Clinical Findings and Evaluation of Newborns Who Were Anonymously Surrendered.

This cohort study examines clinical findings, medical treatment, and outcomes for infants in Indiana who were surrendered under Safe Haven laws.

Preferences of Pregnant and Postpartum Women for Differentiated Service Delivery in Kenya.

BACKGROUND: Differentiated service delivery models are implemented by HIV care programs globally, but models for pregnant and postpartum women living with HIV (PPWH) are lacking. We conducted a discrete choice experiment to determine women's preferences for differentiated service delivery. SETTING: Five public health facilities in western Kenya. METHODS: PPWH were enrolled from April to December 2022 and asked to choose between pairs of hypothetical clinics that differed across 5 attributes: clinic visit frequency during pregnancy (monthly vs. every 2 months), postpartum visit frequency (monthly vs. only with routine infant immunizations), seeing a mentor mother (each visit vs. as needed), seeing a clinician (each visit vs. as needed), and basic consultation cost (0, 50, or 100 Kenya Shillings [KSh]). We used multinomial logit modeling to determine the relative effects (ß) of each attribute on clinic choice. RESULTS: Among 250 PPWH (median age 31 years, 42% pregnant, 58% postpartum, 20% with a gap in care), preferences were for pregnancy visits every 2 months (ß = 0.15), postpartum visits with infant immunizations (ß = 0.36), seeing a mentor mother and clinician each visit (ß = 0.05 and 0.08, respectively), and 0 KSh cost (ß = 0.39). Preferences were similar when stratified by age, pregnancy, and retention status. At the same cost, predicted market choice for a clinic model with fewer pregnant/postpartum visits was 75% versus 25% for the standard of care (ie, monthly visits during pregnancy/postpartum). CONCLUSION: PPWH prefer fewer clinic visits than currently provided within the standard of care in Kenya, supporting the need for implementation of differentiated service delivery for this population.

Human parechovirus encephalitis in infants: a retrospective single-center study (2017-2022).

Parechoviruses cause a spectrum of clinical presentations ranging from self-limited to severe encephalitis. In July 2022, state health departments across the USA received an increase in reports of PeV infections among infants. A retrospective cohort study describing the clinical characteristics and outcomes of PeV encephalitis in infants aged < 90 days. Rates of PeV encephalitis were determined based on the number of PeV encephalitis cases out of all meningoencephalitis multiplex polymerase chain reaction panel (MEP) obtained among infants aged < 90 days per year. Out of 2115 infants evaluated for meningoencephalitis, 32 (1.5%) cases of PeV encephalitis were identified. All cases had an absence of pleocytosis and normal protein and glucose levels on CSF analysis. Half of the cases presented with a symptomatic triad (fever, rash, and fussiness). More than one-third of cases (39%) presented with a sepsis-like syndrome, 13% presented with seizures, and 25% were admitted to the pediatric intensive care unit (PICU). MRI of the brain was obtained in four of the cases presented with seizure, all of which demonstrated characteristic radiological findings of the periventricular white matter with frontoparietal predominance and involving the corpus callosum, thalami, and internal and external capsules. Rates of PeV encephalitis varied from year to year, with the highest rates in 2018 and 2022. PeV was the second most detected pathogen in MEP in both 2018 and 2022, and the fifth most detected pathogen in all positive MEP during the study period 2017-2022. CONCLUSION: PeV can cause encephalitis and sepsis-like syndrome in infants, and it should be considered even with normal CSF parameters. Prospective studies are needed to better understand PeV epidemiology and to monitor outbreaks. WHAT IS KNOWN: • PeV is a frequent cause of encephalitis and clinical sepsis in infants in the first 90 days. • Normal CSF parameters in PeV encephalitis and diagnostic importance of MEP to avoid unnecessary prolonged antibiotics and hospitalization.. • Centers for Disease Control and Prevention (CDC) issued a Health Advisory alert in Summer 2022 of uptick PeV encephalitis cases in the USA likely secondary of COVID-19 mitigation measures relaxation, but no comparison with previous years.. WHAT IS NEW: • Knowledge of radiological MRI brain characteristics in PeV encephalitis can be a clue diagnosis. • Knowledge of the biennial seasonality pattern in PeV infection. • PeV was the second most detected pathogen in BIOFIRE ME panel in both 2018 and 2022 in our cohort sample.

