High Prevalence of Unconfirmed Positive HIV PCR Test Results among African Infants with HIV Exposure in the International epidemiology Databases to Evaluate AIDS (IeDEA) Consortium.

In a large, multi-regional cohort of African infants with HIV exposure, 44% of those with a positive HIV PCR lacked a confirmatory positive test. Efforts are needed to ensure high-fidelity implementation of HIV testing algorithms, so that all positive results are confirmed thereby reducing the risk of potentially false-positive results.

Predictors of Cell-Associated Human Immunodeficiency Virus (HIV)-1 DNA Over 1 Year in Very Early Treated Infants.

BACKGROUND: Younger age of antiretroviral therapy (ART) initiation is associated with smaller viral reservoirs in perinatally acquired HIV-1 infection, but there is wide variability among early-treated infants. Predictors of this variability are not fully described. METHODS: Sixty-three neonates diagnosed with HIV-1 <48 hours after birth in Johannesburg, South Africa, were started on ART as soon as possible. Fifty-nine (94%) infants received nevirapine prophylaxis from birth until ART start. Viably preserved peripheral blood mononuclear cells (PBMCs) collected at regular intervals to 48 weeks, and from mothers at enrollment, were tested using integrase-targeted, semi-nested, real-time quantitative hydrolysis probe (TaqMan) PCR assays to quantify total HIV-1 subtype C viral DNA (vDNA). Predictors were investigated using generalized estimating equation regression. RESULTS: Thirty-one (49.2%) infants initiated ART <48 hours, 24 (38.1%) <14 days, and 8 (12.7%) >14 days of birth. Three-quarters were infected despite maternal antenatal ART (however, only 9.5% of women had undetectable viral load closest to delivery) and 86% were breastfed. Higher infant CD4+ T-cell percentage and viral load <100 000 copies/mL pre-ART were associated with lower vDNA in the first 48 weeks after ART start. No antenatal maternal ART and breastfeeding were also associated with lower vDNA. Older age at ART initiation had a discernible negative impact when initiated >14 days. CONCLUSIONS: Among very early treated infants, higher CD4+ T-cell percentage and viral load <100 000 copies/mL pre-ART, infection occurring in the absence of maternal antenatal ART, and breastfeeding were associated with lower levels of HIV-1 DNA in the first 48 weeks of treatment. Clinical Trials Registration. clinicaltrials.gov (NCT02431975).

Serious adverse drug reactions at two children's hospitals in South Africa.

BACKGROUND: The high HIV prevalence in South Africa may potentially be shaping the local adverse drug reaction (ADR) burden. We aimed to describe the prevalence and characteristics of serious ADRs at admission, and during admission, to two South African children's hospitals. METHODS: We reviewed the folders of children admitted over sequential 30-day periods in 2015 to the medical wards and intensive care units of each hospital. We identified potential ADRs using a trigger tool developed for this study. A multidisciplinary team assessed ADR causality, type, seriousness, and preventability through consensus discussion. We used multivariate logistic regression to explore associations with serious ADRs. RESULTS: Among 1050 patients (median age 11 months, 56% male, 2.8% HIV-infected) with 1106 admissions we found 40 serious ADRs (3.8 per 100 drug-exposed admissions), including 9/40 (23%) preventable serious ADRs, and 8/40 (20%) fatal or near-fatal serious ADRs. Antibacterials, corticosteroids, psycholeptics, immunosuppressants, and antivirals were the most commonly implicated drug classes. Preterm neonates and children in middle childhood (6 to 11 years) were at increased risk of serious ADRs compared to infants (under 1 year) and term neonates: adjusted odds ratio (aOR) 5.97 (95% confidence interval 1.30 to 27.3) and aOR 3.63 (1.24 to 10.6) respectively. Other risk factors for serious ADRs were HIV infection (aOR 3.87 (1.14 to 13.2) versus HIV-negative) and increasing drug count (aOR 1.08 (1.04 to 1.12) per additional drug). CONCLUSIONS: Serious ADR prevalence in our survey was similar to the prevalence found elsewhere. In our setting, serious ADRs were associated with HIV-infection and the antiviral drug class was one of the most commonly implicated. Similar to other sub-Saharan African studies, a large proportion of serious ADRs were fatal or near-fatal. Many serious ADRs were preventable.

Growth and Mortality Outcomes for Different Antiretroviral Therapy Initiation Criteria in Children Ages 1-5 Years: A Causal Modeling Analysis.

