Treatment failure and mortality factors in patients receiving second-line HIV therapy in resource-limited countries.
Affiliation
Epicentre, Médecins Sans Frontières 42-bis, Bd, 8 rue Saint Sabin, 75011 Paris, France. mar.pujades@epicentre.msf.orgIssue Date
2010-07-21
Metadata
Show full item recordAbstract
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.PubMed ID
20639564Additional Links
http://jama.ama-assn.org/cgi/content/full/304/3/303?ijkey=EJ1TcM8xUhnUc&keytype=ref&siteid=amajnlsLanguage
enDescription
To view this article, click on "Additional Links".ISSN
1538-3598ae974a485f413a2113503eed53cd6c53
10.1001/jama.2010.980
Scopus Count
Collections
Related articles
- Rapid scale-up of antiretroviral therapy at primary care sites in Zambia: feasibility and early outcomes.
- Authors: Stringer JS, Zulu I, Levy J, Stringer EM, Mwango A, Chi BH, Mtonga V, Reid S, Cantrell RA, Bulterys M, Saag MS, Marlink RG, Mwinga A, Ellerbrock TV, Sinkala M
- Issue date: 2006 Aug 16
- Switching to second-line antiretroviral therapy in resource-limited settings: comparison of programmes with and without viral load monitoring.
- Authors: ART-LINC of IeDEA Study Group., Keiser O, Tweya H, Boulle A, Braitstein P, Schecter M, Brinkhof MW, Dabis F, Tuboi S, Sprinz E, Pujades-Rodriguez M, Calmy A, Kumarasamy N, Nash D, Jahn A, MacPhail P, Lüthy R, Wood R, Egger M
- Issue date: 2009 Sep 10
- Deferred modification of antiretroviral regimen following documented treatment failure in Asia: results from the TREAT Asia HIV Observational Database (TAHOD).
- Authors: Zhou J, Li PC, Kumarasamy N, Boyd M, Chen YM, Sirisanthana T, Sungkanuparph S, Oka S, Tau G, Phanuphak P, Saphonn V, Zhang FJ, Omar SF, Lee CK, Ditangco R, Merati TP, Lim PL, Choi JY, Law MG, Pujari S, TREAT Asia HIV Observational Database.
- Issue date: 2010 Jan
- Second-line antiretroviral therapy in resource-limited settings: the experience of Médecins Sans Frontières.
- Authors: Pujades-Rodríguez M, O'Brien D, Humblet P, Calmy A
- Issue date: 2008 Jul 11
- Profile of HIV-infected patients receiving second-line antiretroviral therapy in a resource-limited setting in Nigeria.
- Authors: Onyedum CC, Iroezindu MO, Chukwuka CJ, Anyaene CE, Obi FI, Young EE
- Issue date: 2013 Oct