Brief Report: Self-Reported HIV-Positive Status but Subsequent HIV-Negative Test Results in Population-Based HIV Impact Assessment Survey Participants-11 Sub-Saharan African Countries, 2015-2018.

BACKGROUND: HIV testing is a critical step to accessing antiretroviral therapy (ART) because early diagnosis can facilitate earlier initiation of ART. This study presents aggregated data of individuals who self-reported being HIV-positive but subsequently tested HIV-negative during nationally representative Population-Based HIV Impact Assessment surveys conducted in 11 countries from 2015 to 2018. METHOD: Survey participants aged 15 years or older were interviewed by trained personnel using a standard questionnaire to determine HIV testing history and self-reported HIV status. Home-based HIV testing and counseling using rapid diagnostic tests with return of results were performed by survey staff according to the respective national HIV testing services algorithms on venous blood samples. Laboratory-based confirmatory HIV testing for all participants identified as HIV-positives and self-reported positives, irrespective of HIV testing results, was conducted and included Geenius HIV-1/2 and DNA polymerase chain reaction if Geenius was negative or indeterminate. RESULTS: Of the 16,630 participants who self-reported as HIV-positive, 16,432 (98.6%) were confirmed as HIV-positive and 198 (1.4%) were HIV-negative by subsequent laboratory-based testing. Participants who self-reported as HIV-positive but tested HIV-negative were significantly younger than 30 years, less likely to have received ART, and less likely to have received a CD4 test compared with participants who self-reported as HIV-positive with laboratory-confirmed infection. CONCLUSIONS: A small proportion of self-reported HIV-positive individuals could not be confirmed as positive, which could be due to initial misdiagnosis, deliberate wrong self-report, or misunderstanding of the questionnaire. As universal ART access is expanding, it is increasingly important to ensure quality of HIV testing and confirmation of HIV diagnosis before ART initiation.

SLAM-ITseq identifies that Nrf2 induces liver regeneration through the pentose phosphate pathway.

The liver exhibits a remarkable capacity to regenerate following injury. Despite this unique attribute, toxic injury is a leading cause of liver failure. The temporal processes by which the liver senses injury and initiates regeneration remain unclear. Here, we developed a transgenic zebrafish model wherein hepatocyte-specific expression of uracil phosphoribosyltransferase (UPRT) enabled the implementation of SLAM-ITseq to investigate the nascent transcriptome during initiation of liver injury and regeneration. Using this approach, we identified a rapid metabolic transition from the fed to the fasted state that was followed by induction of the nuclear erythroid 2-related factor (Nrf2) antioxidant program. We find that activation of Nrf2 in hepatocytes is required to induce the pentose phosphate pathway (PPP) and improve survival following liver injury. Mechanistically, we demonstrate that inhibition of the PPP disrupts nucleotide biosynthesis to prevent liver regeneration. Together, these studies provide fundamental insights into the mechanism by which early metabolic adaptation to injury facilitates tissue regeneration.

Awareness of and willingness to use oral pre-exposure prophylaxis (PrEP) for HIV prevention among sexually active adults in Malawi: results from the 2020 Malawi population-based HIV impact assessment.

BACKGROUND: The World Health Organization recommends Pre-Exposure Prophylaxis (PrEP) for all populations at substantial risk of HIV infection. Understanding PrEP awareness and interest is crucial for designing PrEP programs; however, data are lacking in sub-Saharan Africa. In Malawi, oral PrEP was introduced in 2018. We analyzed data from the 2020 Malawi Population-based HIV Impact Assessment (MPHIA) to assess PrEP awareness and factors associated with PrEP interest in Malawi. METHODS: MPHIA 2020 was a national cross-sectional household-based survey targeting adults aged 15 + years. Oral PrEP was first described to the survey participants as taking a daily pill to reduce the chance of getting HIV. To assess awareness, participants were asked if they had ever heard of PrEP and to assess interest, were asked if they would take PrEP to prevent HIV, regardless of previous PrEP knowledge. Only sexually active HIV-negative participants are included in this analysis. We used multivariable logistic regression to assess sociodemographic factors and behaviors associated with PrEP interest. All results were weighted. RESULTS: We included 13,995 HIV-negative sexually active participants; median age was 29 years old. Overall, 15.0%, 95% confidence interval (CI): 14.2-15.9% of participants were aware of PrEP. More males (adjusted odds ratio (aOR): 1.3, 95% CI: 1.2-1.5), those with secondary (aOR: 1.5, 95% CI: 1.2-2.0) or post-secondary (aOR: 3.4, 95% CI: 2.4-4.9) education and the wealthiest (aOR: 1.6, 95% CI: 1.2-2.0) were aware of PrEP than female, those without education and least wealthy participants, respectively. Overall, 73.0% (95% CI: 71.8-74.1%) of participants were willing to use PrEP. Being male (aOR: 1.2; 95% CI: 1.1-1.3) and having more than one sexual partner (aOR: 1.7 95% CI: 1.4-1.9), were associated higher willingness to use PrEP. CONCLUSIONS: In this survey, prior PrEP knowledge and use were low while PrEP interest was high. High risk sexual behavior was associated with willingness to use PrEP. Strategies to increase PrEP awareness and universal access, may reduce HIV transmission.

