Early Infant Diagnosis Testing Research Articles

How paediatric HIV services weathered the COVID-19 storm in Tshwane District, South Africa.

The coronavirus disease 2019 (COVID-19) pandemic disrupted paediatric HIV services across South Africa. Shortly before COVID-19, updated national HIV guidelines were released. This study describes COVID-19's impact on paediatric HIV services in Tshwane District, South Africa. A retrospective review of National Institute for Communicable Diseases and District Health Information System data for Tshwane District from April 2019 to March 2022. Data included: Early Infant Diagnosis (EID), HIV viral load (VL) and CD4 monitoring and HIV management among children (< 15 years) living with HIV (CLHIV). Pre-pandemic (2019/2020) and pandemic periods (2020/2021, 2021/2022) were compared. Year-on-year, HIV testing improved at 10 weeks, 6 months, and 18 months, whereas birth testing decreased. HIV EID case rates were 485 (2019/2020), 410 (2020/2021) and 454 (2021/2022). HIV EID test positivity was 0.77% - 1.2%. Antiretroviral treatment initiation declined from 2019/2020 to 2020/2021, but improved in 2021/2022.Initial HIV VL and CD4 testing declined, with HIV VL testing increasing in 2021/2022, and CD4 testing further declining. HIV VL suppression rate among CLHIV ranged from 69% to 73%. Initially, COVID-19 resulted in reduced paediatric HIV services as children disengaged from care. Indicators eventually recovered to proximate pre-pandemic levels; however, compensatory increases did not occur. Thus, some children may not have returned to care.

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

BackgroundUganda 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.MethodsWe 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.ResultsData 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).ConclusionPOC 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.

Human Immunodeficiency Virus Treatment Roll-Up: Challenges for Military Health Facilities in Cameroon in Sample Collection for Viral Load Testing and Early Infant Diagnosis

HIV viral load testing is an important element in the HIV elimination process, as it enables the efficacy of treatment to be assessed and, consequently, the patient’s viral suppression process to be monitored. A number of factors can affect the results of viral load tests, distorting patient outcomes and affecting follow-up. In developing countries, these challenges, linked to the technical platform, are much more likely to be encountered in the health facilities responsible for the pre-analytical phase, and can therefore compromise sample integrity. The aim of the study was to assess the challenges faced by Cameroon’s military health facilities in collecting samples for viral load and early infant diagnosis. A survey was carried out to 22 military health facilities to supervise sample collection activities using a specific grid. Data were recorded into the Google forms interface and followed by analysis using Microsoft office Excel 2013. 95% of facilities had a long working experience of over two (02) years for each type of handling. Only 27% of facilities used blood sampling protocols to the vacuum system in the HIV-VL test. During the survey, 18% of sites did not have a centrifuge and used decantation at room temperature. Additionally, 64% of health facilities did not fill in temperature control sheets properly, 23% jeopardize the cold chain due to insufficient cold accumulators or poorly maintained coolers. Only eight (08) health facilities did a HIV early infant diagnosis testing. The required technical platform was not present in all health facilities, and staff technical skills in charge of the pre-analytical stages were still not as high as expected. This is a call to strengthen the capacity of sample collection sites to achieve the WHO’s goal of eliminating HIV transmission by 2030.

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.

Improved access to HIV diagnosis and linkage to antiretroviral therapy among children in Southern Nigeria: a before-after study

