Enumeration of CD4+ T-Cells Using a Portable Microchip Count Platform in Tanzanian HIV-Infected Patients

Background CD4+ T-lymphocyte count (CD4 count) is a standard method used to monitor HIV-infected patients during anti-retroviral therapy (ART). The World Health Organization (WHO) has pointed out or recommended that a handheld, point-of-care, reliable, and affordable CD4 count platform is urgently needed in resource-scarce settings. Methods HIV-infected patient blood samples were tested at the point-of-care using a portable and label-free microchip CD4 count platform that we have developed. A total of 130 HIV-infected patient samples were collected that included 16 de-identified left over blood samples from Brigham and Women's Hospital (BWH), and 114 left over samples from Muhimbili University of Health and Allied Sciences (MUHAS) enrolled in the HIV and AIDS care and treatment centers in the City of Dar es Salaam, Tanzania. The two data groups from BWH and MUHAS were analyzed and compared to the commonly accepted CD4 count reference method (FACSCalibur system). Results The portable, battery operated and microscope-free microchip platform developed in our laboratory (BWH) showed significant correlation in CD4 counts compared with FACSCalibur system both at BWH (r = 0.94, p<0.01) and MUHAS (r = 0.49, p<0.01), which was supported by the Bland-Altman methods comparison analysis. The device rapidly produced CD4 count within 10 minutes using an in-house developed automated cell counting program. Conclusions We obtained CD4 counts of HIV-infected patients using a portable platform which is an inexpensive (<$1 material cost) and disposable microchip that uses whole blood sample (<10 µl) without any pre-processing. The system operates without the need for antibody-based fluorescent labeling and expensive fluorescent illumination and microscope setup. This portable CD4 count platform displays agreement with the FACSCalibur results and has the potential to expand access to HIV and AIDS monitoring using fingerprick volume of whole blood and helping people who suffer from HIV and AIDS in resource-limited settings.

[1]  U. Unicef,et al.  Global HIV/AIDS response: epidemic update and health sector progress towards universal access: progress report 2011. , 2011 .

[2]  Gladys Mutangadura,et al.  The spread and effect of HIV-1 infection in sub-Saharan Africa , 2002, The Lancet.

[3]  Samuel K Sia,et al.  Lab-on-a-chip devices for global health: past studies and future opportunities. , 2007, Lab on a chip.

[4]  Organización Mundial de la Salud,et al.  Towards universal access: scaling up priority HIV/AIDS interventions in the health sector. Progress report 2009 , 2009 .

[5]  Feng Xu,et al.  Miniaturized lensless imaging systems for cell and microorganism visualization in point‐of‐care testing , 2011, Biotechnology journal.

[6]  Kristen L. Helton,et al.  Microfluidic Overview of Global Health Issues Microfluidic Diagnostic Technologies for Global Public Health , 2006 .

[7]  Feng Xu,et al.  Advances in developing HIV-1 viral load assays for resource-limited settings. , 2010, Biotechnology advances.

[8]  Tae-Hyeong Kim,et al.  Fully integrated lab-on-a-disc for simultaneous analysis of biochemistry and immunoassay from whole blood. , 2011, Lab on a chip.

[9]  Kenneth Hawkins,et al.  Microfluidic diagnostics for low-resource settings , 2010, MOEMS-MEMS.

[10]  P. Yager,et al.  Point-of-care diagnostics for global health. , 2008, Annual review of biomedical engineering.

[11]  J. Margolick,et al.  Evaluation of a Low-Cost Method, the Guava EasyCD4 Assay, to Enumerate CD4-Positive Lymphocyte Counts in HIV-Infected Patients in the United States and Uganda , 2006, Journal of acquired immune deficiency syndromes.

[12]  D. Ho,et al.  HIV/AIDS epidemiology, pathogenesis, prevention, and treatment , 2006, The Lancet.

[13]  M. Boily,et al.  Evaluation design for large-scale HIV prevention programmes: the case of Avahan, the India AIDS initiative , 2008, AIDS.

[14]  S. Menon Early initiation of antiretroviral therapy and universal HIV testing in sub-Saharan Africa: Has WHO offered a milestone for HIV prevention? , 2010, Journal of public health policy.

[15]  A. Syvänen,et al.  Dried reagents for multiplex genotyping by tag-array minisequencing to be used in microfluidic devices. , 2010, The Analyst.

[16]  Ali Khademhosseini,et al.  Integrating microfluidics and lensless imaging for point-of-care testing , 2009, 2009 IEEE 35th Annual Northeast Bioengineering Conference.

[17]  John T McDevitt,et al.  A Microchip CD4 Counting Method for HIV Monitoring in Resource-Poor Settings , 2005, PLoS medicine.

[18]  Mehmet Toner,et al.  A Microchip Approach for Practical Label-Free CD4+ T-Cell Counting of HIV-Infected Subjects in Resource-Poor Settings , 2007, Journal of acquired immune deficiency syndromes.

[19]  BH Weigl,et al.  Simplicity of use: a critical feature for widespread adoption of diagnostic technologies in low-resource settings , 2009, Expert review of medical devices.

[20]  K. Pallangyo,et al.  Estimation of CD4 T-lymphocyte counts from percent CD4 T-lymphocyte determinations in HIV-1-infected subjects in sub-Saharan Africa , 2003, International journal of STD & AIDS.

[21]  E. Hubbard,et al.  Initiative , 2020, Encyclopedia of Creativity, Invention, Innovation and Entrepreneurship.

[22]  Summary TOWARDS UNIVERSAL ACCESS : Scaling up Priority HIV / AIDS Interventions in the Health Sector Progress Report , 2008 .

[23]  S. Kalams,et al.  On-chip counting the number and the percentage of CD4+ T lymphocytes. , 2008, Lab on a chip.

[24]  Ali Khademhosseini,et al.  Nano/Microfluidics for diagnosis of infectious diseases in developing countries. , 2010, Advanced drug delivery reviews.