HIV-1 persistence following extremely early initiation of antiretroviral therapy (ART) during acute HIV-1 infection: An observational study

1. Deeks SG, Lewin SR, Ross AL, Ananworanich J, Benkirane M, Cannon P, et al. International AIDS Society global scientific strategy: towards an HIV cure 2016. Nat Med. 2016 Aug;22(8):839–50. doi: 10.1038/nm.4108 27400264

2. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, 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 Jun;9(6):727–8. doi: 10.1038/nm880 12754504

3. Richman DD, Margolis DM, Delaney M, Greene WC, Hazuda D, Pomerantz RJ. The challenge of finding a cure for HIV infection. Science. 2009 Mar 6;323(5919):1304–7. doi: 10.1126/science.1165706 19265012

4. Ananworanich J, Puthanakit T, Suntarattiwong P, Chokephaibulkit K, Kerr SJ, Fromentin R, et al. Reduced markers of HIV persistence and restricted HIV-specific immune responses after early antiretroviral therapy in children. AIDS. 2014 Apr 24;28(7):1015–20. doi: 10.1097/QAD.0000000000000178 24384692

5. Schuetz A, Deleage C, Sereti I, Rerknimitr R, Phanuphak N, Phuang-Ngern Y, et al. Initiation of ART during early acute HIV infection preserves mucosal Th17 function and reverses HIV-related immune activation. PLoS Pathog. 2014 Dec;10(12):e1004543. doi: 10.1371/journal.ppat.1004543 25503054

6. Persaud D, Gay H, Ziemniak C, Chen YH, Piatak M Jr., Chun TW, et al. Absence of detectable HIV-1 viremia after treatment cessation in an infant. N Engl J Med. 2013 Nov 7;369(19):1828–35. doi: 10.1056/NEJMoa1302976 24152233

7. Luzuriaga K, Gay H, Ziemniak C, Sanborn KB, Somasundaran M, Rainwater-Lovett K, et al. Viremic relapse after HIV-1 remission in a perinatally infected child. N Engl J Med. 2015 Feb 19;372(8):786–8. doi: 10.1056/NEJMc1413931 25693029

8. Announcement: Updated Guidelines for Antiretroviral Postexposure Prophylaxis after Sexual, Injection-Drug Use, or Other Nonoccupational Exposure to HIV—United States, 2016. MMWR Morb Mortal Wkly Rep. 2016 May 06;65(17):458. doi: 10.15585/mmwr.mm6517a5 27149423

9. Grant RM, Lama JR, Anderson PL, McMahan V, Liu AY, Vargas L, et al. Preexposure chemoprophylaxis for HIV prevention in men who have sex with men. N Engl J Med. 2010 Dec 30;363(27):2587–99. doi: 10.1056/NEJMoa1011205 21091279

10. Thigpen MC, Kebaabetswe PM, Paxton LA, Smith DK, Rose CE, Segolodi TM, et al. Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana. N Engl J Med. 2012 Aug 02;367(5):423–34. doi: 10.1056/NEJMoa1110711 22784038

11. Smith DK, Grohskopf LA, Black RJ, Auerbach JD, Veronese F, Struble KA, et al. Antiretroviral postexposure prophylaxis after sexual, injection-drug use, or other nonoccupational exposure to HIV in the United States: recommendations from the U.S. Department of Health and Human Services. MMWR Recomm Rep. 2005 Jan 21;54(RR-2):1–20. 15660015

12. Fiebig EW, Wright DJ, Rawal BD, Garrett PE, Schumacher RT, Peddada L, et al. Dynamics of HIV viremia and antibody seroconversion in plasma donors: implications for diagnosis and staging of primary HIV infection. AIDS. 2003 Sep 05;17(13):1871–9. doi: 10.1097/01.aids.0000076308.76477.b8 12960819

13. McMichael AJ, Borrow P, Tomaras GD, Goonetilleke N, Haynes BF. The immune response during acute HIV-1 infection: clues for vaccine development. Nat Rev Immunol. 2010 Jan;10(1):11–23. doi: 10.1038/nri2674 20010788

14. de Souza MS, Pinyakorn S, Akapirat S, Pattanachaiwit S, Fletcher JL, Chomchey N, et al. Initiation of Antiretroviral Therapy During Acute HIV-1 Infection Leads to a High Rate of Nonreactive HIV Serology. Clin Infect Dis. 2016 Aug 15;63(4):555–61. doi: 10.1093/cid/ciw365 27317797

