Pediatric HIV Research Articles

Slow progression of pediatric HIV associates with early CD8+ T cell PD-1 expression and a stem-like phenotype.

HIV nonprogression despite persistent viremia is rare among adults who are naive to antiretroviral therapy (ART) but relatively common among ART-naive children. Previous studies indicate that ART-naive pediatric slow progressors (PSPs) adopt immune evasion strategies similar to those described in natural hosts of SIV. However, the mechanisms underlying this immunophenotype are not well understood. In a cohort of early-treated infants who underwent analytical treatment interruption (ATI) after 12 months of ART, expression of PD-1 on CD8+ T cells immediately before ATI was the main predictor of slow progression during ATI. PD-1+CD8+ T cell frequency was also negatively correlated with CCR5 and HLA-DR expression on CD4+ T cells and predicted stronger HIV-specific T lymphocyte responses. In the CD8+ T cell compartment of PSPs, we identified an enrichment of stem-like TCF-1+PD-1+ memory cells, whereas pediatric progressors and viremic adults had a terminally exhausted PD-1+CD39+ population. TCF-1+PD-1+ expression on CD8+ T cells was associated with higher proliferative activity and stronger Gag-specific effector functionality. These data prompted the hypothesis that the proliferative burst potential of stem-like HIV-specific cytotoxic cells could be exploited in therapeutic strategies to boost the antiviral response and facilitate remission in infants who received early ART with a preserved and nonexhausted T cell compartment.

Alcohol use, suicidality and virologic non-suppression among young adults with perinatally acquired HIV in Thailand: a cross-sectional study.

Young adults with perinatally acquired HIV (YA-PHIV) are facing transitions to adult life. This study assessed health risk behaviours (including substance use), mental health, quality of life (QOL) and HIV treatment outcomes of Thai YA-PHIV. A cross-sectional study was conducted in Thai YA-PHIV aged 18-25 years who were enrolled in a prospective cohort study at five tertiary paediatric HIV care centres in Thailand. Study data were obtained through face-to-face interviews from November 2020 to July 2021. Assessments were performed for alcohol use (Alcohol Use Disorders Identification Test; AUDIT), smoking (Fagerstrom Test for Nicotine Dependence), drug/substance use (Drug Abuse Screening Test; DAST-10), depression (Patient Health Questionnaire for Adolescents; PHQ-A), anxiety (Generalized Anxiety Disorder; GAD-7) and QOL (World Health Organization QOL Brief-Thai). HIV treatment outcomes were extracted from the National AIDS Program database. Of 355 YA-PHIV, 163 (46%) were males: their median age was 21.7 (interquartile range, IQR 20.2-23.5) years. There were 203 YA-PHIV (58%) who reported ever having sex; 141 (40%) were sexually active in the past 6 months, of whom 86 (61%) reported 100% condom use. Overall, 49 (14%) met the criteria for harmful alcohol use; 28 (7.9%) were alcohol dependent. Sixty (17%) were current smokers and 37 (11%) used drugs/substances. The frequency of moderate up to severe symptoms for depression was 18% and for anxiety was 9.7%. Their overall QOL was good in 180 (51%), moderate in 168 (47%) and poor in five (1.4%). There were 49 YA-PHIV (14%) with CD4 <200 cells/mm3 and 85 (24%) with virologic non-suppression (HIV-RNA >200 copies/ml). On multivariate analyses, the highest education at the primary to high school or vocational school levels (adjusted odds ratio [aOR] 2.02, 95% CI 1.40-3.95, p 0.04), harmful alcohol use (aOR 2.48, 95% CI 1.24-4.99, p 0.01), alcohol dependence (aOR 3.54, 95% CI 1.51-8.31, p <0.01) and lifetime suicidal attempt (aOR 2.66, 95% CI 1.11-6.35, p 0.03) were associated with non-suppression. Regular screening for alcohol use and mental health, including suicidality, would be useful to identify YA-PHIV who need more intensive psychosocial support or referral services to ensure they can achieve and maintain a high QOL into adult life.

