Recommendations and guidelines of integrative medicine for COVID-19 care: The APEC project outcome.

This article - Recommendations and Guidelines of Integrative Medicine (IM) for COVID-19 Care - was one of the outcomes from an Asia-Pacific Economic Cooperation (APEC) Project (Integrative Medicine (IM) and COVID -19 Care) during the time between May 2022 and March 2023. With the efforts from care providers, researchers, health policy makers and healthcare administrative leaders among APEC economies, the purpose of this file was to provide comprehensive IM systems for COVID-19 care as recommendations and suggestive guidelines including care methods, tools, procedures, symptom conditions and targets selections, and points need to be considered during care applications. All cited COVID-19 care practices have confirmed their efficacy and usefulness either used alone or combined with conventional medicine. This article provides current useful medical information on IM for COVID-19 care which could benefit APEC economies and world health communities on their healthcare system.

Eupatorin 3'-O-glucopyranoside, a trimethoxyflavonoid glucoside from the aerial parts of Salvia mellifera.

Salvia mellifera, native to California, Baja California, and Mexico, is a medicinal herb traditionally used to relieve pain, body aches, including chronic pain. A detailed phytochemical investigation of aerial parts of S. mellifera was accomplished to find species-specific markers and to differentiate the closely related, often (un)intentionally substituted with S. apiana. A total of 22 metabolites, including flavonoids (1-14), triterpenoids (15-18), diterpenoids (19-21), and phenylpropanoid (22), were isolated and characterized thoroughly. Among the isolates, eupatorin 3'-O-glucopyranoside (1) was identified as undescribed phytochemical and detailed structure elucidation was achieved through extensive NMR and mass spectral data analysis.

Assessment of Herb-Drug Interaction Potential of Five Common Species of Licorice and Their Phytochemical Constituents.

The dried roots and rhizomes of Glycyrrhiza species (G. glabra, G. uralensis and G. inflata), commonly known as licorice, have long been used in traditional medicine. In addition, two other species, G. echinata and G. lepidota are also considered "licorice" in select markets. Currently, licorice is an integral part of several botanical drugs and dietary supplements. To probe the botanicals' safety, herb-drug interaction potential of the hydroethanolic extracts of five Glycyrrhiza species and their key constituents was investigated by determining their effects on pregnane X receptor, aryl hydrocarbon receptor, two major cytochrome P450 isoforms (CYP3A4 and CYP1A2), and the metabolic clearance of antiviral drugs. All extracts enhanced transcriptional activity of PXR and AhR (>2-fold) and increased the enzyme activity of CYP3A4 and CYP1A2. The highest increase in CYP3A4 was seen with G. echinata (4-fold), and the highest increase in CYP1A2 was seen with G. uralensis (18-fold) and G. inflata (16-fold). Among the constituents, glabridin, licoisoflavone A, glyasperin C, and glycycoumarin activated PXR and AhR, glabridin being the most effective (6- and 27-fold increase, respectively). Licoisoflavone A, glyasperin C, and glycycoumarin increased CYP3A4 activity while glabridin, glyasperin C, glycycoumarin, and formononetin increased CYP1A2 activity (>2-fold). The metabolism of antiretroviral drugs (rilpivirine and dolutegravir) was increased by G. uralensis (2.0 and 2.5-fold) and its marker compound glycycoumarin (2.3 and 1.6-fold). The metabolism of dolutegravir was also increased by G. glabra (2.8-fold) but not by its marker compound, glabridin. These results suggest that licorice and its phytochemicals could affect the metabolism and clearance of certain drugs that are substrates of CYP3A4 and CYP1A2.Supplemental data for this article is available online at https://doi.org/10.1080/19390211.2022.2050875 .

Metabolite variation and discrimination of five licorice (Glycyrrhiza) species: HPTLC and NMR explorations.