Risk Factors for Recent HIV Infections among Adults in 14 Countries in Africa Identified by Population-Based HIV Impact Assessment Surveys, 2015-2019.

Identifying persons who have newly acquired HIV infections is critical for characterizing the HIV epidemic direction. We analyzed pooled data from nationally representative Population-Based HIV Impact Assessment surveys conducted across 14 countries in Africa for recent infection risk factors. We included adults 15-49 years of age who had sex during the previous year and used a recent infection testing algorithm to distinguish recent from long-term infections. We collected risk factor information via participant interviews and assessed correlates of recent infection using multinomial logistic regression, incorporating each survey's complex sampling design. Compared with HIV-negative persons, persons with higher odds of recent HIV infection were women, were divorced/separated/widowed, had multiple recent sex partners, had a recent HIV-positive sex partner or one with unknown status, and lived in communities with higher HIV viremia prevalence. Prevention programs focusing on persons at higher risk for HIV and their sexual partners will contribute to reducing HIV incidence.

Pediatric staff and their perceptions of music therapy services.

PURPOSE: To reveal the benefits, needs, and limitations of music therapy observed by clinical pediatric staff at a children's hospital in the United States of America. DESIGN AND METHODS: Researchers developed an electronic 13-question survey and distributed the survey in the fall of 2022. Questions included demographics, Likert-type scale, and open-ended queries. Data was collected via Qualtrics and analyzed using descriptive statistics and content analysis. RESULTS: A total of 83 pediatric staff completed the survey. Staff observed positive benefits, where the highest reported areas were opportunities for dealing with anxiety/stress (94.7%), opportunities for social interaction (93.3%), and quality of life (89.3%). Analysis of free-response questions suggest that staff expect expertise and a nuanced understanding of the needs of each of their clinical units. CONCLUSION: Results suggest that staff possess an overall positive attitude toward music therapy in all settings served. Music therapists may be valuable for psychosocial and rehabilitative support to hospitalized children and their families. PRACTICE IMPLICATIONS: Nursing staff may utilize music therapists to improve patient outcomes and reduce the negative effects of hospitalization.

Trends in HIV prevalence, incidence, and progress towards the UNAIDS 95-95-95 targets in Malawi among individuals aged 15-64 years: population-based HIV impact assessments, 2015-16 and 2020-21.

