Haploidentical hematopoietic stem cell transplantation with post-transplant cyclophosphamide for Fanconi anemia with/without anti-thymocyte globulin.

Background: We present comparative data of children with Fanconi anemia undergoing haploidentical hematopoietic stem cell transplantation (HSCT) with or without the addition of rabbit anti-thymocyte globulin (r-ATG) to the conditioning regimen. Patients and methods: This retrospective study included children with Fanconi anemia aged up to 18 years who underwent haploidentical HSCT between January 2015 and December 2022. The children were included in two cohorts in this study. Cohort 1 included children who received conditioning with fludarabine/cyclophosphamide/single fraction of 2 Gy TBI. The children in cohort 2 received the same conditioning along with r-ATG. Post-transplant cyclophosphamide was administered at a dose of 25 mg/kg on day3 and day4 in both cohorts. Results: A total of 35 children were included in the study, 25 in cohort 1 and 10 in cohort 2. Neutrophil engraftment was documented around day 14-16 post infusion in 21 children (84%) in cohort 1 and in 8 children (80%) in cohort 2. There was a significant difference in the incidence of the severity of graft versus host disease (GVHD) between the two cohorts (p = 0.003). In cohort 1, acute GVHD was documented in 17 children (68%), with grade 1/2 skin GVHD in 10 children, and grade 3/4 skin and gut GVHD in 7 children. Grade 4 gut GVHD was the cause of death in three children in cohort 1. In cohort 2, acute GVHD was documented in one child (10%) who had grade 4 skin and gut GVHD and succumbed to the above. Chronic GVHD was noted in nine (36%) children in cohort 1, and in one child (10%) in cohort 2. Cytomegalovirus reactivation was documented in 11 children (44%) in cohort 1 and three children (30%) in cohort 2. Overall survival was found to be 16/25 (64%) in cohort 1, with a median follow-up of 49 months, and 7/10 (70%) in cohort 2, with a median follow-up of 12 months. Conclusion: Serotherapy with r-ATG significantly reduced the incidence of GVHD from 68% to 10% in children with Fanconi anemia, with an increase in overall survival from 64% to 70%, although it did not affect graft failure. Further studies should focus on decreasing graft failure rates with early HSCT before multiple transfusions.

Real-World Data on Childhood Relapsed Acute Lymphoblastic Leukemia: A Report on 100 Children Over two Decades From Southern India.

OBJECTIVE: The present study aims to provide outcome data in children with relapsed acute lymphoblastic leukemia (ALL)over two decades and variables that impact survival. METHODS: The retrospective study included children who were diagnosed with ALL and treated at our center and relapsed between March 2002 and March 2021. RESULTS: A total of 100 children (64 boys, 36 girls) were included; 80 had B-ALL, 20 had T-ALL. 50 children had a very early relapse, while 25 each had an early and late relapse. The site of relapse was bone marrow in 57, isolated central nervous system (CNS) in 10, isolated testicular in 1, and combined bone marrow and CNS relapse in 32 children. Thirty-six families opted for the best supportive care; 23 of these had very early relapse. Among the 35 who were in remission following induction chemotherapy, 32 (91%) underwent hematopoietic stem cell transplantation (HSCT); 17/32 (53%) were alive and disease-free. Overall survival (OS) was 19 (19%) with a median follow-up of 23.5 months with a significantly improved survival post-measurable risk of disease (MRD) based risk stratification (4% vs 35%, P = 0.02). The OS with very early, early, and late relapses were 8%, 28%, and 32% (P = 0.018), and 15%, 12.5%, and 50% with bone marrow, combined and isolated CNS relapses (P = 0.008). CONCLUSION: Relapsed ALL remains a challenge, with OS of 19% and 53% among those who underwent HSCT. Abandonment after relapse continues to be prevalent, and we need to integrate social support for providing care and optimal treatment.

Cytomegalovirus Reactivation as a Risk Factor for All-Cause Mortality in Children Undergoing Hematopoietic Stem Cell Transplantation: Experience Over Two Decades from a Tertiary Referral Center in India.

