Incidence and predictors of virological failure among HIV infected children and adolescents receiving second-line antiretroviral therapy in Uganda, a retrospective study.

BACKGROUND: In Uganda, 20% (19,073/94,579) of children and adolescents (0-19 years) living with HIV (CALHIV) were receiving second-line antiretroviral therapy (ART) by the end of March 2020. Data on incidence and predictors of virological failure among these CALHIV on second-line ART is limited. Lack of this information and limited access to HIV drug resistance testing prevents early identification of CALHIV at risk of virological failure on second-line ART. The aim of this study was to determine the incidence and predictors of virological failure among CALHIV on second-line ART in Uganda. METHODOLOGY: This was a retrospective cohort study of all CALHIV aged 0-19 years who were switched to second-line ART regimen between June 2010 and June 2019 at the Baylor Uganda Centre of Excellence clinic. Data was analysed using STATA 14. Cumulative incidence curves were used to assess incidence of virological failure. Factors associated with virological failure were identified using sub-distributional hazard regression analysis for competing risks considering death, transfer out and loss to follow-up as competing risks. RESULTS: Of 1104 CALHIV, 53% were male. At switch to Protease Inhibitor (PI) based second-line ART, majority (47.7%) were aged 5 - 9 years,56.2% had no/mild immune suppression for age while 77% had viral load copies < 100,000 copies/mL. The incidence of virological failure on second-line ART regimen among CALHIV was 3.9 per 100 person-years (PY) with a 10-year cumulative incidence rate of 32%. Factors significantly associated with virological failure were age 10 - 19 years (HR 3.2, 95% 1.6 - 6.2, p < 0.01) and HIV viral load count > 100,000 copies/mL (HR 2.2, 95% CI 1.5 - 3.1), p < 0.01) prior to second-line ART switch. CONCLUSION: Treatment outcomes for children and adolescents on second-line ART are favourable with one third of them developing virological failure at 10 years of follow up. Adolescent age group and high HIV viral load at the start of second-line ART were significantly associated with virological failure on second-line ART. There is need to determine optimal strategies to improve ART treatment outcomes among adolescents with high viral load counts at second-line ART switch.

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.

Hospital admission and its common causes in children on antiretroviral therapy (ART) in Lilongwe Malawi between 2001 and 2016: a retrospective cross-sectional study.

BACKGROUND: Paediatric HIV data shows a variable and sometimes catastrophic response in the initial stage of ART regimen administration. The burden of disease that affects children in their first year of treatment is not comprehensively available. OBJECTIVE: Objective of our study was to describe patterns of admission in children; before ART initiation, within the first six months, and post-six months of ART between 2001 and 2016. METHODS: Principal caregivers of 260 children (45.7% females 54.2% males, all <15 years) on ART for at least six months were interviewed about admissions of their children. Diagnoses were verified from the health passport books. Data on age, sex, date of ART initiation was obtained from the database of Baylor College of Medicine in Lilongwe. Data were analysed using Excel for descriptive analysis. Chi Square Test was used to test for significance. RESULTS: There were more admissions before starting ART 74% (95%CI 68.67-79.33%) vs. 42% (95%CI 36.00-48.00%), after starting ART (p = <0.001 at 5% significance level); after six months of ART 34% (95%CI 28.24-39.76) vs. 20% (95% CI 15.51-24.86%) (p = <0.001 at 5% significance level). The commonest causes of admission were pneumonia, malaria, tuberculosis, anaemia; no difference in causes of admission within the first and after six months of ART initiation. CONCLUSION: ART significantly reduces admission in children living with HIV. The common causes of admission are HIV non-specific conditions. No difference between causes of admission within and after six months of ART.

High prevalence of impaired glucose metabolism among children and adolescents living with HIV in Ghana.

