Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries.

Hdl Handle:
http://hdl.handle.net/10144/112641
Title:
Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries.
Authors:
Pujades-Rodríguez, Mar; Balkan, Suna; Arnould, Line; Brinkhof, Martin A W; Calmy, Alexandra
Journal:
JAMA : the Journal of the American Medical Association
Abstract:
CONTEXT: Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings. OBJECTIVES: To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death. DESIGN, SETTING, AND PARTICIPANTS: Multicohort study of 632 patients > 14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008. MAIN OUTCOME MEASURES: Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death. RESULTS: The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for < 80% vs > or = 95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/microL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/microL vs 200/microL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results. CONCLUSIONS: Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.
Affiliation:
Epicentre, Médecins Sans Frontières 42-bis, Bd, 8 rue Saint Sabin, 75011 Paris, France. mar.pujades@epicentre.msf.org
Issue Date:
21-Jul-2010
URI:
http://hdl.handle.net/10144/112641
DOI:
10.1001/jama.2010.980
PubMed ID:
20639564
Additional Links:
http://jama.ama-assn.org/cgi/content/full/304/3/303?ijkey=EJ1TcM8xUhnUc&keytype=ref&siteid=amajnls
Language:
en
Description:
To view this article, click on "Additional Links".
ISSN:
1538-3598
Appears in Collections:
HIV/AIDS

Full metadata record

DC FieldValue Language
dc.contributor.authorPujades-Rodríguez, Maren
dc.contributor.authorBalkan, Sunaen
dc.contributor.authorArnould, Lineen
dc.contributor.authorBrinkhof, Martin A Wen
dc.contributor.authorCalmy, Alexandraen
dc.date.accessioned2010-10-07T15:29:09Z-
dc.date.available2010-10-07T15:29:09Z-
dc.date.issued2010-07-21-
dc.identifier.citationTreatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries. 2010, 304 (3):303-12 JAMAen
dc.identifier.issn1538-3598-
dc.identifier.pmid20639564-
dc.identifier.doi10.1001/jama.2010.980-
dc.identifier.urihttp://hdl.handle.net/10144/112641-
dc.descriptionTo view this article, click on "Additional Links".en
dc.description.abstractCONTEXT: Long-term antiretroviral therapy (ART) use in resource-limited countries leads to increasing numbers of patients with HIV taking second-line therapy. Limited access to further therapeutic options makes essential the evaluation of second-line regimen efficacy in these settings. OBJECTIVES: To investigate failure rates in patients receiving second-line therapy and factors associated with failure and death. DESIGN, SETTING, AND PARTICIPANTS: Multicohort study of 632 patients > 14 years old receiving second-line therapy for more than 6 months in 27 ART programs in Africa and Asia between January 2001 and October 2008. MAIN OUTCOME MEASURES: Clinical, immunological, virological, and immunovirological failure (first diagnosed episode of immunological or virological failure) rates, and mortality after 6 months of second-line therapy use. Sensitivity analyses were performed using alternative CD4 cell count thresholds for immunological and immunovirological definitions of failure and for cohort attrition instead of death. RESULTS: The 632 patients provided 740.7 person-years of follow-up; 119 (18.8%) met World Health Organization failure criteria after a median 11.9 months following the start of second-line therapy (interquartile range [IQR], 8.7-17.0 months), and 34 (5.4%) died after a median 15.1 months (IQR, 11.9-25.7 months). Failure rates were lower in those who changed 2 nucleoside reverse transcriptase inhibitors (NRTIs) instead of 1 (179.2 vs 251.6 per 1000 person-years; incidence rate ratio [IRR], 0.64; 95% confidence interval [CI], 0.42-0.96), and higher in those with lowest adherence index (383.5 vs 176.0 per 1000 person-years; IRR, 3.14; 95% CI, 1.67-5.90 for < 80% vs > or = 95% [percentage adherent, as represented by percentage of appointments attended with no delay]). Failure rates increased with lower CD4 cell counts when second-line therapy was started, from 156.3 vs 96.2 per 1000 person-years; IRR, 1.59 (95% CI, 0.78-3.25) for 100 to 199/microL to 336.8 per 1000 person-years; IRR, 3.32 (95% CI, 1.81-6.08) for less than 50/microL vs 200/microL or higher; and decreased with time using second-line therapy, from 250.0 vs 123.2 per 1000 person-years; IRR, 1.90 (95% CI, 1.19-3.02) for 6 to 11 months to 212.0 per 1000 person-years; 1.71 (95% CI, 1.01-2.88) for 12 to 17 months vs 18 or more months. Mortality for those taking second-line therapy was lower in women (32.4 vs 68.3 per 1000 person-years; hazard ratio [HR], 0.45; 95% CI, 0.23-0.91); and higher in patients with treatment failure of any type (91.9 vs 28.1 per 1000 person-years; HR, 2.83; 95% CI, 1.38-5.80). Sensitivity analyses showed similar results. CONCLUSIONS: Among patients in Africa and Asia receiving second-line therapy for HIV, treatment failure was associated with low CD4 cell counts at second-line therapy start, use of suboptimal second-line regimens, and poor adherence. Mortality was associated with diagnosed treatment failure.en
dc.language.isoenen
dc.relation.urlhttp://jama.ama-assn.org/cgi/content/full/304/3/303?ijkey=EJ1TcM8xUhnUc&keytype=ref&siteid=amajnlsen
dc.rightsArchived with thanks to the American Medical Association ([url]http://jama.ama-assn.org/[/url])en
dc.subject.meshAdolescenten
dc.subject.meshAdulten
dc.subject.meshAfricaen
dc.subject.meshAnti-HIV Agentsen
dc.subject.meshAsiaen
dc.subject.meshCD4 Lymphocyte Counten
dc.subject.meshCohort Studiesen
dc.subject.meshDeveloping Countriesen
dc.subject.meshFemaleen
dc.subject.meshHIV Infectionsen
dc.subject.meshHealth Services Accessibilityen
dc.subject.meshHumansen
dc.subject.meshMaleen
dc.subject.meshMiddle Ageden
dc.subject.meshPatient Complianceen
dc.subject.meshTreatment Failureen
dc.subject.meshYoung Adulten
dc.titleTreatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries.en
dc.contributor.departmentEpicentre, Médecins Sans Frontières 42-bis, Bd, 8 rue Saint Sabin, 75011 Paris, France. mar.pujades@epicentre.msf.orgen
dc.identifier.journalJAMA : the Journal of the American Medical Associationen

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