The aim of the study was to analyse the burden of cytomegalovirus (CMV) disease in children undergoing hematopoietic stem cell transplantation (HSCT) and its correlation with all-cause mortality. We performed a retrospective study in children up to 18 years of age who underwent allogeneic HSCT between February 2002 to December 2021 in the pediatric blood and marrow transplantation unit. A total of 1035 patients were included where five hundred forty-three (52.4%) patients underwent matched family donor (MFD) HSCT, 213 (20.5%) underwent matched unrelated donor (MUD) HSCT; 279 (26.9%) underwent haploidentical HSCT (T cell replete in 213 and T cell depleted in 66 patients). CMV reactivation was documented in 258 (24.9% patients). CMV was seen in 39 (7.2%) MFD, 77 (36.1%) MUD, 106 T cell replete (49.7%) and 36 T cell depleted (54.5%) transplants. CMV reactivation was predominantly documented in those where donor and recipient were positive (D + /R +) for CMV serostatus (77%)) prior to HSCT. Overall mortality rate was significantly higher in the CMV positive group (103/258, 39.9%), as compared to the CMV negative group (152/777, 19.6%) (p value = 0.0001). CMV was the direct cause of death in 13/1035 children (1.2%). GvHD as a cause of death was found to be significantly higher among those with CMV (n = 32) as compared to those without CMV (n = 14) (35.6 versus 9%, p value = 0.0001). The incidence of CMV reactivation was noted in 25% of HSCT recipients, and predominantly in haploidentical HSCTs. CMV reactivation was shown to significantly impact all-cause mortality and there was a significantly increased risk of mortality due to GvHD among those with CMV reactivation.

Genital Graft-versus-Host Disease in Children: An Underdiagnosed and Undertreated Entity.

Genital graft-versus-host disease (GVHD) is an underdiagnosed and poorly recognized complication, especially in the pediatric population. We report our data on children with genital manifestations of GVHD and their unique clinical features. The study included children up to age 18 years who underwent hematopoietic stem cell transplantation (HSCT) over a 20-year period from February 2002 to February 2022. A total of 1035 children underwent HSCT during the study period. Genital GVHD was documented in 164 children (15.8%). Among these 164 children, 23 (14%) were age <2 years, 98 (59.8%) were age 2 to 10 years, and 43 (26.2%) were age ≥10 years. The conditioning regimen was myeloablative in 122 children (74.4%) and reduced intensity in 42 children (25.6%). Donor type was matched related donor in 62 (37.8%), matched unrelated donor in 44 (26.8%), and haploidentical in 34 (20.7%). Peripheral blood stem cells (PBSCs) were used in 78.7% of the children (n = 129), and sex mismatch was noted in 31.1% of genital GVHD cases (51 of 164). The overall incidence of chronic oral GVHD was 33% (342 of 1035), and of these, 47.9% (164 of 342) also had genital GVHD. Patients with genital GVHD ultimately may require surgical management; 21.5% (22 of 103) of boys with genital GVHD ultimately required circumcision for phimosis, and 1 female patient developed hematocolpos necessitating surgical management. Our case series highlights the significant association between chronic oral GVHD and genital GVHD. Given the strong association between oral GVHD and genital GVHD in children, it is imperative to examine the genital area in all children on follow-up for chronic GVHD. Donor-recipient sex mismatch and use of PBSC grafts predispose to chronic genital GVHD. Early identification and treatment of genital GVHD may help prevent complications, including scarring and phimosis.

Factors Associated With Viral Suppression and Drug Resistance in Children and Adolescents Living With HIV in Care and Treatment Programs in Southern Tanzania.

BACKGROUND: Achieving viral suppression (VS) for persons living with HIV is key to reaching epidemic control. We assessed the prevalence of VS and the frequency of HIV drug resistance mutations (HIVDRM) among children and adolescents living with HIV (CALHIV) in the Southern Highland zone of Tanzania. METHODS: From 2019 to 2021, we enrolled CALHIV aged 1-19 years on ART for >6 months in a cross-sectional study. Participants had viral load (VL) testing; those with VL ≥ 1000 copies/mL underwent HIVDRM testing. VS (<1000 copies/mL) prevalence estimates were calculated and robust Poisson regression was used to estimate prevalence ratios (PRs) and 95% confidence intervals (CIs) for associations with potential predictors of VS. RESULTS: Of 707 participants, 595 had VS (PR: 0.84, 95% CI: 0.81-0.87). Use of an integrase strand transfer inhibitor-containing regimen (aPR 1.15, 95% CI: 0.99-1.34), age 5-9 years (aPR 1.16, 95% CI: 1.07-1.26), and seeking care at a referral center (aPR 1.12, 95% CI: 1.04-1.21) were associated with VS. Factors inversely associated with VS included having one (aPR 0.82, 95% CI: 0.72-0.92) or two or more (aPR 0.79, 95% CI: 0.66-0.94) referrals for adherence counselling, and self-reporting missing one to two (aPR 0.88, 95% CI: 0.78-0.99) or three or more (aPR 0.77, 95% CI: 0.63-0.92) doses of ART in the past month. Of 74 participants with PRRT and INT sequencing done, 60 (81.1%) had HIVDRMs at the following frequencies: 71.6%, 67.6%, 1.4%, and 4.1% for major NNRTI, NRTI, PI, and INSTI respectively. CONCLUSIONS: Higher rates of VS were observed in this cohort, and HIVDRMs were common in those without VS. This evidence supports ART optimization using dolutegravir-based regimens. However, better strategies to improve adherence are needed.