BackgroundGlobally, two out of five children living with HIV (CLHIV) are unaware of their HIV status, and a little more than 50% are receiving antiretroviral therapy (ART). This paper describes case-finding strategies and their contribution to identifying CLHIV and linking them to ART in Nigeria.MethodsThis before-after study used program data abstracted during the implementation of different paediatric-focused strategies (provider-initiated testing and counselling, orphans and vulnerable children testing, family-based index testing, early infant diagnosis (EID), community-driven EID, and community-based testing) delivered in health facilities and in communities to improve HIV case identification. Data were abstracted for children (0 to 14 years) who received HIV testing services and were initiated on ART in Akwa Ibom State, Nigeria during the pre-implementation period (April–June 2021) and during the implementation period (July–September 2021). Descriptive statistics were used to describe the testing coverage, positivity rate (proportion of tests that were positive for HIV), linkage to ART, and ART coverage, by age, sex, and testing modality. Interrupted time series analysis (ITSA) on STATA 14 was used to estimate the effect of the implementation of these strategies on HIV testing uptake and positivity rate at a 0.05 significance level.ResultsA total of 70,210 children were tested for HIV within the six-month period, and 1,012 CLHIV were identified. A total of 78% (n = 54,821) of the tests and 83.4% (n = 844) CLHIV were diagnosed during the implementation period. During implementation, the HIV positivity rate increased from 1.09% (168/15,389) to 1.54% (844/54,821), while linkage to ART increased from 99.4% (167/168) to 99.8% (842/844). The contribution from community-based modalities to CLHIV identified increased from 63% (106/168) to 84% (709/844) during the implementation, with the majority, 60.8% (431/709), from community-based index testing. Overall, ART coverage increased from 39.7 to 55.6% at the end of the intervention period.ConclusionThe findings show that expanding differentiated HIV testing approaches provided mostly in the community significantly increased pediatric case identification. However, ART coverage remains low, especially for younger age groups, and requires further efforts.

Cost-effectiveness of point-of-care versus centralised, laboratory-based nucleic acid testing for diagnosis of HIV in infants: a systematic review of modelling studies

Point-of-care (POC) nucleic acid testing for diagnosis of HIV in infants facilitates earlier initiation of antiretroviral therapy (ART) than with centralised (standard-of-care, SOC) testing, but can be more expensive. We evaluated cost-effectiveness data from mathematical models comparing POC with SOC to provide global policy guidance. In this systematic review of modelling studies, we searched PubMed, MEDLINE, Embase, the National Health Service Economic Evaluation Database, Econlit, and conference abstracts, combining terms for "HIV" + "infant"/"early infant diagnosis" + "point-of-care" + "cost-effectiveness" + "mathematical models", without restrictions from database inception to July 15, 2022. We selected reports of mathematical cost-effectiveness models comparing POC with SOC for HIV diagnosis in infants younger than 18 months. Titles and abstracts were independently reviewed, with full-text review for qualifying articles. We extracted data on health and economic outcomes and incremental cost-effectiveness ratios (ICERs) for narrative synthesis. The primary outcomes of interest were ICERs (comparing POC with SOC) for ART initiation and survival of children living with HIV. Our search identified 75 records through database search. 13 duplicates were excluded, leaving 62 non-duplicate articles. 57 records were excluded and five were reviewed in full text. One article was excluded as it was not a modelling study, and four qualifying studies were included in the review. These four reports were from two mathematical models from two independent modelling groups. Two reports used the Johns Hopkins model to compare POC with SOC for repeat early infant diagnosis testing in the first 6 months in sub-Saharan Africa (first report, simulation of 25 000 children) and Zambia (second report, simulation of 7500 children). In the base scenario, POC versus SOC increased probability of ART initiation within 60 days of testing from 19% to 82% (ICER per additional ART initiation range US$430-1097; 9-month cost horizon) in the first report; and from 28% to 81% in the second ($23-1609, 5-year cost horizon). Two reports compared POC with SOC for testing at 6 weeks in Zimbabwe using the Cost-Effectiveness of Preventing AIDS Complications-Paediatric model (simulation of 30 million children; lifetime horizon). POC increased life expectancy and was considered cost-effective compared with SOC (ICER $711-850 per year of life saved in HIV-exposed children). Results were robust throughout sensitivity and scenario analyses. In most scenarios, platform cost-sharing (co-use with other programmes) resulted in POC being cost-saving compared with SOC. Four reports from two different models suggest that POC is a cost-effective and potentially cost-saving strategy for upscaling of early infant testing compared with SOC. Bill & Melinda Gates Foundation, Unitaid, National Institute of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, WHO, and Massachusetts General Hospital Research Scholars.

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.

The effect of the Xpert HIV-1 Qual test on early infant diagnosis of HIV in Myanmar and Papua New Guinea: a pragmatic, cluster-randomised, stepped-wedge, open-label trial.