The roots and rhizomes of several Glycyrrhiza species are widely used as sweetening and flavoring agents in food, as well as important ingredients in formulations of traditional medicines. Five Glycyrrhiza species, G. uralensis, G. glabra, G. inflata, G. echinata, and G. lepidota, often share the name "licorice roots" in the botanicals' marketplace. Unfortunately, misidentification/mislabeling is very common due to their similarities in morpho-anatomical features. Significant metabolite alterations among the different Glycyrrhiza species and their hybrids have been reported, suggesting that the biological activities could vary with the licorice roots or products derived from different species. Development of simple, effective methods for species identification and differentiation is of key importance. In this study, 78 licorice samples were investigated using HPTLC and NMR as analytical tools. Significant metabolite variations were observed between the five species. The species-specific fingerprint patterns for the five Glycyrrhiza species were determined with HPTLC and NMR; then applied to the sample identification and discrimination. The results obtained from these two orthogonal analytical methods agreed with each other. Furthermore, the NMR signals and the species-specific constituents that made significant contributions to the differentiation of the five Glycyrrhiza species were confirmed based on the multivariate analysis of the NMR spectral data. Using the established OPLS-DA models, the classification of hybrids was evaluated and confirmed. The developed methods, particularly the HPTLC method with its simplicity and low cost, could be used as a rapid and reliable approach for the authentication of licorice species and quality control of licorice raw material and products.

Chemical Authentication and Speciation of Salvia Botanicals: An Investigation Utilizing GC/Q-ToF and Chemometrics.

Members of the genus Salvia are used as culinary herbs and are prized for their purported medicinal attributes. Since physiological effects can vary widely between species of Salvia, it is of great importance to accurately identify botanical material to ensure safety for consumers. In the present study, an in-depth chemical investigation is performed utilizing GC/Q-ToF combined with chemometrics. Twenty-four authentic plant samples representing five commonly used Salvia species, viz. S. apiana, S. divinorum, S. mellifera, S. miltiorrhiza, and S. officinalis, are analyzed using a GC/Q-ToF technique. High-resolution spectral data are employed to construct a sample class prediction (SCP) model followed by principal component analysis (PCA) and partial least square discriminant analysis (PLS-DA). This model demonstrates 100% accuracy for both prediction and recognition abilities. Additionally, the marker compounds present in each species are identified. Furthermore, to reduce the time required and increase the confidence level for compound identification and the classification of different Salvia species, a personal compound database and library (PCDL) containing marker and characteristic compounds is constructed. By combining GC/Q-ToF, chemometrics, and PCDL, the unambiguous identification of Salvia botanicals is achieved. This high-throughput method can be utilized for species specificity and to probe the overall quality of various Salvia-based products.

Quality Standards in State Programs Permitting Cannabis for Medical Uses.

Currently in the United States, there exists a patchwork of state-level laws and regulations surrounding cannabis use. Although cannabis (excluding hemp under the Agricultural Improvement Act of 2018, Public Law 115-334) is illegal at the federal level and is not FDA (U.S. Food and Drug Administration) approved for any indication, many states allow patients with qualifying conditions to register for their medical cannabis program (MCP). To better understand the quality of cannabis found in these programs, we collected laws, regulations, and guidance documents available on public state-run websites and compared them with current good manufacturing practices (CGMPs) applicable to finished drug products. CGMPs for human drugs contain minimum requirements for the methods, facilities, and controls used in manufacturing, processing, and packaging of a drug product to assure it is safe for use. Such a comparison will aid the development of consistent quality standards that could, in turn, improve the quality of a wide range of cannabis medical products in development that may be sold in the United States. States may likewise choose to have the cannabis and cannabis-derived products that fall within their MCP to follow quality-focused guidelines, such as those listed in CGMPs, to ensure the quality of these products and promote public health. This study further solidifies the need for standardized testing protocols and methodologies to keep consumers safe.

Actein contributes to black cohosh extract-induced genotoxicity in human TK6 cells.

