Evaluating patient data quality in South Africa's National Health Laboratory Service Data Warehouse, 2017-2020: implications for monitoring child health programmes.

BACKGROUND: South Africa's National Health Laboratory Service (NHLS), the only clinical laboratory service in the country's public health sector, is an important resource for monitoring public health programmes. OBJECTIVES: We describe NHLS data quality, particularly patient demographics among infants, and the effect this has on linking multiple test results to a single patient. METHODS: Retrospective descriptive analysis of NHLS data from 1st January 2017-1st September 2020 was performed. A validated probabilistic record-linking algorithm linked multiple results to individual patients in lieu of a unique patient identifier. Paediatric HIV PCR data was used to illustrate the effect on monitoring and evaluating a public health programme. Descriptive statistics including medians, proportions and inter quartile ranges are reported, with Chi-square univariate tests for independence used to determine association between variables. RESULTS: During the period analysed, 485 300 007 tests, 98 217 642 encounters and 35 771 846 patients met criteria for analysis. Overall, 15.80% (n = 15 515 380) of all encounters had a registered national identity (ID) number, 2.11% (n = 2 069 785) were registered without a given name, 63.15% (n = 62 020 107) were registered to women and 32.89% (n = 32 304 329) of all folder numbers were listed as either the patient's date of birth or unknown. For infants tested at < 7 days of age (n = 2 565 329), 0.099% (n = 2 534) had an associated ID number and 48.87% (n = 1 253 620) were registered without a given name. Encounters with a given name were linked to a subsequent encounter 40.78% (n = 14 180 409 of 34 775 617) of the time, significantly more often than the 21.85% (n = 217 660 of 996 229) of encounters registered with a baby-derivative name (p-value < 0.001). CONCLUSION: Unavailability and poor capturing of patient demographics, especially among infants and children, affects the ability to accurately monitor routine health programmes. A unique national patient identifier, other than the national ID number, is urgently required and must be available at birth if South Africa is to accurately monitor programmes such as the Prevention of Mother-to-Child Transmission of HIV.

An approach for evaluating early and long term mother-to-child transmission of HIV (MTCT) in low and middle income countries: a South African experience.

BACKGROUND: Eliminating mother-to-child transmission of HIV is a global public health target. Robust, feasible methodologies to measure population level impact of programmes to prevent mother-to-child transmission of HIV (PMTCT) are needed in high HIV prevalence settings. We present a summary of the protocol of the South African PMTCT Evaluation (SAPMTCTE) with its revision over three repeated rounds of the survey, 2010-2014. METHODS: Three cross sectional surveys (2010, 2011-2012 and 2012-2013) were conducted in 580 primary health care immunisation service points randomly selected after stratified multistage probability proportional to size sampling. All infants aged 4-8 weeks receiving their six-week immunisation at a sampled facility on the day of the visit were eligible to participate. Trained research nurses conducted interviews and took infant dried blood spot (iDBS) samples for HIV enzyme immunoassay (EIA) and total nucleic acid polymerase chain reaction (PCR) testing. Interviews were conducted using mobile phones and iDBS were sent to the National Health Laboratory for testing. All findings were adjusted for study design, non-response, and weighted for number of South African live-birth in each study round. In 2012 a national closed cohort of these 4 to 8-week old infants testing EIA positive (HIV Exposed Infants) from the 2012-2013 cross-sectional survey was established to estimate longer-term PMTCT impact to 18 months. Follow-up analyses were to estimate weighted cumulative MTCT until 18 months, postnatal MTCT from 6 weeks until 18 months and a combined outcome of MTCT-or-death, using a competing risks model, with death as a competing risk. HIV-free survival was defined as a child surviving and HIV-negative up to 18 months or last visit seen. A weighted cumulative incidence analysis was conducted, adjusting for survey design effects. DISCUSSION: In the absence of robust high-quality routine medical recording systems, in the context of a generalised HIV epidemic, national surveys can be used to monitor PMTCT effectiveness; however, monitoring long-term outcomes nationally is difficult due to poor retention in care.

Field Evaluation of Performance of Alere and Cepheid Qualitative HIV Assays for Pediatric Point-of-Care Testing in an Academic Hospital in Soweto, South Africa.