Despite proven benefits for child health, coverage of early infant diagnosis of HIV remains suboptimal in many settings. We aimed to assess the effect of a point-of-care early infant diagnosis test on time-to-results communication for infants vertically exposed to HIV. This pragmatic, cluster-randomised, stepped-wedge, open-label trial assessed the effect of the Xpert HIV-1 Qual early infant diagnosis test (Cepheid) on time-to-results communication, compared with standard care laboratory-based testing of dried blood spots using PCR. Hospitals were the unit of randomisation for one-way crossover from control to intervention phase. Each site had between 1 month and 10 months of control phase before transitioning to the intervention, with a total of 33 hospital-months in the control phase and 45 hospital-months in the intervention phase. We enrolled infants vertically exposed to HIV at six public hospitals: four in Myanmar and two in Papua New Guinea. Infants had to have mothers with confirmed HIV infection, be younger than 28 days, and required HIV testing to be eligible for enrolment. Health-care facilities providing prevention of vertical transmission services were eligible for participation. The primary outcome was communication of early infant diagnosis results to the infant's caregiver by 3 months of age, assessed by intention to treat. This completed trial was registered with the Australian and New Zealand Clinical Trials Registry, 12616000734460. In Myanmar, recruitment took place between Oct 1, 2016, and June 30, 2018; in Papua New Guinea, recruitment was between Dec 1, 2016, and Aug 31, 2018. A total of 393 caregiver-infant pairs were enrolled in the study across both countries. Independent of study time, the Xpert test reduced time to early infant diagnosis results communication by 60%, compared with the standard of care (adjusted time ratio 0·40, 95% CI 0·29-0·53, p<0·0001). In the control phase, two (2%) of 102 study participants received an early infant diagnosis test result by 3 months of age compared with 214 (74%) of 291 in the intervention phase. No safety and adverse events were reported related to the diagnostic testing intervention. This study reinforces the importance of scaling up point-of-care early infant diagnosis testing in resource-constrained and low HIV-prevalence settings, typical of the UNICEF East Asia and Pacific region. National Health and Medical Research Council of Australia.

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.

Toward elimination of mother-to-child transmission of HIV in Malawi: Findings from the Malawi Population-based HIV Impact Assessment (2015-2016).

Malawi spearheaded the development and implementation of Option B+ for prevention of mother-to-child transmission of HIV (PMTCT), providing life-long ART for all HIV-positive pregnant and breastfeeding women. We used data from the 2015-2016 Malawi Population-based HIV Impact Assessment (MPHIA) to estimate progress toward 90-90-90 targets (90% of those with HIV know their HIV-positive status; of these, 90% are receiving ART; and of these, 90% have viral load suppression [VLS]) for HIV-positive women reporting a live birth in the previous 3 years. MPHIA was a nationally representative household survey; consenting eligible women aged 15-64 years were interviewed on pregnancies and outcomes, including HIV status during their most recent pregnancy, PMTCT uptake, and early infant diagnosis (EID) testing. Descriptive analyses were weighted to account for the complex survey design. Viral load (VL) results were categorized by VLS (<1,000 copies/mL) and undetectable VL (target not detected/below the limit of detection). Of the 3,153 women included in our analysis, 371 (10.1%, 95% confidence interval [CI]: 8.8%-11.3%) tested HIV positive in the survey. Most HIV-positive women (84.2%, 95% CI: 79.9%-88.6%) reported knowing their HIV-positive status; of these, 94.9% (95% CI: 91.7%-98.2%) were receiving ART; and of these, 91.2% (95% CI: 87.4%-95.0%) had VLS. Among the 371 HIV-positive women, 76.0% (95% CI: 70.4%-81.7%) had VLS and 66.5% (95% CI: 59.8%-73.2%) had undetectable VL. Among 262 HIV-exposed children, 50.8% (95% CI: 42.8%-58.8%) received EID testing within 2 months of birth, whereas 17.9% (95% CI: 11.9%-23.8%) did not receive EID testing. Of 190 HIV-exposed children with a reported HIV test result, 2.1% (95% CI: 0.0%-4.6%) had positive results. MPHIA data demonstrate high PMTCT uptake at a population level. However, our results identify some gaps in VLS in postpartum women and EID testing.

HIV viral load assays when used with whole blood perform well as a diagnostic assay for infants.

