Genotypic Resistance Testing of HIV-1 DNA in Peripheral Blood Mononuclear Cells.

HIV-1 DNA exists in nonintegrated linear and circular episomal forms and as integrated proviruses. In patients with plasma viremia, most peripheral blood mononuclear cell (PBMC) HIV-1 DNA consists of recently produced nonintegrated virus DNA while in patients with prolonged virological suppression (VS) on antiretroviral therapy (ART), most PBMC HIV-1 DNA consists of proviral DNA produced months to years earlier. Drug-resistance mutations (DRMs) in PBMCs are more likely to coexist with ancestral wild-type virus populations than they are in plasma, explaining why next-generation sequencing is particularly useful for the detection of PBMC-associated DRMs. In patients with ongoing high levels of active virus replication, the DRMs detected in PBMCs and in plasma are usually highly concordant. However, in patients with lower levels of virus replication, it may take several months for plasma virus DRMs to reach detectable levels in PBMCs. This time lag explains why, in patients with VS, PBMC genotypic resistance testing (GRT) is less sensitive than historical plasma virus GRT, if previous episodes of virological failure and emergent DRMs were either not prolonged or not associated with high levels of plasma viremia. Despite the increasing use of PBMC GRT in patients with VS, few studies have examined the predictive value of DRMs on the response to a simplified ART regimen. In this review, we summarize what is known about PBMC HIV-1 DNA dynamics, particularly in patients with suppressed plasma viremia, the methods used for PBMC HIV-1 GRT, and the scenarios in which PBMC GRT has been used clinically.

Understanding HIV Pre-Exposure Prophylaxis Questions of U.S. Health Care Providers: Unique Perspectives from the PrEPline Clinical Teleconsultation Service.

Introduction: Fewer than a quarter of people considered to have factors associated with HIV acquisition are prescribed pre-exposure prophylaxis (PrEP) in the United States. Prior studies demonstrate disparities in provider comfort and knowledge regarding PrEP, suggesting a need for provider capacity building to support widespread PrEP availability. This study examined real-world PrEP clinical questions/cases from providers to a teleconsultation service to identify knowledge gaps and improve PrEP-related training materials and clinical guidelines. Methods: The National Clinician Consultation Center (NCCC) PrEPline provides educational teleconsultation services on clinical decision-making related to PrEP for U.S. health care providers. The NCCC PrEP consultation data collected between 2017 and 2020 were reviewed and systematically categorized by clinical topics, subtopics, and complexity levels (low, moderate, and high). Results: Within the study period, the PrEPline provided 1,754 teleconsultations. More than three quarters came from advanced practice nurses and physicians. The topics of questions commonly focused on medication-based HIV prevention strategies (22.7%), PrEP laboratory ordering/monitoring (17.4%), and side effects and contraindications (14.6%). The majority of teleconsultations (57.9%) involved sharing information that was directly available/addressed in the Centers for Disease Control and Prevention (CDC) 2017 PrEP Guidelines (i.e., low complexity). Discussion: The low frequency of consultations from nonphysician and non-nurse practitioner providers may suggest a need for increased training and collaborative opportunities for other types of providers. The high percentage of low-complexity inquiries may reveal a desire for capacity-building materials specifically designed for practicing providers (e.g., abridged versions of guidelines). This study may inform future research, best clinical practices, and aid in the development of training materials to increase providers' HIV prevention comfort and knowledge.

Testing and Clinical Management of Health Care Personnel Potentially Exposed to Hepatitis C Virus - CDC Guidance, United States, 2020.