THE EFFECT OF PREGNANT WOMEN KNOWLEDGE ON COMPLIANCE WITH TRIPLE ELIMINATION EXAMINATION

Background: According to WHO data, in Southeast Asia in 2015 the HIV rate reached 5.1 million patients with 77,000 pregnant women living with HIV, and 19,000 new cases of pediatric HIV infection have been found. This is a number that can be considered fantastic compared to other regions. Meanwhile for syphilis, the incidence rate has shown an increase of 0.32% in the Southeast Asian region. The number of patients shows up to 167,000 cases of syphilis in pregnant women. It had a disastrous impact by producing 65,800 adverse outcomes including early fetal death. For Hepatitis B, Southeast Asia bears 15% of the total number of Hepatitis B patients worldwide with a total of 39 million people. Prevention activities have been carried out by the Ministry of Health of the Republic of Indonesia by holding a program called Triple Elimination in accordance with WHO recommendations (2017). The activity was in the form of carrying out tests for HIV, Hepatitis B and Syphilis (triple Elimination) during Antenatal Care (ANC) for Pregnant. Research Objectives: to find out the factors that influence the triple elimination examination in pregnant women at the Sarageni Health Center, Lebak Regency in 2022. Research Methods: quantitative with cross sectional research design. The sample in this study was 65 pregnant women in the Sarageni Health Center area in November 2022 (Purposive Sampling). Data were collected using a questionnaire given to respondents then processed and analyzed univariate and bivariate and tested with the Chi Square test. The results of the study: the prevalence that affects the compliance of pregnant women Age p-value 0.006 &lt;0.05 Education p-value 0.000 &lt;0.05 Socio-economic p-value 1.000 &gt;0.05 and Husband support p-value 0.000 &lt;0.05.

Cost-effectiveness of broadly neutralizing antibody prophylaxis for HIV-exposed infants in sub-Saharan African settings.

Infant HIV prophylaxis with broadly neutralizing anti-HIV antibodies (bNAbs) could provide long-acting protection against vertical transmission. We sought to estimate the potential clinical impact and cost-effectiveness of hypothetical bNAb prophylaxis programmes for children known to be HIV exposed at birth in three sub-Saharan African settings. We conducted a cost-effectiveness analysis using the CEPAC-Pediatric model, simulating cohorts of infants from birth through death in Côte d'Ivoire, South Africa and Zimbabwe. These settings were selected to reflect a broad range of HIV care cascade characteristics, antenatal HIV prevalence and budgetary constraints. We modelled strategies targeting bNAbs to only WHO-designated "high-risk" HIV-exposed infants (HR-HIVE) or to all HIV-exposed infants (HIVE). We compared four prophylaxis approaches within each target population: standard of care oral antiretroviral prophylaxis (SOC), and SOC plus bNAbs at birth (1-dose), at birth and 3 months (2-doses), or every 3 months throughout breastfeeding (Extended). Base-case model inputs included bNAb efficacy (60%/dose), effect duration (3 months/dose) and costs ($60/dose), based on published literature. Outcomes included paediatric HIV incidence and incremental cost-effectiveness ratios (ICERs) calculated from discounted life expectancy and lifetime HIV-related costs. The model projects that bNAbs would reduce absolute infant HIV incidence by 0.3-2.2% (9.6-34.9% relative reduction), varying by country, prophylaxis approach and target population. In all three settings, HR-HIVE-1-dose would be cost-saving compared to SOC. Using a 50% GDP per capita ICER threshold, HIVE-Extended would be cost-effective in all three settings with ICERs of $497/YLS in Côte d'Ivoire, $464/YLS in South Africa and $455/YLS in Zimbabwe. In all three settings, bNAb strategies would remain cost-effective at costs up to $200/dose if efficacy is ≥30%. If the bNAb effect duration were reduced to 1 month, the cost-effective strategy would become HR-HIVE-1-dose in Côte d'Ivoire and Zimbabwe and HR-HIVE-2-doses in South Africa. Findings regarding the cost-effectiveness of bNAb implementation strategies remained robust in sensitivity analyses regarding breastfeeding duration, maternal engagement in postpartum care, early infant diagnosis uptake and antiretroviral treatment costs. At current efficacy and cost estimates, bNAb prophylaxis for HIV-exposed children in sub-Saharan African settings would be a cost-effective intervention to reduce vertical HIV transmission.

Incident HIV acquisition among pregnant women in Botswana: findings from the Tsepamo birth outcomes surveillance study.

