Point-of-care Early Infant Diagnosis Research Articles

Strategic site selection for placement of HIV early infant diagnosis point-of-care technology within a national diagnostic network in Lesotho.

BackgroundNew technologies for rapid point-of-care (POC) diagnostic tests hold great potential for improving the health outcomes of HIV-exposed infants. POC testing for HIV early infant diagnosis (EID) was introduced in Lesotho in late 2016. Here we highlight critical requirements for selecting routine POC EID sites to ensure a sustainable and optimised EID diagnostic network.InterventionLesotho introduced POC EID in a phased approach that included assessments of national databases to identify sites with high test volumes, the creation of local networks of sites to potentially increase access to POC EID, and a standardised capacity assessment to determine site readiness. Potential site networks comprising ‘hub’ testing sites and ‘spoke’ specimen referring sites were created.Lessons learntAfter determining optimal placement, a total of 29 testing facilities were selected for placement of POC EID to potentially increase access to 189 facilities through the use of a hub-and-spoke model. Site capacity assessments identified vital human resources and infrastructure capacity gaps that needed to be addressed before introducing POC EID and informed appropriate POC platform selection.RecommendationsPOC placement involves more than just purchasing the testing platforms. Considering the relatively small proportion of sites that can be eligible for placement of a POC platform, utilising a hub-and-spoke model can maximise the number of health facilities served by a POC platform while reducing the necessary capacity building and infrastructure investments to fewer sites.

Inpatient Point-of-Care HIV Early Infant Diagnosis in Mozambique to Improve Case Identification and Linkage to Antiretroviral Therapy

Novel approaches to case identification and linkage to antiretroviral therapy (ART) are needed to close gaps in early infant diagnosis (EID) of HIV. Point-of-care (POC) EID is a recent innovation that eliminates the long turnaround times of conventional EID that limit patient management in the inpatient setting. The initial deployment of POC EID in Mozambique focused primarily on outpatient clinics; however, 2 high-volume tier-4 pediatric referral hospitals were also included. To assess the impact of inpatient POC EID, a retrospective review of testing and care data from Hospital Central de Beira (HCB) and Hospital Central de Maputo (HCM) was performed for the period September 2017 to July 2018, with comparison to the 8-month pre-POC period when dried blood spots were used for conventional EID. Monthly testing volume increased from 8.5 tests pre-POC to 17.6 tests with POC (P<.001). Among 511 children with POC testing, the median age was 5 months, there was ongoing breastfeeding in 326 (63.8%), and 136 (26.6%) of mothers and 146 (28.6%) of infants had not received ART or antiretroviral prophylaxis, respectively. POC tests were positive in 152 (29.7%) infants, and 52 (37.5%) had a previous negative DNA polymerase chain reaction through the conventional outpatient EID program. Linkage to ART for infants with HIV-positive tests improved 64% during the POC period (P=.002). Inpatient mortality for infected infants during the POC period was 28.2%. Excluding these deaths, 61.2% of eligible infants initiated ART as inpatients, but only 29.8% of those discharged without ART were confirmed to have initiated as outpatients. Inpatient wards are a high-yield site for EID and ART initiation that have historically been overlooked in programming for prevention of mother-to-child transmission. POC platforms represent a transformative opportunity to increase inpatient testing, make definitive diagnoses, and improve timely linkage to ART. Scale-up plans should prioritize pediatric wards.

Point-of-care testing can achieve same-day diagnosis for infants and rapid ART initiation: results from government programmes across six African countries.

