Rapid antiretroviral therapy initiation following rollout of point-of-care early infant diagnosis testing, Uganda, 2018-2021.

BACKGROUND: Uganda Ministry of Health (MOH) recommends a first HIV DNA-PCR test at 4-6 weeks for early infant diagnosis (EID) of HIV-exposed infants (HEI) and immediate return of results. WHO recommends initiating antiretroviral therapy (ART) ≤ 7 days from HIV diagnosis. In 2019, MOH introduced point-of-care (POC) whole-blood EID testing in 33 health facilities and scaled up to 130 facilities in 2020. We assessed results turnaround time and ART linkage pre-POC and during POC testing. METHODS: We evaluated EID register data for HEI at 10 health facilities with POC and EID testing volume of ≥ 12 infants/month from 2018 to 2021. We abstracted data for 12 months before and after POC testing rollout and compared time to sample collection, results receipt, and ART initiation between periods using medians, Wilcoxon, and log-rank tests. RESULTS: Data for 4.004 HEI were abstracted, of which 1.685 (42%) were from the pre-POC period and 2.319 (58%) were from the period during POC; 3.773 (94%) had a first EID test (pre-POC: 1.649 [44%]; during POC: 2.124 [56%]). Median age at sample collection was 44 (IQR 38-51) days pre-POC and 42 (IQR 33-50) days during POC (p < 0.001). Among 3.773 HEI tested, 3.678 (97%) had test results. HIV-positive infants' (n = 69) median age at sample collection was 94 (IQR 43-124) days pre-POC and 125 (IQR 74-206) days during POC (p = 0.04). HIV positivity rate was 1.6% (27/1.617) pre-POC and 2.0% (42/2.061) during POC (p = 0.43). For all infants, median days from sample collection to results receipt by infants' caregivers was 28 (IQR 14-52) pre-POC and 1 (IQR 0-25) during POC (p < 0.001); among HIV-positive infants, median days were 23 (IQR 7-30) pre-POC and 0 (0-3) during POC (p < 0.001). Pre-POC, 4% (1/23) HIV-positive infants started ART on the sample collection day compared to 33% (12/37) during POC (p < 0.001); ART linkage ≤ 7 days from HIV diagnosis was 74% (17/23) pre-POC and 95% (35/37) during POC (p < 0.001). CONCLUSION: POC testing improved EID results turnaround time and ART initiation for HIV-positive infants. While POC testing expansion could further improve ART linkage and loss to follow-up, there is need to explore barriers around same-day ART initiation for infants receiving POC testing.

Xpert HIV-1 qual point-of-care testing for HIV early infant diagnosis in Tanzania: experiences and perceptions of health care workers in a 2016 study.

BACKGROUND: HIV early infant diagnosis (HEID) at the centralized laboratory faces many challenges that impact the cascade of timely HEID. Point of Care (PoC) HEID has shown to reduce test turnaround times, allow for task shifting and has the potential to reduce infant mortality. We aimed at assessing the feasibility of nurse based PoC-HEID in five facilities of Mbeya region. METHODS: We analysed data from healthcare workers at five obstetric health facilities that participated in the BABY study which enrolled mothers living with HIV and their HIV exposed infants who were followed up until 6 weeks post-delivery. Nurses and laboratory personnel were trained and performed HEID procedures using the Xpert HIV-1 Qual PoC systems. Involved personnel were interviewed on feasibility, knowledge and competency of procedures and overall impression of the use of HIV-1 Qual PoC system in clinical settings. RESULTS: A total of 28 health care workers (HCWs) who participated in the study between 2014 and 2016 were interviewed, 23 being nurses, 1 clinical officer, 1 lab scientist and 3 lab technicians The median age was 39.5 years. Majority of the nurses (22/24) and all lab staff were confident using Gene Xpert PoC test after being trained. None of them rated Gene Xpert handling as too complicated despite minor challenges. Five HCWs (5/24) reported power cut as the most often occurring problem. As an overall impression, all interviewees agreed on PoC HEID to be used in clinical settings however, about half of them (11/24) indicated that the PoC-HEID procedures add a burden onto their routine workload. CONCLUSION: Overall, health care workers in our study demonstrated very good perceptions and experiences of using PoC HEID. Efforts should be invested on quality training, targeted task distribution at the clinics, continual supportive supervision and power back up mechanisms to make the wide-scale adoption of nurse based PoC HEID testing a possibility.

