A high HIV DNA level in PBMCs at antiretroviral treatment interruption predicts a shorter time to treatment resumption, independently of the CD4 nadir

Journal of Medical Virology

Volumn 82, Issue 11, 2010, Pages 1819-1828

  Piketty, Christophe ^a   Weiss, Laurence ^a,b   Assoumou, Lambert ^c,d   Burgard, Marianne ^e   Mélard, Aurélie ^e   Ragnaud, Jean Michel ^f   Bentata, Michele ^g   Girard, Pierre Marie ^h   Rouzioux, Christine ^b,e   Costagliola, Dominique ^c,d,i  

^a HÔPITAL EUROPÉEN GEORGES POMPIDOU   (France)

^b UNIVERSITÉ PARIS DESCARTES   (France)

^c INSERM   (France)

^d SORBONNE UNIVERSITÉ   (France)

^e HÔPITAL NECKER ENFANTS MALADES   (France)

^f HÔPITAL PELLEGRIN   (France)

^g AVICENNE HOSPITAL   (France)

^h HÔPITAL SAINT ANTOINE   (France)

ⁱ PITIÉ SALPÊTRIÈRE HOSPITAL   (France)

Author keywords

ART; CD4 nadir; HIV; HIV DNA; Treatment interruption

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; VIRUS DNA;

ADULT; AGED; ARTICLE; BLOOD; CD4 LYMPHOCYTE COUNT; CLINICAL TRIAL; DRUG ADMINISTRATION; FEMALE; GENETICS; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MALE; MIDDLE AGED; MONONUCLEAR CELL; MULTICENTER STUDY; MULTIVARIATE ANALYSIS; PHYSIOLOGY; PREDICTIVE VALUE; PROPORTIONAL HAZARDS MODEL; TREATMENT OUTCOME; VIROLOGY;

ADULT; AGED; AGED, 80 AND OVER; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4 LYMPHOCYTE COUNT; DNA, VIRAL; DRUG ADMINISTRATION SCHEDULE; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; LEUKOCYTES, MONONUCLEAR; MALE; MIDDLE AGED; MULTIVARIATE ANALYSIS; PREDICTIVE VALUE OF TESTS; PROPORTIONAL HAZARDS MODELS; TREATMENT OUTCOME;

EID: 79952116429     PISSN: 01466615     EISSN: 10969071     Source Type: Journal    
DOI: 10.1002/jmv.21907     Document Type: Article

References (49)