Over the past several years, only approximately 50% of HIV-exposed infants received an early infant diagnosis test within the first two months of life. While high attrition and mortality account for some of the shortcomings in identifying HIV-infected infants early and putting them on life-saving treatment, fragmented and challenging laboratory systems are an added barrier. We sought to determine the accuracy of using HIV viral load assays for infant diagnosis of HIV. We enrolled 866 Ugandan infants between March-April 2018 for this study after initial laboratory diagnosis. The median age was seven months, while 33% of infants were less than three months of age. Study testing was done using either the Roche or Abbott molecular technologies at the Central Public Health Laboratory. Dried blood spot samples were prepared according to manufacturer-recommended protocols for both the qualitative and quantitative assays. Viral load test samples for the Roche assay were processed using two different buffers: phosphate-buffered saline (PBS: free virus elution viral load protocol [FVE]) and Sample Pre-Extraction Reagent (SPEX: qualitative buffer). Dried blood spot samples were processed for both assays on the Abbott using the manufacturer's standard infant diagnosis protocol. All infants received a qualitative test for clinical management and additional paired quantitative tests. 858 infants were included in the analysis, of which 50% were female. Over 75% of mothers received antiretroviral therapy, while approximately 65% of infants received infant prophylaxis. The Roche SPEX and Abbott technologies had high sensitivity (>95%) and specificity (>98%). The Roche FVE had lower sensitivity (85%) and viral load values. To simplify and streamline laboratory practices, HIV viral load may be used to diagnose HIV infection in infants, particularly using the Roche SPEX and Abbott technologies.

"Testing Can Be Done Anywhere": A Qualitative Assessment of Targeted Community-Based Point-of-Care Early Infant Diagnosis of HIV in Lusaka, Zambia.

Delayed HIV diagnosis in HIV-exposed infants (HEIs) results in missed opportunities for early antiretroviral therapy (ART), causing significant morbidity and mortality. Early infant diagnosis (EID) depends on the availability of accessible and reliable testing services. We explored the acceptability, appropriateness, and feasibility of deploying a targeted community-based point-of-care (POC) EID testing model (i.e., "community POC model") to reach high-risk mother-infant pairs (MIPs) in Lusaka, Zambia. We conducted in-depth interviews with a purposive sample of health care workers, study staff, and caregivers in high-risk MIPs at 6 health facilities included in a larger implementation research study evaluating the community POC model. We defined "high-risk MIPs" as mothers who did not receive antenatal testing or an attended delivery or infants who missed EID testing milestones. Interviews were audio-recorded, translated, and transcribed verbatim in English. Content and thematic analysis were done using NVivo 10 software. Health care workers (n=20) and study staff (n=12) who implemented the community POC model noted that the portability and on-screen prompts of the POC platform made it mobile and easy to use, but maintenance and supply chain management were key to field operations. Respondents also felt that the community POC model reached more infants who had never had EID testing, allowing them to find infants with HIV infection and immediately initiate them on ART. Caregivers (n=22) found the community POC model acceptable, provided that privacy could be ensured because the service was convenient and delivered close to home. We demonstrate the acceptability, appropriateness, and feasibility of implementing the community POC model in Zambia, while identifying potential challenges related to client privacy and platform field operations. The community POC model may represent a promising strategy to further facilitate active HIV case finding and linkage to ART for children with undiagnosed HIV infection in the community.

Motivational interviewing retention counseling and adherence to early infant diagnostic HIV testing schedule in South Africa: The PAEDLINK randomized trial.

Introduction:We report the PAEDLINK randomized trial results on the effect of motivational interviewing (MI) retention counseling on the adherence of postpartum women to the early infant diagnostic human immunodeficiency virus (HIV) testing schedule.Methods:HIV positive women and their babies were enrolled 3 to 6 days after delivery at 4 midwife obstetric units in the Gauteng province of South Africa and randomized into (A) MI retention counseling and telephonic tracing, (B) biannual telephonic tracing, and (C) standard care. Mother–baby pairs were followed up for 18 months via medical records. The uptake of child HIV tests and maternal retention in the 0 to 6 and 7 to 18 month periods were modeled using Log-binomial regression.Results:Overall, 501/711 enrolled mother–baby pairs received a second HIV polymerase chain reaction test by 6 months (70.0%, 70.5%, and 70.0% in groups A, B, and C, respectively). A higher proportion of intervention children (60.9%) were tested at 7 to 90 days than group B (48.1%, adjusted risk ratio [aRR] 0.8 for B vs A, 95% confidence interval [CI]: 0.7–0.9) and group C children (52.7%, aRR 0.9 for C vs A, 95% CI: 0.9–1.0). Child testing between 7 and 18-months was also higher in group A than C (10.7% A, vs 5.5% C, RR 2.0, 95% CI: 1.0–3.7). However, maternal retention was similar across groups, with 41.6% and 16.3% retained during the 0 to 6 and the 7 to 18-months periods, respectively.Conclusion:MI retention counseling can reduce delays in the early infant diagnosis testing schedule for HIV-exposed infants. However, further support is necessary to maximize later HIV tests and maternal retention.