Black cohosh extract (BCE) is one of the most popular botanical products for relieving menopausal symptoms. However, recent studies indicate that BCE is not only ineffective for menopausal therapy but also induces genotoxicity through an aneugenic mode of action (MoA). In this study, the cytotoxicity of five constituents of BCE was evaluated in human lymphoblastoid TK6 cells. Among the five constituents, actein (up to 50 µM) showed the highest cytotoxicity and was thus selected for further genotoxicity evaluations. Actein caused DNA damage proportionally to concentration as evidenced by the phosphorylation of the histone protein H2A.X (γH2A.X) and resulted in chromosomal damage as measured by the increased percentage of micronuclei (%MN) in cells. In addition, actein activated DNA damage response (DDR) pathway through induction of p-ATM, p-Chk1, and p-Chk2, which subsequently induced cell cycle changes and apoptosis. Moreover, both BCE and actein increased intracellular reactive oxygen species (ROS) production, decreased glutathione levels, and activated the mitogen-activated protein kinases (MAPK) signaling pathway. N-acetylcysteine, a ROS scavenger, attenuated BCE- and actein-induced ROS production, apoptosis, and DNA damage. These findings indicate that BCE- and actein-induced genotoxicity is mediated, at least partially, through oxidative stress. Taken together, our data show that actein is likely one of the major contributors to BCE-induced genotoxicity.

Licochalcone L, an undescribed retrochalcone from Glycyrrhiza inflata roots.

Glycyrrhiza inflata Batalin is among the three glycyrrhizin producing Glycyrrhiza species and can be distinguished from other species with regard to its retrochalcone contents. Seven retrochalcones, echinatin and licochalcones A, C, D, E, K, and L were isolated and characterized from the chloroform extract of G. inflata roots. Among the isolates, licochalcone L was found to be previously undescribed. Structure elucidation of these specialised metabolites was achieved through NMR and mass spectroscopic data analyses.

Phenoxychromone and 4-hydroxyisoflavans from the roots of Glycyrrhiza uralensis.

In an attempt to find species specific markers, a phenoxychromone (1) and eight isoflavonoids including six isoflavans (2-7) and two isoflavanones (8 and 9) were isolated from the root of Glycyrrhiza uralensis. Among the isolated phenolic compounds, glycyurelone (1), glycyurelvanins A and B (2 and 3) were found to be undescribed while others, (-)-vestitol (4), conferol A (5), glyasperin C (6), glyasperin D (7), (-)-licoisoflavanone (8), and (-)-3'-(γ,γ-dimethylallyl)kievitone (9) were previously reported. All compounds except 4 and 5 were prenylated and majority of these possess isoflavan scaffold with highly conserved stereo specificity at C-3 center. Structure elucidation was mainly based on extensive NMR, ECD and mass spectral data analysis.

The Low Copy Nuclear Gene Region, Granule Bound Starch Synthase (GBSS1), as a Novel Mini-DNA Barcode for the Identification of Different Sage (Salvia) Species.

Morphological similarity within species makes the identification and authentication of Salvia species challenging, especially in dietary supplements that contain processed root or leaf powder of different sage species. In the present study, the species discriminatory power of 2 potential DNA barcode regions from the nuclear genome was evaluated in 7 medicinally important Salvia species from the family Lamiaceae. The nuclear internal transcribed spacer 2 and the exon 9 - 14 region of low copy nuclear gene WAXY coding for granule-bound starch synthase 1 were tested for their species discrimination ability using distance, phylogenetic, and BLAST-based methods. A novel 2-step PCR method with 2 different annealing temperatures was developed to achieve maximum amplification from genomic DNA. The granule-bound starch synthase 1 region showed higher amplification and sequencing success rates, higher interspecific distances, and a perfect barcode gap for the tested species compared to the nuclear internal transcribed spacer 2. Hence, these novel mini-barcodes generated from low copy nuclear gene regions (granule-bound starch synthase) that were proven to be effective barcodes for identifying 7 Salvia species have potential for identification and authentication of other Salvia species.

