Skip to main content
Top
Published in: BMC Infectious Diseases 1/2016

Open Access 01-12-2016 | Research article

Performance of point-of-care CD4 testing technologies in resource-constrained settings: a systematic review and meta-analysis

Authors: Minh D. Pham, M.D., MPH, Paul A. Agius, Lorena Romero, Peter McGlynn, David Anderson, Suzanne M. Crowe, Stanley Luchters

Published in: BMC Infectious Diseases | Issue 1/2016

Login to get access

Abstract

Background

Point-of-care (POC) CD4 testing increases patient accessibility to assessment of antiretroviral therapy eligibility. This review evaluates field performance in low and middle-income countries (LMICs) of currently available POC CD4 technologies.

Methods

Eight electronic databases were searched for field studies published between January 2005 and January 2015 of six POC CD4 platforms: PointCare NOW™, Alere Pima™ CD4, Daktari™ CD4 Counter, CyFlow® CD4 miniPOC, BD FACSPresto™, and MyT4™ CD4. Due to limited data availability, meta-analysis was conducted only for diagnostic performance of Pima at a threshold of 350 cells/μl, applying a bivariate multi-level random-effects modelling approach. A covariate extended model was also explored to test for difference in diagnostic performance between capillary and venous blood.

Results

Twenty seven studies were included. Published field study results were found for three of the six POC CD4 tests, 24 of which used Pima. For Pima, test failure rates varied from 2 to 23 % across study settings. Pooled sensitivity and specificity were 0.92 (95 % CI = 0.88–0.95) and 0.87 (95 % CI = 0.85–0.88) respectively. Diagnostic performance by blood sample type (venous vs. capillary) revealed non-significant differences in sensitivity (0.94 vs 0.89) and specificity (0.86 vs 0.87), respectively in the extended model (Wald χ2(2) = 4.77, p = 0.09).

