Point-of-care CD4 Research Articles

Point of Care CD4 Testing in National Household Surveys - Results and Quality Indicators from Eleven Population-Based HIV Impact Assessment (PHIA) Surveys.

Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants' clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm3 (interquartile range [IQR], 307 to 654) and 811 cells/mm3 (IQR, 647 to 1,013), respectively. Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm3) than those with undetectable ARVs (385.5 cells/mm3). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm3, and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs (P < 0.0001). We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4 < 200 cells/mm3) persists among approximately 11% of HIV-positive individuals. Therefore, it is important that our findings are shared with the scientific community to assist with similar implementations of point-of-care testing and to conduct a review of HIV programmatic gaps.

Advanced HIV disease: A review of diagnostic and prophylactic strategies.

Despite expanded access to antiretroviral therapy (ART) and the rollout of the World Health Organization's (WHO) 'test-and-treat' strategy, the proportion of people with HIV (PWH) presenting with advanced HIV disease (AHD) remains unchanged at approximately 30%. Fifty percent of persons with AHD report prior engagement to care. ART failure and insufficient retention in HIV care are major causes of AHD. People living with AHD are at high risk for opportunistic infections and death. In 2017, the WHO published guidelines for the management of AHD that included a comprehensive package of care for screening and prophylaxis of major opportunistic infections (OIs). In the interim, ART regimens have evolved: integrase inhibitors are first-line therapy globally, and the diagnostic landscape is evolving. The objective of this review is to highlight novel point-of-care (POC) diagnostics and treatment strategies that can facilitate OI screening and prophylaxis for persons with AHD. We reviewed the WHO guidelines for recommendations for persons with AHD. We summarized the scientific literature on current and emerging diagnostics, along with emerging treatment strategies for persons with AHD. We also highlight the key research and implementation gaps together with potential solutions. While POC CD4 testing is being rolled out in order to identify persons with AHD, this alone is insufficient; implementation of the Visitect CD4 platform has been challenging given operational and test interpretation issues. Numerous non-sputum POC TB diagnostics are being evaluated, many with limited sensitivity. Though imperfect, these tests are designed to provide rapid results (within hours) and are relatively affordable for resource-poor settings. While novel POC diagnostics are being developed for cryptococcal infection, histoplasmosis and talaromycosis, implementation science studies are urgently needed to understand the clinical benefit of these tests in the routine care. Despite progress with HIV treatment and prevention, a persistent 20%-30% of PWH present to care with AHD. Unfortunately, these persons with AHD continue to carry the burden of HIV-related morbidity and mortality. Investment in the development of additional POC or near-bedside CD4 platforms is urgently needed. Implementation of POC diagnostics theoretically could improve HIV retention in care and thereby reduce mortality by overcoming delays in laboratory testing and providing patients and healthcare workers with timely same-day results. However, in real-world scenarios, people with AHD have multiple comorbidities and imperfect follow-up. Pragmatic clinical trials are needed to understand whether these POC diagnostics can facilitate timely diagnosis and treatment, thereby improving clinical outcomes such as HIV retention in care.

A profile of the Visitect® CD4 and Visitect® CD4 Advanced Disease for Management of People Living with HIV

ABSTRACT Introduction CD4 testing plays an important role in clinical management and epidemiological surveillance of HIV disease. Rapid, point-of-care (POC) CD4 tests can improve patients’ access to CD4 testing, enabling decentralisation of HIV services. Areas covered We conducted a profile review of the Visitect®CD4 and the Visitect®CD4 Advanced Disease (Omega Diagnostics, UK) – the two lateral flow, equipment-free POC CD4 tests which can be used to identify people with HIV who have CD4 of less than 350 and 200 cells/μl, respectively. Using published data from independent studies, we discussed the performance and utility of these tests, highlighting the advantages as well as their limitations. Expert opinion The tests are user-friendly, acceptable to healthcare workers, feasible to implement in primary healthcare settings and can provide reliable results for clinical decision-making. Hand-on training with pictorial instructions for use are needed to enhance test’s operator confidence in interpretation of test results. Quality assurance program should be in place to ensure the quality of testing. Development of a next generation test with a cut-off of 100-cells/μl is recommended to identify patients with advanced immunosuppression for initiation of prophylaxis to reduce HIV-related death. Operational research is also needed to identify cost-effective implementation strategies in real-world settings.