BACKGROUND: Antiretroviral therapy (ART)-associated metabolic abnormalities, including impairment of glucose metabolism, are prevalent in adults living with HIV. However, the prevalence and pathogenesis of impaired glucose metabolism in children and adolescents living with HIV, particularly in sub-Saharan Africa, are not well characterized. We investigated the prevalence of impaired glucose metabolism among children and adolescents living with perinatally infected HIV in Ghana. METHODS: In this multicentre, cross-sectional study, we recruited participants from 10 paediatric antiretroviral treatment clinics from January to June 2022 in 10 facilities in Greater Accra and Eastern regions of Ghana. We determined impaired glucose metabolism in the study sample by assessing fasting blood sugar (FBS), insulin resistance as defined by the homeostatic model assessment for insulin resistance (HOMA-IR) index and glycated haemoglobin (HbA1c) levels. The prevalence of impaired glucose metabolism using each criterion was stratified by age and sex. The phenotypic correlates of glucose metabolism markers were also assessed among age, sex, body mass index (BMI) and waist-to-hip ratio (WHR). RESULTS: We analysed data from 393 children and adolescents living with HIV aged 6-18 years. A little over half (205/393 or 52.25%) of the children were female. The mean age of the participants was 11.60 years (SD = 3.50), with 122/393 (31.00%) aged 6-9 years, 207/393 (52.67%) aged 10-15 years, and 62/393 (15.78%) aged 16-18 years. The prevalence rates of glucose impairment in the study population were 15.52% [95% confidence interval (CI): 12.26-19.45], 22.39% (95% CI: 18.54-26.78), and 26.21% (95% CI: 22.10-30.78) using HbA1c, HOMA-IR, and FBS criteria, respectively. Impaired glucose metabolism detected by FBS and HOMA-IR was higher in the older age group, whereas the prevalence of abnormal HbA1c levels was highest among the youngest age group. Age and BMI were positively associated with FBS and HOMA-IR (p < 0.001). However, there was negative correlation of WHR with HOMA-IR (p < 0.01) and HbA1c (p = 0.01). CONCLUSION: The high prevalence of impaired glucose metabolism observed among the children and adolescents living with HIV in sub-Saharan Africa is of concern as this could contribute to the development of metabolic syndrome in adulthood.

Asymptomatic malaria parasitaemia and virological non-suppression among children living with HIV in Accra, Ghana: a cross-sectional study.

Background: Human Immunodeficiency Virus (HIV) and malaria are two major diseases in sub-Saharan Africa, with coinfections having an impact on the outcomes of both. We assessed the association between asymptomatic malaria parasitaemia and virological non-suppression among children living with HIV attending a clinic at the Korle Bu Teaching Hospital (KBTH) and the Princess Marie Louis Hospital (PML) in the city of Accra, Ghana. Methods: This was a cross-sectional study of asymptomatic malaria in children receiving care at paediatric HIV clinics at KBTH and PML conducted from September to November 2022. Patients who had been on ART for at least 6 months were eligible to participate. Structured questionnaires were used to collect socio-demographic, malaria prevention behaviors, and ART-related data using in-person interviews. Microscopy and PCR were used to screen for malaria and GeneXpert to determine viral load. To examine the determinants of malaria PCR positivity and virological non-suppression, Chi-square tests and logistic regression were utilized. Results: The participants' median age was 9 years with a range of 6 to 12 years. Males made up 57% of the population. We detected 3.6% (10 of 277) and 7.6% (21 of 277) cases of malaria using microscopy and PCR, respectively. Virological non-suppression (VL > 1000 copies/ml) was seen in 82 (29.6%) of the 277 participants. Among the suppressed individuals, 62 (22.4%) exhibited low-level viraemia (VL level 40-1000 copies/ml) and 133 (48%) had non-detectable viral load levels. There were no factors associated with malaria PCR positivity carriage. Poor adherence to antiretroviral therapy was associated with a fivefold increase in the risk of viral load non-suppression (AOR = 4.89 [CI = 2.00-11.98], p = 0.001). Conclusion: The study showed that the proportion of children living with HIV with asymptomatic malaria parasitaemia was low, with about one third of the study population having virological non suppression. The interaction between malaria parasitemia and viral replication may not be the main culprit for virological non suppression.