Conclusions

POC CD4 testing can provides reliable results for making treatment decision under field conditions in low-resource settings. The Pima test shows a good diagnostic performance at CD4 cut-off of 350 cells/μl. More data are required to evaluate performance of POC CD4 testing using venous versus capillary blood in LMICs which might otherwise influence clinical practice.
Appendix
Available only for authorised users
Literature
2.
go back to reference TEMPRANO. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373:808–22.CrossRef TEMPRANO. A trial of early antiretrovirals and isoniazid preventive therapy in Africa. N Engl J Med. 2015;373:808–22.CrossRef
3.
go back to reference INSIGHTSTART. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373:795–807.CrossRef INSIGHTSTART. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med. 2015;373:795–807.CrossRef
4.
go back to reference WHO. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. Geneva: World Health Organization; 2015. p. 78. WHO. Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV. Geneva: World Health Organization; 2015. p. 78.
5.
go back to reference WHO. Consoldated guidlines on the use of antiretroviral drugs for treating and preventing HIV infection Recommendations for a public health approach. Geneva: World Health Organization; 2013. p. 272. WHO. Consoldated guidlines on the use of antiretroviral drugs for treating and preventing HIV infection Recommendations for a public health approach. Geneva: World Health Organization; 2013. p. 272.
6.
go back to reference Ford N, et al. The future role of CD4 cell count for monitoring antiretroviral therapy. Lancet Infect Dis. 2015;15(2):241–7.CrossRefPubMed Ford N, et al. The future role of CD4 cell count for monitoring antiretroviral therapy. Lancet Infect Dis. 2015;15(2):241–7.CrossRefPubMed
7.
go back to reference Kranzer K, et al. Quantifying and addressing losses along the continuum of care for people living with HIV infection in sub-Saharan Africa: a systematic review. J Int AIDS Soc. 2012;15(2):17383.CrossRefPubMedPubMedCentral Kranzer K, et al. Quantifying and addressing losses along the continuum of care for people living with HIV infection in sub-Saharan Africa: a systematic review. J Int AIDS Soc. 2012;15(2):17383.CrossRefPubMedPubMedCentral
8.
go back to reference Govindasamy D, Ford N, Kranzer K. Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: a systematic review. AIDS. 2012;26(16):2059–67.CrossRefPubMed Govindasamy D, Ford N, Kranzer K. Risk factors, barriers and facilitators for linkage to antiretroviral therapy care: a systematic review. AIDS. 2012;26(16):2059–67.CrossRefPubMed
10.
go back to reference Patten GE, et al. Impact on ART initiation of point-of-care CD4 testing at HIV diagnosis among HIV-positive youth in Khayelitsha, South Africa. J Int AIDS Soc. 2013;16:18518.CrossRefPubMedPubMedCentral Patten GE, et al. Impact on ART initiation of point-of-care CD4 testing at HIV diagnosis among HIV-positive youth in Khayelitsha, South Africa. J Int AIDS Soc. 2013;16:18518.CrossRefPubMedPubMedCentral
11.
go back to reference Mtapuri-Zinyowera S, et al. PIMA Point of Care CD4+ Cell Count Machines in Remote MNCH Settings: Lessons Learned from Seven Districts in Zimbabwe. Infect Dis (Auckl). 2013;6:51–60. Mtapuri-Zinyowera S, et al. PIMA Point of Care CD4+ Cell Count Machines in Remote MNCH Settings: Lessons Learned from Seven Districts in Zimbabwe. Infect Dis (Auckl). 2013;6:51–60.
12.
go back to reference Feyissa G, Demissie T. Effect of point of care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in sub-Saharan African countries: a systematic review. JBI Database System Rev Implement Rep. 2014;12(4):395–429.CrossRef Feyissa G, Demissie T. Effect of point of care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in sub-Saharan African countries: a systematic review. JBI Database System Rev Implement Rep. 2014;12(4):395–429.CrossRef
13.
go back to reference Faal M, et al. Providing immediate CD4 count results at HIV testing improves ART initiation. J Acquir Immune Defic Syndr. 2011;58(3):e54–9.CrossRefPubMed Faal M, et al. Providing immediate CD4 count results at HIV testing improves ART initiation. J Acquir Immune Defic Syndr. 2011;58(3):e54–9.CrossRefPubMed
14.
go back to reference Jani IV, et al. Effect of point-of-care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study. Lancet. 2011;378(9802):1572–9.CrossRefPubMed Jani IV, et al. Effect of point-of-care CD4 cell count tests on retention of patients and rates of antiretroviral therapy initiation in primary health clinics: an observational cohort study. Lancet. 2011;378(9802):1572–9.CrossRefPubMed