IntroductionPoint‐of‐care (POC) early infant diagnosis (EID) testing has been shown to dramatically decrease turnaround times from sample collection to caregiver result receipt and time to ART initiation for HIV‐positive infants compared to centralized laboratory testing. As governments in sub‐Saharan Africa implement POC EID technologies, we report on the feasibility and effectiveness of POC EID testing and the impact of same‐day result delivery on rapid ART initiation within national programmes across six countries.MethodsThis pre‐/post‐evaluation compared centralized laboratory‐based (pre) with POC (post) EID testing in 52 facilities across Cameroon, Democratic Republic of Congo, Ethiopia, Kenya, Senegal and Zimbabwe between April 2017 and October 2019 (country‐dependent). Data were collected retrospectively from routine records at health facilities for all infants tested under two years of age. Hazard ratios and 95% confidence intervals were calculated to compare time‐to‐event outcomes, visualized with Kaplan–Meier curves, and the Somers’ D test was used to compare continuous outcomes.ResultsData were collected for 2892 EID tests conducted on centralized laboratory‐based platforms and 4610 EID tests on POC devices with 127 (4%) and 192 (4%) HIV‐positive infants identified, respectively. POC EID significantly reduced the time from sample collection to caregiver result receipt (POC median: 0 days, IQR: 0 to 0 vs. centralized: 35 days, IQR: 26 to 56) and time from sample collection to ART initiation for HIV‐positive infants (POC median: 1 day, IQR: 0 to 7 vs. centralized: 39 days, IQR: 26 to 57). With POC testing, 72% of infants received results on the same day as sample collection; HIV‐positive infants with a same‐day diagnosis had six times the rate of ART initiation compared to those diagnosed one or more days after sample collection (HR: 6.39; 95% CI: 3.44 to 11.85).ConclusionsSame‐day diagnosis and treatment initiation for infants is possible with POC EID within routine government‐led and ‐supported public sector healthcare facilities in resource‐limited settings. Given that POC EID allows for rapid ART initiation, aligning to the World Health Organization’s recommendation of ART initiation within seven days, its use in public sector programmes has the potential to reduce overall mortality for infants with HIV through early treatment initiation.

Caregiver experience and perceived acceptability of a novel near point-of-care early infant HIV diagnostic test among caregivers enrolled in the PMTCT program, Myanmar: A qualitative study.

The majority of HIV infection among children occurs through mother-to-child transmission. HIV exposed infants are recommended to have virological testing at birth or 4-6 weeks of age but challenges with centralized laboratory-based testing in Myanmar result in low testing rates and delays in result communication and treatment initiation. Decentralized point-of-care (POC) testing when integrated in prevention of mother-to-child transmission of HIV (PMTCT) services, can be an alternative to increase coverage of early infant diagnosis (EID) and timely engagement in HIV treatment and care. This paper aims to explore experiences of caregivers of HIV-exposed infants enrolled in the PMTCT program in Myanmar and the perceived acceptability of point-of-care EID testing compared to conventional centralised laboratory-based testing. This is a sub-study of the cluster randomised controlled stepped-wedge trial (Trial registration number: ACTRN12616000734460) that assessed the impact of near POC EID testing using Xpert HIV-1 Qual assay in four public hospitals in Myanmar. Caregivers of infants who were enrolled in the intervention phase of the main study, had been tested with both Xpert and standard of care tests and had received the results were eligible for this qualitative study. Semi-structured interviews were conducted with 23 caregivers. Interviews were audio recorded, transcribed verbatim and translated into English. Thematic data analysis was undertaken using NVivo 12 Software (QSR International). The majority of caregivers were satisfied with the quality of care provided by PMTCT services. However, they encountered social and financial access barriers to attend the PMTCT clinic regularly. Mothers had concerns about community stigma from the disclosure of their HIV status and the potential consequences for their infants. While medical care at the PMTCT clinics was free, caregivers sometimes experienced financial difficulties associated with out-of-pocket expenses for childbirth and transportation. Some caregivers had to choose not to attend work (impacting their income) or the adult antiretroviral clinic in order to attend the paediatric PMTCT clinic appointment. The acceptability of the Xpert testing process was high among the caregiver participants and more than half received the Xpert result on the same day as testing. Short turnaround time of the near POC EID testing enabled the caregivers to find out their infants' HIV status quicker, thereby shortening the stressful waiting time for results. Our study identified important access challenges facing caregivers of HIV exposed infants and high acceptability of near POC EID testing. Improving the retention rate in the PMTCT and EID programs necessitates careful attention of program managers and policy makers to these challenges, and POC EID represents a potential solution.

Acceptability of Routine Point-of-Care Early Infant Diagnosis in Eight African Countries: Findings From a Qualitative Assessment of Clinical and Laboratory Personnel.