Integration of HIV care into maternal and child health services in the global IeDEA consortium.

The WHO recommends the integration of routine HIV services within maternal and child health (MCH) services to reduce the fragmentation of and to promote retention in care for pregnant and postpartum women living with HIV (WWH) and their infants and children exposed to HIV (ICEH). During 2020-2021, we surveyed 202 HIV treatment sites across 40 low- and middle-income countries within the global International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. We determined the proportion of sites providing HIV services integrated within MCH clinics, defined as full [HIV care and antiretroviral treatment (ART) initiation in MCH clinic], partial (HIV care or ART initiation in MCH clinic), or no integration. Among sites serving pregnant WWH, 54% were fully and 21% partially integrated, with the highest proportions of fully integrated sites in Southern Africa (80%) and East Africa (76%) compared to 14%-40% in other regions (i.e., Asia-Pacific; the Caribbean, Central and South America Network for HIV Epidemiology; Central Africa; West Africa). Among sites serving postpartum WWH, 51% were fully and 10% partially integrated, with a similar regional integration pattern to sites serving pregnant WWH. Among sites serving ICEH, 56% were fully and 9% were partially integrated, with the highest proportions of fully integrated sites in East Africa (76%), West Africa (58%) and Southern Africa (54%) compared to ≤33% in the other regions. Integration was heterogenous across IeDEA regions and most prevalent in East and Southern Africa. More research is needed to understand this heterogeneity and the impacts of integration on MCH outcomes globally.

Demographics and trends of cleft lip and palate patients born in Tennessee from 2000 to 2017.

OBJECTIVE: The goal of this study was to evaluate the prevalence of orofacial clefts (OFCs) in Tennessee over the span of 2000-2017, and evaluate the effects of race/ethnicity, sex, maternal/paternal age and socioeconomic status on the prevalence. METHODS: Records of all live births and demographics of newborns in Tennessee from 2000 to 2017 were requested from the Tennessee Department of Health to calculate the prevalence of OFCs. Data from United States Census was also obtained. Data provided were deidentified. RESULTS: Tennessee showed a significant decrease in prevalence rates of cleft lip, with and without cleft palate (CL ± P), when comparing the time periods of 2000-2007 to 2008-2017. A significant positive correlation was found with CL ± P prevalence rates in regions with higher Caucasian populations and a negative correlation in regions with higher African American populations. The CP prevalence rates showed a negative correlation with increased median household income. CONCLUSION: To our knowledge, this is the first study to show a significant negative correlation with median household income and CP prevalence rates. Our study showing an increase in prevalence rates of OFCs with decreased socioeconomic status indicates that the areas of Tennessee with the lowest median household income averages would likely benefit from understanding other possible modifiable factors that are driving this correlation.

Clinical and programmatic outcomes of HIV-exposed infants enrolled in care at geographically diverse clinics, 1997-2021: A cohort study.

