorenzo-Redondo R, Fryer HR, et al. Persistent HIV-1 replication maintains the tissue reservoir during therapy. Nature 2016; 530:51-56
14. Dinoso JB, Kim SY, et al. Treatment intensification does not reduce residual HIV-1 viremia in patients on highly active antiretroviral therapy. Proc Natl Acad Sci U S A 2009; 106:9403-9408.
15. McMahon D, Jones J, et al. Short-course raltegravir intensification does not reduce persistent low-level viremia in patients with HIV-1 suppression during receipt of combination antiretroviral therapy. Clin Infect Dis 2010; 50:912-919.
16. Hatano H, Hayes TL, et al. A randomized, controlled trial of raltegravir intensification in antiretroviral-treated, HIV-infected patients with a suboptimal CD4+ T cell response. J Infect Dis 2011; 203:960-968.
17. Byakwaga H, Kelly M, et al. Intensification of antiretroviral therapy with raltegravir or addition of hyperimmune bovine colostrum in HIV-infected patients with suboptimal CD4+ T-cell response: a randomized controlled trial. J Infect Dis 2011; 204:1532-1540.
18. Llibre JM, Buzó n MJ, et al. Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression: a randomized 48-week study. Antivir Ther 2012; 17:355-364.
19. Gandhi RT, Coombs RW, et al. No effect of raltegravir intensification on viral replication markers in the blood of HIV-1-infected patients receiving antiretroviral therapy. J Acquir Immune Defic Syndr 2012; 59:229-235.
20. Vallejo A, Gutierrez C, et al. The effect of intensification with raltegravir on the HIV-1 reservoir of latently infected memory CD4 T cells in suppressed patients. AIDS 2012; 26:1885-1894.
21. Hunt PW, Shulman NS, et al. The immunologic effects of maraviroc intensification in treated HIV-infected individuals with incomplete CD4+ T-cell recovery: a randomized trial. Blood 2013; 121:4635-4646.
22. Buzó n MJ, Massanella M, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 2010; 16:460-465.
23. Hatano H, Strain MC, et al. Increasein2-longterminal repeatcircles anddecrease in D-dimer after raltegravir intensification in patients with treated HIV infection: a randomized, placebo-controlled trial. J Infect Dis 2013; 208:1436-1442.
24. Luo R, Cardozo EF, et al. Modelling HIV-1 2-LTR dynamics following raltegravir intensification. J R Soc Interface 2013; 10:20130186.
25. Puertas MC, Massanella M, et al. Intensification of a raltegravir-based regimen with maraviroc in early HIV-1 infection. AIDS 2014; 28:325-334.
26. Massanella M, Esteve A, et al. Dynamics of CD8 T-cell activation after discontinuation of HIV treatment intensification. J Acquir Immune Defic Syndr 2013; 63:152-160.
27. Buzó n MJ, Codoñer FM, et al. Deep molecular characterization of HIV-1 dynamics under suppressive HAART. PLoS Pathog 2011; 7:e1002314.
28. Cardozo EF, Luo R, Piovoso MJ, Zurakowski R. Spatial modeling of HIV cryptic viremia and 2-LTR formation during raltegravir intensification. J Theor Biol 2014; 345:61-69.
29. Barton KM, Rasmussen TA, Tolstrup M, et al. Panobinostat Broadly Activates Latent HIV-1 proviruses in patients. Proceedings of the 22nd Conference on Retroviruses and Opportunistic Infections Seattle, Washington, USA 2015; Abstract 109.
30. Li JZ, Etemad B, et al. The size of the expressed HIV reservoir predicts timing of viral rebound after treatment interruption. AIDS 2016; 30:343-353
31. Yukl SA, Shergill AK, et al. Effect of raltegravir-containing intensification on HIV burden and T-cell activation in multiple gut sites of HIV-positive adults on suppressive antiretroviral therapy. AIDS 2010; 24:2451-2460.
32. O'Connell KA, Brennan TP, et al. Control of HIV-1 in elite suppressors despite ongoing replication and evolution in plasma virus. J Virol 2010; 84:7018-7028.
33. Sigal A, Kim JT, et al. Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature 2011; 477:95-98.
34. Shiu C, Cunningham CK, et al. Identification of ongoing human immunodeficiency virus type 1 (HIV-1) replication in residual viremia during recombinant HIV-1 poxvirus immunizations in patients with clinically undetectable viral loads on durable suppressive highly active antiretroviral therapy. J Virol 2009; 83:9731-9742.
35. Raymond S, Saliou A, et al. Evolution of HIV-1 quasispecies and coreceptor use in cell reservoirs of patients on suppressive antiretroviral therapy. J Antimicrob Chemother 2014; 69:2527-2530.
36. Wang S, Rong L. Stochastic population switch may explain the latent reservoir stability and intermittent viral blips in HIV patients on suppressive therapy. J Theor Biol 2014; 360:137-148
37. Conway JM, Perelson AS. Residual viremia in treated HIV+ individuals. PLoS Comput Biol 2016; 12:e1004677
38. Shen L, Peterson S, et al. Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs. Nat Med 2008; 14:762-766.
39. Shen L, Rabi SA, et al. A critical subset model provides a conceptual basis for the high antiviral activity of major HIV drugs. Sci Transl Med 2011; 3:91ra63.
