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

Background: The coronavirus disease 2019 (COVID-19) pandemic disrupted paediatric HIV services across South Africa. Shortly before COVID-19, updated national HIV guidelines were released. Objectives: This study describes COVID-19's impact on paediatric HIV services in Tshwane District, South Africa. Method: 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. Results: 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%. Conclusion: 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.

Longitudinal Trajectories of Antiretroviral Treatment Adherence and Associations With Durable Viral Suppression Among Adolescents Living With HIV in South Africa.

BACKGROUND: Compared with other age groups, adolescents living with HIV (ALHIV) are estimated to have lower levels of adherence to antiretroviral treatment. Despite this, we lack evidence on adolescents' adherence patterns over time to inform the customization of intervention strategies. SETTING: Eastern Cape province, South Africa. METHODS: We analyzed data from a cohort of ALHIV (N = 1046, aged 10-19 years at baseline) recruited from 53 public health facilities. The cohort comprised 3 waves of data collected between 2014 and 2018 and routine viral load data from the National Institute for Communicable Disease data warehouse (2014-2019). Durable viral suppression was defined as having suppressed viral load (<1000 copies/mL) at ≥2 consecutive study waves. Group-based multitrajectory model was used to identify adherence trajectories using 5 indicators of self-reported adherence. Logistic regression modeling evaluated the associations between adherence trajectories and durable viral suppression. RESULTS: Overall, 933 ALHIV (89.2%) completed all 3 study waves (55.1% female, mean age: 13.6 years at baseline). Four adherence trajectories were identified, namely, "consistent adherence" (49.8%), "low start and increasing" (20.8%), "gradually decreasing" (23.5%), and "low and decreasing" (5.9%). Adolescents experiencing inconsistent adherence trajectories were more likely to be older, live in rural areas, and have sexually acquired HIV. Compared with the consistent adherence trajectory, the odds of durable viral suppression were lower among adolescents in the low start and increasing (adjusted odds ratio [aOR]: 0.62, 95% CI: 0.41 to 0.95), gradually decreasing (aOR: 0.40, 95% CI: 0.27 to 0.59), and the low and decreasing adherence (aOR: 0.25, 95% CI: 0.10 to 0.62) trajectories. CONCLUSIONS: Adherence to antiretroviral treatment remains a challenge among ALHIV in South Africa. Identifying adolescents at risk of nonadherence, based on their adherence trajectories may inform the tailoring of adolescent-friendly support strategies.

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.

Healthcare provisions associated with multiple HIV-related outcomes among adolescent girls and young women living with HIV in South Africa: a cross-sectional study.

INTRODUCTION: Adolescent girls and young women (AGYW) living with HIV experience poor HIV outcomes and high rates of unintended pregnancy. Little is known about which healthcare provisions can optimize their HIV-related outcomes, particularly among AGYW mothers. METHODS: Eligible 12- to 24-year-old AGYW living with HIV from 61 health facilities in a South African district completed a survey in 2018-2019 (90% recruited). Analysing surveys and medical records from n = 774 participants, we investigated associations of multiple HIV-related outcomes (past-week adherence, consistent clinic attendance, uninterrupted treatment, no tuberculosis [TB] and viral suppression) with seven healthcare provisions: no antiretroviral therapy (ART) stockouts, kind and respectful providers, support groups, short travel time, short waiting time, confidentiality, and safe and affordable facilities. Further, we compared HIV-related outcomes and healthcare provisions between mothers (n = 336) and nulliparous participants (n = 438). Analyses used multivariable regression models, accounting for multiple outcomes. RESULTS: HIV-related outcomes were poor, especially among mothers. In multivariable analyses, two healthcare provisions were "accelerators," associated with multiple improved outcomes, with similar results among mothers. Safe and affordable facilities, and kind and respectful staff were associated with higher predicted probabilities of HIV-related outcomes (p<0.001): past-week adherence (62% when neither accelerator was reported to 87% with both accelerators reported), clinic attendance (71%-89%), uninterrupted ART treatment (57%-85%), no TB symptoms (49%-70%) and viral suppression (60%-77%). CONCLUSIONS: Accessible and adolescent-responsive healthcare is critical to improving HIV-related outcomes, reducing morbidity, mortality and onward HIV transmission among AGYW. Combining these provisions can maximize benefits, especially for AGYW mothers.