The Elizabeth Glaser Pediatric AIDS Foundation introduced point-of-care (POC) testing for early infant diagnosis (EID) of HIV in 8 African countries. Understanding experiences and opinions of users can help facilitate introduction and sustainability. Cameroon, Côte d'Ivoire, Eswatini, Kenya, Lesotho, Mozambique, Rwanda, and Zimbabwe. Structured interviews with health care workers (HCWs) providing EID services and semistructured interviews with national and regional laboratory managers or EID program managers were conducted before and after the implementation of POC EID. Survey responses were analyzed and compared; open-ended responses were analyzed by theme. In total, 234 and 175 interviews with HCWs and 28 and 14 interviews with laboratory or program managers were conducted before and after the introduction of POC EID, respectively. In preintervention interviews, challenges identified with laboratory-based EID testing included distance from patients' residence to the health facility, time-consuming sample transportation to central laboratories, stockout of testing kits, and long wait times for results. Postintervention data revealed that HCWs found POC EID easy to use and were very satisfied with the fast turnaround time and ability to initiate treatment for HIV-infected infants sooner. Laboratory managers were also supportive of scaling-up POC testing although cautious of the need for reliable infrastructure to operate platforms. The recommendation was that POC EID be integrated within the national diagnostic testing network. Support for POC EID from key stakeholders is essential for sustainability. Overall, participants supported the rollout of POC testing for EID, noting challenges and opportunities for scaling-up POC EID and recommending integration into the overall EID system.

Point-of-care HIV maternal viral load and early infant diagnosis testing around time of delivery at tertiary obstetric units in South Africa: a prospective study of coverage, results return and turn-around times.

IntroductionMaternal viral load monitoring (mVL) and early infant diagnosis (EID) are necessary to achieve elimination of mother‐to‐child transmission of HIV. Point‐of‐care testing can achieve better outcomes compared to centralized laboratory testing (CLT). We describe the first implementation of point‐of‐care (POC) mVL and EID testing around delivery at four high volume tertiary obstetric units (TOUs) in Gauteng, South Africa.MethodsProspective study of pregnant women living with HIV (WLHIV) and their infants. During the period 1 June 2018 to 31 March 2019, routine staff collected blood specimens from women and their infants around delivery. Specimen collection occurred throughout the week while dedicated POC operators, conducted testing during working hours on weekdays. Descriptive statistics and multivariable Poisson regression with robust error variance were used to describe outcomes and associated factors. Outcomes determined were (i) coverage of mVL and EID testing defined as a proportion of live births to WLHIV admitted at each facility (ii) results returned prior to discharge (iii) turn‐around time (TAT) and iv) performance of POC testing compared to CLT.ResultsIn total, 8147 live births to pregnant WLHIV were recorded in the implementation period. Of these, 2912 mVL and 5074 EID specimens were included in the analysis, with 131 (4.5%) mVL and 715 (14.1%) EID specimens having initial invalid/error results. Overall coverage of POC mVL and EID testing was 35.6% (range 20.9% to 60.1%) and 61.9% (range 47.0% to 88.0%) respectively. Proportions of POC tested mothers and infants with results returned prior to discharge were 74.3% (range 39.0% to 95.7%) and 73.0% (range 50.0 to 97.9%). Return of results was independently associated with TOU, after‐hours specimen collection, having an initial invalid or error result and period of implementation. Overall TAT for specimens collected from mother‐infant pairs where both had POC testing, during weekdays was longer for EID compared to mVL testing (median 3.3 hours vs. 2.9 hours, p‐value sign test <0.001). POC results were comparable to those from laboratory testing.ConclusionAccurate and timely POC mVL and EID testing around delivery was implemented with variable success across TOUs. Further scale up would need to address health system factors at facility level and high analytical error rates.