High prevalence of low high-density lipoprotein cholesterol and insulin resistance among children and adolescents living with HIV in Uganda: harbinger for metabolic syndrome?

BACKGROUND: Antiretroviral therapy-associated adverse effects and comorbidities are still pervasive in people living with HIV, especially metabolic syndrome (MetS). We investigated the age-dependent prevalence of components of MetS and insulin resistance in children and adolescents living with HIV (CALWH). METHODS: A cross-sectional pilot study of CALWH treated at the Baylor Uganda Clinical Centre of Excellence in Kampala, Uganda, May to August 2021. The primary outcome of MetS was defined by both the International Diabetes Federation (IDF) and the Adult Treatment Panel (ATP III) criteria. We estimated the prevalence of MetS and its components for all participants and by the stratification factors. RESULTS: We enrolled 90 children and adolescents, aged 6 to <10 years (n = 30), 10 to <16 years (n = 30), and ≥ 16 to <19 years (n = 30). Fifty-one percent were females. The estimated prevalence of MetS was 1.11% (1 of 90) using either IDF or ATPIII criteria for all participants, and 3.33% in the oldest age group. Notably, while only one among study participants met the criterion based on having central obesity or blood pressure, over 55% of participants had one or more IDF component, with 47% having low high-density lipoprotein (HDL) cholesterol. Two participants (6.67%) in the group aged 10 to <16 years met one of the definitions for insulin resistance (IR) using the Homeostatic Model Assessment (HOMA-IR) index. For every 1-year increase in age, HOMA-IR index increased by 0.04 (95% confidence interval: 0.01-0.08; p = 0.02). CONCLUSIONS: With increasing survival of CALWH into adulthood, lifetime exposure to ART, the frequency of MetS in this population may rise, increasing the lifetime risk for associated health problems. There is a need to study the natural history of MetS in CALWH to inform preventative and treatment interventions as needed.

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.

COVID-19 and HIV viral load suppression in children and adolescents in Durban, South Africa.

Background: The coronavirus disease 2019 (COVID-19) pandemic poses challenges to paediatric and adolescent HIV treatment programme. Modelling exercises raised concerns over potential impact of disruptions. Objectives: To describe the impact of the COVID-19 pandemic on viral load (VL) testing among infants, children and adolescents on antiretroviral treatment (ART) in Durban, South Africa. Method: Routinely collected, aggregated data of monthly VL counts done on all those less than 19 years old from January 2018 to January 2022 was analysed. An interrupted time series analysis using a Prais-Winsten linear regression model, including terms for lockdowns and excess mortality determined VL trends. Results: The unadjusted mean VL was 2166 (confidence interval [CI]: 252.2) and 2016 (CI: 241.9), P = 0.039, and percentage VL suppression rates (72.9%, CI: 2.4% vs 73.6%, CI: 1.8%) across COVID and pre-COVID periods, showing no significant difference, P = 0.262. In the interrupted time series analysis, modelled monthly VL counts did not differ significantly by lockdown level (e.g., level 5 lockdown: -210.5 VLs, 95% CI: -483.0 to +62.1, P = 0.138) or excess mortality (-0.1, 95% CI: -6.3 to 6.1, P = 0.969). A significant downward trend in VL testing over time, including during the pre-COVID-19 period (-6.6 VL per month, 95% CI: -10.4 to -2.7, P = 0.002), was identified. Conclusion: Viral load suppression for children and adolescents were not negatively affected by COVID-19. A trend of decrease in VL testing predated COVID-19. What this study adds: Evidence presented that HIV VL testing and suppression rates in children and adolescents in a high burden setting were sustained through the COVID pandemic.