Resistance Mutation Patterns among HIV-1-Infected Children and Features of the Program for Prevention of Mother-to-Child Transmission in Vietnam's Central Highlands and Southern Regions, 2017-2021.

The Vietnam Ministry of Health (MOH) has intensified efforts in its aim to eliminate AIDS by 2030. Expanding the program for prevention of mother-to-child transmission (PMTCT) is a significant step towards achieving this goal. However, there are still HIV-exposed children who do not have access to PMTCT services, and some who have participated in the program but still contracted HIV. This study focused on assessing the prevalence and profile of HIV mutations among children under 18 months of age who had recently tested positive for HIV, while gaining insights into the implementation of early infant diagnostic (EID) tests. Between 2017 and 2021, 3.43% of 5854 collected dry blood spot (DBS) specimens from Vietnam's Central and Southern regions showed positive EID results. This study identified a high prevalence of resistance mutations in children, totaling 62.9% (95% CI: 53.5-72.3). The highest prevalence of mutations was observed for NNRTIs, with 57.1% (95% CI: 47.5-66.8). Common mutations included Y181C and K103N (NNRTI resistance), M184I/V (NRTI resistance), and no major mutations for PI. The percentage of children with any resistance mutation was significantly higher among those who received PMTCT interventions (69.2%; 95% CI: 50.5-92.6%) compared with those without PMTCT (45.0%; 95% CI: 26.7-71.1%) with χ2 = 6.06, p = 0.0138, and OR = 2.75 (95% CI: 1.13-6.74). Mutation profiles revealed that polymorphic mutations could be present regardless of whether PMTCT interventions were implemented or not. However, non-polymorphic drug resistance mutations were predominantly observed in children who received PMTCT measures. Regarding PMTCT program characteristics, this study highlights the issue of late access to HIV testing for both mothers and their infected children. Statistical differences were observed between PMTCT and non-PMTCT children. The proportion of late detection of HIV infection and breastfeeding rates were significantly higher among non-PMTCT children (p < 0.05). Comparative analysis between children with low viral load (≤200 copies/mL) and high viral load (>200 copies/mL) showed significant differences between the mothers' current ART regimens (p = 0.029) and the ARV prophylaxis regimen for children (p = 0.016). These findings emphasize the need for comprehensive surveillance to assess the effectiveness of the PMTCT program, including potential transmission of HIV drug-resistance mutations from mothers to children in Vietnam.

Effects of the COVID-19 pandemic on early infant diagnosis of HIV in Cape Town, South Africa.

Background: In South Africa, infants who are HIV-exposed are tested for HIV at birth and 10 weeks of age. The COVID-19 pandemic lockdown restrictions resulted in reduced access to healthcare services and uncertain impact on early infant HIV testing. Objectives: To describe the effects of the COVID-19 pandemic lockdown restrictions on early infant HIV testing and diagnosis in Cape Town, South Africa. Method: This retrospective cohort study compares HIV-exposed infants born during the first COVID-19 pandemic lockdown (2020) to those born in the same period the year before (2019). Laboratory and other data were abstracted from the Provincial Health Data Centre. Results: A total of 2888 infants were included: 1474 born in 2020 and 1413 in 2019. Compared to 2019, there was an increase in the 10-week HIV polymerase chain reaction (PCR) uptake in 2020 (71% vs. 60%, P < 0.001). There was also an increase in the proportion of infants who demised without 10-week testing or were lost to follow-up in 2020 compared to 2019 (8% vs. 5%, P = 0.017). Differences detected in birth HIV PCR positivity rates between the two groups (1.1% vs. 0.5%, P = 0.17) did not reach statistical significance; however, a significant increase in vertical transmission of HIV by 10 weeks old was found in the 2020 cohort (1.2% vs. 0.5%. P = 0.046). Conclusion: Vertical transmission of HIV at 10 weeks increased in the Cape Town Metropolitan during the initial COVID-19 lockdown. There was also an increase in the proportion of deaths without testing by 10 weeks in the 2020 group.