1. Ananworanich J, Gayet-Ageron A, Le Braz M, Prasithsirikul W, Chetchotisakd P, Kiertiburanakul S, Munsakul W, Raksakulkarn P, Tansuphasawasdikul S, Sirivichayakul S, Cavassini M, Karrer U, Genne D, Nuesch R, Vernazza P, Bernasconi E, Leduc D, Satchell C, Yerly S, Perrin L, Hill A, Perneger T, Phanuphak P, Furrer H, Cooper D, Ruxrungtham K, Hirschel B. 2006. CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: Results of the Staccato randomised trial. Lancet 368: 459-465.
2. Avettand-Fenoel V, Mahlaoui N, Chaix ML, Milliancourt C, Burgard M, Cavazzana-Calvo M, Rouzioux C, Blanche S. 2007. Failure of bone marrow transplantation to eradicate HIV reservoir despite efficient HAART. AIDS 21: 776-777.
3. Blum A, Hadas V, Burke M, Yust I, Kessler A. 2005. Viral load of the human immunodeficiency virus could be an independent risk factor for endothelial dysfunction. Clin Cardiol 28: 149-153.
4. Boschi A, Tinelli C, Ortolani P, Moscatelli G, Morigi G, Arlotti M. 2004. CD4+ cell-count-guided treatment interruptions in chronic HIV-infected patients with good response to highly active antiretroviral therapy. AIDS 18: 2381-2389.
5. Chomont N, El-Far M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, Boucher G, Boulassel MR, Ghattas G, Brenchley JM, Schacker TW, Hill BJ, Douek DC, Routy JP, Haddad EK, Sekaly RP. 2009. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 15: 893-900.
6. Danel C, Moh R, Minga A, Anzian A, Ba-Gomis O, Kanga C, Nzunetu G, Gabillard D, Rouet F, Sorho S, Chaix ML, Eholie S, Menan H, Sauvageot D, Bissagnene E, Salamon R, Anglaret X. 2006. CD4-guided structured antiretroviral treatment interruption strategy in HIV-infected adults in west Africa (Trivacan ANRS 1269 trial): A randomised trial. Lancet 367: 1981-1989.
7. El-Sadr WM, Lundgren JD, Neaton JD, Gordin F, Abrams D, Arduino RC, Babiker A, Burman W, Clumeck N, Cohen CJ, Cohn D, Cooper D, Darbyshire J, Emery S, Fatkenheuer G, Gazzard B, Grund B, Hoy J, Klingman K, Losso M, Markowitz N, Neuhaus J, Phillips A, Rappoport C. 2006. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 355: 2283-2296.
8. Fagard C, Oxenius A, Gunthard H, Garcia F, Le Braz M, Mestre G, Battegay M, Furrer H, Vernazza P, Bernasconi E, Telenti A, Weber R, Leduc D, Yerly S, Price D, Dawson SJ, Klimkait T, Perneger TV, McLean A, Clotet B, Gatell JM, Perrin L, Plana M, Phillips R, Hirschel B. 2003. A prospective trial of structured treatment interruptions in human immunodeficiency virus infection. Arch Intern Med 163: 1220-1226.
9. Fagard C, Bandelier CY, Ananworanich J, Le Braz M, Gunthard H, Perneger T, Garcia F, Hirschel B. 2005. Biphasic decline of CD4 cell count during scheduled treatment interruptions. AIDS 19: 439-441.
10. Fernandez Guerrero ML, Rivas P, Molina M, Garcia R, De Gorgolas M. 2005. Long-term follow-up of asymptomatic HIV-infected patients who discontinued antiretroviral therapy. Clin Infect Dis 41: 390-394.
11. Giuntini R, Martinelli C, Ambu S, Bartolozzi D, Farese A, Boddi V, Leoncini F. 2005. Prolonged treatment interruption in chronic HIV infection: A new strategy? AIDS 19: 209-211.
12. Goujard C, Bonarek M, Meyer L, Bonnet F, Chaix ML, Deveau C, Sinet M, Galimand J, Delfraissy JF, Venet A, Rouzioux C, Morlat P. 2006. CD4 cell count and HIV DNA level are independent predictors of disease progression after primary HIV type 1 infection in untreated patients. Clin Infect Dis 42: 709-715.
13. Guiguet M, Porter K, Phillips A, Costagliola D, Babiker A. 2008. Clinical progression rates by CD4 cell category before and after the initiation of combination antiretroviral therapy (cART). Open AIDS J 2: 3-9.
14. Hammer SM, Eron JJ, Jr., Reiss P, Schooley RT, Thompson MA, Walmsley S, Cahn P, Fischl MA, Gatell JM, Hirsch MS, Jacobsen DM, Montaner JS, Richman DD, Yeni PG, Volberding PA. 2008. Antiretroviral treatment of adult HIV infection: 2008 recommendations of the International AIDS Society-USA panel. JAMA 300: 555-570.
15. Hatano H, Miller KD, Yoder CP, Yanovski JA, Sebring NG, Jones EC, Davey RT, Jr. 2000. Metabolic and anthropometric consequences of interruption of highly active antiretroviral therapy. AIDS 14: 1935-1942.