BACKGROUND: Although 1·3 million women with HIV give birth annually, care and outcomes for HIV-exposed infants remain incompletely understood. We analyzed programmatic and health indicators in a large, multidecade global dataset of linked mother-infant records from clinics and programs associated with the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. METHODS AND FINDINGS: HIV-exposed infants were eligible for this retrospective cohort analysis if enrolled at <18 months at 198 clinics in 10 countries across 5 IeDEA regions: East Africa (EA), Central Africa (CA), West Africa (WA), Southern Africa (SA), and the Caribbean, Central, and South America network (CCASAnet). We estimated cumulative incidences of DNA PCR testing, loss to follow-up (LTFU), HIV diagnosis, and death through 24 months of age using proportional subdistribution hazard models accounting for competing risks. Competing risks were transfer, care withdrawal, and confirmation of negative HIV status, along with LTFU and death, when not the outcome of interest. In CA and EA, we quantified associations between maternal/infant characteristics and each outcome. A total of 82,067 infants (47,300 EA, 10,699 CA, 6,503 WA, 15,770 SA, 1,795 CCASAnet) born from 1997 to 2021 were included. Maternal antiretroviral therapy (ART) use during pregnancy ranged from 65·6% (CCASAnet) to 89·5% (EA), with improvements in all regions over time. Twenty-four-month cumulative incidences varied widely across regions, ranging from 12·3% (95% confidence limit [CL], 11·2%,13·5%) in WA to 94·8% (95% CL, 94·6%,95·1%) in EA for DNA PCR testing; 56·2% (95% CL, 55·2%,57·1%) in EA to 98·5% (95% CL, 98·3%,98·7%) in WA for LTFU; 1·9% (95% CL, 1·6%,2·3%) in WA to 10·3% (95% CL, 9·7%,10·9%) in EA for HIV diagnosis; and 0·5% (95% CL, 0·2%,1·0%) in CCASAnet to 4·7% (95% CL, 4·4%,5·0%) in EA for death. Although infant retention did not improve, HIV diagnosis and death decreased over time, and in EA, the cumulative incidence of HIV diagnosis decreased substantially, declining to 2·9% (95% CL, 1·5%,5·4%) in 2020. Maternal ART was associated with decreased infant mortality (subdistribution hazard ratio [sdHR], 0·65; 95% CL, 0·47,0·91 in EA, and sdHR, 0·51; 95% CL, 0·36,0·74 in CA) and HIV diagnosis (sdHR, 0·40; 95% CL, 0·31,0·50 in EA, and sdHR, 0·41; 95% CL, 0·31,0·54 in CA). Study limitations include potential misclassification of outcomes in real-world service delivery data and possible nonrepresentativeness of IeDEA sites and the population of HIV-exposed infants they serve. CONCLUSIONS: While there was marked regional and temporal heterogeneity in clinical and programmatic outcomes, infant LTFU was high across all regions and time periods. Further efforts are needed to keep HIV-exposed infants in care to receive essential services to reduce HIV infection and mortality.

High Rates of Viral Suppression and Care Retention Among Youth Born Outside of the United States with Perinatally Acquired HIV.

BACKGROUND: Youth born outside of the US with perinatally acquired HIV infection (YBoUS-PHIV) account for most children living with HIV in the US, but there are few data characterizing their care outcomes. METHODS: We conducted a retrospective study of YBoUS-PHIV receiving care across 3 HIV clinics in the Southeastern US between October 2018 and 2019. Primary outcomes were retention in care and viral suppression defined as (1) proportion of suppressed viral loads (VLs) and (2) having all VLs suppressed (definition 1 presented in the abstract). Primary predictors were age, adoption and disclosure status (full, partial and none/unknown). Multivariable logistic regression and χ 2 tests were used to test for associations with care outcomes. Analysis of disclosure status was restricted to youth greater than or equal to 12 years. RESULTS: The cohort included 111 YBoUS-PHIV. Median age was 14 years (interquartile range, 12-18), 59% were female, and 79% were international adoptees. Overall, 84% of patients were retained in care, and 88% were virally suppressed at each VL measurement. Adopted youth were more likely to be virally suppressed than nonadopted youth [odds ratio (OR), 7.08; P < 0.01] although the association was not statistically significant in adjusted analysis (adjusted OR, 4.26; P = 0.07). Neither age nor adoption status was significantly associated with retention. Among 89 patients greater than or equal to 12 years, 74% were fully disclosed of their HIV status, 12% were partially disclosed, and 13% had not started the disclosure process. There was no significant difference in retention or viral suppression by disclosure status. CONCLUSIONS: YBoUS-PHIV achieved high rates of retention and viral suppression. Adopted youth may be more likely to achieve viral suppression which may reflect the need for tailored interventions for nonadopted youth.

The effect of a Mentor Mothers program on prevention of vertical transmission of HIV outcomes in Zambézia Province, Mozambique: a retrospective interrupted time series analysis.