In Botswana, where almost all pregnant women known to have HIV receive antiretroviral therapy, a large proportion of vertical HIV transmission may occur among women with incident undiagnosed HIV infection during pregnancy. Botswana guidelines recommend repeat HIV testing every 3 months in pregnancy, with at least one test in the third trimester. We evaluated the rate of repeat HIV testing, calculated HIV incidence during pregnancy and estimated missed seroconversions. In the Botswana Tsepamo Study, we abstracted HIV test dates and results from obstetric records of all women who delivered at maternity wards in 18 communities between 7th May 2017 and 20th August 2021. We defined seroconversion as an initial negative/indeterminate HIV test in pregnancy followed by a positive test during pregnancy/at delivery. The incidence rate (IR) of seroconversion was calculated among women with > = 2 known test dates. Missed seroconversions were estimated among women without a test in the third trimester by applying the IR to the time after the last HIV test until delivery. Among 103,529 women delivering in the study period testing negative at the first test and with known conception and HIV test dates, 29,085 (28%) were tested in one trimester of pregnancy, 73,156 (71%) were tested in ≥2 trimesters of pregnancy and 9628 (9%) had a test in all trimesters. A total of 78,162 (75%) women had a third-trimester test. There were 223 seroconversions (2.58/1000 pregnancies, 0.26%) among those with ≥2 known HIV test dates, yielding an IR of 0.69/100 person-years. Among 25,289 women who did not have a test in the third trimester, we estimate approximately 58 seroconversions may have been missed during pregnancy due to a lack of repeat testing. Factors associated with seroconversion during pregnancy included younger age, less education and not being married. More than two-thirds of women had repeat HIV testing in pregnancy and HIV incidence was low. However, an estimated 21% of seroconversions in pregnancy were likely missed due to a lack of re-testing. To reach the goal of zero new paediatric HIV infections, Botswana will need to intensify repeat HIV testing in the third trimester of pregnancy.

1398. Disparities in HIV continuum of care in the pediatric population: a real-life study in Brazil

Abstract Background The pediatric HIV follow-up is challenging, and treatment indicators are markedly distant from UNAIDS goals. In this study, we describe the 2019 Brazilian HIV cascade according to age categories and sociodemographic variables and address temporal trends between 2009-2019. Methods We obtained data from the Brazilian Ministry of Health monitoring database. Cascade outcomes included retention in care, antiretroviral use, and viral suppression. The effect of age on timely initiation of antiretroviral treatment (ART, initiation with CD4+ T cell count ≥350 cells/mm3 or a first ART dispensation ≤30 days after the first CD4+ T cell measurement) and detectable HIV viral load (&amp;gt;50 copies/mL) was assessed in univariable and multivariable analysis adjusted for gender, race, and Social Vulnerability Index (SVI). Temporal trends in timely ART initiation and viral suppression were evaluated graphically. Results Among 771,774 people living with HIV (PLHIV), those from youngest age categories had poorer indicators in the care cascade (Figure 1). PLHIV in younger age groups, those with higher SVI, and those declaring black and native Brazilian race/ethnicity, had higher odds of having detectable viral load and delayed ART initiation (Table 1).Social aspects are also associated with worse outcomes. Although children living with HIV tend to start ART with higher CD4+T cell counts, time-series analysis suggest that improvements observed in the adult population do not extend to the pediatric population (Figure 2) Continuum of care in Brazil, 2019 Retention in care, antiretroviral use and viral load suppression in people living with HIV under care in the Brazilian Unified Health System in 2019, overall and by age category (N=771,774). Temporal trends, Brazil (2009-2019) Temporal trends of timely initiation of ART based on a CD4+ T cell count ≥500m/mm3 (panel A), timely initiation of ART based on a first ART dispensation ≤30 days after the first CD4+ T cell count measurement (panel B) and viral load suppression (panel C) overall and according to age categories between 2009 and 2019 in Brazil. Table 1Associations between demographic variables and timely initiation of ART (based on a CD4+ T cell count ≥350m/mm3 or ≤30 days after the first CD4+ T cell count measurement) and detectable viral load using univariable and multivariable logistic regression models in the 2019 dataset. Conclusion Our results highlight the challenge faced by children and adolescents living with HIV to achieve UNAIDS goals. Lower access to ART among children is a central barrier to improve pediatric care. Disclosures All Authors: No reported disclosures.

