Early Infant Diagnosis Program Research Articles

Caregivers’ experiences of accessing HIV Early Infant Diagnosis (EID) services and its barriers and facilitators, India

BackgroundIndia has rolled out Early Infant Diagnosis (EID) program for HIV infection in all states. EID program consists of testing of Infants exposed to HIV periodically over 18 months of age which is a multi-step complex testing cascade. Caregivers represent the primary beneficiary of EID program i.e., infants exposed to HIV and face multiple challenges to access EID services. As part of national EID program outcome assessment study, this study narrates caregivers’ perspectives on barriers and facilitators to access and utilize EID services.MethodsThe study was conducted in 31 integrated counselling and testing centres (ICTCs) located in 11 high burden HIV states. A total of 66 in-depth interviews were conducted with caregivers’ of infants enrolled in EID program. Thematic analysis was carried out to help identify themes underlying barriers and facilitators to access EID services and utilization from caregivers’ perspectives.ResultsThe stigma and discrimination prevalent in society about HIV remains a key demand side (caregiver-level) barrier. Non-disclosure or selective disclosure of HIV status led to missed or delayed EID tests and delayed HIV diagnosis and initiation of Anti-Retroviral Therapy (ART) for infants exposed to HIV. On supply side (health system-level), accessibility of healthcare facility with EID services was reported as a key barrier. The distance, time and cost were key concerns. Many caregivers faced difficulties to remember the details of complex EID test schedule and relied on a phone call from ICTC counsellor for next due EID test. Delayed EID test results and lack of communication of test results to caregiver were reported as primary barriers for completing the EID test cascade.DiscussionThe study reports caregiver-level and health system-level barriers and facilitators for access to EID services from the caregivers’ perspectives. While, decentralisation and single window approaches can improve the access, timely communication of test results to the caregiver also need to be built in with appropriate use of technology. A holistic intervention including PLHIV support networks and the peer-led support mechanisms would be useful to address societal factors.ConclusionThe study findings have high significance for developing program implementation strategies to improve access and to build right-based and patient-centred EID services.

Incorporating the HIV Infant Tracking System into standard-of-care early infant diagnosis of HIV services in Kenya: a cost-effectiveness analysis of the HITSystem randomised trial

The HITSystem efficacy trial showed significant improvements in early infant diagnosis retention, return and notification of infant test results, and earlier antiretroviral therapy (ART) initiation compared with standard-of-care early infant diagnosis services in Kenya. This study aimed to analyse data from the HITSystem trial to assess the cost-effectiveness of the intervention in Kenya. In this analysis, we extrapolated results from the HITSystem cluster randomised controlled trial to model early infant diagnosis outcomes and cost-effectiveness if the HITSystem was scaled up nationally in Kenya, compared with standard-of-care outcomes. We used a micro-costing method to collect cost data, which were analysed from a health-system perspective, reflecting the investment required to add HITSystem to existing early infant diagnosis services and infrastructure. The base model used to calculate cost-effectiveness was deterministic and calculated the progression of infants through early infant diagnosis. Differences in progression across study arms were used to establish efficacy outcomes. The number of life-years gained per infant successfully initiating ART were based on the Cost Effectiveness of Preventing AIDS Complications model in east Africa. HITSystem cost data were integrated into the model, and the incremental cost-effectiveness ratio was calculated in terms of cost per life-year gained. Sensitivity analyses were done using the deterministic model with triangular stochastic probability functions for key model parameters added. The number of life-years gained was discounted at 3% and costs were adjusted to 2021 values. The cost per life-year gained from the HITSystem was US$82·72. Total cost for national HITSystem coverage in Kenya was estimated to be around $2·6 million; covering 82 230 infants exposed to HIV at a cost of $31·38 per infant and a yield of 1133 infants receiving timely ART, which would result in 31 189 life-years gained. With sensitivity analyses, the cost per life-year gained varied from $40·13 to $215·05. 90% of model values across iterations ranged between $55·58 (lower 5% threshold) and $132·38 (upper 95% threshold). The HITSystem would be very cost-effective in Kenya and can optimise the return on the existing investment in the national early infant diagnosis programme. The US National Institute of Child Health and Human Development.

Early infant diagnosistesting for HIV in a hard-to-reach fishing community in Uganda.