Assessment of POC CD4 Detecting Mode in District or County Labs - Jiangsu Province, China, 2021.

This study seeks to explore efficient and multiple-item detection modes in new-style HIV labs, as well as access the accuracy and reliability of CD4 cell count detected by point of care (POC) to analyze POC work feasibility in district or county labs. POC devices adopted in grassroots-level labs and flow cytometers adopted in prefecture-level labs were used to analyze the same group of blood samples. The individual results were collected and compared for parametric tests in correlation and consistency. The Pearson correlation coefficients (r) between results detected by FACSPresto and those by FACSCalibur, FACSVia, FACSCantoII, and EPICSXL were 0.922, 0.938, 0.914, and 0.823, respectively; the average deviations were -25.64, 24.68, 3.05, and 70.97 cells/μL, respectively; the Pearson correlation coefficient (r) between results by Pima and FACSCalibur, FACSVia, FACSCantoII, and EPICSXL were 0.900, 0.950, 0.954, and 0.876, respectively; and the average deviations were -73.99, -40.78, -29.32, and -22.75 cells/μL, respectively. Strong positive correlations and good consistency were observed between the CD4 count tested by POC and flow cytometers. These findings provide theoretical support for new-style HIV labs and one-stop services, which can provide shorter testing duration and simpler testing processes, so that the most comprehensive testing results can be obtained in the shortest amount of time.

Microparticle-tagged image-based cell counting (ImmunoSpin) for CD4\u2009+\u2009T cells

Affordable point-of-care (POC) CD4 + T lymphocyte counting techniques have been developed as alternatives to flow cytometry-based instruments caring for patients with human immunodeficiency virus (HIV)-1. However, POC CD4 enumeration technologies can be inaccurate. Here, we developed a microparticle-based visual detector of CD4 + T lymphocytes (ImmunoSpin) using microparticles conjugated with anti-CD4 antibodies, independent of microfluidic or fluorescence detection systems. Visual enumeration of CD4 + T cells under conventional light microscope was accurate compared to flow cytometry. Microparticle-tagged CD4 + T cells were well-recognized under a light microscope. ImmunoSpin showed very good precision (coefficients of variation of ImmunoSpin were ≤ 10%) and high correlation with clinical-grade flow cytometry for the enumeration of CD4 + T cells (y = 0.4232 + 0.9485 × for the %CD4 + T cell count, R2 = 0.99). At thresholds of 200 and 350 cells/µL, there was no misclassification of the ImmunoSpin system compared to the reference flow cytometry. ImmunoSpin showed clear differential classification of CD4 + T lymphocytes from granulocytes and monocytes. Because non-fluorescence microparticle-tags and cytospin slides are used in ImmunoSpin, they can be applied to an automatic digital image analyzer. Slide preparation allows long-term storage, no analysis time limitations, and image transfer in remote areas.Graphical abstract

Laboratory Reflex and Clinic-Based Point-of-Care Cryptococcal Antigen Screening for Preventing Meningitis and Mortality Among People Living With HIV.