BACKGROUND: There is limited evidence regarding the optimal timing of initiating antiretroviral therapy (ART) in children. We conducted a causal modeling analysis in children ages 1-5 years from the International Epidemiologic Databases to Evaluate AIDS West/Southern-Africa collaboration to determine growth and mortality differences related to different CD4-based treatment initiation criteria, age groups, and regions. METHODS: ART-naïve children of ages 12-59 months at enrollment with at least one visit before ART initiation and one follow-up visit were included. We estimated 3-year growth and cumulative mortality from the start of follow-up for different CD4 criteria using g-computation. RESULTS: About one quarter of the 5,826 included children was from West Africa (24.6%).The median (first; third quartile) CD4% at the first visit was 16% (11%; 23%), the median weight-for-age z-scores and height-for-age z-scores were -1.5 (-2.7; -0.6) and -2.5 (-3.5; -1.5), respectively. Estimated cumulative mortality was higher overall, and growth was slower, when initiating ART at lower CD4 thresholds. After 3 years of follow-up, the estimated mortality difference between starting ART routinely irrespective of CD4 count and starting ART if either CD4 count <750 cells/mm³ or CD4% <25% was 0.2% (95% CI = -0.2%; 0.3%), and the difference in the mean height-for-age z-scores of those who survived was -0.02 (95% CI = -0.04; 0.01). Younger children ages 1-2 and children in West Africa had worse outcomes. CONCLUSIONS: Our results demonstrate that earlier treatment initiation yields overall better growth and mortality outcomes, although we could not show any differences in outcomes between immediate ART and delaying until CD4 count/% falls below 750/25%.

Augmenting maternal clinical cohort data with administrative laboratory dataset linkages: a validation study.

Background: The use of big data and large language models in healthcare can play a key role in improving patient treatment and healthcare management, especially when applied to large-scale administrative data. A major challenge to achieving this is ensuring that patient confidentiality and personal information is protected. One way to overcome this is by augmenting clinical data with administrative laboratory dataset linkages in order to avoid the use of demographic information. Methods: We explored an alternative method to examine patient files from a large administrative dataset in South Africa (the National Health Laboratory Services, or NHLS), by linking external data to the NHLS database using specimen barcodes associated with laboratory tests. This offers us with a deterministic way of performing data linkages without accessing demographic information. In this paper, we quantify the performance metrics of this approach. Results: The linkage of the large NHLS data to external hospital data using specimen barcodes achieved a 95% success. Out of the 1200 records in the validation sample, 87% were exact matches and 9% were matches with typographic correction. The remaining 5% were either complete mismatches or were due to duplicates in the administrative data. Conclusions: The high success rate indicates the reliability of using barcodes for linking data without demographic identifiers. Specimen barcodes are an effective tool for deterministic linking in health data, and may provide a method of creating large, linked data sets without compromising patient confidentiality.

Cohort profile: Rahima Moosa Mother and Child Hospital maternal HIV cohort, Johannesburg, South Africa.

PURPOSE: The Rahima Moosa Mother and Child Hospital (RMMCH) maternal HIV cohort originated from data systems that were developed to support HIV-related birth care and track outcomes of a complete birth cohort of HIV-exposed infants at Rahima Moosa Hospital and their mothers living with HIV. PARTICIPANTS: Supported by the Empilweni Services and Research Unit, maternal and infant data from 13 654 pregnant women living with HIV who delivered their infants (and a subset also attended antenatal care) were collected at RMMCH in Johannesburg, South Africa since 2013. Maternal data were collected using counsellor-administered interviews and the 2013-2018 subset of this cohort was linked to the National Health Laboratory Services (NHLS) national HIV cohort-a longitudinal cohort of people living with HIV accessing care in the public sector antiretroviral therapy programme in South Africa that can observe national access to HIV care through laboratory testing data. FINDINGS TO DATE: Topics addressed by the cohort include antenatal care history, HIV treatment exposure, delivery/birth management, prophylaxis and maternal blood results relevant to HIV captured at delivery. The cohort was also one of the first to describe implementation of early infant diagnosis procedures in South Africa including evaluations of novel point-of-care testing strategies demonstrating improvements in uptake of HIV care among infants accessing point-of-care services. FUTURE PLANS: Annual linkage of infant delivery and testing data to longitudinal laboratory test data in the NHLS national HIV cohort is planned to allow for analysis of both infant continuity of care outcomes and as well as evaluation of maternal-infant pair treatment and mobility outcomes in the post partum and later period.

Creating a data collection and management platform to support measurement of adolescent HIV care transition processes within low- and middle-income countries: The GRADUATE project.