Effect of Vitamin D Supplementation on CD4 Count in HIV-Infected Children and Adolescents in North India: A Non-Randomized Comparative Study.

BACKGROUND: HIV infection is still a serious public health issue globally. Suboptimal vitamin D status is highly prevalent in HIV-infected children and adolescents throughout the world. OBJECTIVES: To evaluate the outcome of vitamin D supplementation on CD4 count in HIV-infected children and adolescents with suboptimal vitamin D status. METHODS: Vitamin D level of HIV-infected children and adolescents were measured at enrolment. Suboptimal vitamin D level was defined as 25(OH)D < 30 ng/ml. Vitamin D insufficiency and deficiency were defined as 21-29 and <20 ng/ml, respectively. Children with suboptimal vitamin D levels were supplemented with vitamin D. RESULTS: This was a single-centre, non-randomized comparative study enrolling 50 eligible participants. There were 20 patients who were vitamin D sufficient, 7 were vitamin D insufficient and 23 were found to be vitamin D deficient at enrolment. However, after supplementation, the status of sufficient remained same and 7 insufficient become sufficient, whereas in 23 deficient, 18 (78.3%) become sufficient and 5 (21.7%) become insufficient and this change was found statistically significant among the groups (χ2 = 6.52, p = 0.038). There was a significant improvement of CD4 count from baseline to 4 months in deficient group on vitamin D supplementation (p value < 0.001; 1.2-fold rise). No significant change was seen in vitamin D insufficient (p value = 0.791) and sufficient groups (p value = 0.168). CONCLUSION: Vitamin D should be supplemented in HIV-infected children on ART with low CD4 counts.

Optimizing the World Health Organization algorithm for HIV vertical transmission risk assessment by adding maternal self-reported antiretroviral therapy adherence.

BACKGROUND: The World Health Organization (WHO) risk assessment algorithm for vertical transmission of HIV (VT) assumes the availability of maternal viral load (VL) result at delivery and early viral control 4 weeks after initiating antiretroviral treatment (ART). However, in many low-and-middle-income countries, VL is often unavailable and mothers' ART adherence may be suboptimal. We evaluate the inclusion of the mothers' self-reported adherence into the established WHO-algorithm to identify infants eligible for enhanced post-natal prophylaxis when mothers' VL result is not available at delivery. METHODS: We used data from infants with perinatal HIV infection and their mothers enrolled from May-2018 to May-2020 in Mozambique, South Africa, and Mali. We retrospectively compared the performance of the WHO-algorithm with a modified algorithm which included mothers' adherence as an additional factor. Infants were considered at high risk if born from mothers without a VL result in the 4 weeks before delivery and with adherence <90%. RESULTS: At delivery, 143/184(78%) women with HIV knew their status and were on ART. Only 17(12%) obtained a VL result within 4 weeks before delivery, and 13/17(76%) of them had VL ≥1000 copies/ml. From 126 women on ART without a recent VL result, 99(79%) had been on ART for over 4 weeks. 45/99(45%) women reported suboptimal (< 90%) adherence. A total of 81/184(44%) infants were classified as high risk of VT as per the WHO-algorithm. The modified algorithm including self-adherence disclosure identified 126/184(68%) high risk infants. CONCLUSIONS: In the absence of a VL result, mothers' self-reported adherence at delivery increases the number of identified infants eligible to receive enhanced post-natal prophylaxis.

Do not forget the children: a model-based analysis on the potential impact of COVID-19-associated interruptions in paediatric HIV prevention and care.