BACKGROUND: In 2014, UNAIDS set the goal of ending the AIDS epidemic by 2030 through the achievement of testing and treatment cascade targets. To evaluate progress achieved and highlight persisting gaps in HIV epidemic control in Malawi, we aimed to compare key indicators (prevalence, incidence, viral load suppression, and UNAIDS 95-95-95 targets) from the 2015-16 and 2020-21 Malawi Population-based HIV Impact Assessment (PHIA) survey results. METHODS: The Malawi PHIAs were nationally representative, cross-sectional surveys with a two-stage cluster sampling design. The first survey was conducted between Nov 27, 2015, and Aug 26, 2016; the second survey was conducted between Jan 15, 2020, and April 26, 2021. Our analysis included survey participants aged 15-64 years. Participants were interviewed and a 14 mL blood sample was collected and tested for HIV infection using the national rapid testing algorithm. For each survey, we estimated key HIV epidemic indicators and achievement of 95-95-95 targets. The risk ratio (RR) of the indicators between surveys were computed and considered significant at a confidence level of 0·05. All results were weighted, and self-reported awareness and treatment status were adjusted to account for detection of antiretrovirals. FINDINGS: Our analysis included 17 187 participants aged 15-64 years in 2015-16 and 21 208 in 2020-21 who participated in the surveys and blood draw. In the 2020-21 survey, 88·4% (95% CI 86·7-90·0) of people living with HIV were aware of their HIV-positive status; of those aware, 97·8% (97·1-98·5) were on antiretroviral therapy; and of those on treatment, 96·9% (95·9-97·7) were virally suppressed. Between surveys, the national HIV prevalence decreased significantly from 10·6% (10·0-11·2) to 8·9% (8·4-9·5) with RR 0·85 (95% CI 0·78-0·92; p<0·0001). The annual HIV incidence decreased from 0·37% (0·20-0·53) to 0·22% (0·11-0·34) with RR 0·61 (95% CI 0·31-1·20; p=0·15). The population viral load suppression increased from 68·3% (66·0-70·7) in 2015-16 to 87·0% (85·3-88·5) in 2020-21 (RR 1·27 [95% CI 1·22-1·32]; p<0·0001). INTERPRETATION: These results suggest that Malawi had already surpassed the UNAIDS viral load suppression target for 2030 (85·7%) by 2020-21. Through strategies and evidence-informed interventions implemented in the last half decade, especially scale-up of effective HIV treatment, Malawi has made tremendous progress, including decreasing HIV prevalence and incidence and achieving both the second and third 95 targets ahead of 2030. To address the first 95, efforts in HIV diagnosis should focus on males and younger age groups. There is a continued need for effective linkage to care, retention on antiretroviral therapy, and adherence support to maintain and build on progress. FUNDING: US President's Emergency Plan for AIDS Relief through the US Centers for Disease Control and Prevention.

The epidemiology of HIV population viral load in twelve sub-Saharan African countries.

BACKGROUND: We examined the epidemiology and transmission potential of HIV population viral load (VL) in 12 sub-Saharan African countries. METHODS: We analyzed data from Population-based HIV Impact Assessments (PHIAs), large national household-based surveys conducted between 2015 and 2019 in Cameroon, Cote d'Ivoire, Eswatini, Kenya, Lesotho, Malawi, Namibia, Rwanda, Tanzania, Uganda, Zambia, and Zimbabwe. Blood-based biomarkers included HIV serology, recency of HIV infection, and VL. We estimated the number of people living with HIV (PLHIV) with suppressed viral load (<1,000 HIV-1 RNA copies/mL) and with unsuppressed viral load (viremic), the prevalence of unsuppressed HIV (population viremia), sex-specific HIV transmission ratios (number female incident HIV-1 infections/number unsuppressed male PLHIV per 100 persons-years [PY] and vice versa) and examined correlations between a variety of VL metrics and incident HIV. Country sample sizes ranged from 10,016 (Eswatini) to 30,637 (Rwanda); estimates were weighted and restricted to participants 15 years and older. RESULTS: The proportion of female PLHIV with viral suppression was higher than that among males in all countries, however, the number of unsuppressed females outnumbered that of unsuppressed males in all countries due to higher overall female HIV prevalence, with ratios ranging from 1.08 to 2.10 (median: 1.43). The spatial distribution of HIV seroprevalence, viremia prevalence, and number of unsuppressed adults often differed substantially within the same countries. The 1% and 5% of PLHIV with the highest VL on average accounted for 34% and 66%, respectively, of countries' total VL. HIV transmission ratios varied widely across countries and were higher for male-to-female (range: 2.3-28.3/100 PY) than for female-to-male transmission (range: 1.5-10.6/100 PY). In all countries mean log10 VL among unsuppressed males was higher than that among females. Correlations between VL measures and incident HIV varied, were weaker for VL metrics among females compared to males and were strongest for the number of unsuppressed PLHIV per 100 HIV-negative adults (R2 = 0.92). CONCLUSIONS: Despite higher proportions of viral suppression, female unsuppressed PLHIV outnumbered males in all countries examined. Unsuppressed male PLHIV have consistently higher VL and a higher risk of transmitting HIV than females. Just 5% of PLHIV account for almost two-thirds of countries' total VL. Population-level VL metrics help monitor the epidemic and highlight key programmatic gaps in these African countries.