Infants born to HIV-infected mothers are at a high risk of acquiring the infection. The World Health Organization recommends early diagnosis of HIV-exposed infants (HEIs) through deoxyribonucleic acid polymerase chain reaction (DNA PCR) and rapid HIV testing. Early detection of paediatric HIV is critical for access to antiretroviral therapy (ART) and child survival. However, there is limited evidence of the factors associated with receiving early infant diagnosis (EID) tests of the HIV testing protocol among HEIs in fishing communities in Uganda. This study established the factors associated with receiving EID tests of the HIV testing protocol among HEIs in a hard-to-reach fishing community in Uganda. A cross-sectional study was conducted among HEIs in selected healthcare facilities in Buvuma islands, Buvuma district. We obtained secondary data from mother-infant pair files enrolled in the EID program using a data extraction tool. Data were analysed using STATA Version 14. A modified Poisson regression analysis was used to determine the factors associated with not receiving the 1st DNA PCR test among HEIs enrolled in care. None of the HEIs had received all the EID tests prescribed by the HIV testing protocol within the recommended time frame for the period of January 2014-December 2016. The proportion of infants that had received the 1st and 2nd DNA PCR, and rapid HIV tests was 39.5%, 6.1%, and 81.0% respectively. Being under the care of a single mother (PR = 1.11, 95% CI: 1.01-1.23, p = 0.023) and cessation of breastfeeding (PR = 0.90, 95% CI: 0.83-0.98, p = 0.025) were significantly associated with not receiving the 1st DNA PCR. Our study revealed that none of the HEIs had received all the EID tests of the HIV diagnosis testing protocol. Receiving the 1st DNA PCR was positively associated with being an infant born to a single mother, and exclusive breastfeeding. Our findings highlight the need for the creation of an enabling environment for mothers and caregivers in order to increase the uptake of early diagnosis services for HEIs. Awareness-raising on the importance of EID should be scaled up in fishing communities. Demographic characteristics such as marital and breastfeeding status should be used as an entry point to increase the proportion of HEIs who receive EID tests.

Access, timeliness and retention for HIV testing under early infant diagnosis (EID) program, India

Early Infant Diagnosis of HIV infection services are crucial for managing the perinatally acquired HIV infection. Assessing the performance of the EID services and its underlying determinants is important for the National AIDS Control Program, India. The objectives of this study were to find out access to HIV testing, the timeliness of the testing cascade, and the proportion of HIV exposed infants who are followed up to 18 months for a definitive diagnosis of HIV. The study design was a mixed method. A total of 11 states accounting for 80% of HIV-positive pregnant women were selected. Program records from a total of 62 Integrated counselling and testing centres (ICTCs) served as the source of information. The qualitative component included interviews of program managers at the state and district level, service providers at the ICTC level, and caregivers of HIV exposed infants. In the sampled 62 ICTCs, 78% of the HIV exposed infants had at least one HIV test. Of the infants who had HIV tests, 50% had at first sample collected by 8 weeks of age. The median turnaround time from sample collection to DNA PCR testing was 36 (IQR 19–70) days and that to next sample collection in case of detection of virus in the first sample was 66 (IQR 55–116) days. At 18 months of age, 544 (62%) HIV exposed infants were retained in the EID testing cascade. A total of 30 infants were diagnosed with HIV at a median age of 421 (IQR 149–650) days. More than three fourth of the HIV exposed infants had access to early infant diagnosis (EID) services. Both demand and supply-side factors contribute to access, timeliness and retention and there is a need to address these factors.

Male involvement enhances the uptake of early infant diagnosis of HIV services in Thyolo, Malawi: A non-equivalent control group quasi-experimental study.

Poor retention of HIV-exposed infants (HEIs) in the Early Infant Diagnosis (EID) programme remains a significant challenge and impedes progress towards the elimination of Mother to Child Transmission (eMTCT). Suboptimal involvement of a father in his child's participation in the EID of HIV services is one of the reasons for delayed initiation and poor retention in EID. This study compared the uptake of EID of HIV services at 6weeks from 6 months pre and post-implementation of the Partner invitation card and Attending to couples first (PA) strategy for male involvement (MI) at Bvumbwe Health Centre in Thyolo, Malawi. We conducted a non-equivalent control group quasi-experimental study from September 2018 to August 2019 and enrolled 204 HIV positive women with HIV exposed infants who delivered at Bvumbwe health facility. 110 women were in the period before MI in EID of HIV services from September 2018 to February 2019 whereas 94 of them were in the period of MI in EID of HIV services from March to August 2019 receiving PA strategy for MI. Using descriptive and inferential analysis we compared the two groups of women. As age, parity and education levels of women were not associated with the uptake of EID, we proceeded to calculate unadjusted odds ratio. We observed an increase in the proportion of women that took up EID of HIV services such that 64/94 (68.1%) came for EID of HIV services at 6weeks from 44/110 (40%) in the period before MI. The uptake of EID of HIV services had an odds ratio of 3.2(95%CI: 1.8-5.7) P = 0.001) compared to the uptake of EID of HIV services before MI OR of 0.6(95%CI: 0.46-0.98) P = 0.037). Age, parity, and education levels of women were statistically insignificant. The uptake of EID of HIV services at 6 weeks increased during the implementation of MI compared to the period before. Age, parity, and education levels of women were not associated with the EID uptake of HIV services at 6 weeks. Further studies on male involvement and uptake of EID should continue to be carried out to contribute to understanding of how high levels of EID uptake of HIV services can be achieved.