Surgical implications of HIV infection

According to the joint United Nations Programme on HIV/AIDS (UNAIDS), 37.7 million adults and children worldwide were estimated to be living with HIV or acquired immune deficiency syndrome (AIDS) at the end of 2020 [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. Most reside in low- and middle-income countries, with approximately 67% in sub-Saharan Africa (SSA). At the end of 2020, the total number of children less than 15years of age living with HIV infection was 2.6 million, of whom 2.3 million (88%) were living in SSA. Aggressive interventions have reduced the annual number of incident (new) HIV infections among children to around 150,000 [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. However, paediatric HIV infection remains a pandemic affecting children predominantly in SSA but is also seen in Asia and sporadically elsewhere particularly in areas of civil strife such as is currently the case in Ukraine [War in Ukraine. (2022). https://www.unaids.org/en/War-Ukraine-special . Accessed Apr 2022]. New HIV infections among children declined by more than half (54%) from 2010 to 2020, due mainly to the increased provision of antiretroviral therapy to pregnant and breastfeeding women living with HIV [UNAIDS. (2022). http://www.unaids.org . Accessed 30 May 2022]. These programmes include early identification of HIV infection in pregnant or breastfeeding women through routine HIV testing, provision of antiretroviral therapy (ART) to all HIV-infected women who are pregnant or breastfeeding, provision of antiretroviral prophylaxis to their newborn infants during the first 6-12weeks of life, delivery by elective Caesarean section when indicated, promotion of exclusive breastfeeding, early infancy screening for HIV infection, and initiation of ART in infants with HIV infection. HIV-infected children may require surgery either as an emergency to deal with a life-threatening incidental condition unrelated to HIV infection or for a complication of the disease such as tuberculosis or an aggressive soft tissue infection like necrotising fasciitis. Non-emergency surgical procedures may be required to assist in the diagnosis of an HIV-related condition or to correct a routine surgical problem electively. Surgical conditions associated with HIV infection are described under categories of soft tissue or organ-specific infections requiring drainage or debridement; gastrointestinal tract disease and complications; infections in the perineal area; malignancies and HIV-associated vasculitis. Although surgical outcomes are less favourable in HIV-infected children, pre-operative treatment of coinfections, administration of cotrimoxazole prophylaxis, nutritional support and antiretroviral therapy, together with peri-operative antibiotic prophylaxis have resulted in excellent short-term outcomes [World Health Organization. Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection: Recommendations for a public health approach, June 201 http://www.apps.who.int/iris/bitstream/10665/85321/1/9789241505727_eng.pdf?ua=1 ; World Health Organization Guideline on when to start antiretroviral therapy and on pre-exposure prophylaxis for HIV, September 2015. http://www.apps.who.int/iris/bitstream/10665/186275/1/9789241509565_eng.pdf?ua=1;Eley et al. in BMC Infect Dis 2:3, 2002;Karpelowsky et al. in Pediatr Surg Int 28:1007-1014, 2012;].

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

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. 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. 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. 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. Viral load suppression for children and adolescents were not negatively affected by COVID-19. A trend of decrease in VL testing predated COVID-19. Evidence presented that HIV VL testing and suppression rates in children and adolescents in a high burden setting were sustained through the COVID pandemic.

Prevalence of undiagnosed HIV among children in South Africa, Côte d'Ivoire and Zimbabwe: a model-based analysis to inform paediatric HIV screening programmes.

To improve the diagnosis and survival of children living with HIV (CLWH), the World Health Organization recommends testing approaches beyond traditional infant HIV testing programmes. Information about undiagnosed HIV prevalence among children of varying ages in the general population is needed to guide innovative national/subnational case-finding and testing approaches. We used the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model to estimate the prevalence of undiagnosed HIV in 2-, 5- and 10-year-old children in South Africa, Côte d'Ivoire and Zimbabwe in 2018. We simulated cohorts of children born in 2008 (10-year-olds), 2013 (5-year-olds) and 2016 (2-year-olds). Country-/year-specific inputs for pregnant/breastfeeding women included: HIV prevalence (4.2-32.3%), HIV incidence (0.03-0.24%/month), knowledge of HIV status (27-89%) and antiretroviral drug coverage (36-95%). Paediatric inputs included early infant testing coverage (6-95%) and breastfeeding duration (0-20 months). We projected the proportion of surviving CLWH in whom HIV remained undiagnosed and the undiagnosed HIV prevalence among surviving children of each age in the general population. For children born in 2016, we projected survival and diagnosis of all CLWH through 2026. We conducted sensitivity analyses on model parameters. In 2018, the projected proportion of surviving CLWH whose HIV remained undiagnosed in South Africa/Côte d'Ivoire/Zimbabwe was 44.2%/55.8%/52.9% among 2-year-old CLWH; 29.0%/37.8%/33.2% among 5-year-old CLWH; and 18.3%/25.4%/23.1% among 10-year-old CLWH. Projected general population undiagnosed HIV prevalence in South Africa/Côte d'Ivoire/Zimbabwe was 0.44%/0.32%/0.68% among 2-year-olds; 0.25%/0.17%/0.41% among 5-year-olds; and 0.24%/0.14%/0.38% among 10-year-olds. Among all CLWH born in 2016, 50-54% were projected to die without HIV diagnosis (and subsequently without treatment) within 10 years after birth; 80-85% of these deaths occurred in the first 2 years. Projected population-level undiagnosed HIV prevalence is low and sharply decreases after age 2, with more CLWH dying than being diagnosed. Despite low undiagnosed prevalence in the general population of older children, we project that a large proportion of CLWH remain undiagnosed, suggesting that innovative strategies targeting untested children of all ages outside of health facility settings should be prioritized. Programmes could consider routine testing of the general population of children below 2 in all settings and children of all ages in high-prevalence settings.