Exposure to hepatitis viruses is a recognized occupational risk for health care personnel (HCP). This report establishes new CDC guidance that includes recommendations for a testing algorithm and clinical management for HCP with potential occupational exposure to hepatitis C virus (HCV). Baseline testing of the source patient and HCP should be performed as soon as possible (preferably within 48 hours) after the exposure. A source patient refers to any person receiving health care services whose blood or other potentially infectious material is the source of the HCP's exposure. Two options are recommended for testing the source patient. The first option is to test the source patient with a nucleic acid test (NAT) for HCV RNA. This option is preferred, particularly if the source patient is known or suspected to have recent behaviors that increase risk for HCV acquisition (e.g., injection drug use within the previous 4 months) or if risk cannot be reliably assessed. The second option is to test the source patient for antibodies to hepatitis C virus (anti-HCV), then if positive, test for HCV RNA. For HCP, baseline testing for anti-HCV with reflex to a NAT for HCV RNA if positive should be conducted as soon as possible (preferably within 48 hours) after the exposure and may be simultaneous with source-patient testing. If follow-up testing is recommended based on the source patient's status (e.g., HCV RNA positive or anti-HCV positive with unavailable HCV RNA or if the HCV infection status is unknown), HCP should be tested with a NAT for HCV RNA at 3-6 weeks postexposure. If HCV RNA is negative at 3-6 weeks postexposure, a final test for anti-HCV at 4-6 months postexposure is recommended. A source patient or HCP found to be positive for HCV RNA should be referred to care. Postexposure prophylaxis of hepatitis C is not recommended for HCP who have occupational exposure to blood and other body fluids. This guidance was developed based on expert opinion (CDC. Updated U.S. Public Health Service guidelines for the management of occupational exposures to HBV, HCV, and HIV and recommendations for postexposure prophylaxis. MMWR Recommend Rep 2001;50[No. RR-11]; Supplementary Figure, https://stacks.cdc.gov/view/cdc/90288) and reflects updated guidance from professional organizations that recommend treatment for acute HCV infection. Health care providers can use this guidance to update their procedures for postexposure testing and clinical management of HCP potentially exposed to hepatitis C virus.

HIV Infection in Adults: Initial Management.

The HIV epidemic is an important public health priority. Transmissions continue to occur despite effective therapies that make HIV preventable and treatable. Approximately one-half of people with HIV are not receiving suppressive antiretroviral therapy (ART). Starting ART early, followed by continuous lifetime treatment, most effectively achieves durable virologic suppression and restoration of immune function that can improve clinical outcomes and prevent transmission to partners who are seronegative. National treatment guidelines include ART options that can be offered immediately after diagnosis, even before the results of baseline HIV drug-resistance testing are available. Initial ART selection should be guided by co-occurring conditions, including viral hepatitis, medications, and other factors such as pregnancy. Identifying and addressing psychosocial barriers to care is a key element of ensuring long-term adherence to treatment. The initial physical examination typically reveals no clinical manifestations of HIV in the absence of advanced disease. A comprehensive laboratory evaluation, including HIV viral load and CD4 lymphocyte monitoring, is necessary to guide decision-making for treatment, opportunistic infection prophylaxis, and vaccinations. The initial management of people with HIV presents a unique opportunity for family physicians to improve patients' long-term health care and reduce HIV transmissions.

HIV-Associated Complications: A Systems-Based Approach.

Persons with human immunodeficiency virus (HIV) infection often develop complications related directly to the infection, as well as to treatment. Aging, lifestyle factors, and comorbidities increase the risk of developing chronic conditions such as diabetes mellitus and chronic kidney disease. HIV-associated neurologic complications encompass a wide spectrum of pathophysiology and symptomatology. Cardiovascular and pulmonary conditions are common among persons with HIV infection. Although some specific antiretroviral medications have been linked to disease development, traditional risk factors (e.g., smoking) have major roles. Prevention and management of viral hepatitis coinfection are important to reduce morbidity and mortality, and new anti-hepatitis C agents produce high rates of sustained virologic response. Antiretroviral-associated metabolic complications include dyslipidemia, hyperglycemia, and loss of bone mineral density. Newer options generally pose less risk of significant systemic toxicity and are better tolerated. Family physicians who care for patients with HIV infection have a key role in identifying and managing many of these chronic complications.

Initial Management of Patients with HIV Infection.

Human immunodeficiency virus (HIV) infection has become a treatable chronic disease with near-normal life expectancy when patients receive antiretroviral therapy (ART). Family physicians and other primary care clinicians commonly provide long-term comprehensive care for persons with HIV infection. This article describes the scope of initial care, including obtaining a thorough history; physical examination for HIV-associated manifestations; attention to HIV-specific immunization schedules; routine and HIV-specific laboratory evaluation; and ensuring standard health care maintenance to prevent HIV- and non-HIV-related morbidity and mortality. Clinicians should encourage combination ART as early as possible, although careful assessment of patient readiness and ability to sustain lifelong treatment must be weighed. After ART initiation, monitoring viral load and CD4 lymphocyte response is essential to ensure viral suppression and evaluate immune system restoration. Opportunistic infections are now less common than in the past because ART usually prevents or markedly delays progression to advanced HIV disease. The most important reasons for consultation or comanagement with an HIV expert include management of antiretroviral drug resistance or drug toxicities, as well as special circumstances such as viral hepatitis coinfection or pregnancy.