The KEAP1-NRF2 pathway regulates TFEB/TFE3-dependent lysosomal biogenesis.

The maintenance of redox and metabolic homeostasis is integral to embryonic development. Nuclear factor erythroid 2-related factor 2 (NRF2) is a stress-induced transcription factor that plays a central role in the regulation of redox balance and cellular metabolism. Under homeostatic conditions, NRF2 is repressed by Kelch-like ECH-associated protein 1 (KEAP1). Here, we demonstrate that Keap1 deficiency induces Nrf2 activation and postdevelopmental lethality. Loss of viability is preceded by severe liver abnormalities characterized by an accumulation of lysosomes. Mechanistically, we demonstrate that loss of Keap1 promotes aberrant activation of transcription factor EB (TFEB)/transcription factor binding to IGHM Enhancer 3 (TFE3)-dependent lysosomal biogenesis. Importantly, we find that NRF2-dependent regulation of lysosomal biogenesis is cell autonomous and evolutionarily conserved. These studies identify a role for the KEAP1-NRF2 pathway in the regulation of lysosomal biogenesis and suggest that maintenance of lysosomal homeostasis is required during embryonic development.

Point of Care CD4 Testing in National Household Surveys - Results and Quality Indicators from Eleven Population-Based HIV Impact Assessment (PHIA) Surveys.

Population-based HIV Impact Assessments (PHIAs) are national household (HH) surveys that provide HIV diagnosis and CD4 testing with an immediate return of results. Accurate CD4 results improve HIV-positive participants' clinical care and inform the effectiveness of HIV programs. Here, we present CD4 results from the PHIA surveys that were conducted in 11 countries in sub-Saharan Africa between 2015 and 2018. All of the HIV-positive participants and 2 to 5% of the HIV-negative participants were offered Pima CD4 (Abbott, IL, USA) point-of-care (POC) tests. The quality of the CD4 test was ensured by conducting instrument verification, comprehensive training, quality control, a review of testing errors and an analysis of unweighted CD4 data by HIV status, age, gender, and antiretroviral (ARV) treatment status. Overall, CD4 testing was completed for 23,085 (99.5%) of the 23,209 HIV-positive and 7,329 (2.7%) of the 270,741 negative participants in 11 surveys. The instrument error rate was 11.3% (range, 4.4% to 15.7%). The median CD4 values among HIV-positive and HIV-negative participants (aged 15+) were 468 cells/mm3 (interquartile range [IQR], 307 to 654) and 811 cells/mm3 (IQR, 647 to 1,013), respectively. Among the HIV-positive participants (aged 15+), those with detectable ARVs had higher CD4 values (508 cells/mm3) than those with undetectable ARVs (385.5 cells/mm3). Among the HIV-positive participants (aged 15+), 11.4% (2,528/22,253) had a CD4 value of less than 200 cells/mm3, and approximately half of them (1,225/2,528 = 48.5%) had detectable ARVs, whereas 51.5% (1,303/2,528) had no detectable ARVs (P < 0.0001). We successfully implemented high quality POC CD4 testing using Pima instruments. Our data come from nationally representative surveys in 11 countries and provide unique insights regarding the CD4 distribution among HIV-positive individuals as well as the baseline CD4 values among HIV-negative individuals. IMPORTANCE The manuscript describes CD4 levels among HIV-positive individuals and baseline CD4 levels among HIV-negative individuals from 11 sub-Saharan countries, thereby highlighting the importance of CD4 markers in the context of the HIV epidemic. Despite increased ARV access in each country, advanced HIV disease (CD4 < 200 cells/mm3) persists among approximately 11% of HIV-positive individuals. Therefore, it is important that our findings are shared with the scientific community to assist with similar implementations of point-of-care testing and to conduct a review of HIV programmatic gaps.

Multi-substrate Metabolic Tracing Reveals Marked Heterogeneity and Dependency on Fatty Acid Metabolism in Human Prostate Cancer.

