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D. Bangsberg, S. Perry, E. Charlebois, R. Clark, Marjorie Roberston, A. Zolopa, A. Moss (2001)
Non-adherence to highly active antiretroviral therapy predicts progression to AIDS.AIDS, 15 9
D. Bangsberg, T. Porco, C. Kagay, E. Charlebois, S. Deeks, D. Guzman, R. Clark, A. Moss (2004)
Modeling the HIV protease inhibitor adherence-resistance curve by use of empirically derived estimates.The Journal of infectious diseases, 190 1
P. Belœil, Claire Chauvin, K. Proux, Nicolas Rose, S. Quéguiner, E. Eveno, C. Houdayer, Valérie Rose, P. Fravalo, François Madec (2003)
Longitudinal serological responses to Salmonella enterica of growing pigs in a subclinically infected herd.Preventive veterinary medicine, 60 3
O. Gallego, C. Mendoza, M. Pérez-Elías, J. Guardiola, J. Pedreira, D. Dalmau, Juan González, A. Moreno, J. Arribas, A. Rubio, I. García-Arata, M. Leal, P. Domingo, V. Soriano (2001)
Drug resistance in patients experiencing early virological failure under a triple combination including indinavirAIDS, 15
(2003)
Accumulation of antiretroviral resistance in treatment-experienced patients: the impact of medication adherence
D. Bangsberg, A. Moss, S. Deeks (2004)
Paradoxes of adherence and drug resistance to HIV antiretroviral therapy.The Journal of antimicrobial chemotherapy, 53 5
R. Hogg, K. Heath, D. Bangsberg, B. Yip, N. Press, M. O'Shaughnessy, J. Montaner (2002)
Intermittent use of triple-combination therapy is predictive of mortality at baseline and after 1 year of follow-upAIDS, 16
J. Walsh, A. Pozniak, M. Nelson, S. Mandalia, B. Gazzard (2002)
Virologic Rebound on HAART in the Context of Low Treatment Adherence Is Associated With a Low Prevalence of Antiretroviral Drug ResistanceJAIDS Journal of Acquired Immune Deficiency Syndromes, 30
(2004)
Low levels of adherence confer greater risk for non-nucleoside reverse transcriptase inhibitor resistance than protease-inhibitor resistance
(2001)
Lack of multidrug resistance in nonresponders to antiretroviral therapy with poor adherence
A. Delsol, M. Woodward, J. Roe (2004)
Effect of a 5 day enrofloxacin treatment on Salmonella enterica serotype Typhimurium DT104 in the pig.The Journal of antimicrobial chemotherapy, 53 2
D. Bangsberg, F. Hecht, E. Charlebois, A. Zolopa, M. Holodniy, L. Sheiner, J. Bamberger, M. Chesney, A. Moss (2000)
Adherence to protease inhibitors, HIV-1 viral load, and development of drug resistance in an indigent populationAIDS, 14
Correspondence 2. Delsol, A. A., Woodward, M. J. & Roe, J. M. (2004). Effect of a Journal of Antimicrobial Chemotherapy 5 day enrofloxacin treatment on Salmonella enterica serotype DOI: 10.1093/jac/dkh392 Typhimurium DT104 in the pig. Journal of Antimicrobial Chemotherapy Advance Access publication 28 July 2004 53, 396 – 8. 3. Belœil, P. A., Chauvin, C., Proux, K. et al. (2003). Longitudinal serological responses to Salmonella enterica of growing pigs in a Reply subclinically infected herd. Preventive Veterinary Medicine 60, 207 – 26. 4. Katouli, M., Melin, L., Jensen-Waern, M. et al. (1999). The effect 1,2 3 David R. Bangsberg *, Andrew R. Moss and Steven of zinc oxide supplementation on the stability of the intestinal flora with G. Deeks special reference to composition of coliforms in weaned pigs. Journal of Applied Microbiology 87, 564 – 73. Epidemiology and Prevention Interventions Center, San Francisco General Hospital, UCSF; San Francisco General Hospital AIDS Program, UCSF; Department of Epidemiology and Biostatistics, San Francisco General Journal of Antimicrobial Chemotherapy Hospital, UCSF, San Francisco, CA, USA DOI: 10.1093/jac/dkh378 Advance Access publication 28 July 2004 Keywords: antiretroviral, resistance, resource-constrained, countries There are no paradoxes of adherence and drug *Correspondence address. Box 1372, San Francisco General resistance to HIV antiretroviral therapy Hospital, UCSF, 1001 Potrero Avenue, Building 