Cryptococcosis remains a leading cause of meningitis and mortality among people living with HIV (PLHIV) worldwide. We sought to evaluate laboratory-based cryptococcal antigen (CrAg) reflex testing and a clinic-based point-of-care (POC) CrAg screening intervention for preventing meningitis and mortality among PLHIV in South Africa. We conducted a prospective pre-post intervention study of adults presenting for HIV testing in Umlazi township, South Africa, over a 6-year period (2013-2019). Participants were enrolled during 3 phases of CrAg testing: CrAg testing ordered by a clinician (clinician-directed testing, 2013-2015); routine laboratory-based CrAg reflex testing for blood samples with CD4 ≤100 cells/mm3 (laboratory reflex testing, 2015-2017); and a clinic-based intervention with POC CD4 testing and POC CrAg testing for PLHIV with CD4 ≤200 cells/mm3 with continued standard-of-care routine laboratory reflex testing among those with CD4 ≤100 cells/mm3 (clinic-based testing, 2017-2019). The laboratory and clinical teams performed serum CrAg by enzyme immunoassay and lateral flow assay (Immy Diagnostics, Norman, OK). We followed up participants for up to 14 months to compare associations between baseline CrAg positivity, antiretroviral therapy and fluconazole treatment initiation, and outcomes of cryptococcal meningitis, hospitalization, and mortality. Three thousand one hundred five (39.4%) of 7877 people screened were HIV-positive, of whom 908 had CD4 ≤200 cells/mm3 and were included in the analyses. Laboratory reflex and clinic-based testing increased CrAg screening (P < 0.001) and diagnosis of CrAg-positive PLHIV (P = 0.011). When compared with clinician-directed testing, clinic-based CrAg testing showed an increase in the number of PLHIV diagnosed with cryptococcal meningitis (4.5% vs. 1.5%; P = 0.059), initiation of fluconazole preemptive therapy (7.2% vs. 2.5%; P = 0.010), and initiation of antiretroviral therapy (96.8% vs. 91.3%; P = 0.012). Comparing clinic-based testing with laboratory reflex testing, there was no significant difference in the cumulative incidence of cryptococcal meningitis (4.5% vs. 4.1%; P = 0.836) or mortality (8.1% vs. 9.9%; P = 0.557). Laboratory reflex and clinic-based CrAg testing facilitated the diagnosis of HIV-associated cryptococcosis and fluconazole initiation but did not reduce cryptococcal meningitis or mortality. In this nonrandomized cohort, clinical outcomes were similar between laboratory reflex testing and clinic-based POC CrAg testing.

Rapid point-of-care CD4 testing at mobile units and linkage to HIV care: an evaluation of community-based mobile HIV testing services in South Africa

BackgroundMobile HIV testing services (HTS) are effective at reaching undiagnosed people living with HIV. However, linkage to HIV care from mobile HTS is often poor, ranging from 10 to 60%. Point-of-care (POC) CD4 testing has shown to increase retention in health facilities, but little evidence exists about their use in mobile HTS. This study assessed the feasibility of POC CD4 test implementation and investigated linkage to HIV care among clients accepting a POC test at community-based mobile HTS.MethodsThis retrospective study used routinely collected data from clients who utilized community-based mobile HTS in the City of Cape Town Metropolitan district, South Africa between December 2014 and September 2016. A POC CD4 test was offered to all clients with an HIV positive diagnosis during this period, and a CD4 cell count was provided to clients accepting a POC CD4 test. Random effects logistic regression was used to assess factors associated with POC CD4 test uptake and self-reported linkage to care among clients accepting a POC test. Models were adjusted for sex, age, previous HIV test done, tuberculosis status and year of HIV diagnosis.ResultsOne thousand three hundred twenty-five of Thirty-nine thousand seven hundred ninety clients utilizing mobile HTS tested HIV positive (3%). 51% (679/1325) accepted a POC test. The age group with the highest proportion accepting a POC test was 50+ years (60%). Females were less likely to accept a POC test than males (odds ratio = 0.7, 95%CI = 0.6–0.8). Median CD4 count was 429 cells/μl (interquartile range = 290–584). Among 679 clients who accepted a POC CD4 test, 491 (72%) linked to HIV care. CD4 cell count was not associated with linkage to care.ConclusionOur findings suggest that mobile HTS can identify early HIV infection, and show that a high proportion of clients with a POC test result linked to care. Future research should assess factors associated with POC test acceptance and assess the impact of POC CD4 testing in comparison to alternative strategies to engage HIV positive people in care.

