Cumulative viral load and virologic decay patterns after antiretroviral therapy in HIV-infected subjects influence CD4 recovery and AIDS

PLoS ONE

Volumn 6, Issue 5, 2011, Pages

  Marconi, Vincent C ^a,b   Grandits, Greg ^b,c   Okulicz, Jason F ^b,d   Wortmann, Glenn ^b,e   Ganesan, Anuradha ^b,e   Crum Cianflone, Nancy ^b,f   Polis, Michael ^b,g   Landrum, Michael ^b,d   Dolan, Matthew J ^h   Ahuja, Sunil K ^i,j,k   Agan, Brian ^b   Kulkarni, Hemant ^i,j  

^a EMORY UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES   (United States)

^c UNIVERSITY OF MINNESOTA   (United States)

^d SAN ANTONIO MILITARY MEDICAL CENTER   (United States)

^e WALTER REED ARMY MEDICAL CENTER   (United States)

^f NAVAL MEDICAL CENTER SAN DIEGO   (United States)

^g NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

^h HENRY M JACKSON FOUNDATION FOR THE ADVANCEMENT OF MILITARY MEDICINE   (United States)

ⁱ SOUTH TEXAS VETERANS HEALTH CARE SYSTEM   (United States)

^j University of Texas Health Science Center   (United States)

^k UNIVERSITY OF TEXAS HEALTH SCIENCE CENTER AT SAN ANTONIO   (United States)

more..

Author keywords

[No Author keywords available]

Indexed keywords

ANTIRETROVIRUS AGENT;

ACQUIRED IMMUNE DEFICIENCY SYNDROME; ADULT; ARMY; ARTICLE; CD4 LYMPHOCYTE COUNT; CONTROLLED STUDY; CORRELATION ANALYSIS; CUMULATIVE VIRUS LOAD; FEMALE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE RESPONSE; INFECTION RISK; LINEAR REGRESSION ANALYSIS; LINEAR SYSTEM; MAJOR CLINICAL STUDY; MALE; NONLINEAR SYSTEM; OUTCOME ASSESSMENT; POISSON DISTRIBUTION; PROGNOSIS; RISK ASSESSMENT; TREATMENT DURATION; UNITED STATES; VIRAL PHENOMENA AND FUNCTIONS; VIROLOGIC DECAY PATTERN; VIRUS LOAD; CD4+ T LYMPHOCYTE; COHORT ANALYSIS; DRUG EFFECT; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; PROSPECTIVE STUDY; SEROLOGY; TREATMENT OUTCOME; VIROLOGY;

ADULT; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4 LYMPHOCYTE COUNT; CD4-POSITIVE T-LYMPHOCYTES; COHORT STUDIES; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; MALE; PROSPECTIVE STUDIES; SEROLOGIC TESTS; TREATMENT OUTCOME; VIRAL LOAD;

EID: 79956328148     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0017956     Document Type: Article

References (63)