Point-of-care (POC) technologies for HIV diagnosis in infants have the potential to overcome logistical challenges that delay treatment initiation and prevent improvements in morbidity and mortality. This study aimed to evaluate the performance of two POC technologies against the current standard-of-care (SOC) laboratory-based assay in South Africa, when operated by nurses in a hospital environment. Children <18 months of age who were treatment naive (excluding prophylaxis) and in whom an HIV PCR test was indicated were eligible for the study. To increase the rate of enrollment of HIV PCR-positive children, HIV-exposed neonates at high risk of mother-to-child transmission and children requiring confirmatory HIV testing were preferentially enrolled. The two POC technologies demonstrated excellent concordance, with 315 (97.8%) results consistent with the SOC result. The POC technologies yielded 102 positive and 220 negative tests each. The SOC assay had 101 positive, 214 negative, 4 indeterminate, 1 invalid, and 2 specimen-rejected results. To include the indeterminate results in sensitivity/specificity calculations, a sensitivity analysis was performed, which yielded a simulated sensitivity of 0.9904 (interquartile range [IQR], 0.9808 to 0.9904) and a specificity of 0.9954 (IQR, 0.9954 to 1.0). This study confirmed that both POC technologies can be successfully used outside the laboratory environment to yield precise sensitivity/specificity values for pediatric, including neonatal, HIV testing.

Enhancing HIV Treatment Access and Outcomes Amongst HIV Infected Children and Adolescents in Resource Limited Settings.

Introduction Increasing access to HIV-related care and treatment for children aged 0-18 years in resource-limited settings is an urgent global priority. In 2011-2012 the percentage increase in children accessing antiretroviral therapy was approximately half that of adults (11 vs. 21 %). We propose a model for increasing access to, and retention in, paediatric HIV care and treatment in resource-limited settings. Methods Following a rapid appraisal of recent literature seven main challenges in paediatric HIV-related care and treatment were identified: (1) lack of regular, integrated, ongoing HIV-related diagnosis; (2) weak facility-based systems for tracking and retention in care; (3) interrupted availability of dried blood spot cards (expiration/stock outs); (4) poor quality control of rapid HIV testing; (5) supply-related gaps at health facility-laboratory interface; (6) poor uptake of HIV testing, possibly relating to a fatalistic belief about HIV infection; (7) community-associated reasons e.g. non-disclosure and weak systems for social support, resulting in poor retention in care. Results To increase sustained access to paediatric HIV-related care and treatment, regular updating of Policies, review of inter-sectoral Plans (at facility and community levels) and evaluation of Programme implementation and impact (at national, subnational, facility and community levels) are non-negotiable critical elements. Additionally we recommend the intensified implementation of seven main interventions: (1) update or refresher messaging for health care staff and simple messaging for key staff at early childhood development centres and schools; (2) contact tracing, disclosure and retention monitoring; (3) paying particular attention to infant dried blood spot (DBS) stock control; (4) regular quality assurance of rapid HIV testing procedures; (5) workshops/meetings/dialogues between health facilities and laboratories to resolve transport-related gaps and to facilitate return of results to facilities; (6) community leader and health worker advocacy at creches, schools, religious centres to increase uptake of HIV testing and dispel fatalistic beliefs about HIV; (7) use of mobile communication technology (m-health) and peer/community supporters to maintain contact with patients. Discussion and Conclusion We propose that this package of facility, community and family-orientated interventions are needed to change the trajectory of the paediatric HIV epidemic and its associated patterns of morbidity and mortality, thus achieving the double dividend of improving HIV-free survival.

Attrition Rates in HIV Viral Load Monitoring and Factors Associated With Overdue Testing Among Children Within South Africa's Antiretroviral Treatment Program: Retrospective Descriptive Analysis.