INTRODUCTION: Mentor Mothers (MM) provide peer support to pregnant and postpartum women living with HIV (PPWH) and their infants with perinatal HIV exposure (IPE) throughout the cascade of prevention of vertical transmission (PVT) services. MM were implemented in Zambézia Province, Mozambique starting in August 2017. This evaluation aimed to determine the effect of MM on PVT outcomes. METHODS: A retrospective interrupted time series analysis was done using routinely collected aggregate data from 85 public health facilities providing HIV services in nine districts of Zambézia. All PPWH (and their IPE) who initiated antiretroviral therapy (ART) from August 2016 through April 2019 were included. Outcomes included the proportion per month per district of: PPWH retained in care 12 months after ART initiation, PPWH with viral suppression and IPE with HIV DNA PCR test positivity by 9 months of age. The effect of MM on outcomes was assessed using logistic regression. RESULTS: The odds of 12-month retention increased 1.5% per month in the pre-MM period, compared to a monthly increase of 7.6% with-MM (35-61% pre-MM, 56-72% with-MM; p < 0.001). The odds of being virally suppressed decreased by 0.9% per month in the pre-MM period, compared to a monthly increase of 3.9% with-MM (49-85% pre-MM, 59-80% with-MM; p < 0.001). The odds of DNA PCR positivity by 9 months of age decreased 8.9% per month in the pre-MM period, compared to a monthly decrease of 0.4% with-MM (0-14% pre-MM, 4-10% with-MM; p < 0.001). The odds of DNA PCR uptake (the proportion of IPE who received DNA PCR testing) by 9 months of age were significantly higher in the with-MM period compared to the pre-MM period (48-100% pre-MM, 87-100% with-MM; p < 0.001). CONCLUSIONS: MM services were associated with improved retention in PVT services and higher viral suppression rates among PPWH. While there was ongoing but diminishing improvement in DNA PCR positivity rates among IPE following MM implementation, this might be explained by increased uptake of HIV testing among high-risk IPE who were previously not getting tested. Additional efforts are needed to further optimize PVT outcomes, and MM should be one part of a comprehensive strategy to address this critical need.

Case Series of False-Positive HIV Test Results in Pediatric Acute Lymphoblastic Leukemia Patients Following Chimeric Antigen Receptor T-Cell Therapy: Guidance on How to Avoid and Resolve Diagnostic Dilemmas.

Chimeric antigen receptor T-cell (CAR-T) Cell Therapy is approved for the treatment of pediatric patients with relapsed/refractory acute lymphoblastic leukemia B-ALL. Lentiviral vector technology, highly modified from HIV-1, is used to induce stable, long-term transgene expression by integration into the host genome. This integration may interfere with HIV-1 NAAT producing false-positive results. Guidance for HIV diagnostic testing in pediatric B-ALL undergoing this type of therapy is lacking. Herein, we report case series with presented scenarios in which HIV-1 NAAT testing among CAR-T cell patients produced false-positive results, highlighting the importance careful assay selection and performance among this patient population.

Predicting neurodevelopmental risk in children born to mothers living with HIV in Kenya: protocol for a prospective cohort study (Tabiri Study).

INTRODUCTION: For the growing number of children with in utero and postpartum exposure to HIV and/or antiretrovirals, it is unclear which exposures or risk factors play a significant role in predicting worse neurodevelopmental outcomes. This protocol describes a prospective longitudinal cohort study of infants born to mothers living with HIV and those born to mothers without HIV. We will determine which risk factors are most predictive of child neurodevelopment at 24 months. We aim to create a risk assessment tool to help predict which children are at risk for worse neurodevelopment outcomes. METHODS AND ANALYSIS: This study leverages an existing Kenyan cohort to prospectively enrol 500 children born to mothers living with HIV and 500 to those without HIV (n=1000 total) and follow them from birth to age 24 months. The following factors will be measured every 6 months: infectious morbidity and biological/sociodemographic/psychosocial risk factors. We will compare these factors between the two groups. We will then measure and compare neurodevelopment within children in both groups at 24 months of age using the Child Behaviour Checklist and the Bayley Scales of Infant and Toddler Development, third edition. Finally, we will use generalised linear mixed modelling to quantify associations with neurodevelopment and create a risk assessment tool for children ≤24 months. ETHICS AND DISSEMINATION: The study is approved by the Moi University's Institutional Research and Ethics Committee (IREC/2021/55; Approval #0003892), Kenya's National Commission for Science, Technology and Innovation (NACOSTI, Reference #700244) and Indiana University's Institutional Review Board (IRB Protocol #110990). This study carries minimal risk to the children and their mothers, and all mothers will provide written consent for participation in the study. Results will be disseminated to maternal child health clinics within Uasin Gishu County, Kenya and via papers submitted to peer-reviewed journals and presentation at international conferences.