COVID-19 Ignited a Successful Growth Spurt in Pediatric HIV Differentiated Service Delivery Programming.

Pediatric HIV differentiated service delivery (DSD) programming has historically lagged behind adult care despite WHO recommendations to include family-friendly alternatives for children and caregivers. This review explores the status of Pediatric DSD programming before the COVID-19 pandemic and then reviews published differentiated approaches that developed during the pandemic. Differentiated service delivery programming for adults living with HIV has increased worldwide, and patient outcomes from these programs have been positive. Pediatric DSD programming has lagged, with many children ineligible for multi-month refills. Despite WHO recommendations to space ART visits for children, limited access to viral load monitoring and a lack of viral suppression among children have left them out of this more convenient care option. Community ART groups historically were not structured to include children. Furthermore, after-hours clinics and teen clubs with ART dispensing have not reached the majority of CLHIV. This review highlights programs that developed out of necessity during the lockdowns of the pandemic. Ingenuity and creativity forced programmers to provide care to their patients with less patient-clinician interaction. Children became eligible for multi-month dispensing as programs loosened eligibility criteria. Technology helped provide virtual psychological support, and unique ART delivery methods were developed. This rapid expansion or growth spurt, of pediatric DSD programming sped up the inclusion of children into care options that were less burdensome to the family. As we move away from the pandemic and adjust to a new standard, we will remain diligent in ensuring that CLHIV outcomes remain stable or perhaps, improve.

Association between service readiness and PMTCT cascade effectiveness: a 2018 cross-sectional analysis from Manica province, Mozambique

BackgroundDespite high coverage of maternal and child health services in Mozambique, prevention of mother-to-child transmission of HIV (PMTCT) cascade outcomes remain sub-optimal. Delivery effectiveness is modified by health system preparedness. Identifying modifiable factors that impact quality of care and service uptake can inform strategies to improve the effectiveness of PMTCT programs. We estimated associations between facility-level modifiable health system readiness measures and three PMTCT outcomes: Early infant diagnosis (polymerase chain reaction (PCR) before 8 weeks of life), PCR ever (before or after 8 weeks), and positive PCR test result.MethodsA 2018 cross-sectional, facility-level survey was conducted in a sample of 36 health facilities covering all 12 districts in Manica province, central Mozambique, as part of a baseline assessment for the SAIA-SCALE trial (NCT03425136). Data on HIV testing outcomes among 3,427 exposed infants were abstracted from at-risk child service registries. Nine health system readiness measures were included in the analysis. Logistic regressions were used to estimate associations between readiness measures and pediatric HIV testing outcomes. Odds ratios (OR) and 95% confidence intervals (95%CI) are reported.ResultsForty-eight percent of HIV-exposed infants had a PCR test within 8 weeks of life, 69% had a PCR test ever, and 6% tested positive. Staffing levels, glove stockouts, and distance to the reference laboratory were positively associated with early PCR (OR = 1.02 [95%CI: 1.01–1.02], OR = 1.73 [95%CI: 1.24–2.40] and OR = 1.01 [95%CI: 1.00–1.01], respectively) and ever PCR (OR = 1.02 [95%CI: 1.01–1.02], OR = 1.80 [95%CI: 1.26–2.58] and OR = 1.01 [95%CI: 1.00–1.01], respectively). Catchment area size and multiple NGOs supporting PMTCT services were associated with early PCR testing OR = 1.02 [95%CI: 1.01–1.03] and OR = 0.54 [95%CI: 0.30–0.97], respectively). Facility type, stockout of prophylactic antiretrovirals, the presence of quality improvement programs and mothers’ support groups in the health facility were not associated with PCR testing. No significant associations with positive HIV diagnosis were found.ConclusionSalient modifiable factors associated with HIV testing for exposed infants include staffing levels, NGO support, stockout of essential commodities and accessibility of reference laboratories. Our study provides insights into modifiable factors that could be targeted to improve PMTCT performance, particularly at small and rural facilities.

Considerations to Improve Pediatric HIV Testing and Close the Treatment Gap in 16 African Countries.