INTRODUCTION: The COVID-19 pandemic has affected women and children globally, disrupting antiretroviral therapy (ART) services and exacerbating pre-existing barriers to care for both pregnant women and paediatric populations. METHODS: We used the Spectrum modelling package and the CEPAC-Pediatric model to project the impact of COVID-19-associated care disruptions on three key populations in the 21 Global Plan priority countries in sub-Saharan Africa: (1) pregnant and breastfeeding women living with HIV and their children, (2) all children (aged 0-14 years) living with HIV (CLWH), regardless of their engagement in care and (3) CLWH who were engaged in care and on ART prior to the start of the pandemic. We projected clinical outcomes over the 12-month period of 1 March 2020 to 1 March 2021. RESULTS: Compared to a scenario with no care disruption, in a 3-month lockdown with complete service disruption, followed by 3 additional months of partial (50%) service disruption, a projected 755,400 women would have received PMTCT care (a 21% decrease), 187,800 new paediatric HIV infections would have occurred (a 77% increase) and 516,800 children would have received ART (a 35% decrease). For children on ART as of March 2020, we projected 507,200 would have experienced ART failure (an 80% increase). Additionally, a projected 88,400 AIDS-related deaths would have occurred (a 27% increase) between March 2020 and March 2021, with 51,700 of those deaths occurring among children engaged in care as of March 2020 (a 54% increase). CONCLUSIONS: While efforts will continue to curb morbidity and mortality stemming directly from COVID-19 itself, it is critical that providers also consider the immediate and indirect harms of this pandemic, particularly among vulnerable populations. Well-informed, timely action is critical to meet the health needs of pregnant women and children if the global community is to maintain momentum towards an AIDS-free generation.

COVID-19 and HIV viral load suppression in children andadolescents in Durban, South Africa

Background: The coronavirus disease 2019 (COVID-19) pandemic poses challenges to paediatric and adolescent HIV treatment programme. Modelling exercises raised concerns over potential impact of disruptions. Objectives: To describe the impact of the COVID-19 pandemic on viral load (VL) testing among infants, children and adolescents on antiretroviral treatment (ART) in Durban, South Africa. Method: Routinely collected, aggregated data of monthly VL counts done on all those less than 19 years old from January 2018 to January 2022 was analysed. An interrupted time series analysis using a Prais-Winsten linear regression model, including terms for lockdowns and excess mortality determined VL trends. Results: The unadjusted mean VL was 2166 (confidence interval [CI]: 252.2) and 2016 (CI: 241.9), P = 0.039, and percentage VL suppression rates (72.9%, CI: 2.4% vs 73.6%, CI: 1.8%) across COVID and pre-COVID periods, showing no significant difference, P = 0.262. In the interrupted time series analysis, modelled monthly VL counts did not differ significantly by lockdown level (e.g., level 5 lockdown: ­210.5 VLs, 95% CI: ­483.0 to +62.1, P = 0.138) or excess mortality (­0.1, 95% CI: ­6.3 to 6.1, P = 0.969). A significant downward trend in VL testing over time, including during the pre-COVID-19 period (­6.6 VL per month, 95% CI: ­10.4 to ­2.7, P = 0.002), was identified. Conclusion: Viral load suppression for children and adolescents were not negatively affected by COVID-19. A trend of decrease in VL testing predated COVID-19. What this study adds: Evidence presented that HIV VL testing and suppression rates in children and adolescents in a high burden setting were sustained through the COVID pandemic.

Size of HIV-1 reservoir is associated with telomere shortening and immunosenescence in early-treated European children with perinatally acquired HIV-1.