Sustainability of the streamlined ART (START-ART) implementation intervention strategy among ART-eligible adult patients in HIV clinics in public health centers in Uganda: a mixed methods study

BackgroundDespite increasing access to antiretroviral therapy (ART), the proportion of eligible patients initiated on treatment remains suboptimal. Only 64.6% of the people living with HIV (PLHIV) globally were initiated on ART by June 2019. The streamlined ART (START-ART) implementation study was based on the PRECEDE model, which suggests that “predisposing, enabling, and reinforcing” factors are needed to create behavior change. START-ART increased ART initiation within 2 weeks of eligibility by 42%. However, the gains from some implementation interventions erode over time. We evaluated facilitators and barriers to sustainability of this streamlined ART initiation in the year following the implementation period.MethodsWe designed a mixed-methods explanatory sequential study to examine the sustainability of START-ART implementation. Quantitative component consisted of cross-sectional patient chart reviews of routinely collected data; qualitative component consisted of key informant interviews of health workers in START-ART facilities 2 years after conclusion of the implementation period. We analyzed data from 15 public health centers of Mbarara district, where the START-ART implementation was carried out. We included PLHIV aged > 18 years who initiated ART from June 2013 to July 2016. The START-ART implementation took place from June 2013 to June 2015 while the sustainability period was from August 2015 to July 2016.ResultsA total of 863 ART-eligible patients were sampled. The median CD4 count was 348 cells/ml (IQR 215–450). During the intervention, 338 (77.4%) eligible patients initiated on ART within 2 weeks compared with 375 (88.2%) during the sustainability period (risk difference 10.8%; 95% CI 5.9–15.8%). In 14 of the 15 health centers, the intervention was sustained. During key informant interviews, rapid ART initiation sustainability was attributed to counseling skills that were obtained during intervention and availability of point-of-care (POC) CD4 PIMA machine. Failure to sustain the intervention was attributed to three specific barriers: lack of training after the intervention, transfer of trained staff to other health facilities, and shortage of supplies like cartridges for POC CD4 PIMA machine.ConclusionRapid ART initiation was sustained in most health centers. Skills acquired during the intervention and functional POC CD4 machine facilitated while staff transfers and irregular laboratory supplies were barriers to sustainability of rapid ART initiation.

Assessment of the Impact of Rapid Point-of-Care CD4 Testing in Primary Healthcare Clinic Settings: A Survey Study of Client and Provider Perspectives.

Background: The high burden of disease in South Africa presents challenges to public health services. Point-of-care (POC) technologies have the potential to address these gaps and improve healthcare systems. This study ascertained the acceptability and impact of POC CD4 testing on patients’ health and clinical management. Methods: We conducted a qualitative survey study with patients (n = 642) and healthcare providers (n = 13) at the Lancers Road (experienced POC) and Chesterville (non-experienced POC) primary healthcare (PHC) clinics from September 2015 to June 2016. Results: Patients (99%) at Lancers and Chesterville PHCs were positive about POC CD4 testing, identifying benefits: No loss/delay of test results (6.4%), cost/time saving (19.5%), and no anxiety (5.1%), and 58.2% were ready to initiate treatment. Significantly more patients at Chesterville than Lancers Road PHC felt POC would provide rapid clinical decision making (64.7% vs. 48.1%; p < 0.0001) and better clinic accessibility (40.4% vs. 24.7%; p < 0.0001) respectively. Healthcare providers thought same-day CD4 results would impact: Clinical management (46.2%), patient readiness (46.2%), and adherence (23.0%), and would reduce follow-up visits (7.7%), while 38.5% were concerned that further tests and training (15.4%) were required before antiretroviral therapy (ART) initiation. Conclusion: The high acceptability of POC CD4 testing and the immediate health, structural, and clinical management benefits necessitates POC implementation studies.

Point-of-care CD4+ technology implementation in Free State, South Africa, was associated with improved patient health outcomes.