A Randomised Trial of Point-of-Care Early Infant HIV Diagnosis

Background: Early infant diagnosis (EID) of HIV is critical to the care of the 1.3 million infants who are perinatally exposed to the virus each year. Point-of-care (POC) EID provides same-day results and the potential for improved survival through immediate initiation of antiretroviral therapy (ART). Methods: We conducted a pragmatic randomised trial at 6 primary health centres in Lusaka, Zambia. HIV-exposed infants were equally allocated to either: (a) POC EID – on-site testing with the Alere q HIV-1/2 Detect instrument or (b) enhanced standard of care (SOC) EID – off-site testing at a public-sector laboratory. We provided a safety net if off-site EID results did not return within 4 weeks. Infants found to be HIV infected were immediately referred for care in the public sector and followed by the study for 12 months. Our primary outcome was programmatic success, defined as being alive, in care, and virally suppressed (<200 copies/mL) at 12 months. We also compared the time to receipt of result by the facility and by the participant’s parent/guardian. Findings: Between March 2016 and November 2018, we randomised 4,000 HIV-exposed infants at a median age of 6.4 weeks to POC (n=1,989) or enhanced SOC (n=2,011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (IQR: 22-30) days. Most infants randomised to SOC relied on the trial’s diagnostic safety net. Eighty-one (2%, 95% CI: 1.6–2.5%) infants were diagnosed with HIV. Although ART initiation was high overall, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures during follow-up. By 12 months, only 20 of 81 (25%, 95% CI: 15–34%) HIV-infected infants were alive, in care, and virally suppressed: 13 (30%, 95% CI: 16–43%) infants in the POC group vs. 7 (19%, 95% CI: 6–32%) in the enhanced SOC group (RR: 1.56, 95% CI: 0.7–3.50). Interpretation: Outcomes among HIV-infected infants were poor in both randomization groups. Although POC EID eliminated diagnostic delays and accelerated ART initiation, the POC EID strategy did not translate into a statistically significant improvement in programmatic success. Our findings are limited by a lower than anticipated number of HIV-infected infants in the trial, a welcome consequence of the success of Zambia’s perinatal HIV prevention program. Trial Registration: This trial is registered at https://clinicaltrials.gov (NCT02682810). Funding Statement:This research was funded by the U.S. National Institutes of Health (NIH) (U01AI100053). Biostatistical and laboratory support was provided by the UNC Center for AIDS Research, which is supported in part by the NIH (P30AI050410). Additional investigator and trainee support was provided by the NIH for BHC (K24AI120796) and CEF (T32HD075731, D43TW009340). Declaration of Interests: The authors declare no conflicts of interest. Ethics Approval Statement: Ethical approval for the trial (NCT02682810) was granted by the University of Zambia Biomedical Research Ethics Committee (BREC Ref: 010-02-13), the Zambian Ministry of Health, and the University of North Carolina at Chapel Hill Institutional Review Board (IRB Number: 12-1346).

Point-of-Care Early Infant Diagnosis Improves Adherence to the Testing Algorithm in Kenya.

Introduction:We determine the level of adherence to the revised Kenya early infant diagnosis (EID) algorithm during implementation of a point-of-care (POC) EID project.Methods:Data before (August 2016 to July 2017) and after (August 2017 to July 2018) introduction of POC EID were collected retrospectively from the national EID database and registers for 33 health facilities. We assessed the number of HIV-infected infants who underwent confirmatory testing and received baseline viral load test and proportion of infants with an initial negative result who had a subsequent test.Results and Discussion:Significantly higher number of infants accessed confirmatory testing (94.2% versus 38.6%; P < .0001) with POC EID. Baseline viral load test and follow-up testing at 6 months, although higher with POC EID, were not significantly different from the pre-POC EID intervention period.Conclusion:The POC EID implementation has the potential to increase proportion of infants who receive confirmatory testing, thus reducing the risk of false-positive results.

Systematic review of the performance and clinical utility of point of care HIV-1 RNA testing for diagnosis and care.