BACKGROUND: Numerous studies in South Africa have reported low HIV viral load (VL) suppression and high attrition rates within the pediatric HIV treatment program. OBJECTIVE: Using routine laboratory data, we evaluated HIV VL monitoring, including mobility and overdue VL (OVL) testing, within 5 priority districts in South Africa. METHODS: We performed a retrospective descriptive analysis of National Health Laboratory Service (NHLS) data for children and adolescents aged 1-15 years having undergone HIV VL testing between May 1, 2019, and April 30, 2020, from 152 facilities within the City of Johannesburg, City of Tshwane, eThekwini, uMgungundlovu, and Zululand. HIV VL test-level data were deduplicated to patient-level data using the NHLS CDW (Corporate Data Warehouse) probabilistic record-linking algorithm and then further manually deduplicated. An OVL was defined as no subsequent VL determined within 18 months of the last test. Variables associated with the last VL test, including age, sex, VL findings, district type, and facility type, are described. A multivariate logistic regression analysis was performed to identify variables associated with an OVL test. RESULTS: Among 21,338 children and adolescents aged 1-15 years who had an HIV VL test, 72.70% (n=15,512) had a follow-up VL test within 18 months. Furthermore, 13.33% (n=2194) of them were followed up at a different facility, of whom 3.79% (n=624) were in a different district and 1.71% (n=281) were in a different province. Among patients with a VL of ≥1000 RNA copies/mL of plasma, the median time to subsequent testing was 6 (IQR 4-10) months. The younger the age of the patient, the greater the proportion with an OVL, ranging from a peak of 52% among 1-year-olds to a trough of 21% among 14-year-olds. On multivariate analysis, 2 consecutive HIV VL findings of ≥1000 RNA copies/mL of plasma were associated with an increased adjusted odds ratio (AOR) of having an OVL (AOR 2.07, 95% CI 1.71-2.51). Conversely, patients examined at a hospital (AOR 0.86, 95% CI 0.77-0.96), those with ≥2 previous tests (AOR 0.78, 95% CI 0.70-0.86), those examined in a rural district (AOR 0.63, 95% CI 0.54-0.73), and older age groups of 5-9 years (AOR 0.56, 95% CI 0.47-0.65) and 10-14 years (AOR 0.51, 95% CI 0.44-0.59) compared to 1-4 years were associated with a significantly decreased odds of having an OVL test. CONCLUSIONS: Considerable attrition occurs within South Africa's pediatric HIV treatment program, with over one-fourth of children having an OVL test 18 months subsequent to their previous test. In particular, younger children and those with virological failure were found to be at increased risk of having an OVL test. Improved HIV VL monitoring is essential for improving outcomes within South Africa's pediatric antiretroviral treatment program.

Retrospective review of maternal HIV viral load electronic gatekeeping codes in South Africa.

Background: Maternal electronic gatekeeping (eGK) codes for HIV viral load (VL) testing of pregnant and breastfeeding women were developed to permit increased frequency of maternal HIV VL testing without automated gatekeeping cancellation, and to enable virological surveillance. Objectives: This study describes the national uptake of maternal eGK codes and VL suppression (VLS) rates disaggregated by age during antenatal, delivery and postnatal periods in South Africa during 2022. Method: HIV VL tests associated with C#PMTCT (used for antenatal and postnatal testing) and C#DELIVERY (used at delivery) eGK codes between 01 January and 31 December 2022, were extracted from the National Institute for Communicable Diseases Data Warehouse. Uptake of eGK codes was calculated using indicators from the District Health Information System as denominators while HIV VLS rates (< 1000 copies/mL) were calculated as monthly and annual percentages. Results: Overall, national maternal eGK code uptake was 41.8%, 24.5% and 0.12% for the antenatal, delivery and postnatal periods, respectively. The monthly antenatal eGK uptake increased from 27.5% to 58.5% while delivery uptake increased from 17.3% to 30.0%. The overall annual maternal HIV VLS rate was 86.7% antenatally and 87.2% during delivery. The monthly average HIV VLS for adolescent girls and young women (AGYW) was 76.1% antenatally and 79.6% during delivery. Conclusion: Although overall national uptake of maternal HIV VL eGK codes was low, antenatal and delivery uptake improved over time, thereby facilitating use of eGK codes for programmatic monitoring of maternal VLS rates for the first time. Quality of care among pregnant AGYW requires urgent attention.

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.

Early diagnosis of in utero and intrapartum HIV infection in infants prior to 6 weeks of age.