Cancer cells undergo metabolic reprogramming to meet increased bioenergetic demands. Studies in cells and mice have highlighted the importance of oxidative metabolism and lipogenesis in prostate cancer; however, the metabolic landscape of human prostate cancer remains unclear. To address this knowledge gap, we performed radiometric (14C) and stable (13C) isotope tracing assays in precision-cut slices of patient-derived xenografts (PDX). Glucose, glutamine, and fatty acid oxidation was variably upregulated in malignant PDXs compared with benign PDXs. De novo lipogenesis (DNL) and storage of free fatty acids into phospholipids and triacylglycerols were increased in malignant PDXs. There was no difference in substrate utilization between localized and metastatic PDXs and hierarchical clustering revealed marked metabolic heterogeneity across all PDXs. Mechanistically, glucose utilization was mediated by acetyl-CoA production rather than carboxylation of pyruvate, while glutamine entered the tricarboxylic acid cycle through transaminase reactions before being utilized via oxidative or reductive pathways. Blocking fatty acid uptake or fatty acid oxidation with pharmacologic inhibitors was sufficient to reduce cell viability in PDX-derived organoids, whereas blockade of DNL, or glucose or glutamine oxidation induced variable and limited therapeutic efficacy. These findings demonstrate that human prostate cancer, irrespective of disease stage, can effectively utilize all metabolic substrates, albeit with marked heterogeneity across tumors. We also confirm that fatty acid uptake and oxidation are targetable metabolic dependencies in human prostate cancer. IMPLICATIONS: Prostate cancer utilizes multiple substrates to fuel energy requirements, yet pharmacologic targeting of fatty acid uptake and oxidation reveals metabolic dependencies in localized and metastatic tumors.

Male partner age, viral load, and HIV infection in adolescent girls and young women: evidence from eight sub-Saharan African countries.

OBJECTIVE: We aimed to elucidate the role of partnerships with older men in the HIV epidemic among adolescent girls and young women (AGYW) aged 15-24 years in sub-Saharan Africa. DESIGN: Analysis of Population-based HIV Impact Assessments in Eswatini, Lesotho, Malawi, Namibia, Tanzania, Uganda, Zambia, and Zimbabwe. METHODS: We examined associations between reported partner age and recent HIV infection among AGYW, incorporating male population-level HIV characteristics by age-band. Recent HIV infection was defined using the LAg avidity assay algorithm. Viremia was defined as a viral load of more than 1000 copies/ml, regardless of serostatus. Logistic regression compared recent infection in AGYW with older male partners to those reporting younger partners. Dyadic analysis examined cohabitating male partner age, HIV status, and viremia to assess associations with AGYW infection. RESULTS: Among 17 813 AGYW, increasing partner age was associated with higher odds of recent infection, peaking for partners aged 35-44 (adjusted odds ratio = 8.94, 95% confidence interval: 2.63-30.37) compared with partners aged 15-24. Population-level viremia was highest in this male age-band. Dyadic analyses of 5432 partnerships confirmed the association between partner age-band and prevalent HIV infection (male spousal age 35-44-adjusted odds ratio = 3.82, 95% confidence interval: 2.17-6.75). Most new infections were in AGYW with partners aged 25-34, as most AGYW had partners in this age-band. CONCLUSION: These results provide evidence that men aged 25-34 drive most AGYW infections, but partners over 9 years older than AGYW in the 35-44 age-band confer greater risk. Population-level infectiousness and male age group should be incorporated into identifying high-risk typologies in AGYW.

Glutamine addiction promotes glucose oxidation in triple-negative breast cancer.

Glutamine is a conditionally essential nutrient for many cancer cells, but it remains unclear how consuming glutamine in excess of growth requirements confers greater fitness to glutamine-addicted cancers. By contrasting two breast cancer subtypes with distinct glutamine dependencies, we show that glutamine-indispensable triple-negative breast cancer (TNBC) cells rely on a non-canonical glutamine-to-glutamate overflow, with glutamine carbon routed once through the TCA cycle. Importantly, this single-pass glutaminolysis increases TCA cycle fluxes and replenishes TCA cycle intermediates in TNBC cells, a process that achieves net oxidation of glucose but not glutamine. The coupling of glucose and glutamine catabolism appears hard-wired via a distinct TNBC gene expression profile biased to strip and then sequester glutamine nitrogen, but hampers the ability of TNBC cells to oxidise glucose when glutamine is limiting. Our results provide a new understanding of how metabolically rigid TNBC cells are sensitive to glutamine deprivation and a way to select vulnerable TNBC subtypes that may be responsive to metabolic-targeted therapies.