Retention in care and viral suppression in the PMTCT continuum at a large referral facility in western Kenya.

Medical records of pregnant and postpartum women living with HIV and their infants attending a large referral facility in Kenya from 2015 to 2019 were analyzed to identify characteristics associated with retention in care and viral suppression. Women were stratified based on the timing of HIV care enrollment: known HIV-positive (KHP; enrolled pre-pregnancy) and newly HIV-positive (NHP; enrolled during pregnancy). Associations with retention at 18 months postpartum and viral suppression (< 1000 copies/mL) were determined. Among 856 women (20% NHP), retention was 83% for KHPs and 53% for NHPs. Viral suppression was 88% for KHPs and 93% for NHPs, but 19% of women were missing viral load results. In a competing risk model, viral suppression increased by 18% for each additional year of age but was not associated with other factors. Overall, 1.9% of 698 infants with ≥ 1 HIV test result were HIV-positive. Tailored interventions are needed to promote retention and viral load testing, particularly for NHPs, in the PMTCT continuum.

CD4 Trends With Evolving Treatment Initiation Policies Among Children Living With HIV in Zambézia Province, Mozambique, 2012-2018.

BACKGROUND: Historically, antiretroviral therapy (ART) initiation was based on CD4 criteria, but this has been replaced with "Test and Start" wherein all people living with HIV are offered ART. We describe the baseline immunologic status among children relative to evolving ART policies in Mozambique. METHODS: This retrospective evaluation was performed using routinely collected data. Children living with HIV (CL aged 5-14 years) with CD4 data in the period of 2012-2018 were included. ART initiation "policy periods" corresponded to implementation of evolving guidelines: in period 1 (2012-2016), ART was recommended for CD4 <350 cells/mm3; during period 2 (2016-2017), the CD4 threshold increased to <500 cells/mm3; Test and Start was implemented in period 3 (2017-2018). We described temporal trends in the proportion of children with severe immunodeficiency (CD4 <200 cells/mm3) at enrollment and at ART initiation. Multivariable regression models were used to estimate associations with severe immunodeficiency. RESULTS: The cohort included 1815 children with CD4 data at enrollment and 1922 at ART initiation. The proportion of children with severe immunodeficiency decreased over time: 20% at enrollment into care in period 1 vs. 16% in period 3 (P = 0.113) and 21% at ART initiation in period 1 vs. 15% in period 3 (P = 0.004). Children initiating ART in period 3 had lower odds of severe immunodeficiency at ART initiation compared with those in period 1 [adjusted odds ratio (aOR) = 0.67; 95% CI: 0.51 to 0.88]. Older age was associated with severe immunodeficiency at enrollment (aOR = 1.13; 95% CI: 1.06 to 1.20) and at ART initiation (aOR = 1.14; 95% CI: 1.08 to 1.21). CONCLUSIONS: The proportion of children with severe immunodeficiency at ART initiation decreased alongside more inclusive ART initiation guidelines. Earlier treatment of children living with HIV is imperative.

Global HIV mortality trends among children on antiretroviral treatment corrected for under-reported deaths: an updated analysis of the International epidemiology Databases to Evaluate AIDS collaboration.