Early initiation of antiretroviral therapy reduces HIV-related infant mortality. The early peak of pediatric HIV-related deaths in South Africa occurs at 3 months of age, coinciding with the earliest age at which treatment is initiated following PCR testing at 6 weeks of age. Earlier diagnosis is necessary to reduce infant mortality. The performances of the Amplicor DNA PCR, COBAS AmpliPrep/COBAS TaqMan (CAP/CTM), and Aptima assays for detecting early HIV infection (acquired in utero and intrapartum) up to 6 weeks of age were compared. Dried blood spots (DBS) were collected at birth and at 2, 4, and 6 weeks from HIV-exposed infants enrolled in an observational cohort study in Johannesburg, South Africa. HIV status was determined at 6 weeks by DNA PCR on whole blood. Serial DBS samples from all HIV-infected infants and two HIV-uninfected, age-matched controls were tested with the 3 assays. Of 710 infants of known HIV status, 38 (5.4%) had in utero (n = 29) or intrapartum (n = 9) infections. By 14 weeks, when treatment should have been initiated, 13 (45%) in utero-infected and 2 (22%) intrapartum-infected infants had died or were lost to follow-up. The CAP/CTM and Aptima assays identified 76.3% of all infants with early HIV infections at birth and by 4 weeks were 96% sensitive. DNA PCR demonstrated lower sensitivities at birth and 4 weeks of 68.4% and 87.5%, respectively. All assays had the lowest sensitivity at 2 weeks of age. CAP/CTM was the only assay with 100% specificity at all ages. Testing at birth versus 6 weeks of age identifies a higher total number of HIV-infected infants, irrespective of the assay.

Infant HIV Testing Amid the COVID-19 Pandemic and Evolving PMTCT Guidelines in Johannesburg, South Africa.

Background: The COVID-19 pandemic impacted HIV programmes with the diversion of resources and lockdown measures. We assessed the impact of COVID-19 on infant HIV diagnosis in the context of updated 2019 prevention of mother-to-child transmission of HIV (PMTCT) guidelines in Johannesburg, South Africa. Methods: HIV PCR data for children <2 years were extracted from the National Health Laboratory Service database from October 2018 to September 2021, inclusive. Trends in the total number of tests performed and the total number of children with HIV diagnosed, stratified by age, were determined to assess the effect of different COVID-19 lockdown levels and updated guidelines. Results: When comparing three 12-month periods ending September 2019−2021, respectively, the total number of HIV PCR tests performed increased (from 41 879 to 47 265 to 56 813), and the total number of children with HIV decreased (from 659 to 640 to 620), year-on-year. There was a substantial increase in 6-month testing in response to updated guidelines. Excluding 6-month testing, the year-on-year increase in total tests was maintained with birth and 10-week testing closely approximating total live births to women living with HIV. A decrease in the total number of children with HIV diagnosed was noted in Q2 2020, coinciding with the most restrictive lockdown, followed by a rebound in cases. Conclusions: Despite the restrictions and diversion of resources associated with COVID-19, there was a successful implementation of PMTCT guideline updates and minimal disruption to infant HIV testing. However, much work remains in order to achieve the elimination of mother-to-child transmission of HIV.

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.

Cutting Edge: Unusual NK cell responses to HIV-1 peptides are associated with protection against maternal-infant transmission of HIV-1.

Most infants exposed to HIV-1 in utero and at delivery do not acquire infection. We show that mothers and infants who have CD3-negative cells that respond to HIV-1 peptides are substantially less likely to transmit and acquire infection, respectively. The CD3-negative cells, shown to be NK cells, respond with remarkable specificity and high magnitude to HIV-1 peptides from Env (envelope) and Reg (regulatory) protein regions, as measured by a whole blood intracellular cytokine assay only in the context of HIV-1 infection or exposure. These findings identify an important new measure of protective immunity to HIV-1 that highlights the importance of innate immunity in preventing the establishment of HIV-1 infection.

Natural killer cells that respond to human immunodeficiency virus type 1 (HIV­1) peptides are associated with control of HIV­1 infection.