15. Ananworanich J, Chomont N, Eller LA, Kroon E, Tovanabutra S, Bose M, et al. HIV DNA Set Point is Rapidly Established in Acute HIV Infection and Dramatically Reduced by Early ART. EBioMedicine. 2016 Sep;11:68–72. doi: 10.1016/j.ebiom.2016.07.024 27460436

16. Henrich TJ, Hanhauser E, Marty FM, Sirignano MN, Keating S, Lee TH, et al. Antiretroviral-Free HIV-1 Remission and Viral Rebound After Allogeneic Stem Cell Transplantation: Report of 2 Cases. Ann Intern Med. 2014 Jul 22;161(5):319–27. doi: 10.7326/M14-1027 25047577

17. Henrich TJ, Hu Z, Li JZ, Sciaranghella G, Busch MP, Keating SM, et al. Long-term reduction in peripheral blood HIV type 1 reservoirs following reduced-intensity conditioning allogeneic stem cell transplantation. J Infect Dis. 2013 Jun 1;207(11):1694–702. doi: 10.1093/infdis/jit086 23460751

18. Liu AY, Cohen SE, Vittinghoff E, Anderson PL, Doblecki-Lewis S, Bacon O, et al. Preexposure Prophylaxis for HIV Infection Integrated With Municipal- and Community-Based Sexual Health Services. JAMA Intern Med. 2016 Jan;176(1):75–84. doi: 10.1001/jamainternmed.2015.4683 26571482

19. Yukl SA, Gianella S, Sinclair E, Epling L, Li Q, Duan L, et al. Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. J Infect Dis. 2010 Nov 15;202(10):1553–61. doi: 10.1086/656722 20939732

20. Yukl SA, Shergill AK, Ho T, Killian M, Girling V, Epling L, et al. The distribution of HIV DNA and RNA in cell subsets differs in gut and blood of HIV-positive patients on ART: implications for viral persistence. J Infect Dis. 2013 Oct 15;208(8):1212–20. doi: 10.1093/infdis/jit308 23852128

21. Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009 Aug;15(8):893–900. doi: 10.1038/nm.1972 19543283

22. Dahl V, Peterson J, Fuchs D, Gisslen M, Palmer S, Price RW. Low levels of HIV-1 RNA detected in the cerebrospinal fluid after up to 10 years of suppressive therapy are associated with local immune activation. AIDS. 2014 Sep 24;28(15):2251–8. doi: 10.1097/QAD.0000000000000400 25022595

23. Probasco JC, Deeks SG, Lee E, Hoh R, Hunt PW, Liegler T, et al. Cerebrospinal fluid in HIV-1 systemic viral controllers: absence of HIV-1 RNA and intrathecal inflammation. AIDS. 2010 Apr 24;24(7):1001–5. doi: 10.1097/QAD.0b013e328331e15b 20299968

24. Kearney M, Maldarelli F, Shao W, Margolick JB, Daar ES, Mellors JW, et al. Human immunodeficiency virus type 1 population genetics and adaptation in newly infected individuals. J Virol. 2009 Mar;83(6):2715–27. doi: 10.1128/JVI.01960-08 19116249

25. Henrich TJ, Hanhauser E, Hu Z, Stellbrink HJ, Noah C, Martin JN, et al. Viremic control and viral coreceptor usage in two HIV-1-infected persons homozygous for CCR5 Delta32. AIDS. 2015 Feb 27;29(8):867–76. doi: 10.1097/QAD.0000000000000629 25730507

26. Vandergeeten C, Fromentin R, Merlini E, Lawani MB, DaFonseca S, Bakeman W, et al. Cross-clade ultrasensitive PCR-based assays to measure HIV persistence in large-cohort studies. J Virol. 2014 Nov;88(21):12385–96. doi: 10.1128/JVI.00609-14 25122785

27. Kumar AM, Borodowsky I, Fernandez B, Gonzalez L, Kumar M. Human immunodeficiency virus type 1 RNA Levels in different regions of human brain: quantification using real-time reverse transcriptase-polymerase chain reaction. J Neurovirol. 2007 Jun;13(3):210–24. doi: 10.1080/13550280701327038 17613711

28. Strain MC, Lada SM, Luong T, Rought SE, Gianella S, Terry VH, et al. Highly Precise Measurement of HIV DNA by Droplet Digital PCR. PLoS ONE. 2013;8(4):e55943. doi: 10.1371/journal.pone.0055943 23573183

29. Siliciano JD, Siliciano RF. Enhanced culture assay for detection and quantitation of latently infected, resting CD4+ T-cells carrying replication-competent virus in HIV-1-infected individuals. Methods Mol Biol. 2005;304:3–15. doi: 10.1385/1-59259-907-9:003 16061962