15.
go back to reference van Rooyen H, et al. High HIV testing uptake and linkage to care in a novel program of home-based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa. J Acquir Immune Defic Syndr. 2013;64(1):e1–8.CrossRefPubMedPubMedCentral van Rooyen H, et al. High HIV testing uptake and linkage to care in a novel program of home-based HIV counseling and testing with facilitated referral in KwaZulu-Natal, South Africa. J Acquir Immune Defic Syndr. 2013;64(1):e1–8.CrossRefPubMedPubMedCentral
16.
go back to reference Zachariah R, et al. Viewpoint: Why do we need a point-of-care CD4 test for low-income countries? Trop Med Int Health. 2011;16(1):37–41.CrossRefPubMed Zachariah R, et al. Viewpoint: Why do we need a point-of-care CD4 test for low-income countries? Trop Med Int Health. 2011;16(1):37–41.CrossRefPubMed
17.
go back to reference Hyle E, et al. The Clinical and Economic Impact of Point-of-Care CD4 Testing in Mozambique and Other Resource-Limited Settings: A Cost-Effectiveness Analysis. PLoS Med. 2014;11(9), e1001725.CrossRefPubMedPubMedCentral Hyle E, et al. The Clinical and Economic Impact of Point-of-Care CD4 Testing in Mozambique and Other Resource-Limited Settings: A Cost-Effectiveness Analysis. PLoS Med. 2014;11(9), e1001725.CrossRefPubMedPubMedCentral
20.
go back to reference Peeling RW, et al. CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy. PLoS One. 2015;10(3):e0115019.CrossRefPubMedPubMedCentral Peeling RW, et al. CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy. PLoS One. 2015;10(3):e0115019.CrossRefPubMedPubMedCentral
21.
go back to reference Fajardo E, et al. Errors generated by a point-of-care CD4+ T-lymphocyte analyser: a retrospective observational study in nine countries. Bull World Health Organ. 2015;93:623–30.CrossRefPubMedPubMedCentral Fajardo E, et al. Errors generated by a point-of-care CD4+ T-lymphocyte analyser: a retrospective observational study in nine countries. Bull World Health Organ. 2015;93:623–30.CrossRefPubMedPubMedCentral
22.
go back to reference Glencross DK, et al. Performance evaluation of the Pima™ point-of-care CD4 analyser using capillary blood sampling in field tests in South Africa. J Int AIDS Soc. 2012;15(1):3.CrossRefPubMedPubMedCentral Glencross DK, et al. Performance evaluation of the Pima™ point-of-care CD4 analyser using capillary blood sampling in field tests in South Africa. J Int AIDS Soc. 2012;15(1):3.CrossRefPubMedPubMedCentral
24.
go back to reference Counsell C. Formulating questions and locating primary studies for inclusion in systematic reviews. Ann Intern Med. 1997;127(5):380–7.CrossRefPubMed Counsell C. Formulating questions and locating primary studies for inclusion in systematic reviews. Ann Intern Med. 1997;127(5):380–7.CrossRefPubMed
25.
go back to reference Jackson N, et al. Criteria for the systematic review of health promotion and public health interventions. Health Promot Int. 2005;20(4):367–74.CrossRefPubMed Jackson N, et al. Criteria for the systematic review of health promotion and public health interventions. Health Promot Int. 2005;20(4):367–74.CrossRefPubMed
26.
go back to reference Whiting P, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25.CrossRefPubMedPubMedCentral Whiting P, et al. The development of QUADAS: a tool for the quality assessment of studies of diagnostic accuracy included in systematic reviews. BMC Med Res Methodol. 2003;3:25.CrossRefPubMedPubMedCentral
27.
go back to reference Reitsma JB, et al. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005;58(10):982–90.CrossRefPubMed Reitsma JB, et al. Bivariate analysis of sensitivity and specificity produces informative summary measures in diagnostic reviews. J Clin Epidemiol. 2005;58(10):982–90.CrossRefPubMed
28.
go back to reference Huber PJ. The behavior of maximum likelihood estimates under nonstandard conditions. In: Fifth Berkeley Symposium on Mathematical Statistics and Probability. Berkeley: University of California Press; 1967. p. 221–33. Huber PJ. The behavior of maximum likelihood estimates under nonstandard conditions. In: Fifth Berkeley Symposium on Mathematical Statistics and Probability. Berkeley: University of California Press; 1967. p. 221–33.
29.
go back to reference Dwamena BA. Midas: Stata module for Meta-analytical Integration of Diagnostic Accuracy Studies. 2007. Dwamena BA. Midas: Stata module for Meta-analytical Integration of Diagnostic Accuracy Studies. 2007.
30.