Loss to follow-up of HIV-exposed infants for confirmatory HIV test under Early Infant Diagnosis program in India: analysis of national-level data from reference laboratories

BackgroundEarly Infant Diagnosis was launched in India in 2010 and its effect on the diagnosis of HIV-exposed infants needs to be assessed. The present study was done to find out the median age at DBS sample collection for early infant diagnosis and its trend over years, the median age at diagnosis of HIV among the HIV-exposed infants with DNA PCR tests, and the proportion of infants who completed testing cascades after detection of HIV-1 in a sample.MethodsDNA PCR data (from 2013 to 2017) maintained at all regional reference laboratories in India was collated with each infant identified by a unique code. Cohort analysis of the infant data was used to find the median age at sample collection and diagnosis. The outcomes of testing in each cascade and the overall outcomes of testing for infants were prepared.ResultsThe median age at sample collection for the four years combined at all India level was 60 days (48–110 days). The median age at diagnosis of HIV was 285 days (174–418 days). HIV-1 was detected in samples of 1897 (6.3%) infants out of 30,216 infants who had a DNA PCR test, out of whom 1070 (56.4%) completed the testing cascade and the rest were lost to follow-up.ConclusionThe data highlights delay in diagnosis; both due to delay in sample collection and turn-around-times. Loss to follow-up of HIV-exposed infants with virus detection is a significant concern to the Early Infant Diagnosis and tracking systems need to be strengthened.

P-005: COMPARISON OF SICKLE SCAN AND HEMOTYPE SC AS POINT-OF-CARE NEWBORN SCREENING DIAGNOSTICS FOR SICKLE CELL DISEASE IN LUANDA, ANGOLA

Purpose: Despite significant advances in the diagnosis and treatment of sickle cell disease (SCD), most of the >300,000 infants born with SCD will die before the age of 5 years, primarily due to the lack of timely and accurate diagnosis. In high-resource countries, early identification of SCD through newborn screening (NBS) is routine and subsequent delivery of preventive measures and comprehensive care is highly effective in reducing morbidity and early mortality. Despite the proven efficacy of NBS and successful pilot programs across Africa, large-scale implementation remains infeasible in many sub-Saharan countries due to inadequate financial, laboratory, and technical resources. The development and deployment of low-cost, rapid, user-friendly, and accurate diagnostic testing for SCD is imperative. Recently, several promising point-of-care (POC) diagnostics have been developed, but there have been few real-world studies that compare these tests head-to-head, particularly in the setting of NBS, where accurate diagnosis amidst high levels of fetal hemoglobin is critical. Materials and methods: We performed a prospective evaluation of two POC SCD diagnostics (Sickle SCAN and HemoTypeSC) at maternity centers and immunization centers in Luanda, Angola, with confirmation by isoelectric focusing (IEF). To evaluate the real-world feasibility and accuracy, with the guidance of the Angolan Ministry of Health, we planned to test 100 infants ≤6 months of age with each test at 10 different clinical sites (total of 2,000 infants tested). The study was designed to mimic a real-world setting with all POC testing performed and interpreted by local healthcare staff with basic instructions for the use of each test. Results: Of the 2,000 infants tested, 1958 results were included in the final analysis, with the exclusion of 42 tests that were not interpreted in the recommended time frame. Consistent with prior studies in Angola, the burden of sickle cell trait (HbAS, 21.9%) and sickle cell anemia (HbSS, 1.7%) was high. Tests were performed in maternity wards on the day of or following birth (63%) or at immunization centers through 6 months of life (37%). HemoTypeSC took an average of 15 minutes to obtain a result, was repeated 68 times (6.8%) due to invalid results, and was interpreted incorrectly only 4 times (0.4%). Sickle SCAN took an average of 7 minutes to obtain a result, was repeated 2 times (0.2%) due to invalid results, and interpreted incorrectly only 11 times (1.1%). The gold standard of IEF was imperfect with 5.5% of samples needing repeat testing at least once 12 samples with inconclusive results. Importantly, 92% of babies who were diagnosed and informed at the POC followed up in the SCD clinic, compared to the historical 56% who were successfully brought to care during the initial pilot NBS program in Luanda. Conclusion: This study demonstrates the feasibility and accuracy of both HemoTypeSC and Sickle SCAN for diagnosing SCD in newborns in a Luanda, Angola. Given the complexities of testing in the newborn period at busy maternity hospitals, this study suggests that testing at immunization centers using novel POC diagnostics may be a more practical solution to early infant diagnosis programs for SCD. The authors do not declare any conflict of interest