YAP regulates an SGK1/mTORC1/SREBP-dependent lipogenic program to support proliferation and tissue growth.

The coordinated regulation of growth control and metabolic pathways is required to meet the energetic and biosynthetic demands associated with proliferation. Emerging evidence suggests that the Hippo pathway effector Yes-associated protein 1 (YAP) reprograms cellular metabolism to meet the anabolic demands of growth, although the mechanisms involved are poorly understood. Here, we demonstrate that YAP co-opts the sterol regulatory element-binding protein (SREBP)-dependent lipogenic program to facilitate proliferation and tissue growth. Mechanistically, YAP stimulates de novo lipogenesis via mechanistic target of rapamcyin (mTOR) complex 1 (mTORC1) signaling and subsequent activation of SREBP. Importantly, YAP-dependent regulation of serum- and glucocorticoid-regulated kinase 1 (SGK1) is required to activate mTORC1/SREBP and stimulate de novo lipogenesis. We also find that the SREBP target genes fatty acid synthase (FASN) and stearoyl-CoA desaturase (SCD) are conditionally required to support YAP-dependent proliferation and tissue growth. These studies reveal that de novo lipogenesis is a metabolic vulnerability that can be targeted to disrupt YAP-dependent proliferation and tissue growth.

Pharmacologic Reduction of Mitochondrial Iron Triggers a Noncanonical BAX/BAK-Dependent Cell Death.

Cancer cell metabolism is increasingly recognized as providing an exciting therapeutic opportunity. However, a drug that directly couples targeting of a metabolic dependency with the induction of cell death in cancer cells has largely remained elusive. Here we report that the drug-like small-molecule ironomycin reduces the mitochondrial iron load, resulting in the potent disruption of mitochondrial metabolism. Ironomycin promotes the recruitment and activation of BAX/BAK, but the resulting mitochondrial outer membrane permeabilization (MOMP) does not lead to potent activation of the apoptotic caspases, nor is the ensuing cell death prevented by inhibiting the previously established pathways of programmed cell death. Consistent with the fact that ironomycin and BH3 mimetics induce MOMP through independent nonredundant pathways, we find that ironomycin exhibits marked in vitro and in vivo synergy with venetoclax and overcomes venetoclax resistance in primary patient samples. SIGNIFICANCE: Ironomycin couples targeting of cellular metabolism with cell death by reducing mitochondrial iron, resulting in the alteration of mitochondrial metabolism and the activation of BAX/BAK. Ironomycin induces MOMP through a different mechanism to BH3 mimetics, and consequently combination therapy has marked synergy in cancers such as acute myeloid leukemia. This article is highlighted in the In This Issue feature, p. 587.

HIV incidence, viremia, and the national response in Eswatini: Two sequential population-based surveys.

With the highest HIV incidence and prevalence globally, the government of Eswatini started a substantial scale-up of HIV treatment and prevention services in 2011. Two sequential large population-based surveys were conducted before and after service expansion to assess the impact of the national response. Cross-sectional, household-based, nationally representative samples of adults, ages 18 to 49 years, were sampled in 2011 and 2016. We measured HIV prevalence, incidence (recent infection based on limiting antigen ≤1.5 optical density units and HIV RNA ≥1000 copies/mL), viral load suppression (HIV RNA <1000 copies/mL among all seropositive adults) and unsuppressed viremia (HIV RNA ≥1000 copies/mL among all, regardless of HIV status) and assessed for temporal changes by conducting a trend analysis of the log ratio of proportions, using a Z statistic distribution. HIV prevalence remained stable from 2011 to 2016 [32% versus 30%, p = 0.10]. HIV incidence significantly declined 48% [2.48% versus 1.30%, p = 0.01]. Incidence remained higher among women than men [2011: 3.16% versus 1.83%; 2016: 1.76% versus 0.86%], with a smaller but significant relative reduction among women [44%; p = 0.04] than men [53%; p = 0.09]. The proportion of seropositive adults with viral load suppression significantly increased from 35% to 71% [p < .001]. The proportion of the total adult population with unsuppressed viremia decreased from 21% to 9% [p < .001]. National HIV incidence in Eswatini decreased by nearly half and viral load suppression doubled over a five-year period. Unsuppressed viremia in the total population decreased 58%. These population-based findings demonstrate the national impact of expanded HIV services in a hyperendemic country.