INTRODUCTION: Persistence of HIV-1, causing chronic immune activation, is a key determinant of premature senescence. Early antiretroviral therapy (ART) has been associated with a reduced HIV-1 reservoir in children with perinatally acquired HIV-1 (PHIV), but its impact on the senescence process is an open question. We investigated the association between HIV-1 reservoir and biological and immune ageing profile in PHIV enrolled in the multicentre cross-sectional study CARMA (Child and Adolescent Reservoir Measurements on early suppressive ART) conducted within the EPIICAL (Early treated Perinatally HIV Infected individuals: Improving Children's Actual Life) consortium. METHODS: Between September 2017 and June 2018, CARMA enrolled 40 PHIV who started ART before 2 years of age and had undetectable viremia for at least 5 years before sampling date. Samples from 37 children with a median age of 13.8 years were available for this study. HIV-1 DNA copies on CD4 cells, relative telomere length (marker of cellular senescence) and levels of T-cell receptor rearrangement excision circle (TREC, marker of thymic output) on CD4 and CD8 cells were quantified by qPCR. Immunological profile was assessed by flow cytometry. Associations between molecular and phenotypic markers, HIV-1 reservoir and age at ART initiation were explored using a multivariable Poisson regression. RESULTS: Higher HIV-1 reservoir was associated (p<0.001) with telomere shortening (incidence rate ratio [IRR] = 0.15 [0.13-0.17]), immunosenescence (CD28- CD57+ , IRR = 1.23 [1.21-1.26]) and immunoactivation (CD38+ HLADR+ , IRR = 7.29 [6.58-8.09]) of CD4 cells. Late ART initiation (after 6 months of age) correlated with higher HIV-1 reservoir levels (552 [303-1001] vs. 89 [56-365] copies/106 CD4 cells, p = 0.003) and percentage of CD4 senescent cells (2.89 [1.95-6.31] vs. 1.02 [0.45-2.69, p = 0.047). TREC levels in CD8 cells were inversely associated with HIV-1 reservoir (IRR = 0.77 [0.76-0.79]) and were significantly lower in late treated PHIV (1128 [486-1671] vs. 2278 [1425-3314], p = 0.042). CONCLUSIONS: Later ART initiation is associated with higher HIV-1 reservoir size, which correlates with increased telomere shortening and senescence of CD4 cells. Timing of ART initiation in infancy has long-term consequences on the immune and biological ageing profile of children with perinatally acquired HIV-1.

Looking back at paediatric HIV treatment in South Africa. My, how we have grown!

Antiretroviral treatment has undergone major changes in the last 20 years, from monotherapy, to dual therapy and finally to triple therapy. Lately, more focus has been placed on better, more well-tolerated combinations and formulations. As in most other disciplines in medicine, the development of paediatric HIV dosages and formulations always tends to lag behind adult research. Twenty years ago, it could take several years before data were available to enable the use of life-saving antiretrovirals in children. Paediatricians, being ever resourceful, were not prepared to let their paediatric patients suffer despite the lack of data or formulations and so made a plan. This article describes some of the trials and tribulations that we went through trying to make sure that our paediatric HIV patients not only survived but thrived. Clinicians treating paediatric patients today have it so much easier because of what our colleagues and their patients went through in those early days.

Clinical utility of smartphone-based audiometry for early hearing loss detection in HIV-positive children: A feasibility study.

BACKGROUND: Paediatric human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) often manifests with hearing loss (HL). Given the impact of HL, early detection is critical to prevent its associated effects. Yet, the majority of children living with HIV/AIDS (CLWHA) cannot access hearing healthcare services because of the scarcity of audiologists and expensive costs of purchasing screening equipment. Alternative solutions for early detection of HL are therefore necessary. AIM: The overall aim of this study was to assess the feasibility of using self-administered smartphone-based audiometry for early HL detection amongst CLWHA. SETTING: This study was conducted at the paediatrics department of a state hospital in the Eastern Cape province, South Africa. METHODS: This was a feasibility study conducted amongst twenty-seven (27) CLWHA who were in the age group of 6-12 years. The participants self-administered hearing screening tests using a smartphone-based audiometric test. The primary end-points of this study were to determine the sensitivity, specificity and test-retest reliability of self-administered hearing screening. RESULTS: The sensitivity and specificity for self-administered screening were 82% and 94%, respectively, with positive and negative predictive values of 90% and 88%, respectively. Moreover, a strong positive test-retest reliability (r = 0.97) was obtained when participants self-administered the screening test. CONCLUSION: Six- to 12-year-old CLWHA were able to accurately self-administer hearing screening tests using smartphone-based audiometry. These findings show that self-administered smartphone audiometry can be used for serial hearing monitoring in at-risk paediatric patients.