Experiences of the National Post-Exposure Prophylaxis Hotline (PEPline): Occupational PEP consultation needs and trends, 2014 to 2022.

BACKGROUND: The National Clinician Consultation Center operates the Post-Exposure Prophylaxis Hotline (PEPline), a federally-funded educational resource providing bloodborne pathogen exposure management teleconsultation to US clinicians. METHODS: Sixty-seven thousand one hundred nine occupational post-exposure prophylaxis (PEP) consultations (January 2014 to December 2022) were retrospectively analyzed to describe PEPline utilization and common inquiries addressed by National Clinician Consultation Center consultants. RESULTS: Most calls involved percutaneous incidents (70%); blood was the most common body fluid discussed (60%). Inpatient units were the most common exposure setting (35%) and licensed nursing professionals were the most common category of exposed workers (28%). Of 2,295 calls where workers had already initiated PEP for human immunodeficiency virus (HIV) prevention and time to first dose was known, 9% had initiated HIV PEP within 2 hours of exposure; almost 80% had initiated HIV PEP between 2 and 24 hours; 3% after 24 to 36 hours; 5% after 36 to 72 hours; and 2% after 72 hours. Calls from urgent care providers increased by 10% over time. Overall, more than 90% of callers requested support on risk assessment, including source person testing; other common questions involved PEP side effects and follow-up care. CONCLUSIONS: PEPline consultations can help raise awareness about PEP availability and timely initiation, and reduce stigma by addressing common misperceptions about bloodborne pathogen transmission mechanisms and likelihood, particularly regarding HIV.

Prevalence of Emergent Dolutegravir Resistance Mutations in People Living with HIV: A Rapid Scoping Review.

BACKGROUND: Dolutegravir (DTG) is a cornerstone of global antiretroviral (ARV) therapy (ART) due to its high efficacy and favorable tolerability. However, limited data exist regarding the risk of emergent integrase strand transfer inhibitor (INSTI) drug-resistance mutations (DRMs) in individuals receiving DTG-containing ART. METHODS: We performed a PubMed search using the term "Dolutegravir", last updated 18 December 2023, to estimate the prevalence of VF with emergent INSTI DRMs in people living with HIV (PLWH) without previous VF on an INSTI who received DTG-containing ART. RESULTS: Of 2131 retrieved records, 43 clinical trials, 39 cohorts, and 6 cross-sectional studies provided data across 6 clinical scenarios based on ART history, virological status, and co-administered ARVs: (1) ART-naïve PLWH receiving DTG plus two NRTIs; (2) ART-naïve PLWH receiving DTG plus lamivudine; (3) ART-experienced PLWH with VF on a previous regimen receiving DTG plus two NRTIs; (4) ART-experienced PLWH with virological suppression receiving DTG plus two NRTIs; (5) ART-experienced PLWH with virological suppression receiving DTG and a second ARV; and (6) ART-experienced PLWH with virological suppression receiving DTG monotherapy. The median proportion of PLWH in clinical trials with emergent INSTI DRMs was 1.5% for scenario 3 and 3.4% for scenario 6. In the remaining four trial scenarios, VF prevalence with emergent INSTI DRMs was ≤0.1%. Data from cohort studies minimally influenced prevalence estimates from clinical trials, whereas cross-sectional studies yielded prevalence data lacking denominator details. CONCLUSIONS: In clinical trials, the prevalence of VF with emergent INSTI DRMs in PLWH receiving DTG-containing regimens has been low. Novel approaches are required to assess VF prevalence with emergent INSTI DRMs in PLWH receiving DTG in real-world settings.

Treatment Emergent Dolutegravir Resistance Mutations in Individuals Naïve to HIV-1 Integrase Inhibitors: A Rapid Scoping Review.