The effect of weekly interactive text-messaging on early infant HIV testing in Kenya: a randomised controlled trial (WelTel PMTCT)

Mother-to-child transmission of HIV remains a significant concern in Africa despite earlier progress. Early infant diagnosis (EID) of HIV is crucial to reduce mortality among infected infants through early treatment initiation. However, a large proportion of HIV-exposed infants are still not tested in Kenya. Our objective was to investigate whether weekly interactive text-messages improved prevention of mother-to-child transmission (PMTCT) of HIV care outcomes including EID HIV testing. This multicentre, parallel-group, randomised, open-label trial included six antenatal care clinics across western Kenya. Pregnant women living with HIV, aged 18 years or older, with mobile phone access, were randomised in a 1:1 ratio to weekly text messages that continued until 24 months postpartum, asking “How are you?” (“Mambo?”) to which they were asked to respond within 48 h, or a control group. Healthcare workers contacted participants reporting problems and non-responders by phone. Participants in both groups received routine PMTCT care. The prespecified secondary outcome reported in this paper is EID HIV testing by eight weeks of age (blinded outcome assessment). Final 24-months trial results will be published separately. We estimated risk ratios using Poisson regression with robust standard errors. Between June 2015–July 2016, we screened 735 pregnant women, of whom 600 were enrolled: 299 were allocated to the intervention and 301 to the control group. By eight weeks of age, the uptake of EID HIV testing out of recorded live births was 85.5% in the intervention and 84.7% in the control group (71.2% vs. 71.8% of participants randomised, including miscarriages, stillbirths, etc.). The intention-to-treat risk ratio was 0.99; 95% CI: 0.90–1.10; p = 0.89. The proportion of infants diagnosed with HIV was 0.8% in the intervention and 1.2% in the control group. No adverse events were reported. We found no evidence to support that the WelTel intervention improved EID HIV testing. A higher uptake of EID testing than expected in both groups may be a result of lower barriers to EID testing and improved PMTCT care in western Kenya, including the broader standard use of mobile phone communication between healthcare workers and patients. (ISRCTN No. 98818734. Funded by the European-Developing Countries Clinical Trial Partnership and others).

Community-facility linkage models and maternal and infant health outcomes in Malawi's PMTCT/ART program: A cohort study.