AMPK CA(R)Sts a new light on amino acid sensing.

AMP-activated protein kinase (AMPK) is recognized as a critical regulator of cellular energy metabolism impacted by AMP/ATP and ADP/ATP ratios, or glucose- and fatty acid-derived metabolites. However, its ability to sense alterations in amino acid levels is poorly understood. Recent work by Yuan et al (2021) identifies a novel mechanism of AMPK regulation responsive to changes in availability of the sulfur-containing amino acid cysteine.

Optimizing community linkage to care and antiretroviral therapy Initiation: Lessons from the Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS) and their adaptation in Nigeria ART Surge.

BACKGROUND: Ineffective linkage to care (LTC) is a known challenge for community HIV testing. To overcome this challenge, a robust linkage to care strategy was adopted by the 2018 Nigeria HIV/AIDS Indicator and Impact Survey (NAIIS). The NAIIS linkage to care strategy was further adapted to improve Nigeria's programmatic efforts to achieve the 1st 90 as part of the Nigeria Antiretroviral Therapy (ART) Surge initiative, which also included targeted community testing. In this paper we provide an overview of the NAIIS LTC strategy and describe the impact of this strategy on both the NAIIS and the Surge initiatives. METHODS: The NAIIS collaborated with community-based organizations (CBOs) and deployed mobile health (mHealth) technology with real-time dashboards to manage and optimize community LTC for people living with HIV (PLHIV) diagnosed during the survey. In NAIIS, CBOs' role was to facilitate linkage of identified PLHIV in community to facility of their choice. For the ART Surge, we modified the NAIIS LTC strategy by empowering both CBOs and mobile community teams as responsible for not only active LTC but also for community testing, ART initiation, and retention in care. RESULTS: Of the 2,739 PLHIV 15 years and above identified in NAIIS, 1,975 (72.1%) were either unaware of their HIV-positive status (N = 1890) or were aware of their HIV-positive status but not receiving treatment (N = 85). Of these, 1,342 (67.9%) were linked to care, of which 952 (70.9%) were initiated on ART. Among 1,890 newly diagnosed PLHIV, 1,278 (67.6%) were linked to care, 33.7% self-linked and 66.3% were linked by CBOs. Among 85 known PLHIV not on treatment, 64 (75.3%) were linked; 32.8% self-linked and 67.2% were linked by a CBO. In the ART Surge, LTC and treatment initiation rates were 98% and 100%, respectively. Three-month retention for monthly treatment initiation cohorts improved from 76% to 90% over 6 months. CONCLUSIONS: Active LTC strategies by local CBOs and mobile community teams improved LTC and ART initiation in the ART Surge initiative. The use of mHealth technology resulted in timely and accurate documentation of results in NAIIS. By deploying mHealth in addition to active LTC, CBOs and mobile community teams could effectively scale up ART with real-time documentation of client-level outcomes.

The Role of Health Disparities and Socioeconomic Status in Emergent Gastrointestinal Procedures.

