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. This implementation study was conducted at four high volume TOUs in Gauteng during the period 1 June 2018 to 31 March 2019. The TOUs were located in Johannesburg Regions B, D, F, and in Tshwane district. All had average monthly total number of live births of 520 to 1650 in the preceding year, of which 119 to 353 were to pregnant WLHIV and delivered pregnant women referred from lower level obstetric units in their catchment areas. During implementation, routine VL testing around the time of delivery was a newly introduced practice while EID testing at birth for all HIV‐exposed infants had been established practice since 2015. Prospective study of pregnant or early post‐partum WLHIV admitted to labour or post‐delivery wards and their new‐born infants until return of results or discharge. All WLHIV admitted to labour or postnatal wards at the four TOUs during the study period were offered POC VL and or birth PCR testing by routine staff. To be eligible for enrolment and specimen collection for the study, WLHIV and or their infants had to be admitted in labour or postnatal wards and be willing to provide verbal consent. For both WLHIV and infants, two specimens were collected – one for POC and the other for CLT. Specimens were collected by doctors and nurses as part of their routine duties. Non‐study patients could access HIV EID and VL POC testing where clinically indicated and these were labelled “miscellaneous.” POC testing was conducted by a dedicated POC operator working in a designated POC testing room. While specimen collection took place throughout the week including weekends and after‐hours at all but one TOU (Johannesburg Region B), testing took place during working hours – 08:00 to 16:00 – on weekdays only. During the first three months of implementation, all specimens collected were processed and tested while afterwards only weekday specimens and those weekend specimens which had a reasonable probability of results being returned were tested. At two of the busier TOUs (Johannesburg region B and D), two dedicated counsellors hired through the study assisted with return of results and post‐test counselling before discharge. For POC VL testing, Xpert™ HIV‐1 VL was used while POC EID testing was conducted using either the Xpert™ HIV‐1 Qual or the m‐PIMA HIV‐1/2 Detect assays. Upon receiving appropriate samples, POC operators entered specimen details into the instruments’ information management system and tested the specimens according to manufacturers’ specifications and sample volumes. Mothers and infants whose results were reported as error, invalid or no result had the test repeated on the same sample and if there was still no conclusive result, a second sample was collected as soon as possible after the result. Infants with a positive POC EID result were repeat tested on the same assay using the same sample to ensure reproducibility, and a second sample was requested for confirmatory testing on the alternate EID assay. Additional information on specimen collection, testing procedures and quality assurance are provided in Supplementary Document SD1. POC operators printed results and gave them to TOU staff or counsellors for post‐test counselling. High maternal VL and positive EID results were automatically sent to the clinicians responsible for routine care by SMS for action. WLHIV who had high VLs were prescribed enhanced adherence counselling and repeat VL after three months while their EID negative infants were offered high‐risk prophylaxis, consisting of either (i) daily zidovudine (AZT) and nevirapine (NVP) for six weeks OR (ii) daily NVP for 12 weeks. Virally suppressed (VL < 1000 copies/mL) WLHIV were counselled on maintaining viral suppression and their EID negative infants offered low‐risk prophylaxis. All mothers of EID negative infants were counselled about further testing at 10 weeks of age. WLHIV with EID positive infants at birth were counselled and referred to the paediatrics department for ART initiation after a second sample drawn for confirmatory POC EID and CLT. Five different data sources were used to collect data required for the analyses of outcomes. These were (i) specimen request forms, (ii) POC instrument information system (iii) POC results slip (iv) centralized laboratory information system and (v) District Health information system monthly reports. Table S2 describes these data sources and how they were used. Sources (i) (iv) provided data which were captured into a study‐specific REDCap® database. A data coordinator checked completeness of data entries and supported POC operators with collecting good quality data. At the end of implementation, data captured in REDCap® were exported into Stata® 14.2 for data cleaning and analysis. WLHIV or infants whose indications for testing were marked as “miscellaneous” were excluded from analysis as were EQA specimens. Descriptive statistics were used to describe the distribution of mVL and EID testing overall and across TOUs. Table 1 shows the four main outcomes were defined and analysed. Poisson regression with robust error variance was used to determine factors associated with return of results. Additional information on sensitivity analyses and multivariable models are included in Supplementary Document SD1. Description of outcomes and data analysis techniques Number of WLHIV who had a POC VL test done as % of live births to WLHIV during implementation period (Minimum coverage). Maximum coverage a Coverage was measured on the number of unique WLHIV regardless of the number of tests done on each woman. Proportions determined overall and across TOUs categories. Number of HIV‐exposed infants who had POC EID test done as % of live births to WLHIV during the implementation period (Minimum coverage). Maximum coverage a % of WLHIV tested and had their POC results returned before discharge. Minimum % results returned were calculated using the number of live births to WLHIV during implementation period as denominator. Maximum % results returned a Results return was measured on the number of unique WLHIV or HIV‐exposed infants regardless of the number of tests done on each woman. Proportions determined overall and across categories. χ2 tests used to compare differences across categories. Multi‐variable Poisson regression with robust error variance was used to determine sample and TOU‐level factors associated with return of results. All available variables were included in models a priori. ROC curves were used to test for significance difference between models with interaction terms and those without. % of infants tested who had their POC results returned before discharge. Minimum % results returned were calculated using the number of live births to WLHIV during implementation period as denominator. Maximum % results returned a This was measured on all specimens tested, resulted and returned to WLHIV or HIV‐exposed infants. Medians and interquartile ranges overall and across categories. K‐test for equality of medians used to determine differences across categories. These were calculated for specimens with a documented return of result. The sign‐test was used to compare the population level median TAT for POC VL testing versus POC EID testing for mothers‐infant pairs who both had POC testing. Limits of agreement between POC VL results and centralized laboratory VL results. Agreement beyond chance for VL results below limit of detection, VL > 50 copies/mL, VL > 1000 copies/mL Bland‐Altman analysis. Kappa Statistic, sensitivity and specificity of POC testing compared to CLT EID, early infant diagnosis; mVL, maternal HIV viral load; POC, point‐of‐care test. The protocol for this implementation study was approved by the University of the Witwatersrand Human Subjects Research Ethics Committee (M1711115) and the University of Pretoria Research Ethics Committee (50/2018). Approvals were also obtained from the national and provincial Departments of Health as well as from the management at the tertiary hospitals where the obstetric units are situated. Verbal consent to perform POC testing was obtained from admitted women. Written informed consent for research purposes was waived to facilitate measuring routine implementation. Because of this waiver, patient details other than those required for return of results could not be collected. As the REDCap® database collected personal identifiable information such as name, surname, folder number and specimen barcodes required for return of results and linkage to centralized laboratory database, only POC operators and key study staff had access to the database.