40. Jilek BL, Zarr M, et al. A quantitative basis for antiretroviral therapy for HIV-1 infection. Nat Med 2012; 18:446-451.
41. Luo X, He JJ. Cell-cell contact viral transfer contributes to HIV infection and persistence in astrocytes. J Neurovirol 2015; 21:66-80
42. Galloway NL, Doitsh G, et al. Cell-to-cell transmission of HIV-1 is required to trigger pyroptotic death of lymphoid-tissue-derived CD4 T cells. Cell Rep 2015; 12:1555-1563
43. Fletcher CV, Staskus K, et al. Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc Natl Acad Sci U S A 2014; 111:2307-2312
44. Patterson KB, Prince HA, et al. Penetration of tenofovir and emtricitabine in mucosal tissues: implications for prevention of HIV-1 transmission. Sci Transl Med 2011; 3:112re4.
45. Patterson KB, Prince HA, et al. Differential penetration of raltegravir throughout gastrointestinal tissue: implications for eradication and cure. AIDS 2013; 27:1413-1419.
46. Hufert FT, van Lunzen J, et al. Germinal centre CD4+ T cells are an important site of HIV replication in vivo. AIDS 1997; 11:849-857.
47. Perreau M, Savoye AL, et al. Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J Exp Med 2013; 210:143-156.
48. Fukazawa Y, Lum R, et al. B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat Med 2015; 21:132-139
49. Connick E, Mattila T, et al. CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue. J Immunol 2007; 178:6975-6983.
50. Connick E, Folkvord JM, et al. Compartmentalization of simian immunodeficiency virus replication within secondary lymphoid tissues of rhesus macaques is linked to disease stage and inversely related to localization of virusspecific CTL. J Immunol 2014; 193:5613-5625.
51. Gerngross L, Fischer T. Evidence for cFMS signaling in HIV production by brain macrophages and microglia. J Neurovirol 2015; 21:249-256.
52. Hofstra LM, Mudrikova T, et al. Residual viremia is preceding viral blips and persistent low-level viremia in treated HIV-1 patients. PLoS One 2014; 9:e110749.
53. Sahu GK, Sarria JC, Cloyd MW. Recovery of replication-competent residual HIV-1 from plasma of a patient receiving prolonged, suppressive highly active antiretroviral therapy. J Virol 2010; 84:8348-8352.
54. Baroncelli S, Galluzzo CM, et al. Microbial translocation is associated with residual viral replication in HAART-treated HIV+ subjects with <50 copies/ml HIV-1 RNA. J Clin Virol 2009; 46:367-370.
55. Chomont N, El-Far M, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 2009; 15:893-900.
56. Hatano H, Jain V, et al. Cell-based measures of viral persistence are associated with immune activation and programmed cell death protein 1 (PD-1)-expressing CD4+ T cells. J Infect Dis 2013; 208:50-56.
57. Klatt NR, Chomont N, Douek DC, Deeks SG. Immune activation and HIV persistence: implications for curative approaches to HIV infection. Immunol Rev 2013; 254:326-342.
58. Vandergeeten C, Fromentin R, et al. Interleukin-7 promotes HIV persistence during antiretroviral therapy. Blood 2013; 121:4321-4329.
59. Murray JM, Zaunders JJ, et al. HIV DNA subspecies persist in both activated and resting memory CD4+ T cells during antiretroviral therapy. J Virol 2014; 88:3516-3526.
60. Barouch DH, Deeks SG. Immunologic strategies for HIV-1 remission and eradication. Science 2014; 345:169-174.
61. Katlama C, Deeks SG, et al. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs. Lancet 2013; 381:2109-2117.
62. Micci L, Ryan ES, et al. Interleukin-21 combined with ART reduces inflammation and viral reservoir in SIV-infected macaques. J Clin Invest 2015; 125:4497-4513
63. Trezza C, Ford SL, et al. Formulation and pharmacology of long-acting cabotegravir. Curr Opin HIV AIDS 2015; 10:239-245.
64. Sloan RD, Wainberg MA. Harnessing the therapeutic potential of host antiviral restriction factors that target HIV. Expert Rev Anti Infect Ther 2013; 11:1-4.
65. Barouch DH, Whitney JB, et al. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature 2013; 503:224-228.
66. Shingai M, Nishimura Y, et al. Antibody-mediated immunotherapy of macaques chronically infected with SHIV suppresses viraemia. Nature 2013; 503:277-280.
67. Barouch DH, Alter G, et al. Protective efficacy of adenovirus/protein vaccines against SIV challenges in rhesus monkeys. Science 2015; 349:320-324.
68. Gardner MR, Kattenhorn LM, et al. AAV-expressed eCD4-Ig provides durable protection from multiple SHIV challenges. Nature 2015; 519: 87-91.
69. Santangelo PJ, Rogers KA, et al. Whole-body immunoPET reveals active SIV dynamics in viremic and antiretroviral therapy-treated macaques. Nat Methods 2015; 12:427-432.
70. Burbelo PD, Bayat A, et al. HIV antibody characterization as a method to quantify reservoir size during curative interventions. J Infect Dis 2014; 209:1613-1617.