16. Hogg RS, Heath KV, Yip B, Craib KJ, O'Shaughnessy MV, Schechter MT, Montaner JS. 1998. Improved survival among HIV-infected individuals following initiation of antiretroviral therapy. JAMA 279: 450-454.
17. Hogg RS, Yip B, Chan KJ, Wood E, Craib KJ, O'Shaughnessy MV, Montaner JS. 2001. Rates of disease progression by baseline CD4 cell count and viral load after initiating triple-drug therapy. JAMA 286: 2568-2577.
18. Krolewiecki AJ, Zala C, Vanzulli C, Perez H, Iannella Mdel C, Bouzas MB, Gun A, Valiente J, Cassetti I, Cahn P. 2006. Safe treatment interruptions in patients with nadir CD4 counts of more than 350 cells/microL: A randomized trial. J Acquir Immune Defic Syndr 41: 425-429.
19. Lee LM, Karon JM, Selik R, Neal JJ, Fleming PL. 2001. Survival after AIDS diagnosis in adolescents and adults during the treatment era, United States, 1984- 1997. JAMA 285: 1308-1315.
20. Li TS, Tubiana R, Katlama C, Calvez V, Ait Mohand H, Autran B. 1998. Long lasting recovery in CD4 T-cell function and viral-load reduction after highly active antiretroviral therapy in advanced HIV-1 disease. Lancet 351: 1682-1686.
21. Lundgren JD, Babiker A, El-Sadr W, Emery S, Grund B, Neaton JD, Neuhaus J, Phillips AN. 2008. Inferior clinical outcome of the CD4+ cell count-guided antiretroviral treatment interruption strategy in the SMART study: Role of CD4+ Cell counts and HIV RNA levels during follow-up. J Infect Dis 197: 1145-1155.
22. Maggiolo F, Ripamonti D, Gregis G, Quinzan G, Callegaro A, Suter F. 2004. Effect of prolonged discontinuation of successful antiretroviral therapy on CD4 T cells: A controlled prospective trial. AIDS 18: 439-446.
23. Maggiolo F, Airoldi M, Callegaro A, Martinelli C, Dolara A, Bini T, Gregis G, Quinzan G, Ripamonti D, Ravasio V, Suter F. 2008. CD4 cell-guided scheduled treatment interruptions in HIV-infected patients with sustained immunologic response to HAART. AIDS 24: 24.
24. Mata RC, Viciana P, de Alarcon A, Lopez-Cortes LF, Gomez-Vera J, Trastoy M, Cisneros JM. 2005. Discontinuation of antiretroviral therapy in patients with chronic HIV infection: Clinical, virologic, and immunologic consequences. AIDS Patient Care STDS 19: 550-562.
25. Mocroft A, Katlama C, Johnson AM, Pradier C, Antunes F, Mulcahy F, Chiesi A, Phillips AN, Kirk O, Lundgren JD. 2000. AIDS across Europe, 1994-98: The EuroSIDA study. Lancet 356: 291-296.
26. Mouroux M, Descamps D, Izopet J, Yvon A, Delaugerre C, Matheron S, Coutellier A, Valantin MA, Bonmarchand M, Agut H, Massip P, Costagliola D, Katlama C, Brun-Vezinet F, Calvez V. 2001. Low-rate emergence of thymidine analogue mutations and multi-drug resistance mutations in the HIV-1 reverse transcriptase gene in therapy-naive patients receiving stavudine plus lamivudine combination therapy. Antivir Ther 6: 179-183.
27. Murphy EL, Collier AC, Kalish LA, Assmann SF, Para MF, Flanigan TP, Kumar PN, Mintz L, Wallach FR, Nemo GJ. 2001. Highly active antiretroviral therapy decreases mortality and morbidity in patients with advanced HIV disease. Ann Intern Med 135: 17-26.
28. 6cells/L. AIDS 19: 287-294.
29. Ngo-Giang-Huong N, Deveau C, Da Silva I, Pellegrin I, Venet A, Harzic M, Sinet M, Delfraissy JF, Meyer L, Goujard C, Rouzioux C. 2001. Proviral HIV-1 DNA in subjects followed since primary HIV-1 infection who suppress plasma viral load after one year of highly active antiretroviral therapy. AIDS 15: 665-673.
30. Palella FJ, Jr., Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, Aschman DJ, Holmberg SD. 1998. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. N Engl J Med 338: 853-860.
31. Palella FJ, Jr., Deloria-Knoll M, Chmiel JS, Moorman AC, Wood KC, Greenberg AE, Holmberg SD. 2003. Survival benefit of initiating antiretroviral therapy in HIV-infected persons in different CD4+ cell strata. Ann Intern Med 138: 620-626.
32. Parish MA, Tarwater P, Lu M, Raines C, Gallant JE. 2002. Prolonged treatment interruption after immunologic response to HAART. Oral Abstract: The XIV International AIDS Conference, Barcelona, Spain: Abstract no. ThOrB1439.
33. Pellegrin I, Thiebaut R, Blanco P, Viallard JF, Schrive MH, Merel P, Chene G, Fleury H, Moreau JF, Pellegrin JL. 2005. Can highly active antiretroviral therapy be interrupted in patients with sustained moderate HIV RNA and >400 CD4+ cells/microl? Impact on immunovirological parameters. J Med Virol 77: 164-172.