1. Anastos K, Barron Y, Miotti P, Weiser B, Young M, et al. (2002) Risk of progression to AIDS and death in women infected with HIV-1 initiating highly active antiretroviral treatment at different stages of disease. Arch Intern Med 162: 1973-1980.
2. Jacobson LP, Li R, Phair J, Margolick JB, Rinaldo CR, et al. (2002) Evaluation of the effectiveness of highly active antiretroviral therapy in persons with human immunodeficiency virus using biomarker-based equivalence of disease progression. Am J Epidemiol 155: 760-770.
3. Egger M, May M, Chene G, Phillips AN, Ledergerber B, et al. (2002) Prognosis of HIV-1-infected patients starting highly active antiretroviral therapy: a collaborative analysis of prospective studies. Lancet 360: 119-129.
4. Anastos K, Barron Y, Cohen MH, Greenblatt RM, Minkoff H, et al. (2004) The prognostic importance of changes in CD4+ cell count and HIV-1 RNA level in women after initiating highly active antiretroviral therapy. Ann Intern Med 140: 256-264.
5. Lundgren JD, Mocroft A, Gatell JM, Ledergerber B, D'Arminio Monforte A, et al. (2002) A clinically prognostic scoring system for patients receiving highly active antiretroviral therapy: results from the EuroSIDA study. J Infect Dis 185: 178-187.
6. Ghani AC, de Wolf F, Ferguson NM, Donnelly CA, Coutinho R, et al. (2001) Surrogate markers for disease progression in treated HIV infection. J Acquir Immune Defic Syndr 28: 226-231.
7. Lewden C, Raffi F, Cuzin L, Cailleton V, Vilde JL, et al. (2002) Factors associated with mortality in human immunodeficiency virus type 1-infected adults initiating protease inhibitor-containing therapy: role of education level and of early transaminase level elevation (APROCO-ANRS EP11 study). The Antiproteases Cohorte Agence Nationale de Recherches sur le SIDA EP 11 study. J Infect Dis 186: 710-714.
8. Hermankova M, Ray SC, Ruff C, Powell-Davis M, Ingersoll R, et al. (2001) HIV-1 drug resistance profiles in children and adults with viral load of <50 copies/ml receiving combination therapy. Jama 286: 196-207.
9. Barbour JD, Wrin T, Grant RM, Martin JN, Segal MR, et al. (2002) Evolution of phenotypic drug susceptibility and viral replication capacity during long-term virologic failure of protease inhibitor therapy in human immunodeficiency virus-infected adults. J Virol 76: 11104-11112.
10. Panel on Antiretroviral Guidelines for Adults and Adolescents (2009) Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services pp. 161 p.
11. Ahuja SK, Kulkarni H, Catano G, Agan BK, Camargo JF, et al. (2008) CCL3L1-CCR5 genotype influences durability of immune recovery during antiretroviral therapy of HIV-1-infected individuals. Nat Med 14: 413-420.
12. Tan R, Westfall AO, Willig JH, Mugavero MJ, Saag MS, et al. (2008) Clinical outcome of HIV-infected antiretroviral-naive patients with discordant immunologic and virologic responses to highly active antiretroviral therapy. J Acquir Immune Defic Syndr 47: 553-558.
13. Gazzola L, Tincati C, Bellistri GM, Monforte A, Marchetti G, (2009) The absence of CD4+ T cell count recovery despite receipt of virologically suppressive highly active antiretroviral therapy: clinical risk, immunological gaps, and therapeutic options. Clin Infect Dis 48: 328-337.
14. Torti C, Cologni G, Uccelli MC, Quiros-Roldan E, Imberti L, et al. (2004) Immune correlates of virological response in HIV-positive patients after highly active antiretroviral therapy (HAART). Viral Immunol 17: 279-286.
15. Gilson R, Man SL, Copas A, Rider A, Forsyth S, et al. (2009) Discordant responses on starting highly active antiretroviral therapy: suboptimal CD4 increases despite early viral suppression in the UK Collaborative HIV Cohort (UK CHIC) Study. HIV Med 11: 152-60.
16. Kelley CF, Kitchen CM, Hunt PW, Rodriguez B, Hecht FM, et al. (2009) Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 48: 787-794.
17. Weverling GJ, Lange JM, Jurriaans S, Prins JM, Lukashov VV, et al. (1998) Alternative multidrug regimen provides improved suppression of HIV-1 replication over triple therapy. Aids 12: F117-122.
18. Polis MA, Sidorov IA, Yoder C, Jankelevich S, Metcalf J, et al. (2001) Correlation between reduction in plasma HIV-1 RNA concentration 1 week after start of antiretroviral treatment and longer-term efficacy. Lancet 358: 1760-1765.
19. Ghani AC, Ferguson NM, Fraser C, Donnelly CA, Danner S, et al. (2002) Viral replication under combination antiretroviral therapy: a comparison of four different regimens. J Acquir Immune Defic Syndr 30: 167-176.
20. Maggiolo F, Migliorino M, Pirali A, Pravettoni G, Caprioli S, et al. (2000) Duration of viral suppression in patients on stable therapy for HIV-1 infection is predicted by plasma HIV RNA level after 1 month of treatment. J Acquir Immune Defic Syndr 25: 36-43.