Human immunodeficiency virus (HIV)-specific natural killer (CD3- cells), CD4, and CD8 T cellular responses were determined in 79 HIV­1-infected women in response to HIV­1 peptide pools (Gag, Pol, Nef, Reg, and Env) with use of a whole­blood intracellular cytokine staining assay that measures interferon-γ and/or interleukin-2. HIV­specific CD3- cell responses to any region (Env and Reg predominantly targeted) were associated with lower viral load (P = .031) and higher CD4 T cell count (P = .015). Env­specific CD3- cell responses were stronger in women who had both Gag CD4 and CD8 T cell responses and, in turn, was associated with lower viral load (P = .005). CD3- cell responders had significantly higher representation of CD4 T cell responses to Env and Reg (P = .012 and P = .015, respectively) and higher magnitudes of CD4 T cell responses (P = .017 and P = .037, respectively) than did nonresponders. Peptide­specific natural killer cells are associated with markers of less severe disease progression among HIV­1-infected women (lower viral load and higher CD4 T cell count) and with stronger HIV­specific T cell responses.

Achieving maternal viral load suppression for elimination of mother-to-child transmission of HIV in South Africa.

OBJECTIVE: To describe changes in maternal viral control over time in South African women living with HIV (WLHIV) using surveillance data from the National Health Laboratory Service's Corporate Data Warehouse (NHLS CDW). DESIGN: A retrospective cohort analysis of maternal viral load during pregnancy and up to 15 months postpartum was performed amongst WLHIV (15-49 years) within the public-health sector between 2016 and 2017. METHODS: HIV and pregnancy-related test data were used to create a synthetic cohort of pregnant WLHIV from the NHLS CDW. Syphilis-screening, in association with ward type and/or postpregnancy cervical screening and/or birth HIV test and/or positive ß-hCG, was used as a proxy for pregnancy. The syphilis-screening date marked the first antenatal care visit (fANC). Fractional polynomial models described viral load evolution from fANC up to 15 months postdelivery. Piecewise linear regression models determined factors associated with viral load decline. FINDINGS: Among 178 319 pregnant WLHIV, 345 174 viral load tests were performed [median = 2 (IQR: 2-3) per woman]. At fANC, 85 545 (48%) women were antiretroviral therapy (ART) experienced; 88 877 (49.8%) were not and 3897 (2.2%) unknown. Proportions of viraemia (viral load ≥50 copies/ml) were 39 756 (53.6%) at first viral load performed during pregnancy, 14 780 (36.9%) at delivery and 24 328 (33.5%) postpartum. Maternal age at least 25 years, CD4+ cell count at least 500 cells/µl and viral load less than 50 copies/ml at baseline predicted sustained viral load suppression during follow-up. CONCLUSION: Despite high-ART coverage among pregnant women in South Africa, only 63% of WLHIV achieved viral load less than 50 copies/ml at delivery. Maternal viral load monitoring requires prioritization for maternal health and eMTCT.

Evaluation of the Aptima HIV-1 Quant Dx assay for HIV diagnosis at birth in South Africa.

The increased coverage of antiretroviral therapy has resulted in a decrease in the positive predictive value (PPV) and diagnostic sensitivity of early infant diagnosis assays. To evaluate the diagnostic performance of the Aptima HIV-1 Quant DX assay (Aptima) in detecting HIV infection at birth. The study was a cross-sectional laboratory based evaluation using whole blood DBS specimens. Samples were collected from HIV-exposed neonates at birth at two paediatric facilities in Gauteng between 1st March 2018 - 31st January 2020. Performance of the Aptima compared to the Cobas® AmpliPrep/Cobas® TaqMan HIV-1 Qualitative Test v2.0 was calculated using a two-by-two table and reported as proportions with 95% confidence intervals. A total of 363 infants met the inclusion criteria of which 4 (1.1%) had an Aptima result discordant with CAP/CTM HIV status: two (50%) negative and two (50%) positive. The Aptima assay had a sensitivity of 93.75% (95% CI: 79.19%-99.23%), specificity of 99.4% (95% CI: 97.83%-99.93%), PPV of 93.75% (95% CI: 78.98%-98.36%), negative predictive value of 99.4% (95% CI: 97.73%-99.84%), and overall accuracy of 98.9% (95% CI: 97.2%-99.7%). The Aptima yielded an error code on 37 (10.19%) results, of which 35 (94.59%) were resolved on repeat testing. Of the 32 HIV-detected specimens, 20 had a plasma VL result available (18 on Abbott and 2 on Cobas). The absolute median difference was 0.66 log10 (IQR: 0.36-1.71). The Aptima demonstrated good EID performance and can be considered as a qualitative EID assay.