Early warning indicators of HIV drug resistance in the southern highlands region of Tanzania: Lessons from a cross-sectional surveillance study.

The World Health Organization early warning indicators (EWIs) permit surveillance of factors associated with the emergence of HIV drug resistance (HIVDR). We examined cross- and within-region performance on HIVDR EWIs for selected HIV care and treatment clinics (CTCs) in five regions of southern Tanzania. We retrospectively abstracted EWI data from 50 CTCs for the January to December 2013 period. EWIs included the following: on time ART pick-up, retention on ART, ARV stockouts, and pharmacy prescribing and dispensing practices. Data for pediatric and adult people living with HIV were abstracted from source files, and frequencies and proportions were calculated for each EWI overall, as well as stratified by region, facility, and age group. Across and within all regions, on average, on-time pick-up of pills (63.0%), retention on ART (76.0%), and pharmacy stockouts (69.0%) were consistently poor for the pediatric population. Similarly, on-time pill pick up (66.0%), retention on ART (72.0%) and pharmacy stockouts (53.0%) for adults were also poor. By contrast, performance on pharmacy prescribing and dispensing practices were as desired for both pediatric and adult populations with few facility-level exceptions. In this study, regions and facilities in the southern highlands of Tanzania reported widespread presence of HIVDR risk factors, including sub-optimal timeliness of pill pickup, retention on ART, and drug stockouts. There is an urgent need to implement the WHO EWIs monitoring to minimize the emergence of preventable HIV drug resistance and to maintain the effectiveness of first and second-line ART regimens. This is particularly critical in the context of new ART drug roll-out such as dolutegravir during the COVID-19 pandemic when resultant HIV service disruptions require careful monitoring, and for virologic suppression as countries move closer to epidemic control.

Epidemiology of Tuberculosis Among People Living With HIV in the African Cohort Study From 2013 to 2021.

BACKGROUND: The prevalence and incidence of tuberculosis (TB) is high among people living with HIV (PLWH) but is often underdiagnosed in HIV programmatic settings. SETTING: President's Emergency Plan for AIDS Relief (PEPFAR)-supported research sites in Uganda, Kenya, Tanzania, and Nigeria. METHODS: All patients underwent molecular testing at entry into a longitudinal cohort of PLWH and annually thereafter. We assessed the prevalence and incidence of TB and identified clinical and demographic factors associated with prevalent and incident TB using logistic regression and Cox proportional hazard models. RESULTS: From 21 January, 2013, to 1 December 2021, 3171 PLWH were enrolled with a TB prevalence of 3% (n = 93). Of the cases with prevalent TB, 66% (n = 61) were bacteriologically confirmed. The adjusted odds of prevalent TB were significantly higher among those with higher educational attainment, PLWH for 1-5 years since their HIV diagnosis, those who were underweight, and those with CD4 counts <200 cells/mm 3 . The overall TB incidence rate was 600 per 100,000 person-years (95% CI: 481-748). We found that shorter time since HIV diagnosis, being underweight, taking antiretroviral therapy <6 months, and having a CD4 count <200 cells/mm 3 were significantly associated with incident TB. PLWH on dolutegravir/lamivudine/tenofovir had a 78% lower risk of incident TB compared with those on tenofovir/lamivudine/efavirenz (hazard ratio: 0.22; 95% CI: 0.08-0.63). CONCLUSION: The prevalence and incidence of TB was notably high in this cohort sourced from PEPFAR clinics. Aggressive efforts to enhance HIV diagnosis and optimize treatment in programmatic settings are warranted to reduce the risk of HIV-TB co-occurrence in this cohort.