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

BACKGROUND: India 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. METHODS: The 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. RESULTS: The 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. DISCUSSION: The 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. CONCLUSION: The study findings have high significance for developing program implementation strategies to improve access and to build right-based and patient-centred EID services.

Early infant diagnosis of HIV infection: a mixed-method study of uptake and challenges at primary health centers in Lagos State, Nigeria.

INTRODUCTION: Nigeria has a low uptake of early infant diagnosis (EID) of HIV despite its high pediatric HIV infection rate. Efforts to increase the EID of HIV have been limited by many factors. This research assessed EID uptake and challenges service providers experienced in providing routine care for HIV-exposed infants. METHODS: This is a mixed-method study at primary health centers (PHCs) in Lagos state, Nigeria. The quantitative component of the research was a review of the PMTCT Infant Follow-up Register at a purposive sample of 22 PHCs of Lagos State. The number of HIV-exposed infants (HEIs) returned for a dried blood sample (DBS) collection, date of collection, and the infant's EID results for one year preceding the study were captured on Research Electronic Data Capture (RedCap). In-depth interviews were conducted with service providers purposively selected per participating PHC. Electronic transcripts were analyzed using MAXQDA 2020 (VERBI Software, 2019). RESULTS: Twenty-two Lagos State primary health centers participated in the research. Fifteen PHCs (68.2%) had PMTCT HIV counseling and Infant follow-up registers. Documentation of DBS sample collection was observed in 12 (54.6%) PHCs. Both DBS sample collection and EID results documentation were observed in only nine (40.9%) PHCs. In-depth interviews revealed both maternal and health systems' challenges to EID. The denial of HIV status was the only maternal factor reported as a barrier against the use of EID services. Health systems challenges include unavailability of EID services, uncertainty regarding whether EID is performed in a facility, referral to secondary health facilities for EID services (leading to losses to follow-up), and delay in getting results of EID. Task-shifting of DBS collection by nurses was suggested as means to increase access to EID services. CONCLUSIONS: There is a need to expand EID services and address women's denial of HIV infection. Counseling women and linkage to available services are emphasized. Re-training of health workers on DBS collection and proper documentation of EID services were noted as key to improving the implementation of early infant diagnosis of HIV in the state.

Eliminating Vertical Transmission of HIV in South Africa: Establishing a Baseline for the Global Alliance to End AIDS in Children.

To gain a detailed overview of vertical transmission in South Africa, we describe insights from the triangulation of data sources used to monitor the national HIV program. HIV PCR results from the National Health Laboratory Service (NHLS) were analysed from the National Institute of Communicable Diseases (NICD) data warehouse to describe HIV testing coverage and positivity among children <2 years old from 2017-2021. NICD data were compared and triangulated with the District Health Information System (DHIS) and the Thembisa 4.6 model. For 2021, Thembisa estimates a third of children living with HIV go undiagnosed, with NICD and DHIS data indicating low HIV testing coverage at 6 months (49%) and 18 months (33%) of age, respectively. As immunisation coverage is reported at 84% and 66% at these time points, better integration of HIV testing services within the Expanded Programme for Immunization is likely to yield improved case findings. Thembisa projects a gradual decrease in vertical transmission to 450 cases per 100,000 live births by 2030. Unless major advances and strengthening of maternal and child health services, including HIV prevention, diagnosis, and care, can be achieved, the goal to end AIDS in children by 2030 in South Africa is unlikely to be realised.