Comparative analysis of five Salvia species using LC-DAD-QToF.

Several Salvia species, commonly known as sage plants, are an integral part of various culinary and folklore preparations for the perceived wide range of effects from organoleptic to psychological. As a result, many of these species are an integral part of botanical drug applications, highlighting the need for accurate identification and quality control for consumer's safety. Five closely related Salvia species (S. officinalis, S. miltiorrhiza, S. divinorum, S. mellifera, and S. apiana) within a same botanical family were analyzed and differentiated using LC-QToF. Accurate mass measurement (<5 ppm) of protonated and deprotonated molecules together with resulting fragments and product ions allowed unequivocal or tentative identification of more than 180 compounds either by comparison with reference standards or literature data. The leaf part were identified based on various phenolic acids, flavonoids as well as di- and tri-terpenoids. Polyphenolics, viz., salvianolic A/B and rosmarinic acids in S. officinalis, lipophilic diterpenoids, viz., tanshinones in S. miltiorrhiza, abietatriene diterpenes and triterpenoids (ursane-/olean-type) in S. mellifera, and S. apiana were identified as characteristic, significant components. In comparison, salvinorins and divinorins representing a class of neoclerodane diterpenoids were detected only in S. divinorum. The presented methodology can successfully be applied to qualitatively assess sage-based ingredients in various finished products and formulations.

Inflammation and oxidative stress induced by lipid peroxidation metabolite 4-hydroxynonenal in human corneal epithelial cells.

PURPOSE: Oxidative stress is widely known to be a major contributor in the pathogenesis of dry eye disease (DED). 4-Hydroxynonenal (4-HNE), a well-known byproduct frequently measured as an indicator of oxidative stress-induced lipid peroxidation, has been shown to be elevated in both human and murine corneal DED samples. This study aims to investigate if 4-HNE is responsible for the oxidative stress in human corneal epithelial cells (HCECs) and explores the underlying mechanism by which it confers its effects. METHODS: SV40-immortalized HCECs were cultured in minimum essential media (MEM) with 1% penicillin/streptomycin and 10% fetal bovine serum. HCECs were exposed to media with or without 4-HNE and cell culture supernatants were collected at 4 and 24 h. Cellular reactive oxygen species (ROS) measurement was performed using a 2',7'-dichlorofluorescein diacetate (DCFDA) assay kit according to the manufacturer's instructions. Protein levels of antioxidant enzymes copper/zinc superoxide dismutase 1 (SOD1) and NAD(P)H quinone dehydrogenase 1 (NQO1) were analyzed by Western blot. NF-κB activation and expression of IL-6 and IL-8 were measured using an NF-κB p65 Total SimpleStep ELISA Kit and Proteome Profiler Human Cytokine Array Kit. Cell viability was evaluated by LDH cytotoxicity assay. RESULTS: Treatment with 4-HNE decreased cell viability of HCECs. Band intensities corresponding to levels of ROS production showed a significant increase in ROS generation after treatment with 4-HNE. 4-HNE decreased SOD1 levels and upregulated NQO1 expression in HCECs. A significant increase in activation of NF-κB and production of pro-inflammatory cytokines IL-6 and IL-8 was observed after treatment with 4-HNE. Exposure to N-acetylcysteine (NAC), an antioxidant and ROS scavenger, antagonized the oxidative effects of 4-HNE on HCECs. CONCLUSION: 4-HNE induces oxidative stress in corneal epithelial cells by increasing levels of ROS generation and modifying the expression of antioxidant enzyme levels, decreasing cell viability of HCECs in vitro. This study demonstrates a potential pathway by which 4-HNE functions to confer its detrimental effects and provides a new therapeutic target for the treatment of DED.