BackgroundIn sub-Saharan Africa, 3 community-facility linkage (CFL) models—Expert Clients, Community Health Workers (CHWs), and Mentor Mothers—have been widely implemented to support pregnant and breastfeeding women (PBFW) living with HIV and their infants to access and sustain care for prevention of mother-to-child transmission of HIV (PMTCT), yet their comparative impact under real-world conditions is poorly understood.Methods and findingsWe sought to estimate the effects of CFL models on a primary outcome of maternal loss to follow-up (LTFU), and secondary outcomes of maternal longitudinal viral suppression and infant “poor outcome” (encompassing documented HIV-positive test result, LTFU, or death), in Malawi’s PMTCT/ART program. We sampled 30 of 42 high-volume health facilities (“sites”) in 5 Malawi districts for study inclusion. At each site, we reviewed medical records for all newly HIV-diagnosed PBFW entering the PMTCT program between July 1, 2016 and June 30, 2017, and, for pregnancies resulting in live births, their HIV-exposed infants, yielding 2,589 potentially eligible mother–infant pairs. Of these, 2,049 (79.1%) had an available HIV treatment record and formed the study cohort. A randomly selected subset of 817 (40.0%) cohort members underwent a field survey, consisting of a questionnaire and HIV biomarker assessment. Survey responses and biomarker results were used to impute CFL model exposure, maternal viral load, and early infant diagnosis (EID) outcomes for those missing these measures to enrich data in the larger cohort. We applied sampling weights in all statistical analyses to account for the differing proportions of facilities sampled by district. Of the 2,049 mother–infant pairs analyzed, 62.2% enrolled in PMTCT at a primary health center, at which time 43.7% of PBFW were ≤24 years old, and 778 (38.0%) received the Expert Client model, 640 (31.2%) the CHW model, 345 (16.8%) the Mentor Mother model, 192 (9.4%) ≥2 models, and 94 (4.6%) no model. Maternal LTFU varied by model, with LTFU being more likely among Mentor Mother model recipients (adjusted hazard ratio [aHR]: 1.45; 95% confidence interval [CI]: 1.14, 1.84; p = 0.003) than Expert Client recipients. Over 2 years from HIV diagnosis, PBFW supported by CHWs spent 14.3% (95% CI: 2.6%, 26.1%; p = 0.02) more days in an optimal state of antiretroviral therapy (ART) retention with viral suppression than women supported by Expert Clients. Infants receiving the Mentor Mother model (aHR: 1.24, 95% CI: 1.01, 1.52; p = 0.04) and ≥2 models (aHR: 1.44, 95% CI: 1.20, 1.74; p < 0.001) were more likely to undergo EID testing by age 6 months than infants supported by Expert Clients. Infants receiving the CHW and Mentor Mother models were 1.15 (95% CI: 0.80, 1.67; p = 0.44) and 0.84 (95% CI: 0.50, 1.42; p = 0.51) times as likely, respectively, to experience a poor outcome by 1 year than those supported by Expert Clients, but not significantly so. Study limitations include possible residual confounding, which may lead to inaccurate conclusions about the impacts of CFL models, uncertain generalizability of findings to other settings, and missing infant medical record data that limited the precision of infant outcome measurement.ConclusionsIn this descriptive study, we observed widespread reach of CFL models in Malawi, with favorable maternal outcomes in the CHW model and greater infant EID testing uptake in the Mentor Mother model. Our findings point to important differences in maternal and infant HIV outcomes by CFL model along the PMTCT continuum and suggest future opportunities to identify key features of CFL models driving these outcome differences.

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.

Operational experiences associated with the implementation of near point-of-care early infant diagnosis of HIV in Myanmar: a qualitative study

BackgroundTimely diagnosis and early initiation of life-saving antiretroviral therapy are critical factors in preventing mortality among HIV-infected infants. However, resource-limited settings experience numerous challenges associated with centralised laboratory-based testing, including low rates of testing, complex sample referral pathways and unacceptably long turnaround times for results. Point-of-care (POC) HIV testing for HIV-exposed infants can enable same-day communication of results and early treatment initiation for HIV-infected infants. However, complex operational issues and service integration can limit utility and must be well understood prior to implementation.We explored and documented the challenges and enabling factors in implementing the POC Xpert® HIV-1 Qual test (Cepheid, Sunnyvale, CA, USA) for early infant diagnosis (EID) as part of routine services in four public hospitals in Myanmar.MethodsThis sub-study was part of a randomised controlled stepped-wedge trial (Australian and New Zealand Clinical Trials Registry, number 12616000734460) designed to investigate the impact of POC testing for EID in Myanmar and Papua New Guinea. Infants recruited during the intervention phase underwent POC testing at the participating hospitals as part of routine care. Semi-structured interviews with 23 caregivers, 12 healthcare providers and 10 key informants were used to explore experiences of POC-EID testing. The research team and hospital staff documented and discussed implementation challenges throughout the study.ResultsOverall, caregivers and healthcare workers were satisfied with the short turnaround time of the POC test. Occasional delays in POC testing were mostly attributable to late receipt of samples by laboratory technicians and communication constraints among healthcare staff. Hospital staff valued technical assistance from the research group and the National Health Laboratory. Despite staff shortages and infrastructure challenges such as unreliable electricity supply and cramped space, healthcare workers and caregivers found the implementation of the POC test to be feasible at pilot sites.ConclusionsAs plans for national scale-up evolve, there needs to be a continual focus on staff training, communication pathways and infrastructure. Other models of care, such as allowing non-laboratory-trained personnel to perform POC testing, and cost effectiveness should also be evaluated.

Successful Use of Near Point-of-Care Early Infant Diagnosis in NAMPHIA to Improve Turnaround Times in a National Household Survey.