Early infant diagnosis of HIV infection at the John F. Kennedy Medical Center, Monrovia, Liberia

Background: Vertical transmission accounts for majority of new HIV infections among children worldwide. Ninety percent of HIV-positive children reside in Sub- Saharan Africa with their infection predominantly acquired via vertical transmission. In 2004, the vertical transmission rate of HIV in Africa was estimated at 25 − 40% but, remarkably, the rate has significantly decreased to less than 5% in most African countries following implementation and expansion of prevention of MTCT (PMTCT) programs. Objective: To determine the rate of and factors associated with vertical transmission of HIV among attendees of early infant diagnosis (EID) program of an academic and community-based tertiary facility in Liberia. Design: A retrospective cross-sectional analysis. Methods: A retrospective review of medical records of babies seen at Pediatric Unit of Infectious Disease Clinic of John F Kennedy Medical Center (JFKMC) in Monrovia, Liberia between January 1, 2016 and December 31, 2020. All subjects were children born to HIV-positive mothers and who had HIV DNA PCR testing performed between the ages of 6 weeks and 6 months. Children who suffered early neonatal death and those who did not undergo PCR testing were excluded. Demographics of mother to child pairs as well as factors known to influence vertical transmission of HIV such as partial (15.8%) or full (84.2%) participation in prevention of MTCT (PMTCT) programs, mode of delivery, breastfeeding and utilization of post-exposure prophylaxis were collected and assessed. Binomial logistic regression analyses were used to assess factors associated with vertical transmission. Results: During the study timeframe, 284 children had a HIV DNA PCR test with a male:female ratio − 1.3:1. Sixteen tested positive (conducted at a mean of 155 days post birth) giving a vertical transmission rate of 5.6%. For 239 mothers (84.2%) who had full PMTCT, 1.3% of their children tested positive, while for 45 mothers (15.8%) who had partial PMTCT, 28.8% of their children being positive. Two hundred and seventy six children (97%) had exclusive breastfeeding, 13 of whom tested positive while 2 children who were mixed fed tested positive. Children who had Nevirapine vs no prophylaxis (OR = 1.89[95% CI 1.16 − 2.96]), were delivered via caesarian section vs vaginal delivery (OR= 2.26[95% CI 1.92 − 4.12].) and full versus partial participation in PMTCT programs (OR = 4.02[95% CI 2.06 − 4.13] were more likely to have negative HIV test. Conclusion: Vertical transmission rate was found to be high in Liberia and may be driven by suboptimal PMTCT program participation including post-exposure prophylaxis for infants. Therefore, strategies to scale up and improve uptake of PMTCT services are needed to mitigate the burden of HIV among children.

Comparison of Sickle SCAN and Hemotype SC As Point-of-Care Newborn Screening Diagnostics for Sickle Cell Disease in Luanda, Angola