Few national programs and research cohorts within low- and middle-income countries (LMICs) document transition-related processes and outcomes for adolescents and young adults living with HIV (AYLH) transitioning to adulthood. Between 2017-2020, The Global fRAmework of Data collection Used for Adolescent HIV Transition Evaluation (GRADUATE) project convened a collaborative advisory group to identify key variables and definitions capturing the process, predictors, and outcomes across the transition period. In total, 114 variables identified as essential to measuring AYLH transition-related data were identified and formatted into a GRADUATE Data Exchange Standard (DES), which was added to and harmonized with the existing International epidemiology Databases to Evaluate AIDS (IeDEA) DES. In 2019, the GRADUATE DES was pilot tested at four IeDEA facilities in Malawi, South Africa, and Thailand through a cross-sectional study. Upon comparing the variables to routine medical records, available data were too limited to adequately capture transition-related processes and outcomes. However, additional data collection using GRADUATE tools was feasible and improved completeness. Of the 100 (52% female) AYLH included in the pilot study, 71% had transitioned/transferred to adult care, with 42% transitioning from an adolescent-specific model of care within an integrated family clinic to having their clinic visits scheduled on a different day of the week while 58% transferred from a pediatric facility to one offering adult HIV care. While almost all (94%) had a transition-related discussion with their healthcare providers prior to the transition, we found that 69% (95% CI 49-85%) were somewhat or very satisfied/comfortable with the post-transfer clinic and the staff. Utilization of the GRADUATE DES better characterized AYLH transitioning to adulthood across LMICs, and optimally measured transition preparation activities and outcomes. Utilization of the GRADUATE DES in other settings could facilitate comparisons and identify gaps in the care of transitioning adolescents that need to be addressed.

Cervical cancer prevention and care in HIV clinics across sub-Saharan Africa: results of a facility-based survey.

INTRODUCTION: To eliminate cervical cancer (CC), access to and quality of prevention and care services must be monitored, particularly for women living with HIV (WLHIV). We assessed implementation practices in HIV clinics across sub-Saharan Africa (SSA) to identify gaps in the care cascade and used aggregated patient data to populate cascades for WLHIV attending HIV clinics. METHODS: Our facility-based survey was administered between November 2020 and July 2021 in 30 HIV clinics across SSA that participate in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We performed a qualitative site-level assessment of CC prevention and care services and analysed data from routine care of WLHIV in SSA. RESULTS: Human papillomavirus (HPV) vaccination was offered in 33% of sites. Referral for CC diagnosis (42%) and treatment (70%) was common, but not free at about 50% of sites. Most sites had electronic health information systems (90%), but data to inform indicators to monitor global targets for CC elimination in WLHIV were not routinely collected in these sites. Data were collected routinely in only 36% of sites that offered HPV vaccination, 33% of sites that offered cervical screening and 20% of sites that offered pre-cancer and CC treatment. CONCLUSIONS: Though CC prevention and care services have long been available in some HIV clinics across SSA, patient and programme monitoring need to be improved. Countries should consider leveraging their existing health information systems and use monitoring tools provided by the World Health Organization to improve CC prevention programmes and access, and to track their progress towards the goal of eliminating CC.

Transition to dolutegravir-based ART in 35 low- and middle-income countries: a global survey of HIV care clinics.

OBJECTIVE: We studied the transition to dolutegravir-containing antiretroviral therapy (ART) at HIV treatment clinics within the International epidemiology Databases to Evaluate AIDS (IeDEA). DESIGN: Site-level survey conducted in 2020-2021 among HIV clinics in low- and middle-income countries (LMICs). METHODS: We assessed the status of dolutegravir rollout and viral load and drug resistance testing practices for patients on ART switching to dolutegravir-based regimens. We used generalized estimating equations to assess associations between clinic rollout of both first- and second-line dolutegravir-based ART regimens (dual rollout) and site-level factors. RESULTS: Of 179 surveyed clinics, 175 (98%) participated; 137 (78%) from Africa, 30 (17%) from the Asia-Pacific, and 8 (5%) from Latin America. Most clinics (80%) were in low- or lower-middle-income countries, and there were a mix of primary-, secondary- and tertiary-level clinics. Ninety percent reported rollout of first-line dolutegravir, 59% of second-line, 94% of first- or second-line and 55% of dual rollout. The adjusted odds of dual rollout were higher among tertiary-level (aOR 4.00; 95% CI 1.39 to 11.47) and secondary-level clinics (aOR 3.66; 95% CI 2.19 to 6.11) than in primary-level clinics. Over half (59%) of clinics that introduced first- or second-line dolutegravir-based ART required recent viral load testing before switching to dolutegravir, and 15% performed genotypic resistance testing at switch. CONCLUSIONS: Dolutegravir-based ART was rolled out at nearly all IeDEA clinics in LMICs, yet many switched patients to dolutegravir without recent viral load testing and drug resistance testing was rarely performed. Without such testing, drug resistance among patient switching to dolutegravir may go undetected.