Browsing by Author "Carlucci, James G."
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Item 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(MDPI, 2021-03-21) Siriruchatanon, Mutita; Liu, Shan; Carlucci, James G.; Enns, Eva A.; Duarte, Horacio A.; Pediatrics, School of MedicineImprovement 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.Item CD4 Trends With Evolving Treatment Initiation Policies Among Children Living With HIV in Zambézia Province, Mozambique, 2012–2018(Wolters Kluwer, 2022) Carlucci, James G.; De Schacht, Caroline; Graves, Erin; González, Purificación; Bravo, Magdalena; Yu, Zhihong; Amorim, Gustavo; Arinze, Folasade; Silva, Wilson; Tique, Jose A.; Alvim, Maria F. S.; Simione, Beatriz; Fernando, Anibal N.; Wester, C. William; Pediatrics, School of MedicineBackground: 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.Item Clinical and programmatic outcomes of HIV-exposed infants enrolled in care at geographically diverse clinics, 1997-2021: A cohort study(Public Library of Science, 2022-09-15) Edmonds, Andrew; Brazier, Ellen; Musick, Beverly S.; Yotebieng, Marcel; Humphrey, John; Abuogi, Lisa L.; Adedimeji, Adebola; Keiser, Olivia; Msukwa, Malango; Carlucci, James G.; Maia, Marcelle; Pinto, Jorge A.; Leroy, Valériane; Davies, Mary-Ann; Wools-Kaloustian, Kara K.; IeDEA; Biostatistics, School of Public HealthBackground: 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.Item Clinical Findings and Evaluation of Newborns Who Were Anonymously Surrendered(American Medical Association, 2024-01-02) Liepmann, Claire D.; Nafiseh, Amira A.; Carlucci, James G.; Enane, Leslie A.; Pediatrics, School of MedicineThis cohort study examines clinical findings, medical treatment, and outcomes for infants in Indiana who were surrendered under Safe Haven laws.Item Demographics and trends of cleft lip and palate patients born in Tennessee from 2000 to 2017(Elsevier, 2022-12) Belcher, Ryan H.; Patel, Siddharth A.; Kynes, Matthew; Carlucci, James G.; Hodson, Erin; Zhao, Shilin; Lipscomb, Brittany; Heimburger, Douglas C.; Pediatrics, School of MedicineObjective 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.Item 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(Wiley, 2022) Carlucci, James G.; Yu, Zhihong; González, Purificación; Bravo, Magdalena; Amorim, Gustavo; das Felicidades Cugara, Cristina; Guambe, Helga; Mucanhenga, Jaime; Silva, Wilson; Tique, José A.; Sardella Alvim, Maria Fernanda; Graves, Erin; De Schacht, Caroline; Wester, C. William; Pediatrics, School of MedicineIntroduction: 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.Item 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(Wiley, 2021-09) Kassanjee, Reshma; Johnson, Leigh F.; Zaniewski, Elizabeth; Ballif, Marie; Christ, Benedikt; Yiannoutsos, Constantin T.; Nyakato, Patience; Desmonde, Sophie; Edmonds, Andrew; Sudjaritruk, Tavitiya; Pinto, Jorge; Vreeman, Rachel; Dahourou, Désiré Lucien; Twizere, Christelle; Kariminia, Azar; Carlucci, James G.; Kasozi, Charles; Davies, Mary-Ann; Biostatistics, School of Public HealthIntroduction: 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.Item High Rates of Viral Suppression and Care Retention among Youth Born Outside of the United States with Perinatally Acquired HIV(Wolters Kluwer, 2022-12) Desai, Neerav; Jenkins, Cathy A.; Zanoni, Brian; Nmoh, Ashley; Patel, Nehali; Shepherd, Bryan E.; Hussen, Sophia; Doraivelu, Kamini; Pierce, Leslie; Carlucci, James G.; Ahonkhai, Aima A.; Pediatrics, School of MedicineBackground: 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.Item Optimizing Disclosure of HIV Status to a Diverse Population of HIV-Positive Youth at an Urban Pediatric HIV Clinic(Elsevier, 2021) Dantuluri, Keerti L.; Carlucci, James G.; Howard, Leigh M.; Johnson, David P.; Spencer, Hillary; Desai, Neerav A.; Garguilo, Kathryn A.; Wilson, Gregory J.; Pediatrics, School of MedicinePurpose: 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.Item Outcomes After Second-Line Antiretroviral Therapy in Children Living with HIV in Latin America(Wolters Kluwer, 2021) Somerville, Kayla; Jenkins, Cathy A.; Carlucci, James G.; Person, Anna K.; Machado, Daisy Maria; Luque, Marco T.; Pinto, Jorge A.; Rouzier, Vanessa; Khalili Friedman, Ruth; McGowan, Catherine C.; Shepherd, Bryan E.; Rebeiro, Peter F.; Pediatrics, School of MedicineBackground: 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.