Positivity rate, trend and associated risk factors of mother-to-child transmission of HIV among HIV-exposed infants.

BACKGROUND: Mother-To-Child-Transmission (MTCT) of Human Immunodeficiency Virus (HIV) occurs during pregnancy, delivery and breastfeeding, and cause infection among several new-borns. However, there is limited recent evidence on the burden of MTCT of HIV in Ethiopia from a large-scale data. Thus, this study aimed to determine the positivity rate, trend and associated risk factors of MTCT among HIV-exposed infants. METHODOLOGY: A cross-sectional study was conducted among 5,679 infants whose specimen referred to Ethiopian Public Health Institute HIV referral laboratory for Early Infant Diagnosis (EID) from January 01, 2016, to December 31, 2020. Data were extracted from the national EID database. Frequencies and percentages were used to summarize the data on characteristics of infants. Logistic regression analysis was employed to identify factors associated with positivity rate of MTCT of HIV. Level of significance was set at 5%. RESULTS: The mean age of the infants was 12.6 (± 14.6) weeks with an age range of 4 to 72 weeks. Half of the infants (51.4%) were female. The positivity rate of MTCT decreased from 2.9% in 2016 to 0.9% in 2020 with five-year average positivity rate of 2.6%. HIV test after six weeks (Adjusted odds ratio (AOR) = 2.7; 95% confidence interval (CI): (1.8-4.0,)); p < 0.001), absence of prevention of mother-to-child-transmission (PMTCT) service (AOR = 4.6; 95% CI: (2.9-7.4)); p = 0.001), nevirapine prophylaxis not received (AOR = 2.0; 95% CI: (1.3-3.2)); p < 0.001), and unknown ART status of the mother at delivery (AOR = 11; 95% CI: (5.5-22.1)); p < 0.001) were significantly associated with MTCT of HIV. CONCLUSION: The positivity rate of MTCT of HIV was showing declining tendency gradually in the study period. Strengthening PMTCT service, early HIV screening and starting ART for pregnant women, and early infant diagnosis are required to reduce the burden of HIV infection among infants exposed to HIV.

Verification of dried blood spot as a sample type for HIV viral load and early infant diagnosis on Hologic Panther in Zambia.

OBJECTIVE: Zambia has embarked on improving the diagnostic capacity by setting up high throughput and accurate machines in the testing process and introduction of dried blood spot (DBS) as a sample type. This was a cross sectional study to verify dried blood spot as a sample type for HIV viral load and early infant diagnosis (EID) on Hologic Panther platform and Evaluate the analytical performance (precision, linearity and measurement of uncertainty) of the Hologic Panther. RESULTS: The specificity and sensitivity of EID performance of Aptima Quant Dx assay on Hologic panther machine against the gold standard machine COBAS Taqman (CAP/CTM) was 100% with an overall agreement of 100%. The quantitative HIV Viral Load (VL) accuracy had a positive correlation of (0.96) obtained against the gold standard (plasma samples) run on COBAS4800 platform. Analytical performance of the Hologic panther machine was evaluated; Precision low positive repeatability 3.50154 and within lab 2.268915 at mean 2.88 concentration and precision high positive repeatability 1.116955 and within lab 2.010677 at mean 5.09 concentration were obtained confirming manufacturers claims. Uncertainty of measurement for this study was found to be ± 71 copies/ml. Linearity studies were determined and all points were within acceptable limits. We therefore recommend DBS as a sample type alternative to plasma for the estimation of HIV-1 viral load and EID diagnosis on the Hologic panther machine.

Determinants of Turn-Around-Time for Early Infant Diagnosis of HIV Testing: Retrospective Analysis of National Level PCR Testing Data.