Background: Sickle cell disease (SCD) is among the most common, lethal and poorly recognized diseases globally. Over 300,000 children are born each year with SCA and most die by five years, primarily due to the lack of timely and accurate diagnosis. In high-resource countries, early identification of SCD through newborn screening (NBS) is routine and subsequent delivery of preventive measures and comprehensive care is highly effective in reducing morbidity and early mortality. In lower-resource settings, where the incidence of SCD is much higher, NBS is limited to only a few pilot programs. Despite the proven efficacy of NBS, large-scale implementation remains infeasible in many sub-Saharan countries due to inadequate financial, laboratory, and technical resources. In the pilot NBS program in Angola, only 56% of infants with SCD were able to be contacted to relay results due to delays in traditional laboratory diagnostic methods, lack of traditional mailing system or primary care providers, and inconsistent telephone numbers. The development and deployment of low-cost, rapid, user-friendly, and accurate diagnostic testing for SCD is imperative.There are two promising point-of-care (POC) tests (Sickle SCAN and HemoTypeSC) that may allow for a simplified approach to newborn screening for SCD. There have been few real-world studies that compare these tests head to head, particularly in the setting of NBS, where accurate diagnosis amidst high levels of fetal hemoglobin is critical. We performed a study at maternity centers and immunization centers in Luanda, Angola to evaluate the real-world accuracy of these tests.Methods: The study was a prospective evaluation of two rapid, POC tests (Sickle SCANÔ or HemoTypeSCÔ) ain Luanda, Angola, with laboratory confirmation using a dried blood spot (DBS) by isoelectric focusing (IEF), defined as the gold standard. To evaluate the real-world feasibility and accuracy, with the guidance of the Angolan Ministry of Health, we selected 10 sites, including both birth hospitals and vaccination sites, to screen infants < 6 months of age. Due to the complexity of performing more than one POC at once, we focused on one POC test at a time and planned to test 100 infants with each test at each site, for a total of 2,000 infants tested overall. The study was designed to mimic a real-world setting with all POC testing performed and interpreted by local healthcare staff (nurses, students, and laboratory technicians) with basic instructions as to the use of each test.Results: Blood samples were collected from 2,000 infants from age 0 to 6 months of age, including 1,000 with Sickle SCAN and 1,000 with HemoTypeSC. 42 HemoTypeSC samples (4.2%) and 6 Sickle SCAN results (0.6%) were not included in the final analysis, as results were not interpreted in the recommended time frame (5 minutes for Sickle SCAN an 10 minutes for HemoTypeSC). Consistent with prior studies in Angola, the burden of sickle cell trait (AS, 21.9%) and sickle cell anemia (HbSS, 1.7%) was high. 63% of the tests were performed in maternity wards at the time/day of birth and 37% were performed in immunization centers through the first 6 months of life. The HemoTypeSCÔ took an average of 15 minutes to obtain a result, was repeated 68 times (6.8%) due to invalid results, and was read incorrectly 4 times (0.4%). The SickleScanÔ took an average of 7 minutes to run, was repeated 2 times (0.2%) due to invalid results, and read incorrectly 11 times (1.1%). All results were compared to the gold standard IEF and both tests correlated perfectly (100%) with the IEF results, excluding 12 samples that had inconclusive IEF results.Conclusions: This study demonstrates the feasibility and accuracy of both HemoTypeSC and Sickle SCAN for diagnosing SCD in newborns in a limited-resource setting of Luanda, Angola. Given the complexities of testing in the newborn period at busy maternity hospitals, it appears that testing at immunization centers may be a more practical solution to early infant diagnosis programs for SCD. While both HemoTypeSC and Sickle SCAN were accurate, Sickle SCAN was preferred by local staff likely due to the shorter time to interpretation and reduced need for repeating the test. Further implementation studies are needed, including careful analysis of end-user cost, to determine the appropriate strategy for these POC tests in low-resource setting of sub-Saharan Africa. DisclosuresNo relevant conflicts of interest to declare.

Evaluating the performance of the GeneXpert HIV-1 qualitative assay as a consecutive test for a new early infant diagnosis algorithm in South Africa.

Background. The proportion of HIV-exposed infants and young children infected with HIV in South Africa (SA) has declined markedly over the past decade as a result of the country’s comprehensive prevention of mother-to-child transmission programme. This decrease has in turn reduced the positive predictive value (PPV) of diagnostic assays, necessitating review of early infant diagnosis (EID) algorithms to ensure improved accuracy. Objectives. To evaluate the performance of the GeneXpert HIV-1 qualitative assay (Xpert EID) as a consecutive test for infants with an ‘HIV-detected’ polymerase chain reaction screening test at birth. Methods. We retrospectively analysed a longitudinal cohort of HIV-exposed infants on whom birth testing was performed, using whole-blood ethylenediaminetetra-acetic acid samples, from four tertiary sites in Gauteng Province between June 2014 and December 2019. Birth samples from all infants with a Cobas AmpliPrep/Cobas TaqMan HIV-1 Qualitative Test v2.0 (CAP/CTM v2.0) HIV-detected screening test, a concurrent Xpert EID test and a subsequent confirmatory CAP/CTM v2.0 test on a separate specimen were included. Performance of the Xpert EID in predicting final HIV status was determined as proportions with 95% confidence intervals (CIs). A comparison of indeterminate CAP/CTM v2.0 results, as per National Health Laboratory Service resulting practice, with discordant CAP/CTM v2.0 v. Xpert EID results was performed. Results. Of 150 infants who met the inclusion criteria, 6 (3.9%) had an Xpert EID result discordant with final HIV status: 5 (3.3%) were false negatives and 1 (0.7%) was false positive. As a consecutive test, the Xpert EID yielded a sensitivity of 96.5% (95% CI 92 - 98.9), specificity of 85.7% (95% CI 42.1 - 99.6), PPV of 99.3% (95% CI 95.7 - 99.9), negative predictive value of 54.5% (95% CI 32.5 - 74.9) and overall accuracy of 96.1% (95% CI 91.5 - 98.5). Using discordant CAP/CTM v2.0/Xpert EID results as criteria to verify indeterminate results instead of current practice would have reduced the number of indeterminate screening results by 42.1%, from 18 (12.6%) to 11 (7.2%), without increasing the false-positive rate. Conclusions. Addition of the Xpert EID as a consecutive test for specimens with an HIV-detected PCR screening result has the potential to improve the PPV and reduce the indeterminate rate, thereby reducing diagnostic challenges and time to final status, in SA’s EID programme.

