Is it safe to drop CD4+ monitoring among virologically suppressed patients

病毒载量 医学 抗逆转录病毒疗法 人类免疫缺陷病毒(HIV) 重症监护医学 免疫学
作者
Nathan Ford,Kathryn Stinson,Mary‐Ann Davies,Vivian Cox,Gabriela Patten,Carol Cragg,Gilles Van Cutsem,Andrew Boulle
出处
期刊:AIDS [Lippincott Williams & Wilkins]
卷期号:28 (14): 2003-2005 被引量:21
标识
DOI:10.1097/qad.0000000000000406
摘要

For over two decades, the measurement of CD4+ cell count has been the principal means of assessing eligibility for initiation of antiretroviral therapy (ART) and monitoring response to treatment [1]. In high-income settings, treatment response is also supported by routine virologic monitoring as the preferred way to assess adherence and detect virologic failure early and accurately [2,3]. In low-income, high HIV burden settings, access to viral load monitoring remains limited due to the complexity and cost of current technology. However, there has been a progressive evolution favouring increased use of viral load monitoring, and the latest guidelines from the WHO in June 2013 recommend that countries use viral load as the preferred approach to monitoring response to ART [4]. In support of this recommendation, major international agencies are working with countries to support scale-up of viral load capacity in resource-limited settings [5]. In settings where viral load is routinely available, the added value of CD4+ monitoring is increasingly being questioned [6]. Several studies from high-income settings have suggested that CD4+ monitoring provides little additional information in situations where viral load is available and patients are virologically suppressed [7,8]. However, data from low-income, high HIV burden settings are lacking. Differences in immune status at baseline, antiretroviral drug regimens, healthcare delivery, and background opportunistic infections mean that data from high-income settings may not be readily applicable to high HIV burden resource-limited settings. We assessed CD4+ changes among virologically suppressed patients in a routine programme setting in South Africa. Starting in 2001, the Khayelitsha programme is one of the largest and longest standing treatment programmes in South Africa, serving a population of around 500 000 people through 11 primary healthcare facilities. The majority of patients on ART are managed by nurses, with adherence clubs for stable patients facilitated by lay counsellors [9,10]. First-line adult ART regimens have varied over time, with zidovudine (ZDV)/lamivudine (3TC)/efavirenz (EFV) being the predominant regimen in the first 3 years, with stavudine replacing ZDV in 2004, which in turn was replaced by tenofovir. By 2010, TDF/3TC/EFV was used as the first-line ART regimen for the majority of adult patients [11]. Prospective patient-level data have been collected since the start of the programme, using electronic capture of clinical records. We identified adult patients (≥16 years old) started on ART between 2001 and 2012, who achieved a viral load below 400 copies/ml and a CD4+ cell count above 200 cells/μl between 9 and 15 months on ART; and who subsequently (from 21 months onwards) had paired (within a month of each other) viral load and CD4+ cell count measurements while remaining virologically suppressed. Patients were censored if duration between viral loads exceeded 15 months. The proportion of patients maintaining CD4+ cell counts above 200 cells/μl were described by duration on ART. The time to a drop in CD4+ cell count to below 200 cells/μl was assessed using Kaplan–Meier survival curves (Fig. 1).Fig. 1: Kaplan–Meier survival estimates of sustained immunologic recovery.A total of 14 792 adults were followed for 2 years or more, of whom 7250 met the inclusion criteria, and 5697 (79%) additionally had at least one eligible set of paired CD4+ cell count and viral load data for evaluation. Median age at ART initiation was 34 years [interquartile range (IQR) 29–40 years]. Women constituted two-thirds of cohort enrolment over time and were younger at ART initiation than men (median age 32 vs. 37 years; P < 0.001). Median baseline CD4+ cell count increased from 63 cells/μl (IQR 22–122 cells/μl) between 2001 and 2003 to 225 cells/μl (IQR 127–300 cells/μl) in 2012, reflecting both increasing trends in enrolment and South African national guideline changes in CD4+ cell count threshold. Of the 17 991 paired results, 230 CD4+ cell counts (1.3%) were below 200 cells/μl. This proportion was higher earlier on ART (1.5, 1.0 