BackgroundPoint of-care (POC) HIV-1 RNA tests which are accurate and easy to use with limited infrastructure are needed in resource-limited settings (RLS). We systematically reviewed evidence of POC test performance compared to laboratory-based HIV-1 RNA assays and the potential utility of these tests for diagnosis and care in RLS.MethodsStudies published up to July 2018 were identified by a search of PUBMED, EMBASE, Web of Science, CINAHL and Cochrane Central Register of Controlled Trials. Studies evaluating the use of POC HIV-1 RNA testing for early infant diagnosis (EID), acute HIV infection (AHI) diagnosis, or viral load monitoring (VL), compared to centralized testing, were included. Separate search strategies were used for each testing objective.Results197 abstracts were screened and 34 full-text articles were assessed, of which 32 met inclusion criteria. Thirty studies evaluated performance and diagnostic accuracy of POC tests compared to standard reference tests. Two of the thirty and two additional studies with no comparative testing reported on clinical utility of POC results. Five different POC tests (Cepheid GeneXpert HIV-1 Quantitative and Qualitative assays, Alere q HIV‐1/2 Detect, SAMBA, Liat HIV Quant and Aptima HIV‐1 Quant) were used in 21 studies of VL, 11 of EID and 2 of AHI. POC tests were easy to use, had rapid turnaround times, and comparable accuracy and precision to reference technologies. Sensitivity and specificity were high for EID and AHI but lower for VL. For VL, lower sensitivity was reported for whole blood and dried blood spots compared to plasma samples. Reported error rates for Cepheid GeneXpert Qual (2.0%-5.0%), GeneXpert Quant (2.5%-17.0%) and Alere q HIV‐1/2 Detect (3.1%-11.0%) were higher than in WHO prequalification reports. Most errors resolved with retesting; however, inadequate sample volumes often precluded repeat testing. Only two studies used POC results for clinical management, one for EID and another for VL. POC EID resulted in shorter time-to-result, rapid ART initiation, and better retention in care compared to centralised testing.ConclusionsPerformance of POC HIV-1 RNA tests is comparable to reference assays, and have potential to improve patient outcomes. Additional studies on implementation in limited-resources settings are needed.

Evaluation of a routine point-of-care intervention for early infant diagnosis of HIV: an observational study in eight African countries

In 2017, there were 180 000 estimated new HIV infections in children aged 0-14 years. Without early diagnosis and treatment, half of infants with HIV die by age 2 years, with peak mortality around age 8-10 weeks. Conventional early infant diagnosis (EID) systems have not consistently returned results in a timely manner. However, point-of-care (POC) EID devices, which are new to market, could improve outcomes. In December, 2016, POC EID testing was introduced in eight sub-Saharan African countries as part of routine service delivery. We aimed to compare key service delivery and clinical outcomes and costs of POC versus conventional EID. In our observational study, we compared service delivery and clinical outcomes in eight countries (Cameroon, Côte d'Ivoire, Kenya, Lesotho, Mozambique, Rwanda, Swaziland, and Zimbabwe), before and after a POC intervention was introduced for EID of HIV. For the baseline, pre-intervention sample, we sampled 30 consecutive tests for HIV-exposed infants who had a documented date of blood collection for EID within Ministry of Health registers in a subset of Elizabeth Glaser Pediatric AIDS Foundation (EGPAF)-supported sites that would be enrolled in POC. For the post-intervention sample, all infants who were tested with POC EID for HIV at an EGPAF site were included in the sample. For both conventional and POC EID testing, we did not specify an age range, but used national EID guidelines for EID eligibility. A range of sites for conventional data collection were selected to represent both primary testing sites (where POC EID instruments would be placed) and spoke sites, rural and urban environment, and high throughput and low throughput sites. In all countries, except Mozambique, we developed a POC EID test request form in conjunction with the Ministry of Health. In Mozambique, EGPAF-trained staff extracted data from health facility registers and other sources using a data collection form. Certain specific indicators were required for all countries, but countries could collect additional variables, as the POC EID test request form was used for patient management for the duration of the project. These forms were filled in by health-care providers at the facility. Once the form was completed it was collected by EGPAF staff and entered into a project-specific database. The cost per test result returned was approximated by use of the Global Fund's total cost of ownership estimates. Retrospective collection of data on clinical and service delivery outcomes of conventional testing began on Nov 14, 2016, and was completed on Nov 26, 2017, for tests done between March 3, 2014, and March 30, 2017, at 96 health-care facilities using conventional testing. POC tests were done at 339 health-care facilities between Dec 1, 2016, and Dec 31, 2017. We evaluated data from 2875 infants exposed to HIV who were tested with conventional testing methods (2899 tests) and 18 220 infants tested with POC testing (19 071 tests). Several EID outcomes were significantly improved with POC testing relative to conventional testing. The return of results to caregivers within 30 days (in 18 737 [98·3%] of 19 058 infants receiving POC testing vs 542 [18·7%] of 2898 infants receiving conventional testing; p<0·0001), the median time from sample collection to return of results to caregivers (0 vs 55 days; p<0·0001), the number of infants with HIV initiating antiretroviral therapy (ART) within 60 days of sample collection (639 [92·3%] of 692 infants vs 42 [43·3%] of 97 infants; p<0·0001), the median time from sample collection to ART initiation among infants with HIV (0 vs 49 days; p<0·0001), and the median age at ART initiation among infants with HIV who were tested at 6-8 weeks (1·6 vs 3·3 months; p<0·0001) were all improved with POC testing compared with conventional testing. The cost per test result returned within 30 days was less for POC (US$27·24, range 21·39-33·10) than conventional testing ($131·02, 96·26-165·76). POC EID improves the speed of return of HIV test results and enables earlier ART initiation; this approach could potentially reduce morbidity and mortality in infants with HIV. National programmes, funders, and implementing partners should consider POC EID as a preferred testing strategy for implementation. Unitaid.