India has been implementing one of the biggest Early Infant Diagnosis (EID) of HIV intervention globally. The turn-around-time (TAT) for EID test is one of the major factors for success of the program. This study was to assess the turnaround time and its determinants. It is a mixed methods study with quantitative analysis of retrospective data (2013-2016) collected from all the 7 Early Infant Diagnosis testing laboratories (called as regional reference laboratories or RRLs) in India and qualitative component that can help explain the determinants of turn-around-time. The retrospective national level data available from the RRLs was analyzed to measure the turn-around-time from the receipt of samples to the dispatch of results and to understand the determinants for the same. The 3 components transport time, testing time, and dispatch time were also calculated. Transport time was analyzed state-wise and the testing time RRL wise to understand disparities, if any. Qualitative interviews with the RRL officials were conducted to understand the underlying determinants of TAT. The Median turn-around-time ranged between 29 and 53 days over the 4 years. Transport time was significantly higher for states without RRL (42 days) than those with RRL (27 days). Testing time varied from RRL to RRL and was associated with incomplete forms, inadequate samples, kits logistics, staff turnover, staff training, and instrument related issues. The TAT is high and can be potentially reduced with interventions, such as decentralization of RRLs; courier systems for sample transport; and ensuring adequate resources at the RRL level.

Maternal retention and early infant HIV diagnosis in a prospective cohort study of HIV-positive women and their children in Malawi.

BACKGROUND: Post-partum loss to follow-up and lack of early HIV infant diagnosis (EID) can significantly affect the efficiency of programs for the prevention of mother-to-child transmission. METHODS: In a prospective observational study 167 women were enrolled at week 36 of gestation and followed with their infants up to one year after delivery. Retention was defined as the proportion of women who attended the 12 months visit and EID as an HIV PCR test performed within 2 months. Determinants for retention and EID were assessed in univariate analyses and in multivariable logistic regression models. RESULTS: Women lost to follow-up (24/167 or 14.4%) had a shorter duration of antiretroviral therapy (ART) at enrolment in comparison to women retained in care (p = 0.025). Lack of EID (occurring in 18.9% of the cases) was directly correlated, although not significantly, with a history of child death (p = 0.071), a higher educational level (p = 0.083), and female infant gender (p = 0.064). CONCLUSIONS: Longer duration of ART at enrolment significantly predicted a better post-partum retention, suggesting that specific counselling interventions should be targeted to recent ART initiators. A low proportion of infants did not receive an EID, but predictive factors were difficult to identify.

Validation of the point-of-care (POC) technologies Xpert HIV-1 Qual and m-PIMA HIV 1/2 detect for early diagnosis of HIV-1 and HIV-2 in Senegal.

Introduction: early infant diagnosis (EID) is crucial in the prevention of mother to child transmission (PMTCT) of human immunodeficiency virus (HIV) and is an essential component for the elimination of HIV. EID can be strengthened in resource-limited countries by the introduction and the roll out of real-time polymerase chain reaction (PCR) technologies via point-of-care (POC) devices which improves treatment in remote areas and reduces turnaround time for clinicians and patients to receive results and linkage to care. The objective of this study was to evaluate the performance of Xpert® HIV-1 Qual Assay (Cepheid) and m-PIMA™ HIV 1/2 Detect (ABBOTT) for EID of HIV-1 and HIV-2. Methods: the performance of the Xpert® HIV-1 qual device was evaluated with 192 samples including 100 dried blood spot (DBS) samples from the National Reference Laboratory biobank (71 negative and 29 positive samples) and an additional 92 whole blood samples collected from infants from neonatal departments. These infants from seven treatment centers in the Dakar region were born to mothers infected with HIV-1 (n=91), HIV-2 (n= 8) or HIV-1/2 (n=1). The m-PIMA™ HIV 1/2 detect assay was evaluated on whole blood samples (n=100) with 92 HIV-1 samples and 8 HIV-2 samples from children born to HIV-infected mothers. The Cobas AmpliPreP/Cobas TaqMan (CAP/CTM) platform from Roche Diagnostic Laboratories was used as a reference for HIV-1 diagnosis and the Generic HIV-2 Viral Load Assay (Biocentric) was used as a reference for HIV-2 diagnosis. Performance was evaluated by calculating sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and Cohen's kappa coefficient. Results: for HIV-1 detection on GeneXpert and m-PIMA, no discordance was found on the samples tested, i.e. a sensitivity of 100% (95% CI: 93.9-100%), a specificity of 100% (95% CI: 97.5-100%), a positive predictive value (PPV) of 100% (95% CI: 93.9-100%) and a negative predictive value (NPV) of 100% (95% CI: 97.5-100%). Agreement with Cobas AmpliPrep/Cobas TaqMan (CAP/CTM) was 100% with a Kappa coefficient of 1 (p<0.001, 95% CI) for both techniques. Similarly, the comparison between m-PIMA and generic biocentric for the detection of HIV-2 on the 8 samples tested showed perfect agreement. Conclusion: these results confirm the excellent performance of the Xpert® HIV-1 qual and m-PIMA™ HIV1/2 detect tests for the detection of HIV-1 and HIV-2 and encourage the extension of POC tests to improve access to EID in Senegal.