Scientific and Regulatory Approach to Botanical Drug Development: A U.S. FDA Perspective.

The United States FDA has received over 800 botanical investigational new drug applications (IND) and pre-IND meeting requests (PIND) in the years preceding 2018. The current data show that indications for submitted INDs cover nearly every review division of the FDA. Despite increasing global interest in the investigation of botanical mixtures as drug products, only two botanical new drug applications (NDA) have been approved in the U.S.: Veregen in 2006 and Fulyzaq (also known as Mytesi) in 2012. Given botanicals' chemical and biological complexity, efforts in characterizing their pharmacology, demonstrating therapeutic efficacy, and ensuring quality consistency remain scientific and regulatory challenges. The FDA published a revised Botanical Drug Development Guidance for Industry document in December 2016 to address developmental considerations for late-phase trials and to provide recommendations intended to facilitate botanical drug development. Herein, we present an analysis of botanical INDs showing their variety of botanical raw materials (e.g., coming from different geographic regions, single vs multiple herbs), the varied levels of previous human experience, and therapeutic areas, as well as provide an overview of experience and challenges in reviewing botanical drugs.

Shifting Demographics among Research Project Grant Awardees at the National Heart, Lung, and Blood Institute (NHLBI).

The present study was initiated because of concerns expressed by NHLBI-funded mid-career investigators regarding perceived difficulties in the renewal of their grant awards. This led us to ask: "Are mid-career investigators experiencing disproportionate difficulties in the advancement of their professional careers?" Our portfolio analysis indicates that there has been a significant and evolving shift in the demographics of research project grant (RPG) awardees at NHLBI. In 1998, mid-career (ages 41-55) investigators constituted approximately 60% of all investigators with the remaining 40% being equally divided between early-stage (ages 24-40) investigators and established (ages 56 to 70 and older) investigators. However, since 1998, the proportion of established RPG awardees has been increasing in a slowly progressive and strikingly linear fashion. At the same time the proportion of early-stage awardees fell precipitously until 2006 and then stabilized. During the same period, the proportion of mid-career awardees, which had been relatively stable through 2006, began to fall significantly. In examining potential causes of these demographic shifts we have identified certain inherent properties within the RPG award system that appear to promote an increasingly more established awardee population and a persistent decrease in the proportion of mid-career investigators. A collateral result of these demographic shifts, when combined with level or declining funding, is a significant reduction in the number of RPG awards received by NHLBI mid-career investigators and a corresponding decrease in the number of independent research laboratories.

Novel Methods of Determining Urinary Calculi Composition: Petrographic Thin Sectioning of Calculi and Nanoscale Flow Cytometry Urinalysis.

Accurate determination of urinary stone composition has significant bearing on understanding pathophysiology, choosing treatment modalities and preventing recurrence. A need exists for improved methods to determine stone composition. Urine of 31 patients with known renal calculi was examined with nanoscale flow cytometry and the calculi collected during surgery subsequently underwent petrographic thin sectioning with polarized and fluorescent microscopy. Fluorescently labeled bisphosphonate probes (Alendronate-fluorescein/Alendronate-Cy5) were developed for nanoscale flow cytometry to enumerate nanocrystals that bound the fluorescent probes. Petrographic sections of stones were also imaged by fluorescent and polarized light microscopy with composition analysis correlated to alendronate +ve nanocrystal counts in corresponding urine samples. Urine samples from patients with Ca(2+) and Mg(2+) based calculi exhibited the highest alendronate +ve nanocrystal counts, ranging from 100-1000 nm in diameter. This novel urine based assay was in agreement with composition determined by petrographic thin sections with Alendronate probes. In some cases, high alendronate +ve nanocrystal counts indicated a Ca(2+) or Mg(2+) composition, as confirmed by petrographic analysis, overturning initial spectrophotometric diagnosis of stone composition. The combination of nanoscale flow cytometry and petrographic thin sections offer an alternative means for determining stone composition. Nanoscale flow cytometry of alendronate +ve nanocrystals alone may provide a high-throughput means of evaluating stone burden.