and 0.9% before 3 years, 5 years and subsequently). At 2, 5 and 10 years on ART, 99.3, 95.8 and 92.9% of patients with ongoing virologic suppression maintained CD4+ cell counts continuously above 200 cells/μl. This proportion increased in patients with higher 12-month CD4+ cell counts (Fig. 1). A follow-up CD4+ cell count was available in 137 of the 230 patients falling below 200 cells/μl, and had returned above this value in the majority (133, 97%) of cases. In this study, only a very small proportion of virologically suppressed adults with initial immunological recovery had subsequent low CD4+ cell counts, most of which increased again without intervention. These data are consistent with data from randomized trials and observational cohorts which suggest that once HIV-infected patients on ART are virologically suppressed, CD4+ cell count does not decline over time in the vast majority of patients [7,8]. Strengths of this study include the large cohort size, long duration of follow-up, and data which come from a routine programme setting in a high HIV prevalence setting with a high rate of HIV/tuberculosis (TB) co-infection. There is growing appreciation that, from a public health management perspective, CD4+ monitoring adds little additional value to viral load monitoring once patients are stable on ART. Guidelines issued by the Southern African HIV Clinicians Society in 2013 recommend that in patients being monitored with viral loads, CD4+ cell count testing can be stopped once the CD4+ cell count is above 200 cells/μl and the viral load is suppressed; CD4+ cell count should be repeated if virologic or clinical failure occurs [12]. The latest US guidelines for the management of persons infected with HIV recommend that CD4+ measures can be reduced among patients who are virologically suppressed, from 3–4 months to 6–12 months [13–15]. CD4+ cell count at baseline continues to be important for initial clinical management decisions, including screening and prophylaxis for major opportunistic infections, and stratifying risk among patients presenting for care. CD4+ cell count will also continue to play an important role in determining ART eligibility, despite a trend towards an increasing number of CD4+-independent ART initiation scenarios, and will also likely be required for a small minority of patients to support individual clinical decision-making, for example, for those who fail to respond to treatment or patients taking concomitant immunosuppressive therapy. However, once treatment has been initiated, the key focus is ensuring virologic suppression. Research is needed to determine the optimal clinical and virological criteria for stopping CD4+ following ART initiation. In conclusion, these data support considerations to reduce the frequency of CD4+ cell counts, or eliminate them altogether, from routine use once patients are stable on ART in settings where both CD4+ and viral load are routinely available. Acknowledgements Author's contributions: N.F., K.S., and A.B. conceived the study. K.S. and A.B. analysed the data. All authors contributed to writing, critical revision, and finalization of the manuscript. Conflicts of interest There are no conflicts of interest.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
1秒前
2秒前
小马过河应助尼尼采纳,获得10
4秒前
4秒前
4秒前
吾将上下而求索完成签到,获得积分10
4秒前
4秒前
4秒前
科研通AI2S应助LIN采纳,获得10
5秒前
5秒前
5秒前
喜悦的半青完成签到,获得积分10
5秒前
6秒前
好宝宝发布了新的文献求助10
7秒前
上官若男应助程艳采纳,获得80
7秒前
伊可创发布了新的文献求助10
8秒前
Ava应助szh123采纳,获得10
9秒前
锦七发布了新的文献求助10
9秒前
小二郎应助收手吧大哥采纳,获得10
11秒前
12秒前
在水一方应助lm采纳,获得10
12秒前
可爱的函函应助jingjingA采纳,获得10
12秒前
Zdh同学完成签到,获得积分10
13秒前
我是老大应助淡然的铭采纳,获得10
14秒前
girl完成签到,获得积分10
15秒前
16秒前
华仔应助HAHAHA采纳,获得10
16秒前
16秒前
小坤同学发布了新的文献求助10
17秒前
18秒前
musejie应助科研通管家采纳,获得10
18秒前
科研通AI2S应助科研通管家采纳,获得10
18秒前
quhayley应助科研通管家采纳,获得10
18秒前
情怀应助科研通管家采纳,获得10
18秒前
Jasper应助科研通管家采纳,获得10
18秒前
18秒前
18秒前
英俊的铭应助科研通管家采纳,获得10
19秒前
星辰大海应助科研通管家采纳,获得10
19秒前
李爱国应助科研通管家采纳,获得10
19秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
‘Unruly’ Children: Historical Fieldnotes and Learning Morality in a Taiwan Village (New Departures in Anthropology) 400
Indomethacinのヒトにおける経皮吸収 400
Phylogenetic study of the order Polydesmida (Myriapoda: Diplopoda) 370
基于可调谐半导体激光吸收光谱技术泄漏气体检测系统的研究 350
Robot-supported joining of reinforcement textiles with one-sided sewing heads 320
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3988732
求助须知:如何正确求助?哪些是违规求助? 3531027
关于积分的说明 11252281
捐赠科研通 3269732
什么是DOI,文献DOI怎么找? 1804764
邀请新用户注册赠送积分活动 881869
科研通“疑难数据库(出版商)”最低求助积分说明 809021