Modest nonadherence to antiretroviral therapy promotes residual HIV-1 replication in the absence of virological rebound in plasma

Journal of Infectious Diseases

Volumn 206, Issue 9, 2012, Pages 1443-1452

  Pasternak, Alexander O ^a,c   De Bruin, Marijn ^e   Jurriaans, Suzanne ^b   Bakker, Margreet ^a,c   Berkhout, Ben ^a,c   Prins, Jan M ^d   Lukashov, Vladimir V ^a,c  

^a Laboratory of Experimental Virology   (Netherlands)

^b Department of Medical Microbiology   (Netherlands)

^c ACADEMIC MEDICAL CENTER   (Netherlands)

^d UNIVERSITY OF AMSTERDAM   (Netherlands)

^e WAGENINGEN UNIVERSITY   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

ABACAVIR PLUS LAMIVUDINE PLUS ZIDOVUDINE; ATAZANAVIR; EFAVIRENZ; INDINAVIR; LOPINAVIR; NEVIRAPINE; RITONAVIR; SAQUINAVIR; UNCLASSIFIED DRUG; VIRUS DNA; VIRUS RNA; VIRUS UNSPLICED RNA;

ADULT; AGE; ANALYTICAL PARAMETERS; ARTICLE; CD4 LYMPHOCYTE COUNT; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; LIMIT OF DETECTION; LONGITUDINAL STUDY; MALE; NONHUMAN; PATIENT COMPLIANCE; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; REBOUND; TIME WEIGHTED CHANGE; TREATMENT DURATION; TREND STUDY; VIREMIA; VIRUS LOAD; VIRUS REPLICATION; VIRUS TRANSCRIPTION;

ADULT; ANTI-HIV AGENTS; ANTIRETROVIRAL THERAPY, HIGHLY ACTIVE; DNA, VIRAL; FEMALE; HIV INFECTIONS; HIV-1; HUMANS; LONGITUDINAL STUDIES; MALE; MEDICATION ADHERENCE; MIDDLE AGED; PLASMA; RNA, VIRAL; VIRAL LOAD;

EID: 84867534933     PISSN: 00221899     EISSN: None     Source Type: Journal    
DOI: 10.1093/infdis/jis502     Document Type: Article

References (50)