Objectives: There is limited data describing the role of health disparity factors and socioeconomic status (SES) on emergent versus nonemergent gastrointestinal (GI) procedures within pediatrics. We aimed to characterize risk factors and determine the role of SES on emergent versus nonemergent GI care. We hypothesized that patients with lower SES incur higher risk of having emergent procedures performed. Methods: Retrospective chart review was performed between 2012 and 2016, with 2556 patient records reviewed. Demographic data and SES categories were determined. The majority of emergent procedures were performed on an inpatient basis. Health disparity factors analyzed included age, gender, insurance type, race, language, and SES using census tracts. Logistic regression analyses and paired t-tests were utilized. Results: Two hundred eighty-six (11.2%) patients had emergent GI procedures performed. Logistic regression (odds ratio [OR], confidence interval (95% CI)] showed patients from 6-11 to 12-17 years of age were less likely to seek emergent care than the youngest group [0.47, 0.33-0.66 and 0.61, 0.45-0.84]. Patients with Medicaid insurance [1.68, 1.27-2.26], African American or "other" race [2.07, 1.48-2.90 and 2.43, 1.77-3.36, respectively], as well as "other" language [2.1, 1.14-3.99] more often sought emergent care. Using geocoded data, we found that as SES increases by 1, emergent risk for procedures decreased by 2.9% (OR 0.97, p=0.045). Conclusions: Children with lower SES, at extremes of age (<5, >18 years), non-English or Spanish speaking and with Medicaid insurance are at higher risk of undergoing emergent GI procedures. This study gives us an opportunity to plan targeted interventions to improve access and quality of care.

Population-Based HIV Impact Assessments Survey Methods, Response, and Quality in Zimbabwe, Malawi, and Zambia.

BACKGROUND: The population-based HIV impact assessment (population-based HIV impact assessments) surveys are among the first to estimate national adult HIV incidence, subnational prevalence of viral load suppression, and pediatric HIV prevalence. We summarize the survey methods implemented in Zimbabwe, Malawi, and Zambia, as well as response rates and quality metrics. METHODS: Each cross-sectional, household-based survey used a 2-stage cluster design. Survey preparations included sample design, questionnaire development, tablet programming for informed consent and data collection, community mobilization, establishing a network of satellite laboratories, and fieldworker training. Interviewers collected demographic, behavioral, and clinical information using tablets. Blood was collected for home-based HIV testing and counseling (HBTC) and point-of-care CD4+ T-cell enumeration with results immediately returned. HIV-positive blood samples underwent laboratory-based confirmatory testing, HIV incidence testing, RNA polymerase chain reaction (viral load), DNA polymerase chain reaction (early infant diagnosis), and serum antiretroviral drug detection. Data were weighted for survey design, and chi square automatic interaction detection-based methods were used to adjust for nonresponse. RESULTS: Each survey recruited a nationally representative, household-based sample of children and adults over a 6-10-month period in 2015 and 2016. Most (84%-90%) of the 12,000-14,000 eligible households in each country participated in the survey, with 77%-81% of eligible adults completing an interview and providing blood for HIV testing. Among eligible children, 59%-73% completed HIV testing. Across the 3 surveys, 97.8% of interview data were complete and had no errors. CONCLUSION: Conducting a national population-based HIV impact assessment with immediate return of HIV and other point-of-care test results was feasible, and data quality was high.

A Comprehensive Approach to Assuring Quality of Laboratory Testing in HIV Surveys: Lessons Learned From the Population-Based HIV Impact Assessment Project.

BACKGROUND: Conducting HIV surveys in resource-limited settings is challenging because of logistics, limited availability of trained personnel, and complexity of testing. We described the procedures and systems deemed critical to ensure high-quality laboratory data in the population-based HIV impact assessments and large-scale household surveys. METHODS: Laboratory professionals were engaged in every stage of the surveys, including protocol development, site assessments, procurement, training, quality assurance, monitoring, analysis, and reporting writing. A tiered network of household, satellite laboratories, and central laboratories, accompanied with trainings, optimized process for blood specimen collection, storage, transport, and real-time monitoring of specimen quality, and test results at each level proved critical in maintaining specimen integrity and high-quality testing. A plausibility review of aggregate merged data was conducted to confirm associations between key variables as a final quality check for quality of laboratory results. RESULTS: Overall, we conducted a hands-on training for 3355 survey staff across 13 surveys, with 160-387 personnel trained per survey on biomarker processes. Extensive training and monitoring demonstrated that overall, 99% of specimens had adequate volume and 99.8% had no hemolysis, indicating high quality. We implemented quality control and proficiency testing for testing, resolved discrepancies, verified >300 Pima CD4 instruments, and monitored user errors. Aggregate data review for plausibility further confirmed the high quality of testing. CONCLUSIONS: Ongoing engagement of laboratory personnel to oversee processes at all levels of the surveys is critical for successful national surveys. High-quality population-based HIV impact assessments laboratory data ensured reliable results and demonstrated the impact of HIV programs in 13 countries.