Size and characteristics of the biomedical research workforce associated with U.S. National Institutes of Health extramural grants.

The U.S. National Institutes of Health (NIH) annually invests approximately $22 billion in biomedical research through its extramural grant programs. Since fiscal year (FY) 2010, all persons involved in research during the previous project year have been required to be listed on the annual grant progress report. These new data have enabled the production of the first-ever census of the NIH-funded extramural research workforce. Data were extracted from All Personnel Reports submitted for NIH grants funded in FY 2009, including position title, months of effort, academic degrees obtained, and personal identifiers. Data were de-duplicated to determine a unique person count. Person-years of effort (PYE) on NIH grants were computed. In FY 2009, NIH funded 50,885 grant projects, which created 313,049 full- and part-time positions spanning all job functions involved in biomedical research. These positions were staffed by 247,457 people at 2,604 institutions. These persons devoted 121,465 PYE to NIH grant-supported research. Research project grants each supported 6 full- or part-time positions, on average. Over 20% of positions were occupied by postdoctoral researchers and graduate and undergraduate students. These baseline data were used to project workforce estimates for FYs 2010-2014 and will serve as a foundation for future research.

Youth tobacco cessation: quitting intentions and past-year quit attempts.

BACKGROUND: Despite declining use of conventional tobacco products, youth use of non-cigarette tobacco has become prevalent; however, quitting behaviors remain largely unexplored. PURPOSE: To examine nationally representative data on quit intentions and past-year attempts to quit all tobacco use among current youth tobacco users. METHODS: In 2013, data were analyzed from the 2012 National Youth Tobacco Survey (NYTS). Weighted prevalence estimates of quit intentions and past-year quit attempts for current youth tobacco users are presented. RESULTS: Prevalence of quit intentions and past-year attempts to quit all tobacco use were 52.8% and 51.5%, respectively, among current youth tobacco users. Among non-mutually exclusive groups, current cigarette smokers had the highest prevalence of quit intentions (56.8%) and past-year quit attempts (52.5%), whereas current hookah users had the lowest prevalence of quit intentions (41.5%) and past-year quit attempts (43.7%). Quit intentions among black, non-Hispanics (65.0%) and Hispanics (60.4%) were significantly higher versus white, non-Hispanics (47.5%). Youth reporting parental advice against tobacco had significantly higher prevalence of quit intentions (56.7%) and past-year quit attempts (55.0%) than those not reporting parental advice. Youth who agreed all tobacco products are dangerous (58.5%) had significantly higher prevalence of quit intentions than those who disagreed (37.0%). CONCLUSIONS: Continued efforts are needed to better understand youth motivation for quitting all tobacco products. Public health messaging about the dangers of all tobacco and cessation efforts should be aimed at the full range of tobacco products, not just cigarettes, and tailored to meet the needs of youth polytobacco users.

Self-reported exposure to tobacco warning labels among U.S. middle and high school students.

BACKGROUND: Warning labels on tobacco products are a means to communicate information about the negative health effects of tobacco use to current and potential users. Most tobacco use begins in early adolescence, making it particularly important to understand the degree to which warning labels reach adolescents. PURPOSE: To examine the extent to which youth report (1) seeing the current warnings on cigarettes and smokeless tobacco (SLT) products in the U.S. and (2) that seeing warnings makes them think about the health risks associated with tobacco use. METHODS: Exposure to warning labels on cigarettes and SLT, as well as the degree to which adolescents report thinking about health risks in response to warnings, was examined among U.S. middle and high school students using data from the 2012 National Youth Tobacco Survey (NYTS) and analyzed in 2013. RESULTS: Current data suggest that less than half of adolescents who saw a cigarette pack (46.9%) or SLT product (40.3%) reported seeing the warning label "most of the time" or "always." Among adolescents who reported seeing a warning, less than one third reported that cigarette (30.4%) or SLT (25.2%) warning labels made them think about health risks "a lot." These rates were even lower among current tobacco users (<14%). CONCLUSIONS: Current warning labels for cigarettes and SLT could be improved by implementing warnings that incorporate features that make them salient and more likely to evoke thoughts about health risks.

