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.

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.

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).

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.

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.

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.

Infrastructural and human-resource factors associated with return of infant HIV test results to caregivers: secondary analysis of a nationally representative situational assessment, South Africa, 2010.

BACKGROUND: In June 2015, South Africa introduced early infant HIV diagnosis (EID) at birth and ten weeks postpartum. Guidelines recommended return of birth results within a week and ten weeks postpartum results within four weeks. Task shifting was also suggested to increase service coverage. This study aimed to understand factors affecting return of EID results to caregivers. METHODS: Secondary analysis of data gathered from 571 public-sector primary health care facilities (PHCs) during a nationally representative situational assessment, was conducted. The assessment was performed one to three months prior to facility involvement in the 2010 evaluation of the South African programme to prevent mother-to-child HIV transmission (SAPMTCTE). Self-reported infrastructural and human resource EID-related data were collected from managers and designated staff using a structured questionnaire. The main outcome variable was 'EID turn-around-time (TAT) to caregiver' (caregiver TAT), measured as reported number of weeks from infant blood draw to caregiver receipt of results. This was dichotomized as either short (≤3 weeks) or delayed (> 3 weeks) caregiver TAT. Logit-based risk difference analysis was used to assess factors associated with short caregiver TAT. Analysis included TAT to facility (facility TAT), defined as reported number of weeks from infant blood draw to facility receipt of results. RESULTS: Overall, 26.3% of the 571 PHCs reported short caregiver TAT. In adjusted analyses, short caregiver TAT was less achieved when facility TAT was > 7 days (versus ≤7 days) (adjusted risk difference (aRD): - 0.2 (95% confidence interval - 0.3-(- 0.1)), p = 0.006 for 8-14 days and - 0.3 (- 0.5-(- 0.1)), p = 0.006 for > 14 days), and in facilities with staff nurses (compared to those without) (aRD: - 9.4 (- 16.6-(- 2.2), p = 0.011). CONCLUSION: Although short caregiver TAT for EID was only reported in approximately 26% of facilities, these facilities demonstrate that achieving EID TAT of ≤3 weeks is possible, making timely ART initiation within 3 weeks of diagnosis feasible within the public health sector. Our adjusted analyses underpin the need for quick return of results to facilities. They also raise questions around staff mentoring: we hypothesise that facilities with staff nurses were likely to have fewer professional nurses, and thus inadequate senior support.

Prevalence of HIV-1 drug resistance amongst newly diagnosed HIV-infected infants age 4-8 weeks, enrolled in three nationally representative PMTCT effectiveness surveys, South Africa: 2010, 2011-12 and 2012-13.

BACKGROUND: South Africa (SA) has expanded efforts to reduce mother-to-child transmission of HIV (MTCT) to less than 2% at six weeks after birth and to less than 5% at 18 months postpartum by 2016. Despite improved antiretroviral regimens and coverage between 2001 and 2016, there is little data on infant HIV drug resistance. This paper tracks the prevalence of HIV drug resistance patterns amongst HIV infected infants from three nationally representative studies that assessed the effectiveness of national programs to prevent MTCT (PMTCT). The first study was conducted in 2010 (under the dual therapy PMTCT policy), the second from 2011 to 12 (PMTCT Option A policy) and the third from 2012 to 13 (PMTCT Option A policy). From 2010 to 2013, infant non-nucleoside reverse transcriptase inhibitor (NNRTI) exposure increased from single dose to daily throughout breastfeeding; maternal nucleoside reverse transcriptase inhibitor (NRTI) and NNRTI exposure increased with initiation of NNRTI-and NRTI- containing triple antiretroviral therapy (ART) earlier in gestation and at higher CD4 cell counts. METHODS: Three nationally representative surveys were conducted in 2010, 2011-12 and 2012-13. During the surveys, mothers with known, unknown, or no exposure to antiretrovirals for PMTCT and their infants were included, and MTCT was measured. For this paper, infant dried blood spots (iDBS) from HIV PCR positive infants aged 4-8 weeks, with consent for additional iDBS testing, were analysed for HIV drug resistance at the National Institute of Communicable Diseases (NICD), SA, using an in-house assay validated by the Centers for Disease Control and Prevention (CDC). Total viral nucleic acid was extracted from 2 spots and amplified by nested PCR to generate a ~ 1 kb amplicon that was sequenced using Sanger sequencing technologies. Sequence assembly and editing was performed using RECall v3. RESULTS: Overall, HIV-1 drug resistance was detected in 51% (95% Confidence interval (CI) [45-58%]) of HIV PCR positive infants, 37% (95% CI [28-47%]) in 2010, 64% (95% CI [53-74%]) in 2011 and 63% (95% CI [47-77%]) in 2012 (p < 0.0001), particularly to the NNRTI drug class. Pooled analyses across all three surveys demonstrated that infants whose mothers received ART showed the highest prevalence of resistance (74%); 26% (21/82) of HIV PCR positive infants with no or undocumented antiretroviral drug (ARV) exposure harboured NNRTI resistance. CONCLUSIONS: These data demonstrate increasing NNRTI resistance amongst newly-diagnosed infants in a high HIV prevalence setting where maternal ART coverage increased across the years, starting earlier in gestation and at higher CD4 cell counts. This is worrying as lifelong maternal ART coverage for HIV positive pregnant and lactating women is increasing. Also of concern is that resistant virus was detected in HIV positive infants whose mothers were not exposed to ARVs, raising questions about circulating resistant virus. Numbers in this group were too small to assess trends over the three years.