Background: Dolutegravir (DTG)-based antiretroviral therapy (ART) rarely leads to virological failure (VF) and drug resistance in integrase strand transfer inhibitor (INSTI)-naïve persons living with HIV (PLWH). As a result, limited data are available on INSTI-associated drug resistance mutations (DRMs) selected by DTG-containing ART regimens. Methods: We reviewed studies published through July 2023 to identify those reporting emergent major INSTI-associated DRMs in INSTI-naïve PLWH receiving DTG and those containing in vitro DTG susceptibility results using a standardized assay. Results: We identified 36 publications reporting 99 PLWH in whom major nonpolymorphic INSTI-associated DRMs developed on a DTG-containing regimen and 21 publications containing 269 in vitro DTG susceptibility results. DTG-selected DRMs clustered into four largely non-overlapping mutational pathways characterized by mutations at four signature positions: R263K, G118R, N155H, and Q148H/R/K. Eighty-two (82.8%) viruses contained just one signature DRM, including R263K (n = 40), G118R (n = 24), N155H (n = 9), and Q148H/R/K (n = 9). Nine (9.1%) contained ≥1 signature DRM, and eight (8.1%) contained just other DRMs. R263K and G118R were negatively associated with one another and with N155H and Q148H/K/R. R263K alone conferred a median 2.0-fold (IQR: 1.8-2.2) reduction in DTG susceptibility. G118R alone conferred a median 18.8-fold (IQR:14.2-23.4) reduction in DTG susceptibility. N155H alone conferred a median 1.4-fold (IQR: 1.2-1.6) reduction in DTG susceptibility. Q148H/R/K alone conferred a median 0.8-fold (IQR: 0.7-1.1) reduction in DTG susceptibility. Considerably higher levels of reduced susceptibility often occurred when signature DRMs occurred with additional INSTI-associated DRMs. Conclusions: Among INSTI-naïve PLWH with VF and treatment emergent INSTI-associated DRMs, most developed one of four signature DRMs, most commonly R263K or G118R. G118R was associated with a much greater reduction in DTG susceptibility than R263K.

An apoA-I mimetic peptibody generates HDL-like particles and increases alpha-1 HDL subfraction in mice.

The aim of this study is to investigate the capability of an apoA-I mimetic with multiple amphipathic helices to form HDL-like particles in vitro and in vivo. To generate multivalent helices and to track the peptide mimetic, we have constructed a peptibody by fusing two tandem repeats of 4F peptide to the C terminus of a murine IgG Fc fragment. The resultant peptidbody, mFc-2X4F, dose-dependently promoted cholesterol efflux in vitro, and the efflux potency was superior to monomeric 4F peptide. Like apoA-I, mFc-2X4F stabilized ABCA1 in J774A.1 and THP1 cells. The peptibody formed larger HDL particles when incubated with cultured cells compared with those by apoA-I. Interestingly, when administered to mice, mFc-2X4F increased both pre-ß and α-1 HDL subfractions. The lipid-bound mFc-2X4F was mostly in the α-1 migrating subfraction. Most importantly, mFc-2X4F and apoA-I were found to coexist in the same HDL particles formed in vivo. These data suggest that the apoA-I mimetic peptibody is capable of mimicking apoA-I to generate HDL particles. The peptibody and apoA-I may work cooperatively to generate larger HDL particles in vivo, either at the cholesterol efflux stage and/or via fusion of HDL particles that were generated by the peptibody and apoA-I individually.

An epidemic in evolution: the need for new models of HIV care in the chronic disease era.

Since the beginning of the AIDS epidemic, models of HIV care have needed to be invented or modified as the needs of patients and communities evolved. Early in the epidemic, primary care and palliative care predominated; subsequently, the emergence of effective therapy for HIV infection led to further specialization and a focus on increasingly complex antiretroviral therapy as the cornerstone of effective HIV care. Over the past decade, factors including (1) an aging, long-surviving population; (2) multiple co-morbidities; (3) polypharmacy; and (4) the need for chronic disease management have led to a need for further evolution of HIV care models. Moreover, geographic diffusion; persistent disparities in timely HIV diagnosis, treatment access, and outcomes; and the aging of the HIV provider workforce also suggest the importance of reincorporating primary care providers into the spectrum of HIV care in the current era. Although some HIV-dedicated treatment centers offer comprehensive medical services, other models of HIV care potentially exist and should be developed and evaluated. In particular, primary care- and community-based collaborative practices-where HIV experts or specialists are incorporated into existing health centers-are one approach that combines the benefits of HIV-specific expertise and comprehensive primary care using an integrated, patient-centered approach.

Comorbidity-related treatment outcomes among HIV-infected adults in the Bronx, NY.