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.

BACKGROUND: Early 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. METHODS: DNA 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. RESULTS: The 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. CONCLUSION: The 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.

Delays in HIV-1 infant polymerase chain reaction testing may leave children without confirmed diagnoses in the Western Cape province, South Africa.

Background: Early diagnosis and confirmation of HIV infection in newborns is crucial for expedited initiation of antiretroviral therapy. Confirmatory testing must be done for all children with a reactive HIV PCR result. There is no comprehensive data on confirmatory testing and HIV PCR test request rejections at National Health Laboratory Service laboratories in South Africa. Objective: This study assessed the metrics of routine infant HIV PCR testing at the Tygerberg Hospital Virology Laboratory, Cape Town, Western Cape, South Africa, including the proportion of rejected test requests, turn-around time (TAT), and rate of confirmatory testing. Methods: We retrospectively reviewed laboratory-based data on all HIV PCR tests performed on children ≤ 24 months old (n = 43 346) and data on rejected HIV PCR requests (n = 1479) at the Tygerberg virology laboratory over two years (2017-2019). Data from sample collection to release of results were analysed to assess the TAT and follow-up patterns. Results: The proportion of rejected HIV PCR requests was 3.3%; 83.9% of these were rejected for various pre-analytical reasons. Most of the test results (89.2%) met the required 96-h TAT. Of the reactive initial test results, 53.5% had a follow-up sample tested, of which 93.1% were positive. Of the initial indeterminate results, 74.7% were negative on follow-up testing. Conclusion: A high proportion of HIV PCR requests were rejected for pre-analytical reasons. The high number of initial reactive tests without evidence of follow-up suggests that a shorter TAT is required to allow confirmatory testing before children are discharged.

Costs and cost-effectiveness of HIV early infant diagnosis in low- and middle-income countries: a scoping review.