34. Phillips AN, Gazzard B, Gilson R, Easterbrook P, Johnson M, Walsh J, Leen C, Fisher M, Orkin C, Anderson J, Pillay D, Delpech V, Sabin C, Schwenk A, Dunn D, Gompels M, Hill T, Porter K, Babiker A. 2007. Rate of AIDS diseases or death in HIV-infected antiretroviral therapy-naive individuals with high CD4 cell count. AIDS 21: 1717-1721.
35. Pogany K, van Valkengoed IG, Prins JM, Nieuwkerk PT, van der Ende I, Kauffmann RH, Kroon FP, Verbon A, Nievaard MF, Lange JM, Brinkman K. 2007. Effects of active treatment discontinuation in patients with a CD4+ T-cell nadir greater than 350 cells/mm3: 48-week Treatment Interruption in Early Starters Netherlands Study (TRIESTAN). J Acquir Immune Defic Syndr 44: 395-400.
36. Poulton MB, Sabin CA, Fisher M. 2003. Immunological changes during treatment interruptions: Risk factors and clinical sequelae. AIDS 17: 126-128.
37. Rouzioux C, Hubert JB, Burgard M, Deveau C, Goujard C, Bary M, Sereni D, Viard JP, Delfraissy JF, Meyer L. 2005. 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 192: 46-55.
38. Ruiz L, Martinez-Picado J, Romeu J, Paredes R, Zayat MK, Marfil S, Negredo E, Sirera G, Tural C, Clotet B. 2000. Structured treatment interruption in chronically HIV-1 infected patients after long-term viral suppression. AIDS 14: 397-403.
39. Sarmati L, Andreoni C, Nicastri E, Tommasi C, Buonomini A, D'Ettorre G, Corpolongo A, Dori L, Montano M, Volpi A, Narciso P, Vullo V, Andreoni M. 2009. Prognostic factors of long-term CD4+count-guided interruption of antiretroviral treatment. J Med Virol 81: 481-487.
40. Skiest DJ, Morrow P, Allen B, McKinsey J, Crosby C, Foster B, Hardy RD. 2004. It is safe to stop antiretroviral therapy in patients with preantiretroviral CD4 cell counts >250 cells/microL. J Acquir Immune Defic Syndr 37: 1351-1357.
41. Skiest DJ, Su Z, Havlir DV, Robertson KR, Coombs RW, Cain P, Peterson T, Krambrink A, Jahed N, McMahon D, Margolis DM. 2007. Interruption of antiretroviral treatment in HIV-infected patients with preserved immune function is associated with a low rate of clinical progression: A prospective study by AIDS Clinical Trials Group 5170. J Infect Dis 195: 1426-1436.
42. Solages A, Vita JA, Thornton DJ, Murray J, Heeren T, Craven DE, Horsburgh CR, Jr. 2006. Endothelial function in HIV-infected persons. Clin Infect Dis 42: 1325-1332.
43. Strain MC, Gunthard HF, Havlir DV, Ignacio CC, Smith DM, Leigh-Brown AJ, Macaranas TR, Lam RY, Daly OA, Fischer M, Opravil M, Levine H, Bacheler L, Spina CA, Richman DD, Wong JK. 2003. Heterogeneous clearance rates of long-lived lymphocytes infected with HIV: Intrinsic stability predicts lifelong persistence. Proc Natl Acad Sci USA 100: 4819-4824.
44. Tarwater PM, Parish M, Gallant JE. 2003. Prolonged treatment interruption after immunologic response to highly active antiretroviral therapy. Clin Infect Dis 37: 1541-1548.
45. Tebas P, Henry K, Mondy K, Deeks S, Valdez H, Cohen C, Powderly WG. 2002. Effect of prolonged discontinuation of successful antiretroviral therapy on CD4+ T cell decline in human immunodeficiency virus-infected patients: Implications for intermittent therapeutic strategies. J Infect Dis 186: 851-854.
46. Tebas P, Henry WK, Matining R, Weng-Cherng D, Schmitz J, Valdez H, Jahed N, Myers L, Powderly WG, Katzenstein D. 2008. Metabolic and immune activation effects of treatment interruption in chronic HIV-1 infection: Implications for cardiovascular risk. PLoS ONE 3: e2021.
47. Thiebaut R, Pellegrin I, Chene G, Viallard JF, Fleury H, Moreau JF, Pellegrin JL, Blanco P. 2005. Immunological markers after long-term treatment interruption in chronically HIV-1 infected patients with CD4 cell count above 400× 106 cells/L. AIDS 19: 53-61.
48. Wit FW, Blanckenberg DH, Brinkman K, Prins JM, van der Ende ME, Schneider MM, Mulder JW, de Wolf F, Lange JM. 2005. Safety of long-term interruption of successful antiretroviral therapy: The ATHENA Cohort Study. AIDS 19: 345-348.
49. Yeni P. 2008. Prise en charge médicale des personnes infectées par le VIH. Recommandations du groupe d'experts: Médecine-Sciences Flammarion.