Point-of-care (POC) CD4+ technologies have the potential to increase patient access to treatment and care through rapid testing and result delivery at or close to where patients seek care. South African (SA) guidelines suggest the use of CD4+ testing to prioritise patients most in need of antiretroviral therapy (ART) and to support identification of patients with advanced HIV disease and opportunistic management of patients on ART. Understanding the patient impact of implementing POC CD4+ testing in the intended setting and operated by lower cadres of healthcare worker or non-professional healthcare facility staff will provide valuable insight into the appropriate use and placement of POC CD4+ technologies throughout SA. To determine the patient impact (turnaround time of tests, loss to follow-up, and proportions of eligible patients proceeding to the next steps in the testing and treatment cascade) of implementing POC CD4+ testing technologies compared with conventional laboratory-based CD4+ testing. This retrospective cohort study included all HIV-positive adults from 30 healthcare facilities in Free State Province, SA. Healthcare facilities were placed into two groups (POC and laboratory referral) using a stratified randomisation technique based on the presence of a POC CD4+ technology and minimal ART volumes. Patients who received a CD4+ test prior to ART initiation between September 2012 and September 2014 were included. Data were collected from patient charts and the POC devices. For new patients, the average time from HIV diagnosis and CD4+ testing was reduced from 7.6 days in the laboratory referral group to 4.5 days in the POC group, a decrease of almost 60%. Additionally, 59.6% of patients in the POC group received their HIV diagnosis and CD4+ test result on the same day, compared with 37.5% in the laboratory referral group (risk ratio (RR) 1.49; 95% confidence interval (CI)1.01 - 2.18). Fewer patients were lost between HIV diagnosis and CD4+ testing (2.7% v. 8.6%) (RR 0.02; 95% CI 0.05 - 0.78) in the POC group. The average test error rate across the study time period was 8.4%; however, the error rate remained &lt;5% for the final 5 months of the study. Introduction of the Alere Pima POC CD4+ technology in the Free State, operated by nurses and lay counsellors, was associated with positive patient outcomes across all parameters analysed. While this study highlighted an effective conventional laboratory network, a full costing and affordability analysis coupled with patient impact and access data from this study will provide further insight into the potential deployment strategies of POC CD4+ technologies in SA.

Point-of-care CD4 technology invalid result rates in public health care settings across five countries.

BackgroundSince 2010, point-of-care (POC) CD4 testing platforms have been introduced in both urban and rural settings to expand access to testing by bringing diagnostic services closer to patients. We conducted an analysis of routinely collected CD4 testing data to determine the invalid result rates associated with POC CD4 testing.MethodsWe analyzed 981,152 CD4 testing records collected from Alere Pima Analyzers between January 2011 and December 2016 across five countries in sub-Saharan Africa. Routinely collected data and programmatic records were used to determine the rate of invalid test results per month, by facility type, and by operator based on cumulative usage during the study period. In addition, frequency of invalid test types and utilization of control beads were assessed.ResultsAcross the five countries, 75,530 invalid messages were returned, resulting in an overall invalid result rate of 7.7%. The invalid result rate by country ranged from 6.6% to 11.2%. Invalid result rates were consistent across facility types. Invalid result rates were inversely correlated with operator usage: low volume operators (<50 tests over study period) experienced an invalid result rate of 10.2%, while high volume operators (>500 tests over study period) experienced an invalid result rate of 5.5%. Two invalid result types (exposure position control and reagent control) accounted for nearly 50% of invalid results. Routine data showed that control beads were run on 88.3% of days that the device was used.ConclusionsOur analysis found that the rate of invalid results was consistent across all types of health facilities, indicating that decentralization of POC CD4 testing to lower level health facilities did not exhibit high invalid result rates or increase cartridge wastage. Additionally, invalid result rates were inversely correlated to operator usage, with high-volume operators experiencing lower invalid result rates than low-volume operators. POC CD4 testing can, therefore, be performed in decentralized national testing programs; however, adequate training, quality assurance, routine monitoring, and ongoing mentorship should also be implemented for success.

Nut and Bolt Microfluidics with Helical Minichannel for Counting CD4+ T-Cells.

In this study, we developed the prototype of an optical imaging-based point-of-care (POC) device for monitoring human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) progression that can detect CD4+ T-lymphocytes in human blood. The proposed portable cell-counting system, Helios CD4 Analyzer (Helios), can acquire sample images and analyze the cells automatically using a simple fluorescence imaging module and sample cartridge with a three-dimensional (3D) helical minichannel. The helical minichannel formed on the cylindrical surface enables the sample cartridge to hold a cell suspension present in a fixed sample volume for absolute counting of the cells. With a given total channel length, the helical minichannel-based sample cartridge is smaller than the conventional sample cartridge with a planar microchannel. The implemented nut and bolt mechanism allows the scanning of a relatively large volume of the sample along the helical minichannel by just rotating the cylindrical chamber coupled with a single DC motor rather than using a two-axis motorized translation stage, which considerably simplifies the associated electromechanical parts. It has distinct advantages over the existing devices because of its small size and simple scanning mechanism. We optimized various imaging parameters to enhance the fluorescence detection efficiency of the prototype. Performance evaluations using human blood samples demonstrated good agreement for low CD4 count between the Helios and the PIMATM, one of the most widely used POC CD4+ analyzers.