100, Room David A. Green* 301, San Francisco, CA 94110, USA. Tel: +1-415-206-3462; Fax: +1-415-206-4360; E-mail: db@epi-center.ucsf.edu On-Cue, Compliance Service, Hout Bay, Western Cape, South Africa Sir, Keywords: adherence, HAART, HIV, AIDS Dr Green suggests that our claim that antiretroviral drug resist- ance often occurs in highly adherent patients on highly active *E-mail: david@on-cue.co.za antiretroviral therapy (HAART) is misleading. We agree that this point may be confusing and indeed focus on this very ‘para- Sir, dox’ in our leading article. The recent leading article by Bangsberg et al. is misleading in HAART became available in 1996 with the introduction of that it could lead readers to believe that there is increased protease inhibitor therapy used in combination with two nucleo- resistance to highly active antiretroviral (ARV) therapy side analogues. Our data, obtained in a systematic sample of (HAART) with increased levels of adherence. In fact the low-income individuals on HAART, indicate that half of all authors make the case for increased resistance with increased drug resistance occurred among individuals taking >79% of their adherence in ‘.. .cohorts of individuals treated with either medication and a quarter of all drug resistance occurred in indi- sequential monotherapy or earlier, less potent three-drug viduals taking >92% of their medication. In a subsequent math- regimens.. .’. This is precisely why the current modality of ematical model using these empirical estimates, we determined treatment is HAART. High levels of adherence to HAART are that resistance to early protease inhibitor therapy was most com- required in order to achieve adequate and sustained viral sup- 2 mon at 87% adherence. These data are consistent with those of pression and minimize the risk of resistance. To suggest other- several other groups and suggest that early HAART was not wise is to muddy the waters and undermine efforts at achieving active enough to prevent resistance, even in the face of good the unprecedented levels of compliance required for successful 3– 8 adherence. The paradox is that we spent much of the late roll out of HAART. 1990 s debating the public health wisdom of providing therapy Inadequate viral suppression (from using monotherapy or to marginalized populations in the interest of preventing drug poorly selected combinations of ARVs) results in resistance. resistance, whereas the epidemiological evidence suggests that This is not paradoxical and would be predicted from our current the burden of drug resistance fell on those who took most of knowledge of how resistance develops. The authors make an their medication. excellent case for careful selection of the ARV combinations to The relationship between adherence and resistance is clearly make up HAART. However, the article does mislead in that it evolving and is different now from when HAART first became could be read to suggest that lower levels of adherence with a available. Today, high levels of adherence to maximally effec- properly chosen HAART regimen may be acceptable, or even tive therapy (e.g. two nucleoside analogues and either a non- desirable. nucleoside reverse transcriptase inhibitor or a dual protease inhibitor) in a treatment-naive patient invariably results in dur- able viral suppression and no clear evolution of drug resistance. References There may, however, be important differences in the risk of resistance at low levels of adherence between non-nucleoside 1. Bangsberg, D. R., Moss, A. R. & Deeks, S. G. (2004). reverse transcriptase inhibitors and dual protease inhibitors. Paradoxes of adherence and drug resistance to HIV antiretroviral chemotherapy. Journal of Antimicrobial Chemotherapy 53, 696 – 9. Specifically, low levels of adherence may preferentially select
Journal of Antimicrobial Chemotherapy – Oxford University Press
Published: Sep 1, 2004
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