Youth curiosity about cigarettes, smokeless tobacco, and cigars: prevalence and associations with advertising.

BACKGROUND: Curiosity about cigarettes is a reliable predictor of susceptibility to smoking and established use among youth. Related research has been limited to cigarettes, and lacks national-level estimates. Factors associated with curiosity about tobacco products, such as advertising, have been postulated but rarely tested. PURPOSE: To describe the prevalence of curiosity about cigarettes, smokeless tobacco, and cigars among youth and explore the association between curiosity and self-reported tobacco advertising exposure. METHODS: Data from the 2012 National Youth Tobacco Survey, a nationally representative survey of 24,658 students, were used. In 2013, estimates weighted to the national youth school population were calculated for curiosity about cigarettes, smokeless tobacco, and cigars among never users of any tobacco product. Associations between tobacco advertising and curiosity were explored using multivariable regressions. RESULTS: Curiosity about cigarettes (28.8%); cigars (19.5%); and smokeless tobacco (9.7%) was found, and many youth were curious about more than one product. Exposure to point-of-sale advertising (e.g., OR=1.35, 95% CI=1.19, 1.54 for cigarette curiosity); tobacco company communications (e.g., OR=1.70, 95% CI=1.38, 2.09 for cigarette curiosity); and tobacco products, as well as viewing tobacco use in TV/movies (e.g., OR=1.37, 95% CI=1.20, 1.58 for cigarette curiosity) were associated with curiosity about each examined tobacco product. CONCLUSIONS: Despite decreasing use of tobacco products, youth remain curious about them. Curiosity is associated with various forms of tobacco advertising. These findings suggest the importance of measuring curiosity as an early warning signal for potential future tobacco use and evaluating continued efforts to limit exposure to tobacco marketing among youth.

Site migration in seeking care services from multiple providers is associated with worse clinical outcomes among HIV-infected individuals in Washington, DC.

Washington, DC, is a metropolitan city with a severe HIV epidemic and faces challenges in retaining people living with HIV (PLWH) in quality care. This study assessed site migration in seeking care services and its correlates among PLWH in DC. PLWH diagnosed before 2008 and living through the end of 2010 were analyzed. Six scenarios of site migration were examined as patients visited =2, =3, and =4 different providers for their CD4 cell count and/or viral load (VL) tests in the past 3 years from 2008 to 2010 and 2 years from 2009 to 2010, respectively. Of 6480 patients analyzed from 2008 to 2010, 18.4% had CD4 < 200 cells/mm(3), 30.5% had VL > 400 copies/mL, and 76.6% were retained in same care sites; 23.4%, 5.0%, and 0.9% visited =2, =3, and =4 sites in the past 3 years from 2008 to 2010, respectively. Of 5954 patients analyzed from 2009 to 2010, 16.8% had CD4 < 200 cells/mm(3), 29.4% had VL > 400 copies/mL, and 81.9% were retained in same care sites; 18.1%, 3.1%, and 0.6% visited =2, =3, and =4 sites in the past 2 years from 2009 to 2010, respectively. Multivariable logistic regression analyses revealed that migration across six scenarios are consistently associated with CD4 < 200 cells/mm(3) and VL > 400 copies/mL. Site migration was common and associated with lower CD4 and higher VL among PLWH in DC. Frequent migration might be a factor in achieving optimal health outcomes for a subset of patients. Site migration might potentially limit effective delivery of high quality care and treatment services. The preliminary findings underscore the need for further research to assess the predictors of migration and its impact on stage of care.