Long-term antiretroviral therapy initiated during primary HIV-1 infection is key to achieving both low HIV reservoirs and normal T cell counts

Journal of Antimicrobial Chemotherapy

Volumn 68, Issue 5, 2013, Pages 1169-1178

  Hocqueloux, Laurent ^a   Avettand fènoël, Véronique ^b,c   Jacquot, Sophie ^d   Prazuck, Thierry ^a   Legac, Eric ^a   Mélard, Adeline ^b,c   Niang, Mohamadou ^a   Mille, Catherine ^a   Le moal, Gwenaël ^e   Viard, Jean Paul ^c,f   Rouzioux, Christine ^b,c  

^a Service d'urologie andrologie   (France)

^b HÔPITAL NECKER ENFANTS MALADES   (France)

^c UNIVERSITÉ PARIS DESCARTES   (France)

^d UNIVERSITÉ D'ORLÉANS   (France)

^e POITIERS UNIVERSITY HOSPITAL   (France)

^f HÔTEL DIEU   (France)

Author keywords

HIV DNA; Immune reconstitution; Primary infection

Indexed keywords

ANTI HUMAN IMMUNODEFICIENCY VIRUS AGENT; INTEGRASE INHIBITOR; NONNUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITOR; PROTEINASE INHIBITOR; RNA DIRECTED DNA POLYMERASE INHIBITOR; VIRUS DNA;

ADULT; ARTICLE; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; COHORT ANALYSIS; DISEASE CARRIER; FEMALE; FOLLOW UP; GENE DOSAGE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; LONG TERM CARE; LYMPHOCYTE COUNT; MAJOR CLINICAL STUDY; MALE; OUTCOME ASSESSMENT; PERIPHERAL BLOOD MONONUCLEAR CELL; PREDICTOR VARIABLE; PROSPECTIVE STUDY; TREATMENT RESPONSE; VIRUS IMMUNITY; VIRUS LOAD;

ADULT; ANTI-RETROVIRAL AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; CD4 LYMPHOCYTE COUNT; CD4-CD8 RATIO; COHORT STUDIES; DNA, VIRAL; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; MALE; PROSPECTIVE STUDIES; T-LYMPHOCYTES; TIME FACTORS; TREATMENT OUTCOME; VIRAL LOAD;

EID: 84876411341     PISSN: 03057453     EISSN: 14602091     Source Type: Journal    
DOI: 10.1093/jac/dks533     Document Type: Article

References (47)