21. Demeter LM, Hughes MD, Coombs RW, Jackson JB, Grimes JM, et al. (2001) Predictors of virologic and clinical outcomes in HIV-1-infected patients receiving concurrent treatment with indinavir, zidovudine, and lamivudine. AIDS Clinical Trials Group Protocol 320. Ann Intern Med 135: 954-964.
22. Casado JL, Perez-Elias MJ, Antela A, Sabido R, Marti-Belda P, et al. (1998) Predictors of long-term response to protease inhibitor therapy in a cohort of HIV-infected patients. Aids 12: F131-135.
23. Wu H, Kuritzkes DR, McClernon DR, Kessler H, Connick E, et al. (1999) Characterization of viral dynamics in human immunodeficiency virus type 1-infected patients treated with combination antiretroviral therapy: relationships to host factors, cellular restoration, and virologic end points. J Infect Dis 179: 799-807.
24. Wu H, Huang Y, Acosta EP, Rosenkranz SL, Kuritzkes DR, et al. (2005) Modeling long-term HIV dynamics and antiretroviral response: effects of drug potency, pharmacokinetics, adherence, and drug resistance. J Acquir Immune Defic Syndr 39: 272-283.
25. Gutierrez F, Padilla S, Masia M, Iribarren JA, Moreno S, et al. (2006) Clinical outcome of HIV-infected patients with sustained virologic response to antiretroviral therapy: long-term follow-up of a multicenter cohort. PLoS One 1: e89.
26. Marconi VC, Grandits GA, Weintrob AC, Chun H, Landrum ML, et al. (2010) Outcomes of highly active antiretroviral therapy in the context of universal access to healthcare: the U.S. Military HIV Natural History Study. AIDS Res Ther 7: 14.
27. Kuritzkes DR, Sevin A, Young B, Bakhtiari M, Wu H, et al. (2000) Effect of zidovudine resistance mutations on virologic response to treatment with zidovudine-lamivudine-ritonavir: genotypic analysis of human immunodeficiency virus type 1 isolates from AIDS clinical trials group protocol 315.ACTG Protocol 315 Team. J Infect Dis 181: 491-497.
28. Kuritzkes DR, Ribaudo HJ, Squires KE, Koletar SL, Santana J, et al. (2007) Plasma HIV-1 RNA dynamics in antiretroviral-naive subjects receiving either triple-nucleoside or efavirenz-containing regimens: ACTG A5166s. J Infect Dis 195: 1169-1176.
29. Loveday C, Kaye S, Tenant-Flowers M, Semple M, Ayliffe U, et al. (1995) HIV-1 RNA serum-load and resistant viral genotypes during early zidovudine therapy. Lancet 345: 820-824.
30. Weintrob AC, Grandits GA, Agan BK, Ganesan A, Landrum ML, et al. (2009) Virologic Response Differences Between African Americans and European Americans Initiating Highly Active Antiretroviral Therapy With Equal Access to Care. J Acquir Immune Defic Syndr 52: 574-80.
31. Weintrob AC, Fieberg AM, Agan BK, Ganesan A, Crum-Cianflone NF, et al. (2008) Increasing age at HIV seroconversion from 18 to 40 years is associated with favorable virologic and immunologic responses to HAART. J Acquir Immune Defic Syndr 49: 40-47.
32. Centers for Disease Control and Prevention (1993) 1993 revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. JAMA 269: 729-730.
33. Giorgi JV, Lyles RH, Matud JL, Yamashita TE, Mellors JW, et al. (2002) Predictive value of immunologic and virologic markers after long or short duration of HIV-1 infection. J Acquir Immune Defic Syndr 29: 346-355.
34. Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, et al. (1997) Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 126: 946-954.
35. Phillips AN, Sabin CA, Elford J, Bofill M, Janossy G, et al. (1994) Use of CD4 lymphocyte count to predict long-term survival free of AIDS after HIV infection. Bmj 309: 309-313.
36. Vlahov D, Graham N, Hoover D, Flynn C, Bartlett JG, et al. (1998) Prognostic indicators for AIDS and infectious disease death in HIV-infected injection drug users: plasma viral load and CD4+ cell count. Jama 279: 35-40.
37. Hulgan T, Shepherd BE, Raffanti SP, Fusco JS, Beckerman R, et al. (2007) Absolute count and percentage of CD4+ lymphocytes are independent predictors of disease progression in HIV-infected persons initiating highly active antiretroviral therapy. J Infect Dis 195: 425-431.
38. Tomasoni LR, Patroni A, Torti C, Paraninfo G, Gargiulo F, et al. (2003) Predictors of long-term immunological outcome in rebounding patients on protease inhibitor-based HAART after initial successful virologic suppression: implications for timing to switch. HIV Clin Trials 4: 311-323.
39. Notermans DW, Goudsmit J, Danner SA, de Wolf F, Perelson AS, et al. (1998) Rate of HIV-1 decline following antiretroviral therapy is related to viral load at baseline and drug regimen. Aids 12: 1483-1490.
40. Vo TT, Ledergerber B, Keiser O, Hirschel B, Furrer H, et al. (2008) Durability and outcome of initial antiretroviral treatments received during 2000-2005 by patients in the Swiss HIV Cohort Study. J Infect Dis 197: 1685-1694.
