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CD4 T cell measurements in the management of antiretroviral therapy-A review with an emphasis on pediatric HIV-infected patients

Department of Pathology and Laboratory Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Cytometry Part B Clinical Cytometry (Impact Factor: 2.28). 01/2008; 74 Suppl 1(S1):S19-26. DOI: 10.1002/cyto.b.20398
Source: PubMed

ABSTRACT The measurement of both the percentage (in pediatric patients aged less than 5 or 6 years) and the absolute number of circulating CD4+ T cells remains the single most important parameter for establishing prognosis and determining when to treat HIV-1 infected infants. The predictive power of CD4+ T cell measurements in HIV-1 infected individuals has resulted in robust guidelines from numerous agencies on the use of CD4+ T cell measurements ranging from pretreatment evaluations to the initial assessment and monitoring of therapeutic responses and treatment failures. The increase in availability of HIV-1 antiretroviral drugs in resource limited setting has led to the urgent need to develop systems and technologies for the accurate and cost-effective measurement of CD4+ T cells. The establishment of standardized guidelines for antiretroviral therapy (including CD4 testing) along with significant advancements in the development of structured access to health care, centralized CD4 testing programs, improved quality assurance programs, and inexpensive CD4 measurement technologies are making CD4 testing more universally available. Recent evidence suggests that a CD4/CD8 ratio of less than 1 may provide a reliable marker of presumptive HIV-1 infection in HIV-1 exposed infants. This review will summarize the current guidelines for the use of CD4 testing in HIV-1 infected infants and the potential for the CD4:CD8 ratio to be used as a surrogate of HIV-1 infection in resource limited settings.