1. Thompson MA, Aberg JA, Hoy JF et al. Antiretroviral treatment of adult HIV infection: 2012 recommendations of the International Antiviral Society-USA panel. JAMA 2012; 308: 387-402.
2. Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents. Department of Health and Human Services. http://aidsinfo.nih.gov/contentfiles/AdultandAdolescentGL.pdf (1 August 2012, date last accessed).
3. European AIDS Clinical Society. European Guidelines for Treatment of HIV Infected Adults in Europe. http://www.europeanaidsclinicalsociety.org/images/stories/EACS-Pdf/EACSGuidelines-v6.0-English.pdf (1 August 2012, date last accessed).
4. Margolick JB, Gange SJ, Detels R et al. Impact of inversion of the CD4/CD8 ratio on the natural history of HIV-1 infection. J Acquir Immune Defic Syndr 2006; 42: 620-6.
5. 3. Antivir Ther 2009; 14: 451-7.
6. Chomont N, El-Far M, Ancuta P et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 2009; 15: 893-900.
7. Chun T-W, Justement JS, Pandya P et al. Relationship between the size of the human immunodeficiency virus type 1 (HIV-1) reservoir in peripheral blood CD4+ T cells and CD4+:CD8+ T cell ratios in aviremic HIV-1-infected individuals receiving long-term highly active antiretroviral therapy. J Infect Dis 2002; 185: 1672-6.
8. Lang S, Mary-Krause M, Cotte L et al. Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: a case-control study nested within the French Hospital Database on HIV ANRS cohort CO4. Arch Intern Med 2010; 170: 1228-38.
9. Rouzioux C, Hubert J-B, Burgard M et al. 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 2005; 192: 46-55.
10. Avettand-Fenoel V, Prazuck T, Hocqueloux L et al. HIV-DNA in rectal cells is well correlated with HIV-DNA in blood in different groups of patients, including long-term non-progressors. AIDS 2008; 22: 1880-2.
11. Hatzakis AE, Touloumi G, Pantazis N et al. Cellular HIV-1 DNA load predicts HIV-RNA rebound and the outcome of highly active antiretroviral therapy. AIDS 2004; 18: 2261-7.
12. Havlir DV, Koelsch KK, Strain MC et al. Predictors of residual viremia in HIV-infected patients successfully treated with efavirenz and lamivudine plus either tenofovir or stavudine. J Infect Dis 2005; 191: 1164-8.
13. Lewin SR, Rouzioux C. HIV cure and eradication: how will we get from the laboratory to effective clinical trials? AIDS 2011; 25: 885-97.
14. Masquelier B, Taieb A, Reigadas S et al. Cellular HIV-1 DNA quantification and short-term and long-term response to antiretroviral therapy. J Antimicrob Chemother 2011; 66: 1582-9.
15. Yerly S, Günthard HF, Fagard C et al. Proviral HIV-DNA predicts viral rebound and viral setpoint after structured treatment interruptions. AIDS 2004; 18: 1951-3.
16. Piketty C, Weiss L, Assoumou L et al. A high HIV DNA level in PBMCs at antiretroviral treatment interruption predicts a shorter time to treatment resumption, independently of the CD4 nadir. J Med Virol 2010; 82: 1819-28.
17. Lambotte O, Boufassa F, Madec Y et al. HIV controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication. Clin Infect Dis 2005; 41: 1053-6.
18. Hocqueloux L, Prazuck T, Avettand-Fenoel V et al. Long-term immunovirologic control following antiretroviral therapy interruption in patients treated at the time of primary HIV-1 infection. AIDS 2010; 24: 1598-601.
19. Van Gulck E, Bracke L, Heyndrickx L et al. Immune and viral correlates of 'secondary viral control' after treatment interruption in chronically HIV-1 infected patients. PLoS One 2012; 7: e37792.
20. Kitahata MM, Gange SJ, Abraham AG et al. Effect of early versus deferred antiretroviral therapy for HIV on survival. N Engl J Med 2009; 360: 1815-26.
21. HIV-CAUSAL Collaboration. When to initiate combined antiretroviral therapy to reduce mortality and AIDS-defining illness in HIV-infected persons in developed countries. Ann Intern Med 2011; 154: 509-15.
22. When To Start Consortium. Timing of initiation of antiretroviral therapy in AIDS-free HIV-1-infected patients: a collaborative analysis of 18 HIV cohort studies. Lancet 2009; 373: 1352-63.
23. Writing Committee for the CASCADE Collaboration. Timing of HAART initiation and clinical outcomes in human immunodeficiency virus type 1 seroconverters. Arch Intern Med 2011; 171: 1560-9.
24. Bell SK, Little SJ, Rosenberg ES. Clinical management of acute HIV infection: best practice remains unknown. J Infect Dis 2010; 202 Suppl 2: S278-88.
25. Trono D, Van Lint C, Rouzioux C et al. HIV persistence and the prospect of long-term drug-free remissions for HIV-infected individuals. Science 2010; 329: 174-80.
