Shivakoti Rupak, Yang Wei-Teng, Gupte Nikhil, Berendes Sima, Rosa Alberto La, Cardoso Sandra W, Mwelase Noluthando, Kanyama Cecilia, Pillay Sandy, Samaneka Wadzanai, Riviere Cynthia, Sugandhavesa Patcharaphan, Santos Brento, Poongulali Selvamuthu, Tripathy Srikanth, Bollinger Robert C, Currier Judith S, Tang Alice M, Semba Richard D, Christian Parul, Campbell Thomas B, Gupta Amita
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Malawi College of Medicine-Johns Hopkins University Research Project, Blantyre.
Clin Infect Dis. 2015 Jul 1;61(1):102-10. doi: 10.1093/cid/civ265. Epub 2015 Mar 31.
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.
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.
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.
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.
贫血是抗逆转录病毒治疗（ART）后临床治疗失败的已知风险因素。值得注意的是，贫血与炎症相互关联，最近的研究已将炎症标志物C反应蛋白（CRP）升高与人类免疫缺陷病毒（HIV）治疗的不良结局相关联，但其联合作用尚不清楚。本研究的目的是评估HIV感染中贫血的患病率和风险因素，并确定贫血和CRP升高是否共同预测ART后的临床治疗失败。
一项病例队列研究（N = 470 [236例病例，234例对照]）嵌套在一项ART疗效的多国随机试验（资源有限环境中抗逆转录病毒药物的前瞻性评估[PEARLS]）中。病例为在ART治疗96周时出现世界卫生组织3期、4期或死亡（临床治疗失败）的新发患者。多变量逻辑回归用于确定ART前（基线）贫血（女性：血红蛋白<12.0 g/dL；男性：血红蛋白<13.0 g/dL）的风险因素。使用多变量Cox模型评估贫血以及同时存在的基线贫血和炎症（CRP≥10 mg/L）与临床治疗失败的关联。
基线贫血患病率为51%，同时存在贫血和炎症的患病率为15%。在临床治疗失败分析中，与无贫血和炎症的患者相比，同时存在贫血和炎症的多变量调整风险比为6.41（95%置信区间[CI]，2.82 - 14.57），无炎症的贫血患者为0.77（95% CI，0.37 - 1.58），无贫血的炎症患者为0.45（95% CI，0.1 - 1.80）。
未接受过ART治疗、同时存在贫血和炎症的HIV感染者治疗失败的风险特别高，了解其发病机制可能会带来新的干预措施。减轻炎症和贫血可能会改善HIV疾病的结局。或者，同时存在的贫血和炎症可能代表需要进一步筛查隐匿性机会性感染的个体。