go back to reference Rabe-Hesketh S, Pickles A, Taylor C. Generalized linear latent and mixed models. Stata Technical Bulletin 53. Stata Technical Bulletin Reprints. 2000;9:293–307. Rabe-Hesketh S, Pickles A, Taylor C. Generalized linear latent and mixed models. Stata Technical Bulletin 53. Stata Technical Bulletin Reprints. 2000;9:293–307.
31.
go back to reference Harbord RM, Whiting P. metandi: Meta-analysis of diagnostic accuracy using hierarchical logistic regression. Stata Journal. 2009;9(2):211–29. Harbord RM, Whiting P. metandi: Meta-analysis of diagnostic accuracy using hierarchical logistic regression. Stata Journal. 2009;9(2):211–29.
32.
go back to reference Rutter CM, Gatsonis CA. A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med. 2001;20(19):2865–84.CrossRefPubMed Rutter CM, Gatsonis CA. A hierarchical regression approach to meta-analysis of diagnostic test accuracy evaluations. Stat Med. 2001;20(19):2865–84.CrossRefPubMed
33.
go back to reference Arnett N, Chang K, Schmitz M, Lemwayi R, Rwehumbiza P, Mwasekaga M. Healthcare workers’ acceptance and performance of point-of-care CD4 testing in Dar es Salaam, Tanzania, 2011. In: 7th IAS Conference on HIV Pathogenesis and Treatment; Kuala Lumpur; 30 June-3 July 2013, 2013 (Abstract TUPDD0103 - Poster Discussion Session). 2013. Arnett N, Chang K, Schmitz M, Lemwayi R, Rwehumbiza P, Mwasekaga M. Healthcare workers’ acceptance and performance of point-of-care CD4 testing in Dar es Salaam, Tanzania, 2011. In: 7th IAS Conference on HIV Pathogenesis and Treatment; Kuala Lumpur; 30 June-3 July 2013, 2013 (Abstract TUPDD0103 - Poster Discussion Session). 2013.
34.
go back to reference Rioja M, MbohKhan E, Nzuobontane D, Munyaburanga F, PiusMuffih T, Asong T. Improving access to care and treatment by strengthening CD4 count testing capacity in rural health districts in Cameroon through point-of-care technology. In: 7th IAS Conference on HIV Pathogenesis and Treatment; Kuala Lumpur; 30 June-3 July 2013., 2013 (Abstract WEPE609). 2013. Rioja M, MbohKhan E, Nzuobontane D, Munyaburanga F, PiusMuffih T, Asong T. Improving access to care and treatment by strengthening CD4 count testing capacity in rural health districts in Cameroon through point-of-care technology. In: 7th IAS Conference on HIV Pathogenesis and Treatment; Kuala Lumpur; 30 June-3 July 2013., 2013 (Abstract WEPE609). 2013.
35.
go back to reference Zeh C, et al. Evaluation of Pima CD4 Point-Of-Care Device in Western Kenya for Potential Use in Field Settings. In: Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts; March 3–6 2014., (Abstract 624). 2014. Zeh C, et al. Evaluation of Pima CD4 Point-Of-Care Device in Western Kenya for Potential Use in Field Settings. In: Conference on Retroviruses and Opportunistic Infections; Boston, Massachusetts; March 3–6 2014., (Abstract 624). 2014.
36.
37.
go back to reference Rathunde L, et al. Evaluation of the Alere Pima™ for CD4+ T lymphocytes counts in HIV-positive outpatients in Southern Brazil. Int J STD AIDS. 2014;25:956–9.CrossRefPubMed Rathunde L, et al. Evaluation of the Alere Pima™ for CD4+ T lymphocytes counts in HIV-positive outpatients in Southern Brazil. Int J STD AIDS. 2014;25:956–9.CrossRefPubMed
39.
go back to reference Jani IV, et al. Accurate CD4 T-cell enumeration and antiretroviral drug toxicity monitoring in primary healthcare clinics using point-of-care testing. AIDS. 2011;25(6):807–12.CrossRefPubMed Jani IV, et al. Accurate CD4 T-cell enumeration and antiretroviral drug toxicity monitoring in primary healthcare clinics using point-of-care testing. AIDS. 2011;25(6):807–12.CrossRefPubMed
40.
go back to reference Wade D, et al. WHO multicenter evaluation of FACSCount CD4 and Pima CD4 T-cell count systems: instrument performance and misclassification of HIV-infected patients. J Acquir Immune Defic Syndr. 2014;66(5):e98–107.CrossRefPubMedPubMedCentral Wade D, et al. WHO multicenter evaluation of FACSCount CD4 and Pima CD4 T-cell count systems: instrument performance and misclassification of HIV-infected patients. J Acquir Immune Defic Syndr. 2014;66(5):e98–107.CrossRefPubMedPubMedCentral
41.
go back to reference Gumbo P, et al. Analysis of Bias and ART Enrollment for a Point-of-Care CD4/CD4% Analyzer. J AIDS Clin Res. 2013;4:247. Gumbo P, et al. Analysis of Bias and ART Enrollment for a Point-of-Care CD4/CD4% Analyzer. J AIDS Clin Res. 2013;4:247.
42.
go back to reference Wade D, et al. CD4 T-cell enumeration in a field setting: evaluation of CyFlow counter using the CD4 easy count kit-dry and Pima CD4 systems. PLoS One. 2013;8(9):e75484.CrossRefPubMedPubMedCentral Wade D, et al. CD4 T-cell enumeration in a field setting: evaluation of CyFlow counter using the CD4 easy count kit-dry and Pima CD4 systems. PLoS One. 2013;8(9):e75484.CrossRefPubMedPubMedCentral