41. Breban R, Blower S, (2006) Role of parametric resonance in virological failure during HIV treatment interruption therapy. Lancet 367: 1285-1289.
42. Katzenstein DA, Hammer SM, Hughes MD, Gundacker H, Jackson JB, et al. (1996) 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 335: 1091-1098.
43. Kitchen CM, Kitchen SG, Dubin JA, Gottlieb MS, (2001) Initial virological and immunologic response to highly active antiretroviral therapy predicts long-term clinical outcome. Clin Infect Dis 33: 466-472.
44. Marschner IC, Collier AC, Coombs RW, D'Aquila RT, DeGruttola V, et al. (1998) Use of changes in plasma levels of human immunodeficiency virus type 1 RNA to assess the clinical benefit of antiretroviral therapy. J Infect Dis 177: 40-47.
45. Le Moing V, Thiebaut R, Chene G, Leport C, Cailleton V, et al. (2002) Predictors of long-term increase in CD4(+) cell counts in human immunodeficiency virus-infected patients receiving a protease inhibitor-containing antiretroviral regimen. J Infect Dis 185: 471-480.
46. Kousignian I, Abgrall S, Duval X, Descamps D, Matheron S, et al. (2003) Modeling the time course of CD4 T-lymphocyte counts according to the level of virologic rebound in HIV-1-infected patients on highly active antiretroviral therapy. J Acquir Immune Defic Syndr 34: 50-57.
47. Havlir DV, Bassett R, Levitan D, Gilbert P, Tebas P, et al. (2001) Prevalence and predictive value of intermittent viremia with combination hiv therapy. Jama 286: 171-179.
48. Easterbrook PJ, Ives N, Waters A, Mullen J, O'Shea S, et al. (2002) The natural history and clinical significance of intermittent viraemia in patients with initial viral suppression to <400 copies/ml. Aids 16: 1521-1527.
49. Sproat M, Pozniak AL, Peeters M, Winters B, Hoetelmans R, et al. (2005) The influence of the M184V mutation in HIV-1 reverse transcriptase on the virological outcome of highly active antiretroviral therapy regimens with or without didanosine. Antivir Ther 10: 357-361.
50. Kravcik S, Magill A, Sanghvi B, Ogden R, Cameron WD, et al. (2001) Comparative CD4 T-cell responses of reverse transcriptase inhibitor therapy with or without nelfinavir matched for viral exposure. HIV Clin Trials 2: 160-170.
51. Kim S, Hughes MD, Hammer SM, Jackson JB, DeGruttola V, et al. (2000) Both serum HIV type 1 RNA levels and CD4+ lymphocyte counts predict clinical outcome in HIV type 1-infected subjects with 200 to 500 CD4+ cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team. AIDS Res Hum Retroviruses 16: 645-653.
52. HIV Surrogate Marker Collaborative Group (2000) Human immunodeficiency virus type 1 RNA level and CD4 count as prognostic markers and surrogate end points: a meta-analysis. AIDS Res Hum Retroviruses 16: 1123-1133.
53. Journot V, Chene G, Joly P, Saves M, Jacqmin-Gadda H, et al. (2001) Viral load as a primary outcome in human immunodeficiency virus trials: a review of statistical analysis methods. Control Clin Trials 22: 639-658.
54. Zoufaly A, Stellbrink HJ, Heiden MA, Kollan C, Hoffmann C, et al. (2009) Cumulative HIV viremia during highly active antiretroviral therapy is a strong predictor of AIDS-related lymphoma. J Infect Dis 200: 79-87.
55. El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, et al. (2006) CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 355: 2283-2296.
56. Cole SR, Napravnik S, Mugavero MJ, Lau B, Eron JJ Jr, et al. (2010) Copy-years viremia as a measure of cumulative human immunodeficiency virus viral burden. Am J Epidemiol 171: 198-205.
57. Guiguet M, Boue F, Cadranel J, Lang JM, Rosenthal E, et al. (2009) Effect of immunodeficiency, HIV viral load, and antiretroviral therapy on the risk of individual malignancies (FHDH-ANRS CO4): a prospective cohort study. Lancet Oncol 10: 1152-1159.
58. Bruyand M, Thiebaut R, Lawson-Ayayi S, Joly P, Sasco AJ, et al. (2009) Role of uncontrolled HIV RNA level and immunodeficiency in the occurrence of malignancy in HIV-infected patients during the combination antiretroviral therapy era: Agence Nationale de Recherche sur le Sida (ANRS) CO3 Aquitaine Cohort. Clin Infect Dis 49: 1109-1116.
59. Choi AI, Shlipak MG, Hunt PW, Martin JN, Deeks SG, (2009) HIV-infected persons continue to lose kidney function despite successful antiretroviral therapy. Aids 23: 2143-2149.
60. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, et al. (2003) Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 9: 727-728.
61. Nettles RE, Kieffer TL, Kwon P, Monie D, Han Y, et al. (2005) Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. Jama 293: 817-829.
62. 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.
63. Coffin JM, (1995) HIV population dynamics in vivo: implications for genetic variation, pathogenesis, and therapy. Science 267: 483-489.