Sustaining Early Infant Diagnosis of HIV During Coronavirus Disease 2019 Pandemic

To the Editors: Despite advances in prevention of mother to child transmission (PMTCT) of HIV, 160,000 new pediatric HIV infections were reported in 2020.1 Vertical transmission of HIV in Nigeria remains high at 22%, with 37,000 new infections among children 0–14 years annually.2 In Nigeria, access to early infant diagnosis (EID) has improved significantly; however, only 27% of HIV-exposed infants received an HIV test by 2 months of age in 2019.3 EID programs require mothers to bring their infants to the health facility for testing. However, the global coronavirus disease 2019 (COVID-19) pandemic movement restrictions necessitated changes to the PMTCT service delivery model for infant follow-up to ensure uninterrupted service delivery. Nigeria reported its first COVID-19 case on February 27, 2020.4 By March, a mandatory lock down with subsequent movement restrictions limited access to health facilities for nonemergency presentations including PMTCT services.4 The Reaching Impact Saturation and Epidemic (RISE) Control program, which currently provides comprehensive HIV prevention, care and treatment services to over 82,000 recipients of care, rapidly pivoted to a community service delivery model to ensure uninterrupted access to HIV services. To circumvent the challenges faced by mothers and caregivers in accessing health facilities during the COVID-19 lockdown period, RISE deployed trained nurses to collect dried blood spot (DBS) samples for HIV viral load and EID in the communities where children, infants and their caregivers live. EID samples were collected by trained nurses in the home and transported to the health facility for onward transportation to regional labs. When sample collection was not feasible in the home, caregivers were escorted to the nearest health facility for sample collection. Case managers also provided antiretroviral drug refills for recipients of care in the community including antiretroviral prophylaxis refills for infants. Prelock down (October 2019 to March 2020), RISE collected 690 samples of which 57% (393/690) were collected within 2 months of birth with average turnaround time of 30 days. Postlock down (April to September 2020), 634 samples were collected of which 60% (379/634) were within 2 months of birth while maintaining an average turnaround time of 34 days. Regarding actual tests done, prelock down tests were done for 75% of samples for infants <2 months (n = 295) with 1.0 % positivity rate, while postlock down, 77% (n = 291) were tested with 0.3% positivity. Early results from the RISE program have shown that DBS specimens for HIV diagnosis in infants can be safely collected at home while maintaining specimen integrity and delivery of results back to caregivers. Several adaptations have been made to HIV programming to improve service delivery for HIV-infected pregnant, breast-feeding women, infants, children and adolescents.4 We propose that HIV programs consider implementing home-based DBS collection to increase access to timely EID services for HIV-exposed infants both as an adaption during the COVID-19 pandemic and as an enduring solution thereafter.

Indeterminate HIV PCR results within South Africa's early infant diagnosis programme, 2010–2019

ObjectivesWe describe the extent of, and variables associated with, indeterminate HIV-PCR results and final HIV status within South Africa's early infant diagnosis (EID) programme between 2010 and 2019. MethodsRetrospective analysis of routine paediatric HIV-PCR laboratory data from South Africa's National Health Laboratory Service Data Warehouse between 2010 and 2019. Final HIV status was determined by linking patient results (including HIV-PCR, HIV viral load, HIV serology and CD4 counts) using a probabilistic matching algorithm. Multivariate logistic regression was performed to determine variables associated with final HIV status among patients with an indeterminate HIV-PCR result. ResultsAmong 4 429 742 specimens registered for HIV-PCR testing from 3 816 166 patients, 113 209 (2.97%) tested positive and 22 899 (0.6%) tested indeterminate. As a proportion of HIV-detected results, 15.7% (23 896/151 832) of total and 31.5% (4900/15 566), 18.8% (11 400/60 794) and 10.1% (7596/75 472) among patients aged <7 days, 7 days–3 months and ≥3 months, respectively, were reported as indeterminate. Overall, 39.7% of patients with an indeterminate result had a linked HIV test to determine HIV status, of which 53.6% were positive with a median time to repeat testing of 30 days (interquartile range 15–69). Among patients who tested indeterminate, variables associated with a significantly higher odds of having a positive HIV status included testing indeterminate at birth (adjusted odds ratio (AOR) 0.63 (0.48–0.83) and 0.52 (0.39–0.69) for testing indeterminate at 7 days–3 months and ≥3 months respectively compared with birth), within a hospital (AOR 2.45 (1.99–3.03)), and in districts with an intra-uterine transmission rate ≥1.1% (AOR 3.14 (1.84–5.35)) (p < 0.001). DiscussionIndeterminate HIV-PCR results represent a considerable burden of missed diagnostic opportunities, diagnostic dilemmas and delays in making a definite diagnosis among HIV-infected infants within South Africa's EID programme. Alternative EID verification practices are urgently needed.