43.
go back to reference Picken S, et al. The routine paediatric human immunodeficiency virus visit as an intervention opportunity for failed maternal care, and use of point-of-care CD4 testing as an adjunct in determining antiretroviral therapy eligibility. Southern African Journal of Epidemiology and Infection. 2014;29(2):70–4. Picken S, et al. The routine paediatric human immunodeficiency virus visit as an intervention opportunity for failed maternal care, and use of point-of-care CD4 testing as an adjunct in determining antiretroviral therapy eligibility. Southern African Journal of Epidemiology and Infection. 2014;29(2):70–4.
44.
go back to reference Diaw PA, et al. Multisite evaluation of a point-of-care instrument for CD4(+) T-cell enumeration using venous and finger-prick blood: the PIMA CD4. J Acquir Immune Defic Syndr. 2011;58(4):e103–11.CrossRefPubMed Diaw PA, et al. Multisite evaluation of a point-of-care instrument for CD4(+) T-cell enumeration using venous and finger-prick blood: the PIMA CD4. J Acquir Immune Defic Syndr. 2011;58(4):e103–11.CrossRefPubMed
45.
go back to reference Myer L, et al. Comparison of point-of-care versus laboratory-based CD4 cell enumeration in HIV-positive pregnant women. J Int AIDS Soc. 2013;16(1):18649.CrossRefPubMedPubMedCentral Myer L, et al. Comparison of point-of-care versus laboratory-based CD4 cell enumeration in HIV-positive pregnant women. J Int AIDS Soc. 2013;16(1):18649.CrossRefPubMedPubMedCentral
46.
go back to reference Manabe YC, et al. Evaluation of portable point-of-care CD4 counter with high sensitivity for detecting patients eligible for antiretroviral therapy. PLoS One. 2012;7(4):e34319.CrossRefPubMedPubMedCentral Manabe YC, et al. Evaluation of portable point-of-care CD4 counter with high sensitivity for detecting patients eligible for antiretroviral therapy. PLoS One. 2012;7(4):e34319.CrossRefPubMedPubMedCentral
47.
go back to reference Bergeron M, et al. Performance of the PointCare NOW system for CD4 counting in HIV patients based on five independent evaluations. PLoS One. 2012;7(8):e41166.CrossRefPubMedPubMedCentral Bergeron M, et al. Performance of the PointCare NOW system for CD4 counting in HIV patients based on five independent evaluations. PLoS One. 2012;7(8):e41166.CrossRefPubMedPubMedCentral
48.
50.
go back to reference Mtapuri-Zinyowera S, et al. Evaluation of the PIMA point-of-care CD4 analyzer in VCT clinics in Zimbabwe. J Acquir Immune Defic Syndr. 2010;55(1):1–7.CrossRefPubMed Mtapuri-Zinyowera S, et al. Evaluation of the PIMA point-of-care CD4 analyzer in VCT clinics in Zimbabwe. J Acquir Immune Defic Syndr. 2010;55(1):1–7.CrossRefPubMed
51.
go back to reference Mnyani CN, McIntyre JA, Myer L. The reliability of point-of-care CD4 testing in identifying HIV-infected pregnant women eligible for antiretroviral therapy. J Acquir Immune Defic Syndr. 2012;60(3):260–4.CrossRefPubMed Mnyani CN, McIntyre JA, Myer L. The reliability of point-of-care CD4 testing in identifying HIV-infected pregnant women eligible for antiretroviral therapy. J Acquir Immune Defic Syndr. 2012;60(3):260–4.CrossRefPubMed
52.
go back to reference Gous N, et al. Feasibility of performing multiple point of care testing for HIV anti-retroviral treatment initiation and monitoring from multiple or single fingersticks. PLoS One. 2013;8(12):e85265.CrossRefPubMedPubMedCentral Gous N, et al. Feasibility of performing multiple point of care testing for HIV anti-retroviral treatment initiation and monitoring from multiple or single fingersticks. PLoS One. 2013;8(12):e85265.CrossRefPubMedPubMedCentral
54.
go back to reference Bossuyt PM, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD Initiative. Ann Intern Med. 2003;138(1):40–4.CrossRefPubMed Bossuyt PM, et al. Towards complete and accurate reporting of studies of diagnostic accuracy: The STARD Initiative. Ann Intern Med. 2003;138(1):40–4.CrossRefPubMed
Metadata
Title
Performance of point-of-care CD4 testing technologies in resource-constrained settings: a systematic review and meta-analysis
Authors
Minh D. Pham, M.D., MPH
Paul A. Agius
Lorena Romero
Peter McGlynn
David Anderson
Suzanne M. Crowe
Stanley Luchters
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Infectious Diseases / Issue 1/2016
Electronic ISSN: 1471-2334
DOI
https://doi.org/10.1186/s12879-016-1931-2

Other articles of this Issue 1/2016

BMC Infectious Diseases 1/2016 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.