Low Pretreatment Viral Loads in Infants With HIV in an Era of High-maternal Antiretroviral Therapy Coverage.

BACKGROUND: With expansion of antiretroviral therapy (ART) programs, transmission rates are low but new infant infections still occur. We investigated predictors of pre-ART viral load (VL) and CD4+ T-cell counts and percentages in infants diagnosed with HIV at birth in a setting with high coverage of maternal ART and infant prophylaxis. METHODS: As part of an early treatment study, 97 infants with confirmed HIV-infection were identified at a hospital in Johannesburg, South Africa. Infant VL and CD4+ T-cell parameters were measured before ART initiation. Data were collected on maternal characteristics, including VL, CD4+ T-cell counts and ART, and infant characteristics, including sex, birth weight, and mode of delivery. RESULTS: Pre-ART, median infant VL was 28,405 copies/mL [interquartile range (IQR): 2515-218,150], CD4+ T-cell count 1914 cells/mm (IQR: 1474-2639) and percentage 40.8% (IQR: 32.2-51.2). Most (80.4%) infants were born to mothers who received ART during pregnancy and 97.9% of infants received daily nevirapine prophylaxis until ART initiation at median of 2 days of age (IQR: 1-7). Infant pre-ART VL was more likely to be ≥1000 copies/mL when their mothers had VL ≥1000 copies/mL [Odds Ratio (OR): 6.88, 95% confidence interval (CI): 2.32-20.41] and was higher in boys than girls (OR: 3.29, 95% CI: 1.07-9.95). Lower maternal CD4+ T-cell count (<350 cells/mm) was associated with lower infant CD4+ T-cell count (<1500 cells/mm) (OR: 3.59, 95% CI: 1.24-10.43). CONCLUSIONS: Pre-ART VL and CD4+ T-cell parameters of intrauterine-infected infants were associated with VL and CD4+ T-cell counts of their mothers. Maternal ART during pregnancy may begin treatment of intrauterine infection and may mask the severity of disease in infected infants identified in the current era with high-maternal ART coverage.

The geographic distribution of priority population groups for the elimination of mother-to-child transmission of HIV in South Africa.

BACKGROUND: Women of reproductive age living with HIV (WRLHIV), HIV-positive pregnant women, adolescent girls and young women (AGYW) are key populations for eliminating mother-to-child of HIV (eMTCT) in South Africa. We describe the geographical distribution of WRLHIV, their pregnant counterparts and AGYW for risk-adjusted allocation of eMTCT interventions. METHODS: For the year 2018, we triangulated data from the Thembisa Model with five routine HIV-related and demographic data sources to determine the distribution of WRLHIV (15-49 years) and AGYW (15-24 years) nationally and by province. Data analysed included total population estimates, number of live-births, live-births to HIV-positive women, age-specific HIV prevalence rates, intrauterine (IU)-transmission rates and IU-case rates/100 000 live-births. IU-transmission rates and IU-case rates were calculated from de-duplicated routine HIV test-data for neonates (aged <7days). Data de-duplication was achieved by a patient-linking algorithm that uses probabilistic matching of demographics (name, surname, date of birth), supplemented by manual matching to account for spelling errors. RESULTS: There were 58 million people in South Africa in 2018. Females (all ages) constituted 51% of the population. Women of reproductive age constituted 27% and AGYW constituted 8% of the total population. WRLHIV, AGYW living with HIV and HIV-positive pregnant women accounted for 7%, 0.8% and 0.4% of the total population respectively. Gauteng was the most populous province followed by KwaZulu-Natal, with Western Cape and Eastern Cape in third and fourth positions. The distribution of WRLHIV and AGYW followed a similar trend. However, Mpumalanga and Limpopo provinces had higher proportions of WRLHIV and AGYW living with HIV ahead of Western Cape. KwaZulu-Natal had the highest number of live-births to HIV-positive women. The national IU-transmission rate of <1% translated into 241 cases/100 000. While provincial IU-case rates were fairly similar at 179-325, districts IU-case rates varied, ranging from 87-415 cases/100 000 live-births. CONCLUSION: Findings suggest that the need for eMTCT interventions is greatest in Gauteng, KwaZulu-Natal, Western Cape and Eastern Cape. Limpopo and Mpumalanga provinces may require more HIV prevention and family planning services because of high fertility rates, high number of WRLHIV and AGYW living with HIV. eMTCT will require robust viral load monitoring among WRLHIV, pregnant and breastfeeding women. The national laboratory database can provide this service near-real time.