Early infant diagnosis HIV-1 PCR cycle-threshold predicts infant viral load at birth

BackgroundHIV-1 viral load (VL) has been found to be an independent predictor for disease progression among untreated HIV-infected children. However, qualitative polymerase chain reaction (PCR) assays are routinely used for early infant diagnosis (EID). ObjectivesTo predict HIV-1 VL at birth using qualitative EID real-time PCR cycle-threshold (Ct) values. Study designThis study was a secondary analysis of results from a cohort of intrauterine HIV-1 infected neonates. Neonates were enrolled at Rahima Moosa Mother & Child Hospital in Johannesburg, South Africa between June 2014 and November 2017. Laboratory EID HIV-1 PCR testing was performed at birth using COBAS AmpliPrep/COBAS TaqMan HIV-1 Qualitative Test v2.0 (EID CAP/CTM). Some infants had simultaneous EID point-of-care (POC) testing using Xpert HIV-1 Qualitative assay (EID Xpert). Neonates with a confirmed HIV-1 detected EID result and plasma HIV-1 RNA VL test were included in this analysis. Bland-Altman analysis was used to determine extent of agreement between Ct values of both EID assays. Multivariable linear regression models adjusting for time between EID and VL testing were used to describe the association between EID Ct values and VL and to predict VL at given EID Ct values. ResultsAmong 107 HIV-1 infected neonates included in the study, 59 had POC EID testing. Median VL was 28 400 copies per millilitre (cps/ml) (IQR: 1 918-218 358) - two neonates had VL < 100 cps/ml prior to antiretroviral therapy initiation. There was good correlation between Ct values of both EID assays (Spearman correlation coefficient 0.9, 95% CI: 0.8–1.0). The limits of agreement between EID CAP/CTM and Xpert Ct values were 4–11 cycles. For every one cycle increase in Ct value there was 0.3 log10 RNA decrease (95% CI: −0.3 to −0.2) for both EID assays. An EID CAP/CTM Ct value ≤ 23 and an EID Xpert Ct value ≤ 31 predicted a VL of > 5.0 log10 cps/ml in 82.2% (95% CI: 73.9–88.3) and 84.7% (95% CI: 73.7–91.8) of cases, respectively. ConclusionEID Ct values at birth predict VL and accurately identify infants with VL > 5.0 log10 cps/ml.

Significant Patient Impact Observed Upon Implementation of Point-of-Care Early Infant Diagnosis Technologies in an Observational Study in Malawi.