Aging, HIV infection, and antiretroviral therapy have been associated with increasing rates of chronic comorbidities in patients with HIV. Urban minority populations in particular are affected by both the HIV/AIDS and chronic disease epidemics. Our objectives were to estimate the prevalence of and risk factors for hypertension, dyslipidemia, and diabetes among HIV-infected adults in the Bronx and describe comorbidity-related treatment outcomes. This was a cross-sectional study of 854 HIV-positive adults receiving care at 11 clinics which provide HIV primary care services; clinics were affiliated with a large urban academic medical center. Data on blood pressure (BP), cholesterol, and glycemic control were collected through standardized chart review of outpatient medical records. We found prevalence rates of 26%, 48%, and 13% for hypertension, dyslipidemia, and diabetes, respectively. Older age, obesity, family history, and current protease inhibitor use were consistently associated with comorbidity. Diabetes treatment goals were achieved less often than BP and lipid goals, and concurrent diabetes was a significant predictor for BP and lipid control. In conclusion, major cardiovascular-related comorbidities are prevalent among HIV-positive adults in the Bronx, especially older and obese individuals. Differences exist in comorbidity-related treatment outcomes, especially for patients with concurrent diabetes. Because cardiovascular risk is modifiable, effective treatment of related comorbidities may improve morbidity and mortality in HIV-infected patients.

Complications of HIV infection: a systems-based approach.

Patients with human immunodeficiency virus (HIV) infection often develop multiple complications and comorbidities. Opportunistic infections should always be considered in the evaluation of symptomatic patients with advanced HIV/AIDS, although the overall incidence of these infections has decreased. Primary care of HIV infection includes the early detection of some complications through screening at-risk and symptomatic patients with routine laboratory monitoring (e.g., comprehensive metabolic and lipid panels) and validated tools (e.g., the HIV Dementia Scale). Treatment of many chronic complications is similar for patients with HIV infection and those without infection; however, combination antiretroviral therapy has shown benefit for some conditions, such as HIV-associated nephropathy. For other complications, such as cardiovascular disease and lipoatrophy, management may include switching antiretroviral regimens to reduce exposure to HIV medications known to cause toxicity.

Tobacco Control as an LGBTQ+ Issue: Knowledge, Attitudes, and Recommendations from LGBTQ+ Community Leaders.

Tobacco companies use price discounts, including coupons and rebates, to market their products. Lesbian, gay, bisexual, transgender, and queer (LGBTQ+) communities are targeted by these marketing strategies, contributing to inequitably high tobacco use. Some localities have adopted policies restricting tobacco price discounts; for successful implementation, community buy-in is crucial. From July-October 2018, Equality California staff conducted semi-structured interviews with seven participants in Los Angeles, CA. Themes included familiarity with tobacco price discounts, their perceived impact on tobacco use in LGBTQ+ communities, and attitudes toward potential policy restrictions. Interview notes were analyzed using a deductive approach to qualitative analysis. Awareness of tobacco price discounts varied; some interviewees were familiar, while others expressed surprise at their ubiquity. Price discounts were seen to disproportionately impact LGBTQ+ individuals, especially those who additionally identify with other vulnerable groups, including young people and communities of color. Support for policy restrictions was unanimous; however, interviewees expressed concern over political opposition and emphasized a need for culturally competent outreach to LGBTQ+ communities. Community organizations are essential in mobilizing support for policy reform. Understanding the perceptions and recommendations of community leaders provides tools for policy action, likely improving outcomes to reduce LGBTQ+ tobacco use through restricting tobacco price discounts.

Diagnosis and initial management of acute HIV infection.

Recognition and diagnosis of acute human immunodeficiency virus (HIV) infection in the primary care setting presents an opportunity for patient education and health promotion. Symptoms of acute HIV infection are nonspecific (e.g., fever, malaise, myalgias, rash), making misdiagnosis common. Because a wide range of conditions may produce similar symptoms, the diagnosis of acute HIV infection involves a high index of suspicion, a thorough assessment of HIV exposure risk, and appropriate HIV-related laboratory tests. HIV RNA viral load testing is the most useful diagnostic test for acute HIV infection because HIV antibody testing results are generally negative or indeterminate during acute HIV infection. After the diagnosis of acute HIV infection is confirmed, physicians should discuss effective transmission risk reduction strategies with patients. The decision to initiate antiretroviral therapy should be guided by consultation with an HIV specialist.

Current health disparities in HIV/AIDS.

The CDC and other public health organizations have identified numerous disparities in the incidence and outcomes of HIV disease among different population groups. Data suggest that some disparities are expected and unavoidable (eg, HIV incidence by age), while others imply inequalities or inequalities that are potentially remediable (eg, differential access by race or sex to HIV prevention and treatment services). Women and minorities, especially those in South and rural areas, have recently been identified as underserved populations at high risk for increased morbidity and mortality from HIV/AIDS. This article reviews current epidemiological trends in HIV/AIDS outcomes, key contributors to observed and emerging health disparities, and strategies that are being employed to overcome important modifiable disparities.