26. Schmid A, Gianella S, von Wyl V et al. Profound depletion of HIV-1 transcription in patients initiating antiretroviral therapy during acute infection. PLoS One 2010; 5: e13310.
27. Cellerai C, Harari A, Stauss H et al. Early and prolonged antiretroviral therapy is associated with an HIV-1-specific T-cell profile comparable to that of long-term non-progressors. PLoS One 2011; 6: e18164.
28. Yeni P. Prise en charge médicale des personnes infectées par le VIH. Paris: La documentation francaise, 2010.
29. Avettand-Fènoël V, Chaix M-L, Blanche S et al. LTR real-time PCR for HIV-1 DNA quantitation in blood cells for early diagnosis in infants born to seropositive mothers treated in HAART area (ANRS CO 01). J Med Virol 2009; 81: 217-23.
30. Avettand-Fènoël V, Boufassa F, Galimand J et al. HIV-1 DNA for the measurement of the HIV reservoir is predictive of disease progression in seroconverters whatever the mode of result expression is. J Clin Virol 2008; 42: 399-404.
31. Pinheiro JC, Bates DM. Mixed-Effects Models in S and S-PLUS. New York: Springer, 2000.
32. Koelsch KK, Liu L, Haubrich R et al. Dynamics of total, linear nonintegrated, and integrated HIV-1 DNA in vivo and in vitro. J Infect Dis 2008; 197: 411-9.
33. Ananworanich J, Schuetz A, Vandergeeten C et al. Impact of multi-targeted antiretroviral treatment on gut T cell depletion and HIV reservoir seeding during acute HIV infection. PLoS One 2012; 7: e33948.
34. Archin NM, Vaidya NK, Kuruc JD 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 USA 2012; 109: 9523-8.
35. Viard J-P, Burgard M, Hubert J-B et al. Impact of 5 years of maximally successful highly active antiretroviral therapy on CD4 cell count and HIV-1 DNA level. AIDS 2004; 18: 45-9.
36. Strain MC, Little SJ, Daar ES et al. Effect of treatment, during primary infection, on establishment and clearance of cellular reservoirs of HIV-1. J Infect Dis 2005; 191: 1410-8.
37. von Wyl V, Gianella S, Fischer M et al. Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption. PLoS One 2011; 6: e27463.
38. Kelley CF, Kitchen CMR, Hunt PW et al. Incomplete peripheral CD4+ cell count restoration in HIV-infected patients receiving long-term antiretroviral treatment. Clin Infect Dis 2009; 48: 787-94.
39. Guihot A, Tubiana R, Breton G et al. Immune and virological benefits of 10 years of permanent viral control with antiretroviral therapy. AIDS 2010; 24: 614-7.
40. Lifson AR, Krantz EM, Eberly LE et al. Long-term CD4+ lymphocyte response following HAART initiation in a U.S. military prospective cohort. AIDS Res Ther 2011; 8: 2.
41. Autran B, Descours B, Avettand-Fenoel V et al. Elite controllers as a model of functional cure. Curr Opin HIV AIDS 2011; 6: 181-7.
42. Buzon M, Seiss K, Stone A et al. Treatment of early HIV infection reduces viral reservoir to levels found in Elite controllers. In: Abstracts of the Nineteenth Conference on Retroviruses and Opportunistic Infections, Seattle, WA, 2012. Abstract 151. Foundation for Retrovirology and Human Health, Alexandria, VA, USA.
43. Bacchus C, Hocqueloux L, Avettand-Fenoel V et al. Distribution of the HIV reservoir in patients spontaneously controlling HIV infection after treatment interruption. In: Abstracts of the Nineteenth International AIDS Conference, Washington, DC, 2012. Abstract 16010 (A30). International AIDS Society, Geneva, Switzerland.
44. Saez-Cirion A, Hocqueloux L, Avettand-Fenoel V et al. Long-term HIV-1 control after interruption of a treatment initiated at the time of primary infection is associated to low cell-associated HIV DNA levels: ANRS VISCONTI study. In: Abstracts of the Eighteenth Conference on Retroviruses and Opportunistic Infections, Boston, MA, 2011. Abstract 515. Foundation for Retrovirology and Human Health, Alexandria, VA, USA.
45. Chun T-W, Justement JS, Murray D et al. Rebound of plasma viremia following cessation of antiretroviral therapy despite profoundly low levels of HIV reservoir: implications for eradication. AIDS 2010; 24: 2803-8.
46. Ghosn J, Deveau C, Chaix ML et al. Despite being highly diverse, immunovirological status strongly correlates with clinical symptoms during primary HIV-1 infection: a cross-sectional study based on 674 patients enrolled in the ANRS CO 06 PRIMO cohort. J Antimicrob Chemother 2010; 65: 741-8.
47. Cohen MS, Chen YQ, McCauley M et al. Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 2011; 365: 493-505.