30. Laird GM, Eisele EE, Rabi SA, Lai J, Chioma S, Blankson JN, et al. Rapid quantification of the latent reservoir for HIV-1 using a viral outgrowth assay. PLoS Pathog. 2013;9(5):e1003398. doi: 10.1371/journal.ppat.1003398 23737751

31. Procopio FA, Fromentin R, Kulpa DA, Brehm JH, Bebin AG, Strain MC, et al. A Novel Assay to Measure the Magnitude of the Inducible Viral Reservoir in HIV-infected Individuals. EBioMedicine. 2015 Aug;2(8):874–83. doi: 10.1016/j.ebiom.2015.06.019 26425694

32. Bruner KM, Murray AJ, Pollack RA, Soliman MG, Laskey SB, Capoferri AA, et al. Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat Med. 2016 Aug 8;22(9):1043–9. doi: 10.1038/nm.4156 27500724

33. Cillo AR, Vagratian D, Bedison MA, Anderson EM, Kearney MF, Fyne E, et al. Improved single-copy assays for quantification of persistent HIV-1 viremia in patients on suppressive antiretroviral therapy. J Clin Microbiol. 2014 Nov;52(11):3944–51. doi: 10.1128/JCM.02060-14 25187636

34. Metcalf Pate KA, Pohlmeyer CW, Walker-Sperling VE, Foote JB, Najarro KM, Cryer CG, et al. A Murine Viral Outgrowth Assay to Detect Residual HIV Type 1 in Patients With Undetectable Viral Loads. J Infect Dis. 2015 Nov 1;212(9):1387–96. doi: 10.1093/infdis/jiv230 25883388

35. Hill AL, Rosenbloom DI, Fu F, Nowak MA, Siliciano RF. Predicting the outcomes of treatment to eradicate the latent reservoir for HIV-1. Proc Natl Acad Sci U S A. 2014 Sep 16;111(37):13475–80. doi: 10.1073/pnas.1406663111 25097264

36. Hill AL, Rosenbloom DI, Goldstein E, Hanhauser E, Kuritzkes DR, Siliciano RF, et al. Real-Time Predictions of Reservoir Size and Rebound Time during Antiretroviral Therapy Interruption Trials for HIV. PLoS Pathog. 2016;12(4):e1005535. doi: 10.1371/journal.ppat.1005535 27119536

37. Archin NM, Vaidya NK, Kuruc JD, Liberty AL, Wiegand A, Kearney MF, et al. Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection. Proc Natl Acad Sci U S A. 2012 Jun 12;109(24):9523–8. doi: 10.1073/pnas.1120248109 22645358

38. Rosenbloom DI, Elliott O, Hill AL, Henrich TJ, Siliciano JM, Siliciano RF. Designing and Interpreting Limiting Dilution Assays: General Principles and Applications to the Latent Reservoir for Human Immunodeficiency Virus-1. Open Forum Infect Dis. 2015 Dec;2(4):ofv123. doi: 10.1093/ofid/ofv123 26478893

39. Sender R, Fuchs S, Milo R. Revised Estimates for the Number of Human and Bacteria Cells in the Body. PLoS Biol. 2016;14(8):e1002533. doi: 10.1371/journal.pbio.1002533 27541692

40. Ganusov VV, De Boer RJ. Do most lymphocytes in humans really reside in the gut? Trends Immunol. 2007 Dec;28(12):514–8. doi: 10.1016/j.it.2007.08.009 17964854

41. Ribeiro RM, Qin L, Chavez LL, Li D, Self SG, Perelson AS. Estimation of the initial viral growth rate and basic reproductive number during acute HIV-1 infection. J Virol. 2010 Jun;84(12):6096–102. doi: 10.1128/JVI.00127-10 20357090

42. Pinkevych M, Cromer D, Tolstrup M, Grimm AJ, Cooper DA, Lewin SR, et al. Correction: HIV Reactivation from Latency after Treatment Interruption Occurs on Average Every 5–8 Days-Implications for HIV Remission. PLoS Pathog. 2016;12(8):e1005745. doi: 10.1371/journal.ppat.1005745 27561082

43. Bloch MT, Smith DE, Quan D, Kaldor JM, Zaunders JJ, Petoumenos K, et al. The role of hydroxyurea in enhancing the virologic control achieved through structured treatment interruption in primary HIV infection: final results from a randomized clinical trial (Pulse). J Acquir Immune Defic Syndr. 2006 Jun;42(2):192–202. doi: 10.1097/01.qai.0000219779.50668.e6 16688094