Early Infant Diagnosis of HIV in Primary Health Care Centers

Background: Early diagnosis of HIV to identify infected children for early therapy is aimed at preventing high mortalities associated with child HIV infection. Early infant diagnosis (EID) intervention occurs across the three tiers of the Nigerian health care delivery system, including the primary health care centers (PHC). This study evaluates the implementation of early infant diagnosis of HIV in PHCs in a southern state of Nigeria. Methods: This was a cross-sectional descriptive study that took place between September and November 2019. Primary data were obtained from an interviewer-administered questionnaire on 120 health workers in six Local Government Areas (LGA) that were selected through a multi-stage, random sampling method. Secondary data were from the records of program implementation at the state headquarters of Ministry of Health and the PHCs. Results: A total of 116 (96.6%) health workers were interviewed; 17.2% were males, and 82.8% were females. More than two-thirds of respondents were aged between 41 and 60 years and 84.5% of them had worked in the PHC system for 11 years and above. Rural or urban location of the PHC, educational level of the health workers, and years of service in the PHC system did not have any significant effect on implementation of EID program in the health facilities. Implementation of EID program was ineffective in both rural and urban PHCs of Akwa Ibom state with the p-value of 0.337. In multiple regression analysis, access to EID program and provision of adequate supplies significantly affected implementation of the program with p = 0.001 and p = 0.000 respectively. Conclusion and Implication for Translation: The study indicates general ineffectiveness in the implementation of EID in a Southern State of Nigeria. There is need to improve access to EID services and provide needed supplies if the state, and by extension Nigeria, hopes to meet the target of joining the global community in ending HIV by 2030. Copyright © 2021 Markson. Published by Global Health and Education Projects, Inc. This is an open-access article distributed under the terms of the Creative Commons Attribution License CC BY 4.0.

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.

Uganda's "EID Systems Strengthening" model produces significant gains in testing, linkage, and retention of HIV-exposed and infected infants: An impact evaluation.

IntroductionA review of Uganda’s HIV Early Infant Diagnosis (EID) program in 2010 revealed poor retention outcomes for HIV-exposed infants (HEI) after testing. The review informed development of the ‘EID Systems Strengthening’ model: a set of integrated initiatives at health facilities to improve testing, retention, and clinical care of HIV-exposed and infected infants. The program model was piloted at several facilities and later scaled countrywide. This mixed-methods study evaluates the program’s impact and assesses its implementation.MethodsWe conducted a retrospective cohort study at 12 health facilities in Uganda, comprising all HEI tested by DNA PCR from June 2011 to May 2014 (n = 707). Cohort data were collected manually at the health facilities and analyzed. To assess impact, retention outcomes were statistically compared to the baseline study’s cohort outcomes. We conducted a cross-sectional qualitative assessment of program implementation through 1) structured clinic observation and 2) key informant interviews with health workers, district officials, NGO technical managers, and EID trainers (n = 51).ResultsThe evaluation cohort comprised 707 HEI (67 HIV+). The baseline study cohort contained 1268 HEI (244 HIV+). Among infants testing HIV+, retention in care at an ART clinic increased from 23% (57/244) to 66% (44/67) (p < .0001). Initiation of HIV+ infants on ART increased from 36% (27/75) to 92% (46/50) (p < .0001). HEI receiving 1st PCR results increased from 57% (718/1268) to 73% (518/707) (p < .0001). Among breastfeeding HEI with negative 1st PCR, 55% (192/352) received a confirmatory PCR test, a substantial increase from baseline period. Testing coverage improved significantly: HIV+ pregnant women who brought their infants for testing after birth increased from 18% (67/367) to 52% (175/334) (p < .0001). HEI were tested younger: mean age at DBS test decreased from 6.96 to 4.21 months (p < .0001). Clinical care for HEI was provided more consistently. Implementation fidelity was strong for most program components. The strongest contributory interventions were establishment of ‘EID Care Points’, integration of clinical care, longitudinal patient tracking, and regular health worker mentorship. Gaps included limited follow up of lost infants, inconsistent buy-in/ownership of health facility management, and challenges sustaining health worker motivation.DiscussionUganda’s ‘EID Systems Strengthening’ model has produced significant gains in testing and retention of HEI and HIV+ infants, yet the country still faces major challenges. The 3 core concepts of Uganda’s model are applicable to any country: establish a central service point for HEI, equip it to provide high-quality care and tracking, and develop systems to link HEI to the service point. Uganda’s experience has shown the importance of intensively targeting systemic bottlenecks to HEI retention at facility level, a necessary complement to deploying rapidly scalable technologies and other higher-level initiatives.