A novel deep learning approach for sickle cell anemia detection in human RBCs using an improved wrapper-based feature selection technique in microscopic blood smear images.

Sickle Cell Anemia (SCA) is a disorder in Red Blood Cells (RBCs) of human blood. Children under five years and pregnant women are mostly affected by SCA. Early diagnosis of this ailment can save lives. In recent years, the computer aided diagnosis of SCA is preferred to resolve this issue. A novel and effective deep learning approach for identification of sickle cell anemia is proposed in this work. Around nine hundred microscopic images of human red blood cells are obtained from the public database 'erythrocytes IDB'. All the images are resized uniformly. About 2048 deep features are extracted from the fully connected layer of pre-trained model InceptionV3. These features are further subjected to classification using optimization-based methods. An improved wrapper-based feature selection technique is implemented using Multi- Objective Binary Grey Wolf Optimization (MO-BGWO) approach with KNN and SVM for classification. The detection of sickle cell is also performed using typical InceptionV3 model by using SoftMax layer. It is observed that the performance of the proposed system seems to be high when compared to the classification using the original InceptionV3 model. The results are validated by various evaluation metrics such as accuracy, precision, sensitivity, specificity and F1-score. The SVM classifier yields high accuracy of about 96%. The optimal subset of deep features along with SVM enhances the system performance in the proposed work. Thus, the proposed approach is appropriate for pathologists to take early clinical decisions on detection of sickle cells.

Prevalence and correlates of human immunodeficiency virus infection among spouses of married men who have sex with men in India.

BACKGROUND: Men who have sex with men (MSM) in low-to-middle-income countries bear a high burden of HIV and a significant proportion marry women to satisfy socio-cultural norms. It has previously been demonstrated that HIV prevalence is higher among married versus unmarried MSM, but limited data are available on HIV prevalence among their wives. METHODS: We recruited 149 married MSM couples where the husband disclosed his MSM behavior to his wife (disclosed MSM) and 150 married MSM who had not disclosed their MSM behavior to their wives (undisclosed MSM), in three Indian cities. All participants completed interviewer-administered surveys and underwent HIV testing. Multivariable logistic regression was used to assess correlates of HIV among wives of MSM. Descriptive statistics were used to compare characteristics of disclosed and undisclosed MSM. RESULTS: HIV prevalence in disclosed MSM, their wives, and undisclosed MSM was 46.9%, 27.9%, and 34.9%, respectively. In multivariable analysis, the strongest predictor of HIV prevalence among wives of MSM was husband's HIV positive status (adjusted odds ratio: 13.4; 95% confidence interval: 5.44-33.2). Both disclosed and undisclosed MSM reported high levels of risk behavior including infrequent condom use. Most undisclosed MSM reported that they did not intend to disclose MSM behavior due to stigma. CONCLUSIONS: We observed an extremely high HIV prevalence among women married to MSM despite low levels of individual risk behavior. Interventions are urgently needed in this vulnerable population particularly given the challenges related to disclosure of same sex behavior among their husbands.

Prevalence and Correlates of Viral Load Suppression and Human Immunodeficiency Virus (HIV) Drug Resistance Among Children and Adolescents in South Rift Valley and Kisumu, Kenya.

BACKGROUND: Children and adolescents living with HIV (CALHIV) face unique challenges, including poorer treatment outcomes, risk for drug-resistance mutations (HIVDRMs), and limited drug formulations. We estimated viral suppression (VS) prevalence and evaluated predictors of VS and HIVDRMs in Kenya. METHODS: From 2018-2020, CALHIV 1-19 years on antiretroviral therapy (ART) >6 months were enrolled in this cross-sectional study. Participants underwent viral load (VL) testing; those with VL ≥1000 copies/mL had HIVDRM testing. Sociodemographic questionnaires and medical record abstraction were completed. VS prevalence (VL <1000 copies/mL) was estimated; robust Poisson regression models were used to estimate prevalence ratios (PRs) and 95% CIs for associations between potential predictors of VS. RESULTS: Nine hundred and sixty-nine participants were enrolled. VS prevalence was .80 (95% CI: .78-.83). Being on ART >24 months (adjusted PR [aPR]: 1.22; 95% CI: 1.06-1.41), an integrase strand transfer inhibitor-containing regimen (1.13; 1.02-1.26), and attending a level 3 health facility (1.23; 1.11-1.36) were associated with VS. Missing ≥3 doses of ART in the past month (aPR: .73; 95% CI: .58-.92), having a viremic mother with HIV (.72; .53-.98), and having 3-7 (.90; .83-.97), 8-13 (.89; .82-.97), or ≥14 (.84; .77-.92) compared with <2 adherence counseling referrals were inversely associated with VS. A high proportion (n = 119, 81.5%) of unsuppressed participants had evidence of any major HIVDRM. CONCLUSIONS: HIV treatment programs should target interventions for pediatric patients at risk for treatment failure-namely, those with a caregiver with failed VS and those struggling with adherence.