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.

Early Diagnosis of HIV Infection in Infants - One Caribbean and Six Sub-Saharan African Countries, 2011-2015.

Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged <15 years were estimated to be living with HIV (including 170,000 infants born in 2015), with the vast majority living in sub-Saharan Africa (1). In 2014, 150,000 children died from HIV-related causes worldwide (2). Access to timely HIV diagnosis and treatment for HIV-infected infants reduces HIV-associated mortality, which is approximately 50% by age 2 years without treatment (3). Since 2011, the annual number of HIV-infected children has declined by 50%. Despite this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test for HIV (2), and in 2015, only 51% of children living with HIV received antiretroviral therapy (1). Access to services for early infant diagnosis of HIV (which includes access to testing for HIV-exposed infants and clinical diagnosis of HIV-infected infants) is critical for reducing HIV-associated mortality in children aged <15 years. Using data collected from seven countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the provision of HIV testing services for early infant diagnosis was assessed. During 2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as recommended by the World Health Organization (WHO) increased in all seven countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi, South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV positivity among those tested declined in all seven countries, with three countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda) reporting >50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection.

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.

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.

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.

Eliminating mother-to-child HIV transmission in South Africa.

PROBLEM: The World Health Organization has produced clear guidelines for the prevention of mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV). However, ensuring that all PMTCT programme components are implemented to a high quality in all facilities presents challenges. APPROACH: Although South Africa initiated its PMTCT programme in 2002, later than most other countries, political support has increased since 2008. Operational research has received more attention and objective data have been used more effectively. LOCAL SETTING: In 2010, around 30% of all pregnant women in South Africa were HIV-positive and half of all deaths in children younger than 5 years were associated with the virus. RELEVANT CHANGES: Between 2008 and 2011, the estimated proportion of HIV-exposed infants younger than 2 months who underwent routine polymerase chain reaction (PCR) tests to detect early HIV transmission increased from 36.6% to 70.4%. The estimated HIV transmission rate decreased from 9.6% to 2.8%. Population-based surveys in 2010 and 2011 reported transmission rates of 3.5% and 2.7%, respectively. LESSONS LEARNT: CRITICAL ACTIONS FOR IMPROVING PROGRAMME OUTCOMES INCLUDED: ensuring rapid implementation of changes in PMTCT policy at the field level through training and guideline dissemination; ensuring good coordination with technical partners, such as international health agencies and international and local nongovernmental organizations; and making use of data and indicators on all aspects of the PMTCT programme. Enabling health-care staff at primary care facilities to initiate antiretroviral therapy and expanding laboratory services for measuring CD4+ T-cell counts and for PCR testing were also helpful.