External quality assessment of point-of-care CD4 testing in Thailand and Southeast Asia

In recent years, the use of point-of-care (POC) CD4 testing technologies has increased dramatically in Thailand and other Southeast Asian (SEA) countries. However, no data regarding external quality assessment of these POC CD4 testing technologies have been reported. The current study aimed to evaluate the performance of POC CD4 testing technologies, including BD FACSPresto, CyFlow, Guava, Muse, and PIMA, used in the participating laboratories in Thailand, Myanmar, Laos, Indonesia, and Nepal from 2014 to 2017. The results showed a trend toward an increasing number of participating laboratories using POC CD4 testing technologies between trial numbers 73 and 90. In the laboratories participating in the study, CyFlow technologies were the most used POC CD4 testing technologies. In addition, a trend of decreasing coefficients of variation (%CVs) was demonstrated across the trials, and the final trial showed an overall %CV of 14 %. In trial numbers 73 and 77, 57 % and 68 % of measurements showed standard deviation index (SDI) values ranging between − 1 and + 1. In trial numbers 80 and 90, the proportion of measurements with SDI values ranging between − 1 and + 1 had increased to 100 % and 72 %. These results suggest an improvement in POC CD4 testing in Thailand and other SEA countries.

The value of point-of-care CD4+ and laboratory viral load in tailoring antiretroviral therapy monitoring strategies to resource limitations.

To examine the clinical and economic value of point-of-care CD4 (POC-CD4) or viral load monitoring compared with current practices in Mozambique, a country representative of the diverse resource limitations encountered by HIV treatment programs in sub-Saharan Africa. We use the Cost-Effectiveness of Preventing AIDS Complications-International model to examine the clinical impact, cost (2014 US$), and incremental cost-effectiveness ratio [$/year of life saved (YLS)] of ART monitoring strategies in Mozambique. We compare: monitoring for clinical disease progression [clinical ART monitoring strategy (CLIN)] vs. annual POC-CD4 in rural settings without laboratory services and biannual laboratory CD4 (LAB-CD4), biannual POC-CD4, and annual viral load in urban settings with laboratory services. We examine the impact of a range of values in sensitivity analyses, using Mozambique's 2014 per capita gross domestic product ($620) as a benchmark cost-effectiveness threshold. In rural settings, annual POC-CD4 compared to CLIN improves life expectancy by 2.8 years, reduces time on failed ART by 0.6 years, and yields an incremental cost-effectiveness ratio of $480/YLS. In urban settings, biannual POC-CD4 is more expensive and less effective than viral load. Compared to biannual LAB-CD4, viral load improves life expectancy by 0.6 years, reduces time on failed ART by 1.0 year, and is cost-effective ($440/YLS). In rural settings, annual POC-CD4 improves clinical outcomes and is cost-effective compared to CLIN. In urban settings, viral load has the greatest clinical benefit and is cost-effective compared to biannual POC-CD4 or LAB-CD4. Tailoring ART monitoring strategies to specific settings with different available resources can improve clinical outcomes while remaining economically efficient.

Task-shifting point-of-care CD4+ testing to lay health workers in HIV care and treatment services in Namibia.

