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JAIDS Journal of Acquired Immune Deficiency Syndromes:
doi: 10.1097/QAI.0000000000000240
Original Article: PDF Only

Evaluation of Rapid Progressors in HIV Infection as an Extreme Phenotype.

Olson, Ashley D.; Guiguet, Marguerite; Zangerle, Robert; Gill, John; Perez-Hoyos, Santiago; Lodi, Sara; Ghosn, Jade; Dorrucci, Maria; Johnson, Anne; Sannes, Mette; Moreno, Santiago; Porter, Kholoud; for CASCADE Collaboration in EuroCoord

Published Ahead-of-Print
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Abstract

Design: Rapid CD4 cell loss represents an HIV phenotype used to identify causal variants of accelerated disease progression. The optimal rate and threshold for identifying this extreme phenotype in recently-infected individuals is unclear.

Methods: Using a cohort of patients with known dates of HIV-1 seroconversion, CASCADE, we identified proportions experiencing nadir CD4 cell levels within one year of seroconversion (SC), and assessed their mean AIDS-free survival time at 10 years follow-up and hazard of AIDS/death, compared to those whose CD4 remained >500 cells/mm3. Follow-up was censored at 31/12/1996 to avoid bias due to cART initiation.

Results: Of 4876 individuals, 2.8%, 7.3% and 24.9% experienced >=1 CD4 <100, 200 and 350 cells/mm3, respectively, within one year of SC. Minimum CD4 levels of 30, 166, 231 and 506 cells/mm3 were experienced during this period by 1%, 5%, 10% and 50% of individuals, respectively. Mean (95%CI) AIDS-free survival at 10 years follow-up was 2.9(2.3,3.6), 5.5(5.0,6.1), 6.7(6.5,7.0), 7.4(7.2,7.6) and 8.1(7.9,8.3), for those with minimum counts <=100, 100-200, 200-350, 350-500, >500 cells/mm3, respectively. Using counts of >500 cells/mm3 as reference, the hazard ratios (95%CI) of AIDS/death were 15.0(11.9,18.9), 3.6(2.9,4.5), 2.1(1.8,2.4) and 1.5(1.3,1.7), respectively. The hazard ratio increased to 37.5(26.5,53.1) when a minimum CD4 count <100 was confirmed within one year of SC.

Conclusion: At least one CD4 <=100 cells/mm3 within the first year of seroconversion identifies a rare group of individuals at high risk of disease progression and could form the basis for defining the rapid progressor phenotype.

(C) 2014 by Lippincott Williams & Wilkins

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