BACKGROUND: Continuing progress in the global pediatric human immunodeficiency virus (HIV) response depends on timely identification and care of infants with HIV. As countries scale-out improvements to HIV early infant diagnosis (EID), economic evaluations are needed to inform program design and implementation. This scoping review aimed to summarize the available evidence and discuss practical implications of cost and cost-effectiveness analyses of HIV EID. METHODS: We systematically searched bibliographic databases (Embase, MEDLINE and EconLit) and grey literature for economic analyses of HIV EID in low- and middle-income countries published between January 2008 and June 2021. We extracted data on unit costs, cost savings, and incremental cost-effectiveness ratios as well as outcomes related to health and the HIV EID care process and summarized results in narrative and tabular formats. We converted unit costs to 2021 USD for easier comparison of costs across studies. RESULTS: After title and abstract screening of 1278 records and full-text review of 99 records, we included 29 studies: 17 cost analyses and 12 model-based cost-effectiveness analyses. Unit costs were 21.46-51.80 USD for point-of-care EID tests and 16.21-42.73 USD for laboratory-based EID tests. All cost-effectiveness analyses stated at least one of the interventions evaluated to be cost-effective. Most studies reported costs of EID testing strategies; however, few studies assessed the same intervention or reported costs in the same way, making comparison of costs across studies challenging. Limited data availability of context-appropriate costs and outcomes of children with HIV as well as structural heterogeneity of cost-effectiveness modelling studies limits generalizability of economic analyses of HIV EID. CONCLUSIONS: The available cost and cost-effectiveness evidence for EID of HIV, while not directly comparable across studies, covers a broad range of interventions and suggests most interventions designed to improve EID are cost-effective or cost-saving. Further studies capturing costs and benefits of EID services as they are delivered in real-world settings are needed.

Usability of HIV-1 Assay Using DBS for Early Infant Diagnosis in Field Settings in Kenya.

BACKGROUND: The Xpert HIV-1 Qualitative assay has been in use in Kenya since 2016 for infant diagnosis of HIV. Recently, the assay has been improved and its impact of this on ease of use is yet to be determined. We sought to determine the usability of Xpert® HIV-1 Qual XC assay using dried blood spots (DBS) for early infant diagnosis following this improvement. METHODS: This was a cross-sectional usability study undertaken in 2 selected health facilities in Kenya from October 2020 to February 2021. The laboratory technicians were retrained for this study. HIV-exposed infants were recruited with the consent of their parents. Patient data were recorded, and DBS samples were collected from the infants and tested for HIV on the improved assay. Each laboratory technician performing the assay documented usability characteristics on the provided questionnaire. Data on test errors were collected from the machine logs and analyzed using STATA for Windows. RESULTS: Of 313 test cartridges, 265 (84.66%) were successfully tested on the GeneXpert platform, and 263 valid outcomes were used for comparison with the Roche CAP/CTM HIV-1 Qualitative assay. The sensitivity, specificity, and accuracy of the Xpert HIV-1 Qualitative assay on DBS was 100%. Overall, 48 (15.34%) errors were recorded; 40 (83.33%) were user related and 8 (16.67%) were hardware related. All 4 (4/4, 100%) participating laboratory technicians said the assay had a simple workflow, was easy to use, the tests results were easy to interpret, and the assay throughput was sufficient for their workload. CONCLUSIONS: The improved Xpert HIV-1 Qual XC assay is highly accurate, has a simple workflow, and is easy to use and easy to interpret. Both hardware- and user- related errors are common.

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

OBJECTIVES: We 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. METHODS: Retrospective 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. RESULTS: Among 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). DISCUSSION: Indeterminate 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.

A Randomized Trial of Point-of-Care Early Infant Human Immunodeficiency Virus (HIV) Diagnosis in Zambia.

BACKGROUND: Point-of-care (POC) early infant diagnosis (EID) provides same-day results and the potential for immediate initiation of antiretroviral therapy (ART). METHODS: We conducted a pragmatic trial at 6 public clinics in Zambia. HIV-exposed infants were individually randomized to either (1) POC EID (onsite testing with the Alere q HIV-1/2 Detect) or (2) enhanced standard of care (SOC) EID (off-site testing at a public laboratory). Infants with HIV were referred for ART and followed for 12 months. Our primary outcome was defined as alive, in care, and virally suppressed at 12 months. RESULTS: Between March 2016 and November 2018, we randomized 4000 HIV-exposed infants to POC (n=1989) or SOC (n=2011). All but 2 infants in the POC group received same-day results, while the median time to result in the SOC group was 27 (interquartile range: 22-30) days. Eighty-one (2%; 95% confidence interval [CI]: 1.6-2.5%) infants were diagnosed with HIV. Although ART initiation was high, there were 15 (19%) deaths, 15 (19%) follow-up losses, and 31 (38%) virologic failures. By 12 months, only 20 of 81 (25%; 95% CI: 15-34%) infants with HIV were alive, in care, and virally suppressed: 13 (30%; 16-43%) infants in the POC group vs 7 (19%; 6-32%) in the SOC group (RR: 1.56; .7-3.50). CONCLUSIONS: POC EID eliminated diagnostic delays and accelerated ART initiation but did not translate into definitive improvement in 12-month outcomes. In settings where centralized EID is well functioning, POC EID is unlikely to improve pediatric HIV outcomes. CLINICAL TRIALS REGISTRATION: This trial is registered at https://clinicaltrials.gov (NCT02682810).