INTRODUCTION: The Joint United Nations Programme on HIV/AIDS (UNAIDS) projections of paediatric HIV prevalence and deaths rely on the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium for mortality estimates among children living with HIV (CHIV) receiving antiretroviral therapy (ART). Previous estimates, based on data through 2014, may no longer be accurate due to expanded paediatric HIV care and treatment eligibility, and the possibility of unreported deaths in CHIV considered lost to follow-up (LTFU). We therefore estimated all-cause mortality and its trends in CHIV (<15 years old) on ART using extended and new IeDEA data. METHODS: We analysed (i) IeDEA observational data from CHIV in routine care globally, and (ii) novel data from an IeDEA tracing study that determined outcomes in a sample of CHIV after being LTFU in southern Africa. We included 45,711 CHIV on ART during 2004 to 2017 at 72 programmes in Africa, Asia-Pacific and Latin America. We used mixed effects Poisson regression to estimate mortality by age, sex, CD4 at ART start, time on ART, region and calendar year. For Africa, in an adjusted analysis that accounts for unreported deaths among those LTFU, we first modified the routine data by simulating mortality outcomes within six months after LTFU, based on a Gompertz survival model fitted to the tracing data (n = 221). RESULTS: Observed mortality rates were 1.8 (95% CI: 1.7 to 1.9) and 9.4 (6.3 to 13.4) deaths per 100 person-years in the routine and tracing data, respectively. We found strong evidence of higher mortality at shorter ART durations, lower CD4 values, and in infancy. Averaging over covariate patterns, the adjusted mortality rate was 54% higher than the unadjusted rate. In unadjusted analyses, mortality reduced by an average 60% and 73% from 2005 to 2017, within and outside of Africa, respectively. In the adjusted analysis for Africa, this temporal reduction was 42%. CONCLUSIONS: Mortality rates among CHIV have decreased substantially over time. However, when accounting for worse outcomes among those LTFU, mortality estimates increased and temporal improvements were slightly reduced, suggesting caution in interpreting analyses based only on programme data. The improved and updated IeDEA estimates on mortality among CHIV on ART support UNAIDS efforts to accurately model global HIV statistics.

Patterns of mobility and its impact on retention in care among people living with HIV in the Manhiça District, Mozambique.

INTRODUCTION: Retention in HIV care is a challenge in Mozambique. Mozambique´s southern provinces have the highest mobility levels of the country. Mobility may result in poorer response to HIV care and treatment initiatives. METHODS: We conducted a cross-sectional survey to explore the impact of mobility on retention for HIV-positive adults on ART presenting to the clinic in December 2017 and January 2018. Survey data were linked to participant clinical records from the HIV care and treatment program. This study took place in Manhiça District, southern Mozambique. We enrolled self-identified migrants (moved outside of Manhiça District ≤12 months prior to survey) and non-migrants, matched by age and sex. RESULTS: 390 HIV-positive adults were included. We found frequent movement: 45% of migrants reported leaving the district 3-5 times over the past 12 months, usually for extended stays. South Africa was the most common destination (71%). Overall, 30% of participants had at least one delay (15-60 days) in ART pick-up and 11% were delayed >60 days, though no significant difference was seen between mobile and non-mobile cohorts. Few migrants accessed care while traveling. CONCLUSION: Our population of mobile and non-mobile participants showed frequent lapses in ART pick-up. Mobility could be for extended time periods and HIV care frequently did not continue at the destination. Studies are needed to evaluate the impact of Mozambique´s approach of providing 3-months ART among mobile populations and barriers to care while traveling, as is better education on how and where to access care when traveling.

Poor retention and care-related sex disparities among youth living with HIV in rural Mozambique.

BACKGROUND: There are few studies that characterize sex-related differences in HIV outcomes among adolescents and young adults (AYA) 15-24 years of age. METHODS: We conducted a retrospective cohort study among AYA who enrolled in a comprehensive HIV program in Mozambique between 2012-2016. We assessed patients by sex and pregnancy/lactation status, comparing time to combination antiretroviral therapy (ART) initiation using Cox proportional hazard models. We employed multivariable logistic regression to investigate pre- and post-ART retention. Patients were defined as 'retained pre-ART' if they attended at least 3 of 4 required visits or started ART in the 6 months after enrollment, and 'retained post-ART' if they had any ART pickup or clinical visit during the last 90 days of the one-year follow-up period. RESULTS: Of 47,702 patients in the cohort, 81% (n = 38,511) were female and 19% (n = 9,191) were male. Of the females, 57% (n = 21,770) were non-pregnant and non-lactating (NPNL) and 43% (n = 16,741) were pregnant or lactating (PL). PL (aHR 2.64, 95%CI:2.47-2.81) and NPNL females (aHR 1.36, 95%CI:1.30-1.42) were more likely to initiate ART than males. PL females had higher odds of pre-ART retention in care (aOR 3.56, 95%CI: 3.30-3.84), as did NPNL females (aOR 1.71, 95%CI: 1.62-1.81), compared to males. This was also true for retention post-ART initiation, with higher odds for both PL (aOR 1.78, 95%CI:1.63-1.94) and NPNL females (aOR 1.50, 95%CI:1.35-1.65) compared to males. CONCLUSIONS: PL females were most likely to initiate ART and remain in care post-ART in this AYA cohort, likely reflecting expansion of Option B+. Despite pregnancy and policy driven factors, we observed important sex-related disparities in this cohort. NPNL females were more likely to initiate ART and be retained in care before and after ART initiation than males. These data suggest that young males need targeted interventions to improve these important care continuum outcomes.