Hippocampus segmentation and classification for dementia analysis using pre-trained neural network models.

The diagnostic and clinical overlap of early mild cognitive impairment (EMCI), mild cognitive impairment (MCI), late mild cognitive impairment (LMCI) and Alzheimer disease (AD) is a vital oncological issue in dementia disorder. This study is designed to examine Whole brain (WB), grey matter (GM) and Hippocampus (HC) morphological variation and identify the prominent biomarkers in MR brain images of demented subjects to understand the severity progression. Curve evolution based on shape constraint is carried out to segment the complex brain structure such as HC and GM. Pre-trained models are used to observe the severity variation in these regions. This work is evaluated on ADNI database. The outcome of the proposed work shows that curve evolution method could segment HC and GM regions with better correlation. Pre-trained models are able to show significant severity difference among WB, GM and HC regions for the considered classes. Further, prominent variation is observed between AD vs. EMCI, AD vs. MCI and AD vs. LMCI in the whole brain, GM and HC. It is concluded that AlexNet model for HC region result in better classification for AD vs. EMCI, AD vs. MCI and AD vs. LMCI with an accuracy of 93, 78.3 and 91% respectively.

Persons living with HIV in sero-discordant partnerships experience improved HIV care engagement compared with persons living with HIV in sero-concordant partnerships: a cross-sectional analysis of four African countries.

BACKGROUND: Persons living with HIV (PLWH) who are members of sero-discordant and sero-concordant relationships may experience psychological stressors or motivators that affect HIV care. We assessed the association between sero-discordance status, antiretroviral therapy (ART) uptake, and viral suppression in the African Cohort Study (AFRICOS). METHODS: AFRICOS enrolls PLWH and HIV-uninfected individuals at 12 sites in Uganda, Kenya, Tanzania, and Nigeria. At enrollment, we determined ART use through self-report. Viral suppression was defined as HIV RNA < 1000 copies/mL. We analyzed PLWH who were index participants within two types of sexual dyads: sero-discordant or sero-concordant. Binomial regression models were used to estimate prevalence ratios (PRs) and 95% confidence intervals (95% CIs) for factors associated with ART use and viral suppression at study enrollment. RESULTS: From January 2013 through March 2018, 223 index participants from sero-discordant dyads and 61 from sero-concordant dyads were enrolled. The majority of the indexes were aged 25-34 years (50.2%), female (53.4%), and married (96.5%). Sero-discordant indexes were more likely to disclose their status to partners compared with sero-concordant indexes (96.4% vs. 82.0%, p < 0.001). After adjustment, sero-discordant index participants were more likely to be on ART (aPR 2.8 [95% CI 1.1-6.8]), but no more likely to be virally suppressed. Results may be driven by unique psycho-social factors and global implementation of treatment as prevention. CONCLUSIONS: PLWH in sero-discordant sexual partnerships demonstrated improved uptake of ART compared with those in sero-concordant partnerships. Interventions are needed to increase care engagement by individuals in sero-concordant relationships to improve HIV outcomes.

A Case Report on Type 2 Amiodarone Induced Thyrotoxicosis and Hypercalcemia.

Amiodarone, the most commonly used antiarrhythmic drug, can cause either hypothyroidism by inhibiting iodide transport into the thyroid gland or hyperthyroidism. We present a rare case of type 2 amiodarone-induced thyrotoxicosis with hypercalcemia. A 64-year-old man with systolic heart failure, hypertension, and hyperthyroidism presented with complaints of dyspnea on exertion, orthopnea, and vomiting for several days. Laboratory tests showed low thyroid stimulating hormone <0.01 mIU/L, high free triiodothyronine (FT3) of 24.8 ng/dL, free thyroxine (FT4) of >5.0 ng/dL, and hypercalcemia of 12.9 mg/dL. Hypercalcemia, a rare presentation of AIT, was treated with calcitonin and intravenous fluids. The patient was taken off methimazole and started on propylthiouracil for the persistent elevation of thyroid hormones, especially FT3, and to reduce the conversion of T4 to T3. The patient was not completely responding to treatment with propylthiouracil alone, so prednisone was added to the regimen on day 12, effectively returning the patient to the euthyroid state.