Delays in HIV-1 infant polymerase chain reaction testing may leave children without confirmed diagnoses in the Western Cape province, South Africa

Background: Early diagnosis and confirmation of HIV infection in newborns is crucial for expedited initiation of antiretroviral therapy. Confirmatory testing must be done for all children with a reactive HIV PCR result. There is no comprehensive data on confirmatory testing and HIV PCR test request rejections at National Health Laboratory Service laboratories in South Africa.Objective: This study assessed the metrics of routine infant HIV PCR testing at the Tygerberg Hospital Virology Laboratory, Cape Town, Western Cape, South Africa, including the proportion of rejected test requests, turn-around time (TAT), and rate of confirmatory testing.Methods: We retrospectively reviewed laboratory-based data on all HIV PCR tests performed on children ≤ 24 months old (n = 43346) and data on rejected HIV PCR requests (n = 1479) at the Tygerberg virology laboratory over two years (2017­2019). Data from sample collection to release of results were analysed to assess the TAT and follow-up patterns.Results: The proportion of rejected HIV PCR requests was 3.3%; 83.9% of these were rejected for various pre-analytical reasons. Most of the test results (89.2%) met the required 96-h TAT. Of the reactive initial test results, 53.5% had a follow-up sample tested, of which 93.1% were positive. Of the initial indeterminate results, 74.7% were negative on follow-up testing.Conclusion: A high proportion of HIV PCR requests were rejected for pre-analytical reasons. The high number of initial reactive tests without evidence of follow-up suggests that a shorter TAT is required to allow confirmatory testing before children are discharged.

Evaluation of an SMS-based mHealth intervention to enhance early infant diagnosis follow-up testing and assessment of postnatal prophylaxis.

BACKGROUND: Adherence to infant antiretroviral (ARV) postnatal prophylaxis and early infant diagnosis (EID) uptake is low in Africa. Promoting EID and adherence are necessary for this age group. OBJECTIVES: We evaluated an SMS-based mobile health (mHealth) intervention to enhance adherence to ARV prophylaxis and knowledge of EID and prevention of mother-to-child transmission (PMTCT) among high-risk and low-risk mother-infant pairs. METHOD: Two hundred and fifty-one mothers were recruited from King Edward VIII Hospital between December 2018 and October 2019. Participant information was captured, and SMS reminders were sent postnatally to promote immunisation attendance. Follow-up HIV polymerase chain reaction (PCR) test results were reviewed, and telephonic interviews were utilised for qualitative data. RESULTS: In all, 73.3% of infants had HIV PCR tests performed at 10 weeks. This high rate could be attributed to the mHealth intervention as this is considerably higher than other national studies, though not statistically significant compared to rates reported in the district at the same time. Factors that have impacted follow-up EID rates include poor maternal knowledge of EID time points and inadequate implementation of national PMTCT protocols. High-risk mothers were younger, commenced antenatal clinic visit later, were less knowledgeable on prophylaxis and have lower-birthweight infants than lower-risk mothers. CONCLUSION: mHealth can play an important role in improving EID by increasing maternal knowledge. Further studies should focus on whether maternal education over an mHealth platform can increase knowledge on PMTCT and subsequently increase EID.