Khan Maryam, Bradshaw Daniel, Brown Colin S, Haddow Jana, Patel Poorvi, Tosswill Jennifer H C, Pollock Katrina, Elliott Tamara, Wang Xinzhu, Alagaratnam Jasmini, Mora-Peris Borja, Kaye Steve, McClure Myra O, Muir David, Randell Paul, Taylor Graham P, Fidler Sarah J
Section of Virology, Department of Infectious Disease, Imperial College London, London, United Kingdom.
Imperial College National Institute of Health Research, Imperial College London, London, United Kingdom.
Open Forum Infect Dis. 2023 Mar 1;10(5):ofad108. doi: 10.1093/ofid/ofad108. eCollection 2023 May.
We report outcomes and novel characterization of a unique cohort of 42 individuals with persistently indeterminate human immunodeficiency virus (HIV) status, the majority of whom are HIV viral controllers.
Eligible individuals had indeterminate or positive HIV serology, but persistently undetectable HIV ribonucleic acid (RNA) by commercial assays and were not taking antiretroviral therapy (ART). Routine investigations included HIV Western blot, HIV viral load, qualitative HIV-1 deoxyribonucleic acid (DNA), coinfection screen, and T-cell quantification. Research assays included T-cell activation, ART measurement, single-copy assays detecting HIV-1 RNA and DNA, and plasma cytokine quantification. Human immunodeficiency virus seropositivity was defined as ≥3 bands on Western blot; molecular positivity was defined as detection of HIV RNA or DNA.
Human immunodeficiency virus infection was excluded in 10 of 42 referrals, remained unconfirmed in 2 of 42, and was confirmed in 30 of 42, who were identified as HIV elite controllers (ECs), normal CD4 T-cell counts (median 820/mL, range 805-1336), and normal CD4/CD8 ratio (median 1.8, range 1.2-1.9). Elite controllers had a median duration of elite control of 6 years (interquartile range = 4-14). Antiretroviral therapy was undetected in all 23 subjects tested. Two distinct categories of ECs were identified: molecular positive (n = 20) and molecular negative (n = 10).
Human immunodeficiency virus status was resolved for 95% of referrals with the majority diagnosed as EC. The clinical significance of the 2 molecular categories among ECs requires further investigation.
我们报告了42名人类免疫缺陷病毒（HIV）状态持续不确定个体的独特队列的结果及新特征，其中大多数是HIV病毒控制者。
符合条件的个体HIV血清学检测结果不确定或呈阳性，但通过商业检测持续检测不到HIV核糖核酸（RNA），且未接受抗逆转录病毒治疗（ART）。常规检查包括HIV免疫印迹法、HIV病毒载量、定性HIV-1脱氧核糖核酸（DNA）、合并感染筛查和T细胞定量。研究检测包括T细胞活化、ART测量、检测HIV-1 RNA和DNA的单拷贝检测以及血浆细胞因子定量。HIV血清阳性定义为免疫印迹法出现≥3条带；分子阳性定义为检测到HIV RNA或DNA。
42例转诊患者中，10例排除HIV感染，42例中有2例仍未确诊，42例中有30例确诊，这些患者被确定为HIV精英控制者（ECs），CD4 T细胞计数正常（中位数820/mL，范围805 - 1336），CD4/CD8比值正常（中位数1.8，范围1.2 - 1.9）。精英控制者的精英控制中位持续时间为6年（四分位间距 = 4 - 14）。在所有检测的23名受试者中均未检测到抗逆转录病毒治疗。确定了两类不同的ECs：分子阳性（n = 20）和分子阴性（n = 10）。
95%的转诊患者的HIV状态得以明确，大多数被诊断为EC。ECs中这两类分子的临床意义需要进一步研究。