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Available from: Lynn S Zijenah, Oct 13, 2014
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    • "Affordable CD4 T cell enumeration has gradually become possible through the use of simple, compact and robust low-cost new generation, point-of-care flow cytometers. These devices operate as single-platform volumetric instruments without the use of expensive microbeads [8-10]. Introduced in 2005, the recently developed Auto40 flow cytometer (Apogee Flow Systems Ltd, Hemel Hempstead, UK; http://www.ApogeeFlow.com) "
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    ABSTRACT: Field and community evaluation of the routine usage of CD4 T counting platforms is essential in resource-poor countries for efficient and cost-effective monitoring of HIV-infected adults and children attending health care centers. We herein addressed the principal issues raised by the implementation of the single-platform, volumetric Auto40 flow cytometer (Apogee Flow Systems Ltd, Hemel Hempstead, UK) in 8 community HIV monitoring laboratories of different levels throughout Chad. This is a country with particularly difficult conditions, both in terms of climate and vast geographical territory, making the decentralization of the therapeutic management of HIV-infected patients challenging. The routine usage of the Auto40 flow cytometers for a period of 5 years (2008--2013) confirms the reliability and robustness of the analyzer for community-based CD4 T cell enumeration in terms of both absolute numbers and percentages to enable accurate monitoring of HIV-infected adults and children. However, our observations suggest that the Auto40 mini flow cytometer is not suitable for all laboratories as it is oversized and ultimately very expensive. The Chad experience with the Auto40 flow cytometer suggests that its usage in resource-limited settings should be mainly reserved to reference (level 1) or district (level 2) laboratories, rather than to laboratories of health care centres (level 3).
    BMC Health Services Research 10/2013; 13(1):373. DOI:10.1186/1472-6963-13-373 · 1.66 Impact Factor
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    • "Immediate access to CD4 T cells results may also enable more rapid initiation of prophylactic treatment for opportunistic infections as well as chemotherapy for prevention of mother-to-child transmission at sites where CD4 T lymphocytes levels define the prophylactic drug regimen [10,11]. Affordable CD4 T cell counting has gradually become possible by using simple, compact and robust low-cost new generation of POC flow cytometers operating as single-platform volumetric instruments without the use of expensive microbeads [7,12-14]. Introduced in 2005, the recently developed Auto40 flow cytometer (Apogee Flow Systems Ltd, Hemel Hempstead, UK; http://www.Apogeeflow.com) was originally designed for military applications [15]. "
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    ABSTRACT: Background Validation of new affordable CD4 T cell measurement technologies is crucial specifically in resource-poor countries for antiretroviral treatment eligibility and immunologic CD4 monitoring of HIV-infected patients. Methods The absolute and percentage CD4 T cell counts of 258 HIV-1-infected blood samples (182 adults and 76 children), living in N’Djamena, Chad, were performed by single-platform, volumetric, CD45-assisted pan-leucogating Auto40 flow cytometer (Apogee Flow Systems Ltd, Hemel Hempstead, UK) comparing to the FACSCalibur flow cytometer as a reference method. Results Absolute and percentage CD4 T cell counts obtained by Auto40 and FACSCalibur of 258 HIV-1-infected blood samples were highly correlated (r = 0.99 and r = 0.96, respectively). The mean absolute bias and percent bias between Apogee Auto40 and FACSCalibur absolute CD4 T cell counts, were −9.4 cells/μl with limits of agreement from −15 to 93 cells/μl, and +2.0% with limits of agreement from −0.9 to 4.9%, respectively. The mean of absolute bias and percent bias between Apogee Auto40 and FACSCalibur of CD4 percentage results were +0.4% (95% CI: -0.02 – 0.86) with limits of agreement from −2.4 to 0.3%, and +3.0% with limits of agreement from −6.6 to 0.6%, respectively. The Auto40 counting allowed to identify the majority of adults with CD4 T cells below 200 cells/μl (sensitivity: 89%; specificity: 99%) or below 350 cells/μl (sensitivity: 94%; specificity:98%); and of children below 750 cells/μl (sensitivity: 99%; specificity: 96%) or below 25% CD4+ (sensitivity: 94%; specificity: 98%). Conclusion The Auto40 analyzer is an alternative flow cytometer for CD4 T lymphocyte enumeration to be used in routine for immunological monitoring according to the current WHO recommendations in HIV-infected adults as well as children living in resource-constrained settings like Chad.
    BMC Research Notes 04/2013; 6(1):169. DOI:10.1186/1756-0500-6-169
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    • "A wide assortment of more cost-efficient and technically less complex analyzers using proven flow cytometry-based technology have been developed in response to the overarching challenge of increasing access to CD4 T cell enumeration, and are especially suitable for resource-constrained settings [40]. Affordable CD4 T cell measurement, in absolute number and percentage, has gradually been possible by using simple, compact and robust low-cost new generation flow cytometers operating as single-platform volumetric instruments without the use of expensive micro beads [9]. Currently available mini flow cytometers present convenient efficiency when performed by well-trained laboratory technicians and when combined with good sample transport systems [9,40]. "
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    ABSTRACT: A mobile health unit may be useful to follow up adult and pediatric patients on antiretroviral treatment and living in remote areas devoid of laboratory facilities. The study evaluated the use of the simplified, robust, single-plateform, volumetric, pan-leucogating Auto40 flow cytometer (Apogee Flow Systems Ltd, Hemel Hempstead, UK) for CD4 T cell numeration in a mobile unit, compared against a reference flow cytometry method. The therapeutic mobile unit of the Laboratoire National de Santé Hygiène Mobile, Yaoundé, Cameroon, was equipped with the Auto40. A FACSCalibur flow cytometer (Becton Dickinson Immuno-cytometry System, San Jose, CA, USA) was used as reference method. EDTA-blood samples from volunteers were first subjected to CD4 T cell count in the mobile unit, and an aliquot was sent within 4 hours to Centre International de Référence Chantal Biya, Yaoundé, for FACSCalibur assay. Two HIV screening campaigns with the mobile unit were organised in December 2009 and January 2010. The campaign in the suburb of Yaoundé which was 20 km from the reference laboratory included 188 volunteers comprising 93 children less than 5 years old. The campaign in Ambang Bikok (53 km far from Yaoundé) included 69 adult volunteers. In Yaoundé suburb, mean ± standard deviation (SD) CD4 T cell count was 996 ± 874 cells/μl by Auto40, and 989 ± 883 cells/μl by FACSCalibur; in Ambang Bikok, mean ± SD CD4 T cell count was 1041 ± 317 cells/μl by Auto40, and 1032 ± 294 cells/μl by FACSCalibur. Results by Auto40 and FACSCalibur were highly correlated in Yaoundé (r(2) = 0.982) as in Ambang Bikok (r(2) = 0.921). Bland-Altman analysis showed a close agreement between Auto40 and FACSCalibur results expressed in absolute count as in percentage in Yaoundé and Ambang Bikok. When pooling the 257 CD4 T cell count measurements, the Auto40 yielded a mean difference of +7.6 CD4 T cells/μl higher than by reference flow cytometry; and the sensitivity and specificity of Auto40 in enumerating absolute CD4 T cell counts of less than 200 cells/μl were 87% and 99%, respectively, and in enumerating absolute CD4 T cell counts of less than 350 cells/μl were 87% and 98%, respectively. The intrarun and interun precisions of the Auto40 assay assessed in the mobile unit were 5.5% and 7.9%, respectively. The Auto40 flow cytometer installed in a therapeutic mobile unit and operated far from its reference laboratory gave a perfect correlation with the reference method, and could be useful in carrying out immunological monitoring of HIV-infected patients living in areas without access to laboratory facilities.
    Journal of Translational Medicine 02/2012; 10(1):22. DOI:10.1186/1479-5876-10-22 · 3.99 Impact Factor
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