Compliance to Viral Load Monitoring Schedules Among Women Attending Prevention of Vertical HIV Transmission Services Before and During the COVID-19 Pandemic in Ehlanzeni District, Mpumalanga, South Africa.

Human immunodeficiency virus (HIV) viral load (VL) monitoring was likely interrupted during the Coronavirus disease 2019 (COVID-19) pandemic. We used routine data on repeat VL testing among 667 prevention of vertical HIV transmission (PVT) clients in Ehlanzeni district, to determine compliance to VL testing recommendations and associated factors during different time periods: pre-COVID-19, transition, and COVID-19. Descriptive and multivariable Poisson regression analyses were conducted, with and without including revised PVT-guidelines rolled out in January-2020. Among 405 women with ≥ 2 VL tests, the overall median age was 30 years (interquartile range: 26-35 years). Compliance to recommended VL testing guidelines ranged between 81.5% (172/211) and 92.3% (191/207) at different time periods. Across all three periods and when revised PVT-guidelines were used, being compliant was significantly reduced among those with earliest VL = 50-999 copies/ml (incidence rate ratio (IRR) = 0.71 [95% confidence interval (CI) 0.61-0.82], p value < 0.001) and VL ≥ 1000 copies/ml (IRR = 0.18 [95% CI 0.09-0.36], p value < 0.001). When guideline revisions were excluded, compliance was only significantly reduced among those with VL ≥ 1000 copies/ml (IRR = 0.14 [95% CI 0.06-0.32], p value < 0.001) and increased during the COVID-19 period versus pre-COVID-19 (IRR = 1.10 [95% CI 1.05-1.15], p value < 0.001). Similar significant associations between compliance and VL level were observed when the COVID-19 period was analyzed separately. Significantly increased compliance to VL testing among the 25-34 years age-group versus younger women was also observed across all periods. These results highlight the importance of strengthening strategies such as short message service reminders and educational messaging, reaching all age-groups, to fast-track implementation targets for VL monitoring.

More Frequent HIV Viral Load Testing With Point-Of-Care Tests Detects Elevated Viral Load Earlier in Postpartum HIV-Positive Women in a Randomized Controlled Trial in Two Clinics in Johannesburg, South Africa.

BACKGROUND: Elevated maternal HIV viral load (VL) increases vertical transmission risk for breastfeeding children. This randomized controlled trial in Johannesburg primarily evaluated whether 3-monthly point-of-care testing, with laboratory-based standard-of-care testing (arm 2), compared with 6-monthly laboratory-based VL testing (arm 1) in postpartum women living with HIV receiving first-line tenofovir-emtricitabine-efavirenz antiretroviral treatment improved VL suppression, factors associated with nonsuppression, and drug resistance in those with virologic failure. METHODS: Mother-child pairs were enrolled July 2018-April 2019 at the child's 6/10/14-week clinic visit. Women were randomized 1:1 to arm 1 or 2. Trained staff performed point-of-care VL testing using the Cepheid's Xpert HIV-1 VL assay. We fitted a generalized linear mixed model with VL suppression (<50 copies/mL (cps/mL) and <1000 cps/mL) at enrollment and 6, 12, and 18 months postpartum as the outcome and indicator variables for time, study site, study arm, and interaction variables. The final model tested for a difference by study arm, pooling across time points. RESULTS: Of 405 women enrolled (204 arm 1 and 201 arm 2), 249 (61%) remained in follow-up through 18 months. There was no difference in VL suppression between arms at 6, 12, or 18 months. VL suppression rate (<50 cps/mL) at 18 months was 64.8% in arm 1 and 63.0% in arm 2 (P = 0.27). On bivariate analysis, there was an association with late antenatal booking and being in arm 2 for nonsuppressed VL, but no significant association with breastfeeding. HIV drug resistance was found in 12 of 23 participants (52.2%). CONCLUSION: We found no significant difference in VL suppression with more frequent VL testing in postpartum women living with HIV receiving first-line efavirenz-based antiretroviral treatment.

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.

Resistance is common in paediatric patients failing ART in South Africa.