In 2019, South Africa, Nigeria, Tanzania, Democratic Republic of Congo, Uganda, Mozambique, Zambia, Angola, Cameroon, Zimbabwe, Ghana, Ethiopia, Malawi, Kenya, South Sudan and Côte d'Ivoire accounted for 80% of children living with HIV (CLHIV) not receiving HIV treatment. This manuscript describes pediatric HIV testing to inform case-finding strategies. We analyzed US President's Emergency Plan for AIDS Relief monitoring, evaluation, and reporting data (October 1, 2018 to September 30, 2019) for these 16 countries. Number of HIV tests and positive results were reported by age band, country, treatment coverage and testing modality. The number needed to test (NNT) to identify 1 new CLHIV 1-14 years was measured by testing modality and country. The pediatric testing gap was estimated by multiplying the estimated number of CLHIV unaware of their status by NNT per country. Among children, 6,961,225 HIV tests were conducted, and 101,762 CLHIV were identified (NNT 68), meeting 17.6% of the pediatric testing need. Index testing accounted for 13.0% of HIV tests (29.7% of positive results, NNT 30), provider-initiated testing and counseling 65.9% of tests (43.6% of positives, NNT 103), and universal testing at sick entry points 5.3% of tests (6.5% of positives, NNT 58). As countries near HIV epidemic control for adults, the need to increase pediatric testing continues. Each testing modality - PITC, universal testing at sick entry points, and index testing - offers unique benefits. These results illustrate the comparative advantages of including a strategic mix of testing modalities in national programs to increase pediatric HIV case finding.

A national household survey on HIV prevalence and clinical cascade among children aged ≤15 years in Kenya (2018).

We analyzed data from the 2018 Kenya Population-Based HIV Impact Assessment (KENPHIA), a cross-sectional, nationally representative survey, to estimate the burden and prevalence of pediatric HIV infection, identify associated factors, and describe the clinical cascade among children aged < 15 years in Kenya. Interviewers collected information from caregivers or guardians on child's demographics, HIV testing, and treatment history. Blood specimens were collected for HIV serology and if HIV-positive, the samples were tested for viral load and antiretrovirals (ARV). For participants <18 months TNA PCR is performed. We computed weighted proportions with 95% confidence intervals (CI), accounting for the complex survey design. We used bivariable and multivariable logistic regression to assess factors associated with HIV prevalence. Separate survey weights were developed for interview responses and for biomarker testing to account for the survey design and non-response. HIV burden was estimated by multiplying HIV prevalence by the national population projection by age for 2018. Of 9072 survey participants (< 15 years), 87% (7865) had blood drawn with valid HIV test results. KENPHIA identified 57 HIV-positive children, translating to an HIV prevalence of 0.7%, (95% CI: 0.4%-1.0%) and an estimated 138,900 (95% CI: 84,000-193,800) of HIV among children in Kenya. Specifically, children who were orphaned had about 2 times higher odds of HIV-infection compared to those not orphaned, adjusted Odds Ratio (aOR) 2.2 (95% CI:1.0-4.8). Additionally, children whose caregivers had no knowledge of their HIV status also had 2 times higher odds of HIV-infection compared to whose caregivers had knowledge of their HIV status, aOR 2.4 (95% CI: 1.1-5.4)". From the unconditional analysis; population level estimates, 78.9% of HIV-positive children had known HIV status (95% CI: 67.1%-90.2%), 73.6% (95% CI: 60.9%-86.2%) were receiving ART, and 49% (95% CI: 32.1%-66.7%) were virally suppressed. However, in the clinical cascade for HIV infected children, 92% (95% CI: 84.4%-100%) were receiving ART, and of these, 67.1% (95% CI: 45.1%-89.2%) were virally suppressed. The KENPHIA survey confirms a substantial HIV burden among children in Kenya, especially among orphans.

Advances in Pediatric HIV-1 Cure Therapies and Reservoir Assays.

Significant advances in the field of HIV-1 therapeutics to achieve antiretroviral treatment (ART)-free remission and cure for persons living with HIV-1 are being made with the advent of broadly neutralizing antibodies and very early ART in perinatal infection. The need for HIV-1 remission and cure arises due to the inability of ART to eradicate the major reservoir for HIV-1 in resting memory CD4+ T cells (the latent reservoir), and the strict adherence to lifelong treatment. To measure the efficacy of these cure interventions on reservoir size and to dissect reservoir dynamics, assays that are sensitive and specific to intact proviruses are critical. In this review, we provided a broad overview of some of the key interventions underway to purge the reservoir in adults living with HIV-1 and ones under study in pediatric populations to reduce and control the latent reservoir, primarily focusing on very early treatment in combination with broadly neutralizing antibodies. We also summarized assays currently in use to measure HIV-1 reservoirs and their feasibility and considerations for studies in children.

A focused multi-state model to estimate the pediatric and adolescent HIV epidemic in Thailand, 2005-2025.