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.

Clinical Features of HIV Arthropathy in Children: A Case Series and Literature Review.

Background: HIV infection has been associated with a non-erosive inflammatory arthritis in children, although few published reports exist. This study describes the clinical, laboratory and imaging features of this noncommunicable disease in a series of HIV-infected children in South Africa. Methods: A database search was conducted to identify HIV-infected children enrolled in a Paediatric Rheumatology service in Cape Town, South Africa between 1 January 2010 and 31 December 2020. Retrospective data were collected from individuals classified with HIV arthropathy, based on a predefined checklist. Demographic, clinical, laboratory, sonographic, therapeutic, and outcomes data were extracted by chart review. Descriptive statistical analysis was performed using R (v4.0.3). Results: Eleven cases of HIV arthropathy were included in the analysis. Cases predominantly presented in older boys with low CD4+ counts. Median age at arthritis onset was 10.3 years (IQR 6.9 - 11.6) and the male-female ratio was 3.0. The median absolute CD4+ count was 389 cells/uL (IQR 322 - 449). The clinical presentation was variable, with both oligoarthritis and polyarthritis being common. Elevated acute phase reactants were the most consistent laboratory feature, with a median ESR of 126 mL/h (IQR 67 - 136) and median CRP of 36 mg/L (IQR 25 - 68). Ultrasonography demonstrated joint effusions and synovial hypertrophy. Response to therapy was slower than has generally been described in adults, with almost all cases requiring more than one immunosuppressive agent. Five children were discharged in established remission after discontinuing immunotherapy, however outcomes data were incomplete for the remaining six cases. Conclusions: In this case series, HIV arthropathy was associated with advanced immunosuppression. Therapeutic modalities included immunomodulators and antiretroviral therapy, which consistently induced disease remission although data were limited by a high rate of attrition. Prospective studies are needed to define and understand this HIV-associated noncommunicable disease.

HIV virological non-suppression and its associated factors in children on antiretroviral therapy at a major treatment centre in Southern Ghana: a cross-sectional study.

BACKGROUND: Children living with human immunodeficiency virus (HIV) infection require lifelong effective antiretroviral therapy (ART). The goal of ART in HIV-infected persons is sustained viral suppression. There is limited information on virological non-suppression or failure and its associated factors in children in resource limited countries, particularly Ghana. METHODS: A cross-sectional study of 250 children aged 8 months to 15 years who had been on ART for at least 6 months attending the Paediatric HIV clinic at Korle Bu Teaching hospital in Ghana was performed. Socio-demographic, clinical, laboratory and ART Adherence related data were collected using questionnaires as well as medical records review. Blood samples were obtained for viral load and CD4+ count determination. Viral load levels > 1000 copies/ml on ART was considered virological non-suppression. Logistic regression was used to identify factors associated with virological non-suppression. RESULTS: The mean (±SD) age of the study participants was 11.4 ± 2.4 years and the proportion of males was 53.2%. Of the 250 study participants, 96 (38.4%) had virological non-suppression. After adjustment for significant variables, the factors associated with non-suppressed viral load were female gender (AOR 2.51 [95% CI 1.04-6.07], p = 0.041), having a previous history of treatment of tuberculosis (AOR 4.95 [95% CI 1.58-15.5], p = 0.006), severe CD4 immune suppression status at study recruitment (AOR 24.93 [95% CI 4.92-126.31], p < 0.001) and being on a nevirapine (NVP) based regimen (AOR 7.93 [95% CI 1.58-1.15], p = 0.005). CONCLUSION: The prevelance of virological non-suppression was high. Virological non-suppression was associated with a previous history of TB treatment, female gender, severe CD4 immune suppression status at study recruitment and being on a NVP based regimen. Early initiation of ART and phasing out NVP-based regimen might improve viral load suppression in children. In addition, children with a history of TB may need focused measures to maximize virological suppression.