In Malawi in 2014, <20% of human immunodeficiency virus (HIV)-exposed infants received an early infant diagnosis (EID) test in the first 2 months of life and only 30% of HIV-infected children were on antiretroviral therapy (ART). We sought to understand the potential patient impact of improving timely infant diagnosis and treatment initiation through implementation of point-of-care (POC) EID technologies in Malawi. In this observational study, POC EID technologies were introduced into routine services at 7 health facilities across Malawi in September 2015. The primary outcome was the proportion of HIV-infected infants initiating ART within 60 days of sample collection in the POC arm compared to the baseline arm with conventional laboratory-based EID testing. The time from sample collection to result received by the patient decreased significantly from 56 days (interquartile range [IQR], 30-81 days) in the baseline arm to <1 day in the POC arm (P < .001). Of the HIV-infected infants, the time between sample collection and ART initiation was reduced from 38 days (IQR, 30-54 days) in the baseline arm to <1 day (IQR, 0-1 day) in the POC arm (P = .019). Furthermore, the proportion of HIV-infected infants initiated on ART within 60 days of sample collection increased significantly from 41.9% to 91.1% after the introduction of POC (adjusted risk ratio, 2.28; P < .001). ART initiation rates were significantly improved with the implementation of same-day POC EID testing compared with referred, longer-turnaround laboratory-based testing.

HIV birth testing and linkage to care for HIV-infected infants.

: On 5-6 May 2016, the division of AIDS of the National Institute of Allergy and Infectious Diseases convened a workshop on 'HIV Birth Testing and Linkage to Care for HIV Infected Infants.' The goal of the workshop was to evaluate birth testing for early infant diagnosis (EID) of HIV, delineate technological resources for advancing a point-of-care (POC) HIV test implementable at birth and chart out the implementation hurdles for initiating early antiretroviral therapy to HIV-infected infants diagnosed at birth. The workshop addressed research and regulatory needs involved in the optimization of POC EID testing and challenges associated with implementation of EID, focusing on testing at birth. Scientific gaps and areas of intervention to accelerate and scale-up EID initiatives and birth testing were identified. These include discussion of the evidence supporting an early mortality peak among HIV-infected infant and justifying a role for birth HIV testing, including POC testing; evaluation of the current POC EID technology pipeline and test performance characteristics required for effective programmatic uptake; mathematical modeling of different testing scenarios and solutions with inclusion of birth testing; the adoption of setting-specific EID testing algorithms to achieve efficient linkage to care including early antiretroviral therapy initiation; the development of appropriate quality assurance programs to ensure accuracy of test results and enable sustainability of the testing program. Addressing these gaps and answering these challenges will be important in helping improve outcomes for HIV-infected infants and accelerate achieving the Joint United Nations Program for HIV and AIDS 90-90-90 targets in children.

Point-of-Care Virologic Testing to Improve Outcomes of HIV-Infected Children in Zambia: A Clinical Trial Protocol.

Introduction:In the absence of early infant diagnosis (EID) and immediate antiretroviral therapy (ART), some 50% of untreated HIV-infected infants die before age 2. Conventional EID requires sophisticated instruments that are typically placed in centralized or reference laboratories. In low-resource settings, centralized systems often lead to result turnaround times of several months, long delays in diagnosis, and adverse outcomes for HIV-infected children. Our clinical trial tests the effectiveness of a new point-of-care (POC) diagnostic technology to identify HIV-infected infants and start providing them life-saving ART as soon as possible.Methods and Design:The study uses a randomized, controlled design to test whether the Alere q platform for HIV DNA polymerase chain reaction (PCR) testing improves outcomes of HIV-infected children in Zambia. We aim to enroll 2867 HIV-exposed infants aged 4–12 weeks and to follow those who are HIV infected for 12 months as they receive HIV care at 6 public health facilities in Lusaka. The trial's primary endpoint is the proportion of HIV-infected infants in each study arm who start ART and remain alive, in care, and virally suppressed 12 months after their diagnostic blood draw.Discussion:Our trial will provide evidence for the incremental benefit of implementing a POC EID strategy in low-resource settings where only off-site PCR services are currently available. The results will be useful in guiding future decisions regarding investments in POC virologic testing as part of overall pediatric AIDS mitigation strategies in sub-Saharan Africa.Trial Registration:clinicaltrials.gov NCT02682810.