Résumé PROBLÈME: L'Organisation mondiale de la Santé a élaboré des lignes directrices claires pour la prévention de la transmission mère-enfant (PTME) du virus de l'immunodéficience humaine (VIH). S'assurer que tous les éléments du programme de PTME soient mis en œuvre de manière qualitative dans tous les établissements présente cependant des défis. APPROCHE: Bien que l'Afrique du Sud ait lancé son programme de PTME en 2002, plus tard que la plupart des autres pays, le soutien politique a augmenté depuis 2008. La recherche opérationnelle a reçu davantage d'attention, et les données objectives ont été utilisées plus efficacement. ENVIRONNEMENT LOCAL: En 2010, environ 30% de toutes les femmes enceintes en Afrique du Sud étaient séropositives, et la moitié de tous les décès d'enfants de moins de 5 ans étaient associée au virus. CHANGEMENTS SIGNIFICATIFS: Entre 2008 et 2011, la proportion estimée de nourrissons de moins de 2 mois exposés au VIH, ayant subi une réaction en chaîne par polymérase (PCR) de routine visant à détecter la transmission précoce du VIH, est passée de 36,6% à 70,4%. Le taux estimé de transmission du VIH a diminué, passant de 9,6% à 2,8%. Les enquêtes basées sur la population en 2010 et 2011 ont signalé des taux de transmission de 3,5% et 2,7%, respectivement. LEÇONS TIRÉES: Voici certaines actions essentielles pour améliorer les résultats du programme: assurer la mise en œuvre rapide des changements de politique de PTME sur le terrain, grâce à la formation et à la diffusion des lignes directrices; assurer une bonne coordination avec les partenaires techniques, comme les agences de santé internationales et locales et les organisations non gouvernementales; et utiliser les données et les indicateurs relatifs à tous les aspects du programme de PTME. Il est aussi utile de permettre au personnel soignant des établissements de soins de santé primaires d'initier un traitement antirétroviral et de développer les services de laboratoire pour les décomptes de cellules CD4 + T et les tests PCR.

Resumen SITUACIÓN: La Organización Mundial de la Salud ha presentado unas directrices claras para la prevención de la transmisión del virus de la inmunodeficiencia humana (VIH) de la madre al niño. No obstante, habrá que superar algunos desafíos para asegurar la puesta en marcha de todos los elementos del programa de prevención a fin de alcanzar un nivel de calidad elevado en todas las instalaciones. ENFOQUE: Aunque Sudáfrica inició su programa de prevención en el año 2002, más tarde que la mayoría de los países, el apoyo político ha aumentado desde 2008. Se ha prestado más atención a las investigaciones operativas y los datos objetivos se han utilizado con mayor eficacia. MARCO REGIONAL: En 2010, alrededor del 30% de las mujeres embarazadas en Sudáfrica eran seropositivas, y la mitad de todas las muertes en niños menores de cinco años estuvieron asociadas al virus. CAMBIOS IMPORTANTES: Entre los años 2008 y 2011, la proporción estimada de niños menores de dos meses expuestos al VIH que se sometió a las pruebas rutinarias de reacción en cadena de la polimerasa aumentó del 36,6% al 70,4%, y la tasa estimada de transmisión del VIH se redujo del 9,6% al 2,8%. Las encuestas de población de los años 2010 y 2011 reflejaron unas tasas de transmisión del 3,5% y el 2,7%, respectivamente LECCIONES APRENDIDAS: Las actividades fundamentales para mejorar los resultados del programa incluyeron: garantizar la implementación rápida de los cambios en la política de prevención de la transmisión a nivel de campo mediante cursos formativos y la difusión de las directrices; garantizar una coordinación adecuada entre los socios técnicos, tales como las agencias sanitarias internacionales y las ONG locales e internacionales; y utilizar los datos e indicadores acerca de todos los aspectos del programa de prevención de la transmisión del VIH de la madre al niño. También resultó muy útil permitir al personal sanitario de los centros de atención primaria iniciar terapias antirretrovirales y ampliar los servicios de laboratorio para realizar los recuentos de linfocitos T CD4+ y las pruebas de reacción en cadena de la polimerasa.

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.

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.

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.