Factors Influencing Loss to Follow-up among Human Immunodeficiency Virus Exposed Infants in the Early Infant Diagnosis Program in Phalombe, Malawi

The efforts to prevent mother to child transmission of HIV in Malawi are impeded by the loss to follow-up of HIV-exposed infants (HEI) in care. Early infant diagnosis (EID) of HEI and linkage to care reduces morbidity and mortality. There has been limited attention to infants who are lost to follow up despite their mothers being compliant to the PMTCT program. This study explored factors that influence loss-to-follow up among HEI in the EID program whose mothers were retained in care for up to 24 months in Phalombe district, Malawi. We conducted a descriptive phenomenological qualitative study from May 2017 to July 2018. We purposively conducted 18 in-depth interviews among HIV positive mothers whose HEI were enrolled in the follow-up program and 7 key informant interviews among healthcare workers (HCW). All interviews were digitally recorded, transcribed, and translated verbatim. Data were analyzed manually using a thematic step-by-step approach. Results showed that retention in care is facilitated by aspirations to have a healthy infant and linkage to a nearer facility to a mother’s place of residency. The barriers to retention were non-disclosure of HIV status, inadequate resources, and support, suboptimal guidelines for, a lack of privacy, and unsynchronized hospital visits between a mother and her baby. The study has shown that successful implementation of EID services requires concerted efforts from various contextualized stakeholders whilst focusing on family-centered care. To maximize retention in EID and innovative ways of reaching mothers and babies through flexible guidelines are urgently needed.

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.

Surveillance for sickle cell disease, United Republic of Tanzania

ObjectiveTo determine the regional- and district-level newborn prevalence of sickle cell trait and disease, and the prevalence of haemoglobin variants and genetic modifiers of sickle cell disease, in the nine regions of north-western United Republic of Tanzania.MethodsWe repurposed dried blood spot samples from children (aged 0–24 months) born to mothers living with human immunodeficiency virus (HIV), collected as part of the HIV Early Infant Diagnosis programme, for sickle cell diagnosis. We performed isoelectric focusing to determine whether samples had normal haemoglobin, sickle cell trait, sickle cell disease or a rare haemoglobin variant. We shipped samples diagnosed as disease or variant to Cincinnati Children’s Hospital in the United States of America for deoxyribonucleic-acid-based analyses to determine the prevalence of α-thalassaemia, glucose-6-phosphate dehydrogenase (G6PD) deficiency or fetal haemoglobin genetic modifiers.FindingsWe analysed a total of 17 200 specimens during February 2017–May 2018. We observed a prevalence of sickle cell trait and disease of 20.3% (3492/17 200) and 1.2% (210/17 200), respectively. District-level trait varied from 8.6% (5/58) to 28.1% (77/274). Among confirmed sickle cell disease specimens, we noted 42.7% (61/143) had 1-gene deletion and 14.7% (21/143) had 2-gene deletion α-thalassaemia trait. We documented G6PD A– deficiency in 19.2% (14/73) of males.ConclusionOur calculated prevalence is twice as high as previously reported and reinforces the need for enhanced sickle cell diagnostic services. Our district-level data will inform public health policy, allowing screening and disease-modifying hydroxyurea therapy to be focused on high-prevalence areas, until universal newborn screening is available.

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.

"It was my obligation as mother": 18-Month completion of Early Infant Diagnosis as identity control for mothers living with HIV in Kenya.

Early Infant Diagnosis (EID) is critical to timely identification of HIV and rapid treatment initiation for infants found to be infected. Completing the EID cascade involves a series of age-specific tests between birth and 18 months and can be challenging for mother- infant pairs in low-resource settings. Even prior to recent increases in Kenya's testing recommendations, approximately 22% of mother-infant pairs enrolled in EID were lost to follow-up. As EID cascades become increasingly complex, identifying strategies to maximize retention becomes even more essential. Despite ongoing health system improvements, we still lack a framework for understanding the individual-level, psychosocial processes underlying EID completion-insight that could be essential for shaping strategies to support patients and close gaps in retention. Our objective was to explain individual-level processes that lead to EID completion among mothers who successfully completed the EID cascade. Using qualitative methods informed by grounded theory, we conducted 65 interviews with Kenyan mothers who completed EID. We identified three themes related to completion: (1) Negative motivation, from the consequences of infant infection, fear of postnatal transmission, and burden of maternal failure; (2) Positive motivation, from achieving a final goal, responding to provider support, and maximizing infant health; and (3) Overcoming challenges, through resolve/resiliency, planning/privatizing and rejecting stigma/leveraging support. Overall, the EID cascade served as a framing process for women to secure an identity as a good mother. Successful EID completion was the product of a strong motivational foundation channeled into strategies to surmount persistent challenges. Participant accounts of overcoming challenges highlight their resiliency as well as the outstanding need to address financial, logistical, and social barriers to care. Future EID programs may capitalize on these findings by affirming patients' quest for identity control, leveraging positive motivators, and expanding peer support structures to help mothers feel connected throughout the cascade.