44. Ruiz L, Martinez-Picado J, Romeu J, Paredes R, Zayat MK, Marfil S, et al. Structured treatment interruption in chronically HIV-1 infected patients after long-term viral suppression. AIDS. 2000 Mar 10;14(4):397–403. 10770542

45. Frost SD, Martinez-Picado J, Ruiz L, Clotet B, Brown AJ. Viral dynamics during structured treatment interruptions of chronic human immunodeficiency virus type 1 infection. J Virol. 2002 Feb;76(3):968–79. doi: 10.1128/JVI.76.3.968-979.2002 11773372

46. Davey RT Jr., Bhat N, Yoder C, Chun TW, Metcalf JA, Dewar R, et al. HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc Natl Acad Sci U S A. 1999 Dec 21;96(26):15109–14. 10611346

47. Pilcher CD, Ospina-Norvell C, Dasgupta A, Jones D, Hartogensis W, Torres S, et al. The Effect of Same-Day Observed Initiation of Antiretroviral Therapy on HIV Viral Load and Treatment Outcomes in a US Public Health Setting. J Acquir Immune Defic Syndr. 2017 Jan 01;74(1):44–51. doi: 10.1097/QAI.0000000000001134 27434707

48. Colby D, Chomont N, Kroon E, Leyre L, Pinyakorn S, Michael NL, et al. HIV RNA Rebound Post-Interruption in Persons Suppressed in Fiegiv I Acute HIV. Abstract #124, Conference on Retroviruses and Opportunistic Infections, Seattle, WA, February 13–16. 2017.

49. Saez-Cirion A, Bacchus C, Hocqueloux L, Avettand-Fenoel V, Girault I, Lecuroux C, et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI Study. PLoS Pathog. 2013;9(3):e1003211. doi: 10.1371/journal.ppat.1003211 23516360

50. Lifson JD, Rossio JL, Arnaout R, Li L, Parks TL, Schneider DK, et al. Containment of simian immunodeficiency virus infection: cellular immune responses and protection from rechallenge following transient postinoculation antiretroviral treatment. J Virol. 2000 Mar;74(6):2584–93. 10684272

51. Lifson JD, Rossio JL, Piatak M Jr., Parks T, Li L, Kiser R, et al. Role of CD8(+) lymphocytes in control of simian immunodeficiency virus infection and resistance to rechallenge after transient early antiretroviral treatment. J Virol. 2001 Nov;75(21):10187–99. doi: 10.1128/JVI.75.21.10187-10199.2001 11581387

52. Lifson JD, Piatak M Jr., Cline AN, Rossio JL, Purcell J, Pandrea I, et al. Transient early post-inoculation anti-retroviral treatment facilitates controlled infection with sparing of CD4+ T cells in gut-associated lymphoid tissues in SIVmac239-infected rhesus macaques, but not resistance to rechallenge. J Med Primatol. 2003 Aug;32(4–5):201–10. 14498980

53. Whitney JB, Hill AL, Sanisetty S, Penaloza-MacMaster P, Liu J, Shetty M, et al. Rapid seeding of the viral reservoir prior to SIV viraemia in rhesus monkeys. Nature. 2014 Aug 07;512(7512):74–7. doi: 10.1038/nature13594 25042999

54. Charlins P, Schmitt K, Remling-Mulder L, Hogan LE, Hanhauser E, Hobbs KS, et al. A humanized mouse-based HIV-1 viral outgrowth assay with higher sensitivity than in vitro qVOA in detecting latently infected cells from individuals on ART with undetectable viral loads. Virology. 2017 Jul;507:135–9. doi: 10.1016/j.virol.2017.04.011 28432928

55. Falini B, Pileri S, Pizzolo G, Durkop H, Flenghi L, Stirpe F, et al. CD30 (Ki-1) molecule: a new cytokine receptor of the tumor necrosis factor receptor superfamily as a tool for diagnosis and immunotherapy. Blood. 1995 Jan 1;85(1):1–14. 7803786

56. Chiarle R, Podda A, Prolla G, Gong J, Thorbecke GJ, Inghirami G. CD30 in normal and neoplastic cells. Clin Immunol. 1999 Feb;90(2):157–64. doi: 10.1006/clim.1998.4636 10080826

57. Biswas P, Mantelli B, Delfanti F, Ferrarini M, Poli G, Lazzarin A. CD30 ligation differentially affects CXCR4-dependent HIV-1 replication and soluble CD30 secretion in non-Hodgkin cell lines and in gamma delta T lymphocytes. Eur J Immunol. 2003 Nov;33(11):3136–45. doi: 10.1002/eji.200324344 14579282

58. Biswas P, Smith CA, Goletti D, Hardy EC, Jackson RW, Fauci AS. Cross-linking of CD30 induces HIV expression in chronically infected T cells. Immunity. 1995 Jun;2(6):587–96. 7540942