We estimated the magnitude of the HIV epidemic among children and youth living with HIV (CYHIV) aged 0-25 years in Thailand, projecting forward from 2005 to 2025, and identified underreported input parameters that influence epidemic projections, in order to inform future public health and research priorities. We developed a focused multi-state transition model incorporating perinatally-acquired HIV and non-perinatally-acquired HIV, stratified by population, including men who have sex with men (MSM), female sex workers (FSW), people who inject drugs (PWID), and the remainder of the population ("other"). We populated the model with published and programmatic data from the Thai national AIDS program when available. We projected the period from 2005-2025 and compared model results to programmatic data and projections from other models. In a scenario analysis, we projected the potential impact of pre-exposure prophylaxis (PrEP) for MSM from 2018-2025. The initial 2005 cohort was comprised of 66,900 CYHIV; 8% CYHIV were &lt;5 years, 21% were 5-14 years, and 71% were 15-25 years of age. By 2020, 94% were projected to be &gt;15 years and infections among MSM constituted 83% of all new HIV infections. The numbers of CYHIV decreased over time, projected to reach 30,760 by 2020 (-54%) and 22,640 by 2025 (-66%). The proportion of all CYHIV aged 0-25 who were diagnosed and on ART increased from 37 to 60% over the 2005-2025 period. Projections were sensitive to variations in assumptions about initial HIV prevalence and incidence among MSM, PWID, and "other" youth. More data on incidence rates among sexual and gender minority youth and PWID are needed to characterize the role of specific exposures and key populations in the adolescent HIV epidemic. More accurate estimates will project shifts in population and inform more targeted interventions to prevent and care for Thai CYHIV.

Recognition of infants at high risk for vertical HIV transmission at delivery in rural Western Cape Province, South Africa.

Despite South Africa’s substantial reduction in vertical HIV transmission (VHT), national paediatric HIV elimination is not yet attained. National and Western Cape Province (WC) HIV guidelines recommend enhanced postnatal prophylaxis for infants at high risk for VHT, identified in the WC 2015/2016 guidelines by any single high-risk criterion (maternal antiretroviral therapy (ART) <12 weeks, absent/ unsuppressed maternal HIV viral load (HIV-VL) <12 weeks before/including delivery, spontaneous preterm labour, prolonged rupture of membranes, chorioamnionitis). Accuracy of high-risk infant identification is unknown. Primarily, to determine the proportion of infants at high risk for VHT, the accuracy of labour-ward risk classification, the criteria determining high-risk statuses and the criteria missed among unrecognised high-risk infants; secondarily, to determine maternal factors associated with high-risk infants. Infants born to women living with HIV at a rural regional hospital (May 2016 - April 2017) were retrospectively evaluated using data from the labour ward VHT register, standardised maternity case records, National Health Laboratory Service database and WC Provincial Health Data Centre. The study-derived risk status for each infant was determined using documented presence/absence of risk criteria and compared with labour ward assigned risk to determine accuracy. Proportions of high-risk and unrecognised high-risk infants with each high-risk criterion were determined. Maternal characteristics associated with having a high-risk infant were evaluated using multivariable logistic regression. For liveborn infants, labour ward assigned risk classifications were 40% (n=75/188) high risk, 50% (n=94/188) low risk and 10% (n=19/188) unclassified. Study-derived risk was high risk for 69% (n=129/188) and low risk for 31% (n=59/188), yielding a high-risk classification sensitivity of 51% (95% confidence interval (CI) 42 - 60) and specificity of 69% (95% CI 56 - 80). Absent/unsuppressed HIVVL <12 weeks before delivery accounted for 83% (n=119/143) of study-derived high-risk exposures and 81% (n=60/74) of missed high-risk exposures. Fewer mothers of high-risk infants had >4 antenatal visits (38% v. 81%, p<0.01) and first antenatal visit <20 weeks’ gestation (57% v. 77%, p=0.01). Only the number of antenatal visits remained associated with having a high-risk infant after adjusting for gestation at first visit and timing of HIV diagnosis and ART initiation: each additional antenatal visit conferred a 39% (95% CI 25 - 50) reduction in the odds of having a high-risk infant. Labour ward risk classification failed to recognise half of high-risk infants. Infant high-risk status as well as non-detection thereof were driven by suboptimal maternal HIV-VL monitoring. Reinforcing visit frequency later in pregnancy may improve antenatal HIV-VL monitoring, and point-of-care HIV-VL monitoring at delivery could improve recognition of virally unsuppressed mothers and their high-risk infants.