1. Arnsten JH, Demas PA, Farzadegan H, et al. Antiretroviral therapy adherence and viral suppression in HIV-infected drug users: Comparison of self-report and electronic monitoring. Clin Infect Dis 2001; 33:1417-23. (Pubitemid 32955198)
2. Bangsberg DR, Perry S, Charlebois ED, et al. Non-adherence to highly active antiretroviral therapy predicts progression to AIDS. AIDS 2001; 15:1181-3. (Pubitemid 32549871)
3. Bangsberg DR. Preventing HIV antiretroviral resistance through better monitoring of treatment adherence. J Infect Dis 2008; 197(Suppl 3): S272-8. (Pubitemid 351717317)
4. Paterson DL, Swindells S, Mohr J, et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV infection. Ann Intern Med 2000; 133:21-30. (Pubitemid 30432540)
5. Shuter J. Forgiveness of non-adherence to HIV-1 antiretroviral therapy. J Antimicrob Chemother 2008; 61:769-73. (Pubitemid 351426058)
6. Parienti JJ, Ragland K, Lucht F, et al. Average adherence to boosted protease inhibitor therapy, rather than the pattern of missed doses, as a predictor of HIV RNA replication. Clin Infect Dis 2010; 50:1192-7.
7. Parienti JJ, Das-Douglas M, Massari V, et al. Not all missed doses are the same: Sustained NNRTI treatment interruptions predict HIV rebound at low-to-moderate adherence levels. PLoS One 2008; 3:e2783.
8. Bangsberg DR. Less than 95% adherence to nonnucleoside reversetranscriptase inhibitor therapy can lead to viral suppression. Clin Infect Dis 2006; 43:939-41. (Pubitemid 44435526)
9. Gardner EM, Burman WJ, Steiner JF, Anderson PL, Bangsberg DR. Antiretroviral medication adherence and the development of classspecific antiretroviral resistance. AIDS 2009; 23:1035-46.
10. Maggiolo F, Airoldi M, Kleinloog HD, et al. Effect of adherence to HAART on virologic outcome and on the selection of resistanceconferring mutations in NNRTI-or PI-treated patients. HIV Clin Trials 2007; 8:282-92. (Pubitemid 350099562)
11. Podsadecki TJ, Vrijens BC, Tousset EP, Rode RA, Hanna GJ. Decreased adherence to antiretroviral therapy observed prior to transient human immunodeficiency virus type 1 viremia. J Infect Dis 2007; 196:1773-8. (Pubitemid 351411937)
12. Miller LG, Golin CE, Liu H, et al. No evidence of an association between transient HIV viremia ("Blips") and lower adherence to the antiretroviral medication regimen. J Infect Dis 2004; 189:1487-96. (Pubitemid 38543599)
13. Nettles RE, Kieffer TL, Kwon P, et al. Intermittent HIV-1 viremia (Blips) and drug resistance in patients receiving HAART. JAMA 2005; 293:817-29. (Pubitemid 40250365)
14. Shen L, Siliciano RF. Viral reservoirs, residual viremia, and the potential of highly active antiretroviral therapy to eradicate HIV infection. J Allergy Clin Immunol 2008; 122:22-8. (Pubitemid 351899083)
15. Maldarelli F. Targeting viral reservoirs: Ability of antiretroviral therapy to stop viral replication. Curr Opin HIV AIDS 2011; 6:49-56.
16. Buzon MJ, Massanella M, Llibre JM, et al. HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects. Nat Med 2010; 16:460-5.
17. Sharkey M, Babic DZ, Greenough T, Gulick R, Kuritzkes DR, Stevenson M. Episomal viral cDNAs identify a reservoir that fuels viral rebound after treatment interruption and that contributes to treatment failure. PLoS Pathog 2011; 7:e1001303.
18. Sigal A, Kim JT, Balazs AB, et al. Cell-to-cell spread of HIV permits ongoing replication despite antiretroviral therapy. Nature 2011; 477:95-8.
19. de Bruin M, Hospers HJ, van Breukelen GJ, Kok G, Koevoets WM, Prins JM. Electronic monitoring-based counseling to enhance adherence among HIV-infected patients: A randomized controlled trial. Health Psychol 2010; 29:421-8.
20. de Bruin M, Hospers HJ, van den Borne HW, Kok G, Prins JM. Theory-and evidence-based intervention to improve adherence to antiretroviral therapy among HIV-infected patients in the Netherlands: A pilot study. AIDS Patient Care STDS 2005; 19:384-94. (Pubitemid 40962013)
21. Pasternak AO, Adema KW, Bakker M, et al. Highly sensitive methods based on seminested real-time reverse transcription-PCR for quantitation of human immunodeficiency virus type 1 unspliced and multiply spliced RNA and proviral DNA. J Clin Microbiol 2008; 46:2206-11.
22. Pasternak AO, Jurriaans S, Bakker M, Prins JM, Berkhout B, Lukashov VV. Cellular levels of HIV unspliced RNA from patients on combination antiretroviral therapy with undetectable plasma viremia predict the therapy outcome. PLoS One 2009; 4:e8490.
23. Pasternak AO, Jurriaans S, Bakker M, Berkhout B, Lukashov VV. Steady increase in cellular HIV-1 load during the asymptomatic phase of untreated infection despite stable plasma viremia. AIDS 2010; 24:1641-9.
24. Fischer M, Huber W, Kallivroussis A, et al. Highly sensitive methods for quantitation of human immunodeficiency virus type 1 RNA from plasma, cells, and tissues. J Clin Microbiol 1999; 37:1260-4. (Pubitemid 29187780)
25. 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.