IntroductionAccess to CD4+ testing remains a common barrier to early initiation of antiretroviral therapy among persons living with HIV/AIDS in low- and middle-income countries. The feasibility of task-shifting of point-of-care (POC) CD4+ testing to lay health workers in Namibia has not been evaluated.MethodsFrom July to August 2011, Pima CD4+ analysers were used to improve access to CD4+ testing at 10 selected public health facilities in Namibia. POC Pima CD4+ testing was performed by nurses or lay health workers. Venous blood samples were collected from 10% of patients and sent to centralised laboratories for CD4+ testing with standard methods. Outcomes for POC Pima CD4+ testing and patient receipt of results were compared between nurses and lay health workers and between the POC method and standard laboratory CD4+ testing methods.ResultsOverall, 1429 patients received a Pima CD4+ test; 500 (35.0%) tests were performed by nurses and 929 (65.0%) were performed by lay health workers. When Pima CD4+ testing was performed by a nurse or a lay health worker, 93.2% and 95.2% of results were valid (p = 0.1); 95.6% and 98.1% of results were received by the patient (p = 0.007); 96.2% and 94.0% of results were received by the patient on the same day (p = 0.08). Overall, 97.2% of Pima CD4+ results were received by patients, compared to 55.4% of standard laboratory CD4+ results (p < 0.001).ConclusionsPOC CD4+ testing was feasible and effective when task-shifted to lay health workers. Rollout of POC CD4+ testing via task-shifting can improve access to CD4+ testing and retention in care between HIV diagnosis and antiretroviral therapy initiation in low- and middle-income countries.

Point-of-care CD4 Cell Counting for Monitoring HIV/AIDS Patients in Resource-confined Regions

We developed a prototype of optical imaging-based pointof-care (POC) devices that can detect CD4+ T-lymphocytes in human blood for HIV/AIDS monitoring. The proposed portable cell-counting system, Helios CD4, can acquire sample images and analyze particles or cells automatically, by using a simple imaging module and a sample cartridge with a three-dimensional (3D) helical mini-channel. This device has advantages over the existing devices because of its small size and simple scanning mechanism. A performance evaluation was conducted by comparing the cell count obtained using Helios with that obtained using PIMA, one of the most widely used POC CD4+ cell counter.

Impact of Point-of-Care CD4 Testing on Retention in Care Among HIV-Positive Pregnant and Breastfeeding Women in the Context of Option B+ in Zimbabwe: A Cluster Randomized Controlled Trial.

Scale-up of Option B+ in Zimbabwe has increased antiretroviral therapy (ART) coverage but patient loss-to-follow-up remains high; thus, effective strategies to improve retention in care are needed. Evidence for Elimination, a cluster randomized controlled trial, evaluated the impact of point-of-care (POC) CD4 testing with CD4 count-specific adherence counseling on rates of retention among 1150 HIV-positive pregnant women initiating ART in Zimbabwe. Thirty-two primary care health facilities were randomized to offer either standard-of-care (SOC) or POC CD4 testing plus CD4-specific counseling to clients (POC Plus). The primary outcome was the proportion of HIV-positive pregnant women retained on ART after 12 months, calculated by cluster-adjusted proportions, unadjusted and adjusted relative risks (RR and aRR, respectively). Retention in care 12 months after initiation was 50.7% and 54.5% in the POC Plus and SOC arms, respectively (RR 0.93, 95% confidence interval [CI]: 0.78 to 1.11; aRR 0.91, 95% CI: 0.77 to 1.07). Although considered not retained, 9.7% transferred to another facility and 0.2% died. Most women, 95.3% in POC Plus and 92.9% in SOC, initiated ART within 1 month of antenatal booking (RR 1.03, 95% CI: 0.97 to 1.08). Although patient retention was similar in both arms, women in the POC Plus arm were more likely to have received a CD4 test at booking and a repeat CD4 test later in care. CD4 is no longer required for treatment initiation but is still recommended in national guidelines and is of value in clinical management. Further work is needed to identify effective strategies to increase patient retention in ART care.

