Rupak Shivakoti1, Wei-Teng Yang1, Nikhil Gupte1, Sima Berendes2, Alberto La Rosa3, Sandra W Cardoso4, Noluthando Mwelase5, Cecilia Kanyama6, Sandy Pillay7, Wadzanai Samaneka8, Cynthia Riviere9, Patcharaphan Sugandhavesa10, Brento Santos11, Selvamuthu Poongulali12, Srikanth Tripathy13, Robert C Bollinger1, Judith S Currier14, Alice M Tang15, Richard D Semba16, Parul Christian17, Thomas B Campbell18, Amita Gupta1. 1. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland. 2. Malawi College of Medicine-Johns Hopkins University Research Project, Blantyre. 3. Asociacion Civil Impacta Salud y Educacion, Lima, Peru. 4. STD/AIDS Clinical Research Laboratory, Instituto de Pesquisa Clinica Evandro Chagas, Fundacao Oswaldo Cruz, Rio de Janeiro, Brazil. 5. Department of Medicine, University of Witwatersrand, Johannesburg, South Africa. 6. University of North Carolina Lilongwe, Malawi. 7. Durban International Clinical Research Site, Durban University of Technology, South Africa. 8. University of Zimbabwe Clinical Research Centre, Harare. 9. Les Centres GHESKIO, Port-Au-Prince, Haiti. 10. Research Institute for Health Sciences, Chiang Mai, Thailand. 11. Hospital Nossa Senhora de Conceição, Porto Alegre, Brazil. 12. Y. R. Gaitonde Center for AIDS Research and Education, Chennai. 13. National AIDS Research Institute, Pune, India. 14. Department of Medicine, University of California, Los Angeles. 15. Department of Public Health and Community Medicine, Tufts University School of Medicine, Boston, Massachusetts. 16. Department of Ophthalmology, Johns Hopkins University School of Medicine. 17. Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. 18. Department of Medicine, Division of Infectious Diseases, University of Colorado School of Medicine, Aurora.
Abstract
BACKGROUND: Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. METHODS: A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥ 10 mg/L) with clinical failure were assessed using multivariable Cox models. RESULTS:Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82-14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37-1.58) for anemia without inflammation, and 0.45 (95% CI, .11-1.80) for inflammation without anemia compared to those without anemia and inflammation. CONCLUSIONS: ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of additional screening.
RCT Entities:
BACKGROUND:Anemia is a known risk factor for clinical failure following antiretroviral therapy (ART). Notably, anemia and inflammation are interrelated, and recent studies have associated elevated C-reactive protein (CRP), an inflammation marker, with adverse human immunodeficiency virus (HIV) treatment outcomes, yet their joint effect is not known. The objective of this study was to assess prevalence and risk factors of anemia in HIV infection and to determine whether anemia and elevated CRP jointly predict clinical failure post-ART. METHODS: A case-cohort study (N = 470 [236 cases, 234 controls]) was nested within a multinational randomized trial of ART efficacy (Prospective Evaluation of Antiretrovirals in Resource Limited Settings [PEARLS]). Cases were incident World Health Organization stage 3, 4, or death by 96 weeks of ART treatment (clinical failure). Multivariable logistic regression was used to determine risk factors for pre-ART (baseline) anemia (females: hemoglobin <12.0 g/dL; males: hemoglobin <13.0 g/dL). Association of anemia as well as concurrent baseline anemia and inflammation (CRP ≥ 10 mg/L) with clinical failure were assessed using multivariable Cox models. RESULTS: Baseline anemia prevalence was 51% with 15% prevalence of concurrent anemia and inflammation. In analysis of clinical failure, multivariate-adjusted hazard ratios were 6.41 (95% confidence interval [CI], 2.82-14.57) for concurrent anemia and inflammation, 0.77 (95% CI, .37-1.58) for anemia without inflammation, and 0.45 (95% CI, .11-1.80) for inflammation without anemia compared to those without anemia and inflammation. CONCLUSIONS: ART-naive, HIV-infected individuals with concurrent anemia and inflammation are at particularly high risk of failing treatment, and understanding the pathogenesis could lead to new interventions. Reducing inflammation and anemia will likely improve HIV disease outcomes. Alternatively, concurrent anemia and inflammation could represent individuals with occult opportunistic infections in need of additional screening.
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