Chronic kidney disease among children living with the human immunodeficiency virus in sub-Saharan Africa

BackgroundChronic kidney disease (CKD) remains an important comorbid condition in people living with HIV. However, data in children living with HIV/AIDS (CLWHA) in sub-Saharan Africa is limited. We sought to establish the prevalence and identify risk factors of CKD among CLWHA in SSA. MethodsThis was a retrospective chart review across five SSA countries HIV/AIDS care sites, March 2000 and June 2016. Results4,859 children with at least two clinic visits were enrolled in the study. The median age at the first clinic visit was 5.7 (IQR; 2.5, 9.5) years, and median follow-up time was 22.6 (IQR 9.8, 46.1) months. 11.2% CLWHA had an eGFR of <60 mL/min/1.73m2 on at least one clinic visit. The prevalence of CKD was 1.6%. In a multivariable Poisson regression analysis, CKD was associated with severe immunosuppression, incident rate ratio (IRR) 2.69 (95% CI, 1.11, 6.51). Risk of CKD decreased with increasing age (IRR 0.51 (95% CI, 0.39, 0.67). There was no association between CKD and ART regimen. ConclusionCKD was not as prevalent as previously reported in children in other studies. Kidney function monitoring should be incorporated into the pediatric HIV care monitoring guidelines to allow for better evaluation of kidney disease in CLWHA.

Socio-Demographic Correlates of Antiretroviral Treatment Adherence among Paediatric HIV Patients Under Care at A Tertiary Health Institution in South-East Nigeria

Socio-Demographic Correlates of Antiretroviral Treatment Adherence among Paediatric HIV Patients Under Care at A Tertiary Health Institution in South-East Nigeria

“I…Tell Her Not to Take Medicines”: Understanding Engagement in the Prevention of Mother to Child Transmission (PMTCT) Care Continuum through the Socio-Ecological Model

With ten percent of the world’s children living with Human Immunodeficiency Virus (HIV/ AIDS) in India, achieving elimination of parent/mother to-child transmission (EPTCT/EMTCT) is far away. Timely initiation and optimal adherence to the prevention of parent/mother to child transmission (PPTCT/PMTCT) may reduce new paediatric HIV infections to zero. This qualitative study applies the Socio-ecological Model (SEM) to understand country, region and context-specific factors influencing mothers’ engagement in the PMTCT care continuum. Maximum variation sampling and saturation tenets determined the sample size. An in-depth interview guide based on SEM “a priori” and emerging themes captured narratives of the parental dyad. The translated and transcribed audio records were coded by direct content analysis method, both manually and with Atlas Ti software. The coding reports were discussed for consensus and final analysis. Male partner, peers, community health workers (CHWs), hope for healthy baby, knowledge about HIV and preventive services, free anti-retroviral therapy, transportation and the early infant diagnosis (EID) tool influenced PMTCT care continuum. Testing and referral policies of the private sector facilitated internalized or self-stigma. Future interventions should seek to develop pregnant women’s support system by engaging male partners, peers, and CHWs. Strategies addressing private sector and community awareness about freely available HIV prevention and care programs may enable optimal PMTCT utilization.

Machine learning outperformed logistic regression classification even with limit sample size: A model to predict pediatric HIV mortality and clinical progression to AIDS.

Logistic regression (LR) is the most common prediction model in medicine. In recent years, supervised machine learning (ML) methods have gained popularity. However, there are many concerns about ML utility for small sample sizes. In this study, we aim to compare the performance of 7 algorithms in the prediction of 1-year mortality and clinical progression to AIDS in a small cohort of infants living with HIV from South Africa and Mozambique. The data set (n = 100) was randomly split into 70% training and 30% validation set. Seven algorithms (LR, Random Forest (RF), Support Vector Machine (SVM), K-Nearest Neighbor (KNN), Naïve Bayes (NB), Artificial Neural Network (ANN), and Elastic Net) were compared. The variables included as predictors were the same across the models including sociodemographic, virologic, immunologic, and maternal status features. For each of the models, a parameter tuning was performed to select the best-performing hyperparameters using 5 times repeated 10-fold cross-validation. A confusion-matrix was built to assess their accuracy, sensitivity, and specificity. RF ranked as the best algorithm in terms of accuracy (82,8%), sensitivity (78%), and AUC (0,73). Regarding specificity and sensitivity, RF showed better performance than the other algorithms in the external validation and the highest AUC. LR showed lower performance compared with RF, SVM, or KNN. The outcome of children living with perinatally acquired HIV can be predicted with considerable accuracy using ML algorithms. Better models would benefit less specialized staff in limited resources countries to improve prompt referral in case of high-risk clinical progression.