Laboratory-based performance evaluation of PIMA CD4 + T-lymphocyte count point-of-care by lay-counselors in Kenya

BackgroundCD4+ T-lymphocyte count testing at the point-of-care (POC) may improve linkage to care of persons diagnosed with HIV-1 infection, but the accuracy of POC devices when operated by lay-counselors in the era of task-shifting is unknown. We examined the accuracy of Alere's Pima™ POC device on both capillary and venous blood when performed by lay-counselors and laboratory technicians. MethodsIn Phase I, we compared the perfomance of POC against FACSCalibur™ for 280 venous specimens by laboratory technicians. In Phase II we compared POC performance by lay-counselors versus laboratory technicians using 147 paired capillary and venous specimens, and compared these to FACSCalibur™. Statistical analyses included Bland-Altman analyses, concordance correlation coefficient, sensitivity, and specificity at treatment eligibility thresholds of 200, 350, and 500cells/μl. ResultsPhase I: POC sensitivity and specificity were 93.0% and 84.1% at 500cells/μl, respectively. Phase II: Good agreement was observed for venous POC results from both lay-counselors (concordance correlation coefficient (CCC)=0.873, bias −86.4cells/μl) and laboratory technicians (CCC=0.920, bias −65.7cells/μl). Capillary POC had good correlation: lay-counselors (CCC=0.902, bias −71.2cells/μl), laboratory technicians (CCC=0.918, bias −63.0cells/μl). Misclassification at the 500 cells/μl threshold for venous blood was 13.6% and 10.2% for lay-counselors and laboratory technicians and 12.2% for capillary blood in both groups. POC tended to under-classify the CD4 values with increasingly negative bias at higher CD4 values. ConclusionsPima™ results were comparable to FACSCalibur™ for both venous and capillary specimens when operated by lay-counselors. POC CD4 testing has the potential to improve linkage to HIV care without burdening laboratory technicians in resource-limited settings.

Rapid, label-free CD4 testing using a smartphone compatible device.

The most recent guidelines have called for a significant shift towards viral load testing for HIV/AIDS management in developing countries; however point-of-care (POC) CD4 testing still remains an important component of disease staging in multiple developing countries. Advancements in micro/nanotechnologies and consumer electronics have paved the way for mobile healthcare technologies and the development of POC smartphone-based diagnostic assays for disease detection and treatment monitoring. Here, we report a simple, rapid (30 minutes) smartphone-based microfluidic chip for automated CD4 testing using a small volume (30 μL) of whole blood. The smartphone-based device includes an inexpensive (<$5) cell phone accessory and a functionalized disposable microfluidic device. We evaluated the performance of the device using spiked PBS samples and HIV-infected and uninfected whole blood, and compared the microfluidic chip results with the manual analysis and flow cytometry results. Through t-tests, Bland-Altman analyses, and regression tests, we have shown a good agreement between the smartphone-based test and the manual and FACS analysis for CD4 count. The presented technology could have a significant impact on HIV management in developing countries through providing a reliable and inexpensive POC CD4 testing.

Implementation and Operational Research: Cost and Efficiency of a Hybrid Mobile Multidisease Testing Approach With High HIV Testing Coverage in East Africa

In 2013-2014, we achieved 89% adult HIV testing coverage using a hybrid testing approach in 32 communities in Uganda and Kenya (SEARCH: NCT01864603). To inform scalability, we sought to determine: (1) overall cost and efficiency of this approach; and (2) costs associated with point-of-care (POC) CD4 testing, multidisease services, and community mobilization. We applied microcosting methods to estimate costs of population-wide HIV testing in 12 SEARCH trial communities. Main intervention components of the hybrid approach are census, multidisease community health campaigns (CHC), and home-based testing for CHC nonattendees. POC CD4 tests were provided for all HIV-infected participants. Data were extracted from expenditure records, activity registers, staff interviews, and time and motion logs. The mean cost per adult tested for HIV was $20.5 (range: $17.1-$32.1) (2014 US$), including a POC CD4 test at $16 per HIV+ person identified. Cost per adult tested for HIV was $13.8 at CHC vs. $31.7 by home-based testing. The cost per HIV+ adult identified was $231 ($87-$1245), with variability due mainly to HIV prevalence among persons tested (ie, HIV positivity rate). The marginal costs of multidisease testing at CHCs were $1.16/person for hypertension and diabetes, and $0.90 for malaria. Community mobilization constituted 15.3% of total costs. The hybrid testing approach achieved very high HIV testing coverage, with POC CD4, at costs similar to previously reported mobile, home-based, or venue-based HIV testing approaches in sub-Saharan Africa. By leveraging HIV infrastructure, multidisease services were offered at low marginal costs.