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

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

Characterizing Viral Load Burden Among HIV-Infected Women Around the Time of Delivery: Findings From Four Tertiary Obstetric Units in Gauteng, South Africa.

BACKGROUND: Elimination of mother-to-child transmission of HIV requires sustained viral load suppression during pregnancy and breastfeeding among women living with HIV (WLHIV). Antenatal antiretroviral therapy coverage is reported at >95% in South Africa, but viral load suppression rates are unknown. We describe maternal VL burden around time of delivery at 4 tertiary obstetric units (TOUs) in Gauteng Province. METHODS: Between June 2018 and March 2019, routine point-of-care (PoC) maternal HIV VL and early infant diagnosis (EID) testing were implemented at 3 TOUs in Johannesburg and 1 in Tshwane district. WLHIV and HIV-exposed neonates were eligible for HIV VL (Xpert HIV-1 VL) and EID (Xpert HIV-1 EID or m-PIMA HIV1/2 detection) testing around time of delivery, respectively. Proportions of viremic women and intrauterine (IU)-infected neonates were calculated among valid PoC results. RESULTS: Among 8147 live births to WLHIV, 2769 (34.0%) women and 4333 (53.2%) neonates had valid PoC results. Median VL at delivery was <40 copies/mL (interquartile range: 0-398). The proportion of women with a VL < 50, 50 to <1000, and ≥1000 copies/mL was 63.6%, 13.9% and 22.4%, respectively. There were 65/4333 (1.5%) IU-infected neonates. Among 1449 mother-neonate pairs with both VL and EID results, IU transmission by VL threshold was 3/946 (0.3%), 6/187 (3.2%), and 25/316 (7.9%) for VL < 50, 50 to <1000, and ≥1000 copies/mL, respectively (P < 0.001). CONCLUSIONS: Despite high antiretroviral therapy coverage, >1/3 of WLHIV had a VL ≥50 copies/mL at delivery. Among mother-neonate pairs, maternal VL ≥50 copies/mL accounted for 31/34 (91%) IU infections. Improvement in the quality of HIV care among WLHIV is essential if South Africa is to achieve elimination of mother-to-child transmission.

Diagnosis of human immunodeficiency virus type 1 infection in infants by use of dried blood spots and an ultrasensitive p24 antigen assay.

We tested 617 dried blood spots (DBS) from human immunodeficiency virus-exposed infants from five countries using an ultrasensitive p24 antigen assay (Up24). The sensitivity was 94.4% (67/71) and the specificity was 100% (431/431) for infants with DBS specimens

Evolving complexities of infant HIV diagnosis within Prevention of Mother-to-Child Transmission programs.

Early diagnosis of HIV infection among infants and children is critical as prompt initiation of antiretroviral therapy prevents morbidity and death. Yet despite advances in the accuracy and availability of infant HIV diagnostic testing, there are increasing challenges with making an early definitive diagnosis. These challenges relate primarily to advances in prevention of mother-to-child transmission (PMTCT) of HIV. Although PMTCT programs have proven to be highly effective in reducing infant HIV infection, infants who are HIV-infected may achieve virological suppression and loss of detectability of HIV nucleic acid prior to diagnosis because of antiretroviral drug exposure. Hence, false-negative and indeterminate HIV polymerase chain reaction (PCR) results can occur, especially among high-risk infants given multi-drug prophylactic regimens. However, the infant HIV diagnostic landscape is also complicated by the inevitable decline in the positive predictive value of early infant diagnosis (EID) assays. As PMTCT programs successfully reduce the mother-to-child transmission rate, the proportion of false-positive EID results will increase. Consequently, false-negative and false-positive HIV PCR results are increasingly likely despite highly accurate diagnostic assays. The problem is compounded by the seemingly intractable prevalence of maternal HIV within some settings, resulting in a considerable absolute burden of HIV-infected infants despite a low mother-to-child transmission rate.