Addressing Pediatric HIV Pretreatment Drug Resistance and Virologic Failure in Sub-Saharan Africa: A Cost-Effectiveness Analysis of Diagnostic-Based Strategies in Children ≥3 Years Old.

Improvement of antiretroviral therapy (ART) regimen switching practices and implementation of pretreatment drug resistance (PDR) testing are two potential approaches to improve health outcomes for children living with HIV. We developed a microsimulation model of disease progression and treatment focused on children with perinatally acquired HIV in sub-Saharan Africa who initiate ART at 3 years of age. We evaluated the cost-effectiveness of diagnostic-based strategies (improved switching and PDR testing), over a 10-year time horizon, in settings without and with pediatric dolutegravir (DTG) availability as first-line ART. The improved switching strategy increases the probability of switching to second-line ART when virologic failure is diagnosed through viral load testing. The PDR testing strategy involves a one-time PDR test prior to ART initiation to guide choice of initial regimen. When DTG is not available, PDR testing is dominated by the improved switching strategy, which has an incremental cost-effectiveness ratio (ICER) of USD 579/life-year gained (LY), relative to the status quo. If DTG is available, improved switching has a similar ICER (USD 591/LY) relative to the DTGstatus quo. Even when substantial financial investment is needed to achieve improved regimen switching practices, the improved switching strategy still has the potential to be cost-effective in a wide range of sub-Saharan African countries. Our analysis highlights the importance of strengthening existing laboratory monitoring systems to improve the health of children living with HIV.

Outcomes After Second-Line Antiretroviral Therapy in Children Living With HIV in Latin America.

BACKGROUND: Little is known about the long-term outcomes of children living with HIV in Latin America. Few studies have examined antiretroviral therapy (ART) regimen switches in the years after the introduction of ART in this population. This study aimed to assess clinical outcomes among children who started second-line ART in the Caribbean, Central and South America network for HIV epidemiology. METHODS: Children (<18 years old) with HIV who switched to second-line ART at sites within Caribbean, Central and South America network for HIV epidemiology were included. The cumulative incidence and relative hazards of virologic failure while on second-line ART, loss to follow-up, additional major ART regimen changes, and all-cause mortality were evaluated using competing risks methods and Cox models. RESULTS: A total of 672 children starting second-line ART were included. Three years after starting second-line ART, the cumulative incidence of death was 0.10 [95% confidence interval (CI) 0.08 to 0.13], loss to follow-up was 0.14 (95% CI: 0.11 to 0.17), and major regimen change was 0.19 (95% CI: 0.15 to 0.22). Of those changing regimens, 35% were due to failure and 11% due to toxicities/side effects. Among the 312 children with viral load data, the cumulative incidence of virologic failure at 3 years was 0.62 (95% CI: 0.56 to 0.68); time to virologic failure and regimen change were uncorrelated (rank correlation -0.001; 95% CI -0.18 to 0.17). CONCLUSIONS: Poor outcomes after starting second-line ART in Latin America were common. The high incidence of virologic failure and its poor correlation with changing regimens was particularly worrisome. Additional efforts are needed to ensure children receive optimal ART regimens.

Optimizing Disclosure of HIV Status to a Diverse Population of HIV-Positive Youth at an Urban Pediatric HIV Clinic.