26. Yukl SA, Gianella S, Sinclair E, et al. Differences in HIV burden and immune activation within the gut of HIV-positive patients receiving suppressive antiretroviral therapy. J Infect Dis 2010; 202:1553-61.
27. Lima VD, Bangsberg DR, Harrigan PR, et al. Risk of viral failure declines with duration of suppression on highly active antiretroviral therapy irrespective of adherence level. J Acquir Immune Defic Syndr 2010; 55:460-5.
28. Rosenblum M, Deeks SG, van der Laan M, Bangsberg DR. The risk of virologic failure decreases with duration of HIV suppression, at greater than 50% adherence to antiretroviral therapy. PLoS One 2009; 4:e7196.
29. Hockett RD, Kilby JM, Derdeyn CA, 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; 189:1545-54. (Pubitemid 29240879)
30. Maldarelli F, Palmer S, King MS, et al. ART suppresses plasma HIV-1 RNA to a stable set point predicted by pretherapy viremia. PLoS Pathog 2007; 3:e46.
31. Palmer S, Maldarelli F, Wiegand A, 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; 105:3879-84. (Pubitemid 351723493)
32. Chun TW, Nickle DC, Justement JS, et al. HIV-infected individuals receiving effective antiviral therapy for extended periods of time continually replenish their viral reservoir. J Clin Invest 2005; 115:3250-5. (Pubitemid 41567589)
33. Joos B, Fischer M, Kuster H, et al. HIV rebounds from latently infected cells, rather than from continuing low-level replication. Proc Natl Acad Sci U S A 2008; 105:16725-30.
34. Ramratnam B, Mittler JE, Zhang L, et al. The decay of the latent reservoir of replication-competent HIV-1 is inversely correlated with the extent of residual viral replication during prolonged anti-retroviral therapy. Nat Med 2000; 6:82-5. (Pubitemid 30048531)
35. Zhang L, Ramratnam B, Tenner-Racz K, et al. Quantifying residual HIV-1 replication in patients receiving combination antiretroviral therapy. N Engl J Med 1999; 340:1605-13.
36. Yukl SA, Shergill AK, McQuaid K, 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; 24:2451-60.
37. Gandhi RT, Zheng L, Bosch RJ, et al. The effect of raltegravir intensification on low-level residual viremia in HIV-infected patients on antiretroviral therapy: A randomized controlled trial. PLoS Med 2010; 7: E1000321.
38. Hermankova M, Siliciano JD, Zhou Y, et al. Analysis of human immunodeficiency virus type 1 gene expression in latently infected resting CD4+ T lymphocytes in vivo. J Virol 2003; 77:7383-92. (Pubitemid 36734507)
39. Lewin SR, Vesanen M, Kostrikis L, et al. Use of real-time PCR and molecular beacons to detect virus replication in human immunodeficiency virus type 1-infected individuals on prolonged effective antiretroviral therapy. J Virol 1999; 73:6099-103. (Pubitemid 29274900)
40. Zanchetta M, Walker S, Burighel N, et al. Long-term decay of the HIV-1 reservoir in HIV-1-infected children treated with highly active antiretroviral therapy. J Infect Dis 2006; 193:1718-27. (Pubitemid 43839477)
41. Fischer M, Joos B, Niederost B, et al. Biphasic decay kinetics suggest progressive slowing in turnover of latently HIV-1 infected cells during antiretroviral therapy. Retrovirology 2008; 5:107.
42. Tam LW, Chui CK, Brumme CJ, et al. The relationship between resistance and adherence in drug-naive individuals initiating HAART is specific to individual drug classes. J Acquir Immune Defic Syndr 2008; 49:266-71.
43. Bangsberg DR, Charlebois ED, Grant RM, et al. High levels of adherence do not prevent accumulation of HIV drug resistance mutations. AIDS 2003; 17:1925-32. (Pubitemid 37070278)
44. Hunt PW, Martin JN, Sinclair E, et al. T cell activation is associated with lower CD4+ T cell gains in human immunodeficiency virus-infected patients with sustained viral suppression during antiretroviral therapy. J Infect Dis 2003; 187:1534-43. (Pubitemid 36578959)
45. Deeks SG. HIV infection, inflammation, immunosenescence, and aging. Annu Rev Med 2011; 62:141-55.
46. Sodora DL, Silvestri G. Immune activation and AIDS pathogenesis. AIDS 2008; 22:439-46. (Pubitemid 351317285)
47. Lohse N, Hansen AB, Pedersen G, et al. Survival of persons with and without HIV infection in Denmark, 1995-2005. Ann Intern Med 2007; 146:87-95. (Pubitemid 351640011)
48. van Sighem A, Danner S, Ghani AC, Gras L, Anderson RM, de Wolf F. Mortality in patients with successful initial response to highly active antiretroviral therapy is still higher than in non-HIV-infected individuals. J Acquir Immune Defic Syndr 2005; 40:212-8. (Pubitemid 41395721)
49. The Antiretroviral Therapy Cohort Collaboration. Life expectancy of individuals on combination antiretroviral therapy in high-income countries: A collaborative analysis of 14 cohort studies. Lancet 2008; 372:293-9.
50. Fischer M, Wong JK, Russenberger D, et al. Residual cell-associated unspliced HIV-1 RNA in peripheral blood of patients on potent antiretroviral therapy represents intracellular transcripts. Antivir Ther 2002; 7:91-103. (Pubitemid 36427150)