In the population-based HIV impact assessment surveys, early infant diagnosis (EID) was provided to infants <18 months without a prior diagnosis. For the Namibia population-based HIV impact assessment (NAMPHIA), the GeneXpert platform was assessed for the feasibility of near POC EID testing compared with the standard Roche COBAS AmpliPrep/COBAS TaqMan (CAP/CTM) platform. Quality assurance measures and turnaround time were compared to improve EID results reporting. NAMPHIA participants were screened for HIV exposure using Determine HIV-1/2 rapid test; samples reactive on Determine received EID testing on the GeneXpert instrument and Xpert HIV-1 Qual assay using whole blood. Results were confirmed at the Namibia Institute of Pathology using dried blood spots on the Roche CAP/CTM platform per national guidelines. Of the 762 screened infants, 61 (8.0%) were Determine-reactive and considered HIV-exposed. Of the 61 exposed infants, 2 were found to be HIV-infected whereas 59 were negative on both GeneXpert and Roche platforms, achieving 100% concordance. Average turnaround time was 3.4 days for the Xpert HIV-1 Qual assay, and average time from collection to testing was 1.0 days for GeneXpert compared with 10.7 days for Roche. No samples failed using GeneXpert whereas 1 sample failed using Roche and was repeated. Quality POC EID testing is feasible in a national survey through extensive training and external quality assurance measures. The use of decentralized POC EID for national testing would provide rapid diagnosis and improve TATs which may prevent loss to follow-up, ensure linkage to care, and improve clinical outcomes for infants.

Feasibility and impact of near-point-of-care integrated tuberculosis/HIV testing in Malawi and Zimbabwe

Near-point-of-care (POC) testing for early infant diagnosis (EID) and viral load expedites clinical action and improves outcomes but requires capital investment. We assessed whether excess capacity on existing near-POC devices used for TB diagnosis could be leveraged to increase near-POC HIV molecular testing, termed integrated testing, without compromising TB services. Preimplementation/postimplementation studies in 10 health facilities in Malawi and 8 in Zimbabwe. Timeliness of EID and viral load test results and clinical action were compared between centralized and near-POC testing using Somers' D tests (continuous indicators) and risk ratios (RR, binary indicators); TB testing/treatment rates and timeliness were analyzed preintegration/postintegration. With integration, average device utilization increased but did not exceed 55%. Despite the addition of HIV testing, TB test volumes, timeliness, and treatment initiations were maintained. Although few HIV-positive infants were identified, near-POC EID testing improved treatment initiation within 1 month by 57% compared with centralized EID [Malawi RR: 1.57, 95% confidence interval (CI) 0.98-2.52], and near-POC viral load testing significantly increased the proportion of patients with elevated viral load receiving clinical action within 1 month (Zimbabwe RR: 5.26, 95% CI 3.38-8.20; Malawi RR: 3.90, 95% CI 2.58-5.91). Integrating TB/HIV testing using existing multidisease platforms is feasible and enables increased access to rapid diagnostics without disrupting existing TB services. Our results serve as an example of a novel, efficient implementation model that can increase access to critical testing services across disease silos and should be considered for additional clinical applications.

The NSEBA Demonstration Project: implementation of a point-of-care platform for early infant diagnosis of HIV in rural Zambia.

OBJECTIVESTo describe the experience and resource requirements of implementing point-of-care testing for early infant diagnosis of HIV in rural Zambia.METHODSA demonstration project was conducted using a hub-and-spoke model in 2018–2019 at five clinics in rural Zambia. Two testing hubs were established, and all HIV-exposed infants were tested with the GeneXpert system. Data on costs, turnaround times and test results were collected.RESULTSSeven hundred and eighty six tests were conducted. At the hubs, results were available a median of 2.4 (IQR: 2.1, 2.8) hours after sample collection and most mothers (84%) received same-day results. At the spoke facilities, results were available a median of 9 days (IQR: 7, 12) after sample collection and provided to the mother a median of 16 days (IQR: 10, 28) after sample collection. Eleven children tested positive, and 9 (82%) started treatment a median of 13 days (IQR: 7, 21) after sample collection and on the day mothers received results. In contrast, results from matching samples sent for routine testing were available a median of 38 days (IQR: 27, 61) after sample collection and provided to the mother a median of 91 days (IQR: 47, 135) after sample collection.CONCLUSIONSImplementing point-of-care testing in a network of rural health centres in Zambia required significant initial and ongoing investment in infrastructure, training and supervision. However, point-of-care testing can rapidly diagnose HIV-infected infants, so they can benefit from early treatment.