Combined renal and common hepatic artery denervation as a novel approach to reduce cardiometabolic risk: technical approach, feasibility and safety in a pre-clinical model.

BACKGROUND: Cardiovascular and metabolic regulation is governed by neurohumoral signalling in relevant organs such as kidney, liver, pancreas, duodenum, adipose tissue, and skeletal muscle. Combined targeting of relevant neural outflows may provide a unique therapeutic opportunity for cardiometabolic disease. OBJECTIVES: We aimed to investigate the feasibility, safety, and performance of a novel device-based approach for multi-organ denervation in a swine model over 30 and 90 days of follow-up. METHODS: Five Yorkshire cross pigs underwent combined percutaneous denervation in the renal arteries and the common hepatic artery (CHA) with the iRF Denervation System. Control animals (n = 3) were also studied. Specific energy doses were administered in the renal arteries and CHA. Blood was collected at 30 and 90 days. All animals had a pre-terminal procedure angiography. Tissue samples were collected for norepinephrine (NEPI) bioanalysis. Histopathological evaluation of collateral structures and tissues near the treatment sites was performed to assess treatment safety. RESULTS: All animals entered and exited the study in good health. No stenosis or vessel abnormalities were present. No significant changes in serum chemistry occurred. NEPI concentrations were significantly reduced in the liver (- 88%, p = 0.005), kidneys (- 78%, p < 0.001), pancreas (- 78%, p = 0.018) and duodenum (- 95%, p = 0.028) following multi-organ denervation treatment compared to control animals. Histologic findings were consistent with favourable tissue responses at 90 days follow-up. CONCLUSIONS: Significant and sustained denervation of the treated organs was achieved at 90 days without major safety events. Our findings demonstrate the feasibility of multi-organ denervation using a novel iRF Denervation System in a single procedure.

Green Synthesis of Self-Passivated Fluorescent Carbon Dots Derived from Rice Bran for Degradation of Methylene Blue and Fluorescent Ink Applications.

Recently, natural products are the powerful carbon source to synthesize carbon dots (CDs) with interesting physical and chemical properties. In this present work, we report a facile hydrothermal synthesis method for preparing fluorescent carbon dots using a biogenic precursor of rice bran without any surface passivation agent. The synthetic methodology was easy, simple, environmental friendly and convenient. Structural and optical properties of the RB-CDs have been studied by UV-visible, Fourier transform infrared spectroscopy (FTIR), Field emission scanning electron microscopy (FESEM), Fluorescence spectra and X-ray photoelectron spectroscopy (XPS) techniques. The prepared RB-CDs exhibited green emission upon irradiation with UV light and the calculated fluorescence quantum yield (QY) was found to be 7.4%. The morphological features of the synthesized RB-CDs were characterized by High-Resolution Transmission Electron Microscopy (HR-TEM), the average size of the RB-CDs was found to be 2.96 nm. The synthesized RB-CDs were beneficially applied as a catalyst for the catalytic degradation of methylene blue (MB) dye using NaBH4 as the reducing agent in the ambient conditions. The degradation of MB dye under light illumination was 89.20% in 30 min. Further, the obtained highly fluorescent RB-CDs were efficiently utilized as a fluorescent ink for luminescent pattern printing (patterning agent) in the anti-counterfeiting applications.

Attaining 95-95-95 through Implementation Science: 15 Years of Insights and Best Practices from the Walter Reed Army Institute of Research's Implementation of the U.S. President's Emergency Plan for AIDS Relief.

The Walter Reed Army Institute of Research (WRAIR) supports more than 350,000 people on lifesaving HIV treatment in Kenya, Nigeria, Tanzania, and Uganda through funding from the U.S. President's Emergency Plan for AIDS Relief (PEPFAR). Here, we review and synthesize the range of impacts WRAIR's implementation science portfolio has had on PEPFAR service delivery for military and civilian populations since 2003. We also explore how investments in implementation science create institutional synergies within the U.S. Department of Defense, contributing to broad global health engagements and improving health outcomes for populations served. Finally, we discuss WRAIR's contributions to PEPFAR priorities through use of data to drive and improve programming in real time in the era of HIV epidemic control and public health messaging that includes prevention, the 95-95-95 goals, and comorbidities.