PURPOSE: The purpose of the study was to increase the proportion of youth living with HIV (YLWH) aged ≥11 years who undergo developmentally appropriate disclosure about their HIV status. METHODS: A quality improvement project was initiated at an urban pediatric HIV clinic between July 2018 and March 2020. The primary outcome measure was the proportion of YLWH aged ≥11 years who were disclosed to about their HIV status. The proportion of undisclosed YLWH who had documented nondisclosure status was also assessed as a process measure. Plan-Do-Study-Act (PDSA) cycles for change included monthly clinic staff check-ins to discuss new disclosures, quarterly team meetings to discuss strategies to improve disclosure, and modifying a clinic note template to prompt providers to document disclosure status. Annotated run charts were used to analyze the data. RESULTS: Before the first PDSA cycle, 26/46 (57%) of the target population of YLWH aged ≥11 years had their HIV status disclosed to them, and none of the undisclosed youth had disclosure status documented in their medical record. After 20 months and six PDSA cycles, the proportion of YLWH aged ≥11 years disclosed to about their HIV status increased to 80% and the proportion of undisclosed YLWH with documentation of their disclosure status increased to 100%. CONCLUSIONS: Several interventions integrated throughout the pediatric HIV care process were associated with an increase in the proportion of YLWH with developmentally appropriate HIV disclosure and documentation of disclosure status, an important psychosocial aspect of care in these individuals.

Hepatitis C Testing Among Perinatally Exposed Infants.

BACKGROUND: Hepatitis C virus (HCV) prevalence doubled among pregnant women from 2009 to 2014, reaching 3.4 per 1000 births nationwide. Infants exposed to HCV may acquire HCV by vertical transmission. National guidelines recommend that infants exposed to HCV be tested; however, it is unclear if these recommendations are being followed. Our objectives were to determine if infants exposed to HCV were tested and to determine hospital- and patient-level factors associated with differences in testing. METHODS: In this retrospective cohort study of infants exposed to HCV who were enrolled in the Tennessee Medicaid program, we used vital statistics-linked administrative data for infants born between January 1, 2005, and December 31, 2014. Infants were followed until 2 years old. Multilevel logistic regression was used to assess the association of HCV testing and hospital- and patient-level characteristics. RESULTS: Only 23% of 4072 infants exposed to HCV were tested. Infants whose mothers were white versus African American (96.6% vs 3.1%; P <.001), used tobacco (78% vs 70%; P <.001), and had HIV (1.3% vs 0.4%; P = .002) were more likely to be tested. Infants exposed to HCV who had a higher median of well-child visits (7 vs 6; P <.001) were more likely to be tested. After accounting for maternal and infant characteristics and health care use patterns, African American infants were less likely to undergo general testing (adjusted odds ratio 0.32; 95% confidence interval, 0.13-0.78). CONCLUSIONS: Testing occurred in <1 in 4 infants exposed to HCV and less frequently among African American infants. Public health systems need to be bolstered to ensure that infants exposed to HCV are tested for seroconversion.

Immunodeficiency at Antiretroviral Therapy Start: Five-Year Adult Data (2012-2017) Based on Evolving National Policies in Rural Mozambique.

Before the 2015 implementation of "Test and Start," the initiation of combination antiretroviral therapy (ART) was guided by specific CD4 cell count thresholds. As scale-up efforts progress, the prevalence of advanced HIV disease at ART initiation is expected to decline. We analyzed the temporal trends in the median CD4 cell counts among adults initiating ART and described factors associated with initiating ART with severe immunodeficiency in Zambézia Province, Mozambique. We included all HIV-positive, treatment-naive adults (age ≥ 15 years) who initiated ART at a Friends in Global Health (FGH)-supported health facility between September 2012 and September 2017. Quantile regression and multivariable logistic regression models were applied to ascertain the median change in CD4 cell count and odds of initiating ART with severe immunodeficiency, respectively. A total of 68,332 patients were included in the analyses. The median change in CD4 cell count under "Test and Start" was higher at +68 cells/mm3 (95% CI: 57.5-78.4) compared with older policies. Younger age and female sex (particularly those pregnant/lactating) were associated with higher median CD4 cell counts at ART initiation. Male sex, advanced age, WHO Stage 4 disease, and referrals to the health facility through inpatient provider-initiated testing and counseling (PITC) were associated with higher odds of initiating ART with severe immunodeficiency. Although there were reassuring trends in increasing median CD4 cell counts with ART initiation, ongoing efforts are needed that target universal HIV testing to ensure the early initiation of ART in men and older patients.