BACKGROUND: Minimal data exist on HIV drug resistance patterns and prevalence among paediatric patients failing ART in resource-limited settings. We assessed levels of HIV drug resistance in children with virological failure. METHODS: This cross-sectional study, performed from March 2017 to March 2019 in South Africa, enrolled HIV-positive children aged ≤19 years, receiving ART through public health facilities with recent evidence suggestive of virological failure (at least one viral load ≥1000 copies/mL), across 45 randomly selected high-volume clinics from all nine provinces. Resistance genotyping was performed using next-generation sequencing technologies. Descriptive analysis taking into account survey design was used to determine outcomes. RESULTS: Among 899 participants enrolled, the adjusted proportion of HIV drug resistance among children with virological failure was 87.5% (95% CI 83.0%-90.9%). Resistance to NNRTIs was detected in 77.4% (95% CI 72.5%-81.7%) of participants, and resistance to NRTIs in 69.5% (95% CI 62.9%-75.4%) of participants. Overall, resistance to PIs was detected in 7.7% (95% CI 4.4%-13.0%) of children. CONCLUSIONS: HIV drug resistance was highly prevalent in paediatric patients failing ART in South Africa, with 9 in 10 patients harbouring resistance to NNRTIs and/or NRTIs. PI-based regimens are predicted to be highly efficacious in achieving virological suppression amongst patients failing NNRTI-based regimens. Scaling up resistance testing amongst patients would facilitate access to second- and third-line regimens in South Africa.

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.

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.

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.

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.

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).

Data protection, data management, and data sharing: Stakeholder perspectives on the protection of personal health information in South Africa.

The Protection of Personal Information Act (POPIA) 2013 came into force in South Africa on 1 July 2020. It seeks to strengthen the processing of personal information, including health information. While POPIA is to be welcomed, there are concerns about the impact it will have on the processing of health information. To ensure that the National Health Laboratory Service [NHLS] is compliant with these new strict processing requirements and that compliance does not negatively impact upon its current screening, treatment, surveillance and research mandate, it was decided to consider the development of a NHLS POPIA Code of Conduct for Personal Health. As part of the process of developing such a Code and better understand the challenges faced in the processing of personal health information in South Africa, 19 semi-structured interviews with stakeholders were conducted between June and September 2020. Overall, respondents welcomed the introduction of POPIA. However, they felt that there are tensions between the strengthening of data protection and the use of personal information for individual patient care, treatment programmes, and research. Respondents reported a need to rethink the management of personal health information in South Africa and identified 5 issues needing to be addressed at a national and an institutional level: an understanding of the importance of personal information; an understanding of POPIA and data protection; improve data quality; improve transparency in data use; and improve accountability in data use. The application of POPIA to the processing of personal health information is challenging, complex, and likely costly. However, personal health information must be appropriately managed to ensure the privacy of the data subject is protected, but equally that it is used as a resource in the individual's and wider public interest.

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.

Trends in RPR Seropositivity among Children Younger than 2 Years in South Africa, 2010-2019.

A positive rapid plasma reagin (RPR) result in children under the age of 2 years indicates either passive transplacental transfer of maternal antibodies or active infection with syphilis (possible congenital syphilis). We describe trends in RPR seropositivity in this population using centralized laboratory data. A secondary analysis of laboratory data collected through the National Health Laboratory Service, Corporate Data Warehouse from 2010 to 2019 was conducted. Of the 127 150 children <2 years included in the analysis, 10 969 [8.6%; 95% confidence interval (95% CI) 85-88]) were RPR seropositive. RPR seropositivity increased from 6.5% to 13.0% between 2010 and 2019. Overall, the annual rate of RPR seropositivity was relatively stable between 2010 and 2018 with a range of 89-127/100 000 live births, increasing sharply to 165/100 000 livebirths in 2019. KwaZulu-Natal and North West provinces recorded the largest increases in annual seropositivity rate, while Eastern Cape and Western Cape had the most significant declines. Although this analysis is limited to laboratory results, in the absence of major changes in testing practices, there may be a rise in the burden of antenatal syphilis exposure in utero indicating an increase in maternal syphilis and syphilis transmission in the general population. South Africa needs to intensify Mother-to-Child Transmission of syphilis elimination efforts to reach the WHO target of ≤50 cases per 100 live births by 2030.

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.

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.