Automated two-step chromatography using an ÄKTA equipped with in-line dilution capability.

There has been a great emphasis on developing higher-throughput protein purification techniques to screen potential human therapeutics faster and more efficiently. Not only is it desirable to have high-throughput purification for initial screens but it is also desirable to efficiently purify selected protein therapeutics in the amounts and purity required for definitive assays. Current automated tandem technologies involve size exclusion as a second step that often fails to generate the required purity, is not robust and can only be operated at a limited scale. We have modified an ÄKTA to enable in-line dilution, assuring that the automated loading of a second column from a first column elution can be modified to a pH and ionic strength which is suitable for binding to the second column. For example, Protein A can be employed as a first step followed by direct loading on to a cation exchange column by conditioning the Protein A elution using the in-line diluter. Using this method as described, up to six samples of 1L each can be purified through two columns without human intervention per day per machine, and the system produces good yields of purified protein over a wide range of loading levels (12-300mg). In addition, the system employs guanidine HCl regeneration, followed by a sodium hydroxide wash between purification runs, minimizing the possibility of carryover contamination. The system is described at the 5mL and the 10mL column sizes; however, it could readily be programed for 100mL columns to enable larger-scale purifications. Using this system to automate two-column purifications minimizes human intervention, increases efficiency and minimizes the risk of human error.

Comparable sustained virologic suppression between community- and academic-based HIV care settings.

PURPOSE: The human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome epidemic in the United States is evolving because of factors such as aging and geographic diffusion. Provider shortages are also driving the restructuring of HIV care delivery away from specialized settings, and family medicine providers may play a larger role in the future. We attempted to compare the effectiveness of HIV treatment delivered at community versus hospital care settings. METHODS: The outcome of interest was sustained virologic suppression defined as 2 consecutive HIV-1 RNA measurements ≤400 copies/mL within 1 year after antiretroviral initiation. We used data from the multistate HIV Research Network cohort to compare sustained virologic suppression outcomes among 15,047 HIV-infected adults followed from 2000 to 2008 at 5 community- and 8 academic hospital-based ambulatory care sites. Community-based sites were mostly staffed by family medicine and general internal medicine physicians with HIV expertise, whereas hospital sites were primarily staffed by infectious disease subspecialists. Multivariate mixed effects logistic regression controlling for potential confounding variables was applied to account for clustering effects of study sites. RESULTS: In an unadjusted analysis the rate of sustained virologic suppression was significantly higher among subjects treated in community-based care settings: 1,646 of 2,314 (71.1%) versus 8,416 of 12,733 (66.1%) (P < .01). In the adjusted multivariate model with potential confounding variables, the rate was higher, although not statistically significant, in the community-based settings (adjusted odds ratio, 1.26; 95% confidence interval, 0.73-2.16). CONCLUSION: Antiretroviral therapy can be delivered effectively through community-based treatment settings. This finding is potentially important for new program development, shifting HIV care into community-based settings as the landscape of accountable care, health reform, and HIV funding and resources evolves.

Bridging the Gap: Developing a Tool to Support Local Civilian and Military Disaster Preparedness.

U.S. policymakers have stepped up systematic disaster preparedness efforts sharply since the terrorist attacks of September 11, 2001, including the creation of the U.S. Department of Homeland Security and a plethora of federal initiatives. Against a backdrop of natural disasters that occur each year in the United States and heightened concern about pandemic influenza, there is an emerging national consensus that the best path is an all-hazards approach to disaster preparedness planning and that effective local planning is critical. Military installations and their civilian counterparts-local government and local health-care providers, especially the U.S. Department of Veterans Affairs-can strengthen local-level disaster preparedness planning. This is an interim report for the first phase of a larger study aiming to develop a planning support tool for local military and civilian planners. It describes current policies and programs-especially those with nationwide application-for domestic emergency preparedness, risk analysis, and capabilities-based planning. It also describes results from interviews with local military and civilian planners at five selected sites to help understand how local preparedness planning currently operates and identify the needs of local planners. Collectively, these form the basis for a proposed tool, for which the framework is described in this article. The next phase of the study will include development and field testing of a proof-of-concept prototype of the tool.