Cognitive outcomes at ages seven and nine years in South African children from the children with HIV early antiretroviral (CHER) trial: a longitudinal investigation.

INTRODUCTION: Many children living with HIV (CLWH) display impaired cognition. Although early combination antiretroviral therapy (ART) produces improved cognitive outcomes, more long-term outcome data are needed. After concluding the Children with HIV Early antiRetroviral (CHER) trial in 2011, we investigated cognitive performance, at seven and nine years of age. Participants had been randomized to deferred ART (ART-Def; n = 22); immediate time-limited ART for 40 weeks (ART-40W; n = 30) and immediate time-limited ART for 96 weeks (ART-96W; n = 18). We also recruited HIV-exposed uninfected (CHEU; n = 28) and HIV-unexposed (CHU; n = 35) children. METHODS: Data were collected between May 2012 and December 2017. Mixed-model repeated-measures ANOVAs assessed differences over time between CLWH (ART-40W, ART-96W and ART-Def) and CHIV- CHEU and CHU between ART-Early (ART-40W and ART-96W), ART-Def, CHEU and CHU; and between ART-40W, ART-96W, ART-Def, CHEU and CHU. RESULTS: All comparisons found significant effects of Time for most outcome variables (better scores at nine than at seven years; ps < 0.05). The first ANOVAs found that for (a) motor dexterity, CLWH performed worse than CHIV- at seven years (p < 0.001) but improved to equivalence at nine years, (b) visual-spatial processing and problem solving, only CLWH (p < 0.04) showed significant performance improvement over time and (c) working memory and executive function, CLWH performed worse than CHIV- at both seven and nine years (p = 0.03 and 0.04). The second ANOVAs found that for (a) working memory, CHU performed better than ART-Early and CHEU (p < 0.01 and <0.04), and (b) motor dexterity, ART-Def performed worse than ART-Early, CHEU and CHU at seven years (p = 0.02, <0.001 and <0.001 respectively) but improved to equivalence at nine years (ps > 0.17). Similarly, for motor dexterity, ART-Def performed worse than ART-96W, CHEU and CHU at seven years (p < 0.04, <0.001 and <0.001) but improved to equivalence at nine years (ps > 0.20). CONCLUSIONS: Although neurocognitive developmental trajectories for treatment groups and controls were largely similar (i.e. performance improvements from 7 to 9), all ART-treated children, regardless of treatment arm, remain at risk for cognitive deficits over early school ages. Although the nature of these deficits may change as cognitive development proceeds, there are potential negative consequences for these children's future learning, reasoning and adaptive functioning.

Executive function in HIV-affected children and adolescents: a systematic review and meta-analyses.

This review aimed to determine: whether EF is affected in children and adolescents (2-24-years-old) with perinatal HIV infection, perinatal HIV exposure without infection, and behaviourally acquired HIV. A systematic review (PROSPERO number: CRD42017067813) was conducted using 11 electronic databases (01.01.1981-09.07.2019) and 8 conference websites. Primary quantitative studies with EF scores on cognitive tasks and/or behavioural report measures were included. Meta-analyses were performed by EF subtype and subpopulations compared. 1789 records were found. Sixty-one studies were included in the narrative synthesis; 32 (N = 7884 participants) were included in meta-analyses. There was a distinct pattern of reduced EF in those with perinatal HIV infection on antiretroviral therapy compared to controls: pooled effect sizes were largest for verbal and visuospatial working memory, with smaller effects on planning, inhibitory control and set-shifting. Data were limited for other HIV-affected subpopulations. Perinatal HIV infection is associated with reduced EF with varying effect sizes for the different EF subtypes.