59. Agrawal B, Reddish M, Longenecker BM. CD30 expression on human CD8+ T cells isolated from peripheral blood lymphocytes of normal donors. J Immunol. 1996 Oct 15;157(8):3229–34. 8871616

60. Biswas P, Cozzi-Lepri A, Delfanti F, Galli A, Colangeli V, Moioli MC, et al. Significant link between sCD30 changes and HIV viremia in patients treated with HAART. J Med Virol. 2006 Dec;78(12):1513–9. doi: 10.1002/jmv.20733 17063513

61. Gilfillan MC, Noel PJ, Podack ER, Reiner SL, Thompson CB. Expression of the costimulatory receptor CD30 is regulated by both CD28 and cytokines. J Immunol. 1998 Mar 1;160(5):2180–7. 9498756

62. Higuchi M, Matsuda T, Mori N, Yamada Y, Horie R, Watanabe T, et al. Elevated expression of CD30 in adult T-cell leukemia cell lines: possible role in constitutive NF-kappaB activation. Retrovirology. 2005;2:29. doi: 10.1186/1742-4690-2-29 15876358

63. Makino M, Yashiki S, Fujiyoshi T, Baba M, Sonoda S. An expression of anaplastic large cell lymphoma-associated antigens on HTLV-I-infected CD4+ T cells. Ann Hematol. 1998 Jan;76(1):31–5. 9486922

64. Smith KJ, Barrett TL, Neafie R, Tomaszewski MM, Yeager J, Nelson A, et al. Is CD30 (Ki-1) immunostaining in cutaneous eruptions useful as a marker of Th1 to Th2 cytokine switching and/or as a marker of advanced HIV-1 disease? Br J Dermatol. 1998 May;138(5):774–9. 9666821

65. Pizzolo G, Vinante F, Nadali G, Krampera M, Morosato L, Chilosi M, et al. High serum level of soluble CD30 in acute primary HIV-1 infection. Clin Exp Immunol. 1997 May;108(2):251–3. doi: 10.1046/j.1365-2249.1997.d01-1005.x 9158093

66. Tsitsikov EN, Wright DA, Geha RS. CD30 induction of human immunodeficiency virus gene transcription is mediated by TRAF2. Proc Natl Acad Sci U S A. 1997 Feb 18;94(4):1390–5. 9037063

67. Silvestri G, Munoz C, Butini L, Bagnarelli P, Montroni M. Changes in CD8 cell subpopulations induced by antiretroviral therapy in human immunodeficiency virus infected patients. Viral Immunol. 1997;10(4):207–12. doi: 10.1089/vim.1997.10.207 9473151

68. Rizzardi GP, Barcellini W, Tambussi G, Lillo F, Malnati M, Perrin L, et al. Plasma levels of soluble CD30, tumour necrosis factor (TNF)-alpha and TNF receptors during primary HIV-1 infection: correlation with HIV-1 RNA and the clinical outcome. AIDS. 1996 Nov;10(13):F45–50. 8931778

69. Manetti R, Annunziato F, Biagiotti R, Giudizi MG, Piccinni MP, Giannarini L, et al. CD30 expression by CD8+ T cells producing type 2 helper cytokines. Evidence for large numbers of CD8+CD30+ T cell clones in human immunodeficiency virus infection. J Exp Med. 1994 Dec 1;180(6):2407–11. 7964515

70. Pizzolo G, Vinante F, Morosato L, Nadali G, Chilosi M, Gandini G, et al. High serum level of the soluble form of CD30 molecule in the early phase of HIV-1 infection as an independent predictor of progression to AIDS. AIDS. 1994 Jun;8(6):741–5. 8086130

71. Sadeghi M, Susal C, Daniel V, Naujokat C, Zimmermann R, Huth-Kuhne A, et al. Short communication: decreasing soluble CD30 and increasing IFN-gamma plasma levels are indicators of effective highly active antiretroviral therapy. AIDS Res Hum Retroviruses. 2007 Jul;23(7):886–90. doi: 10.1089/aid.2006.0228 17678471

72. Jain V, Hartogensis W, Bacchetti P, Hunt PW, Hatano H, Sinclair E, et al. Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size. J Infect Dis. 2013 Oct 15;208(8):1202–11. doi: 10.1093/infdis/jit311 23852127

73. Cohen MS, Chen YQ, McCauley M, Gamble T, Hosseinipour MC, Kumarasamy N, et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med. 2011 Aug 11;365(6):493–505. doi: 10.1056/NEJMoa1105243 21767103