Impact of age on CD4 recovery and viral suppression over time among adults living with HIV who initiated antiretroviral therapy in the African Cohort Study.

INTRODUCTION: With increased use of antiretroviral therapy (ART), HIV mortality rates are declining and people living with HIV (PLWH) are surviving longer. We characterized CD4 recovery and viral suppression among adults aged < 50 and ≥ 50 years living with HIV who initiated ART in the African Cohort Study (AFRICOS). METHODS: Beginning in January 2013, PLWH at twelve clinics in Kenya, Uganda, Tanzania and Nigeria underwent medical history review, CD4 and viral load testing as part of the ongoing African Cohort Study (AFRICOS). ART-naïve PLWH who initiated ART within 30 days of enrollment and had at least one year of follow-up were included in these analyses. To compare ART response in participants < 50 years and ≥ 50 years old, changes in CD4 count and viral load suppression after ART initiation were examined at different time points using linear and binomial regression with generalized estimating equations. Variables for time since ART initiation and the interaction between age group and time on ART were included in the model to evaluate longitudinal changes in CD4 recovery and viral suppression by age. RESULTS: Between January 2013 and September 2019, 2918 PLHV were enrolled in the cohort. Of these, 443 were ART naïve and initiated on ART within 30 days of enrollment, with 90% (n = 399) aged < 50 years old at ART initiation. At ART initiation, participants aged 50 and older had a higher median CD4 count compared to participants younger than 50 years of age although it did not reach statistical significance (306 cells/mm3, IQR:130-547 vs. 277cells/mm3, IQR: 132-437). In adjusted models examining CD4 recovery and viral suppression there were no significant differences by age group over time. By the end of follow-up viral suppression was high among both groups of adults (96% of adults ≥ 50 years old and 92% of adults < 50 years old). CONCLUSION: This study found no difference in long-term CD4 recovery or viral suppression by age at ART initiation. We found that particularly among younger adults participants had lower median CD4 counts at ART initiation, suggesting the importance of identifying and putting this population on treatment earlier in the disease course.

Calorie Restriction and Intermittent Fasting: Impact on Glycemic Control in People With Diabetes.

Intermittent fasting has been suggested as an option for managing overweight and obesity. The purpose of this article is to present a balanced review of the practice of intermittent fasting and its impact on glycemic control in people with diabetes.

Noninfectious Comorbidity in the African Cohort Study.

BACKGROUND: Noninfectious comorbid diseases (NCDs) contribute to morbidity and mortality in human immunodeficiency virus (HIV)-infected populations in resource-rich countries. With antiretroviral therapy (ART) scale-up in Africa, understanding burden NCD informs public health strategy. METHODS: At enrollment, participants at 11 HIV clinics in Kenya, Uganda, Tanzania, and Nigeria underwent medical history, physical, laboratory, and neuropsychological assessments to identify elevated blood pressure, hypercholesterolemia, dysglycemia, renal insufficiency, and cognitive impairment. Poisson regression models estimated adjusted relative risks (ARRs) and 95% confidence intervals (CIs) for the number of NCDs associated with factors of interest. Logistic regression was used to evaluate each NCD separately among HIV-infected participants. RESULTS: Among 2720 participants with complete NCD data, 2159 (79.4%) were HIV-infected. Of those, 1426 (66.0%) were taking ART and 813 (37.7%) had at least 1 NCD. HIV infection was associated with more NCDs, especially with ART (ARR, 1.42; 95% CI, 1.22-1.66). In addition to age, body mass index, and program site, ART usage was associated with more NCDs (ARR, 1.50; 95% CI, 1.27-1.78 for virologically suppressed and ARR, 1.38; 95% CI, 1.13-1.68 for viremic) among HIV-infected participants. In participants taking ART, CD4 nadir below 200 cells/mm3 was associated with more NCDs (ARR, 1.43; 95% CI, 1.06-1.93). ART use was independently associated with hypercholesterolemia and dysglycemia. Program site was significantly associated with all comorbidities except renal insufficiency. CONCLUSIONS: HIV infection was a risk for NCDs, which were common in HIV-infected participants, geographically variable, and largely consistent with metabolic complications of first-line ART.