1991 — 1992 |
Eshleman, Susan H |
F32Activity Code Description: To provide postdoctoral research training to individuals to broaden their scientific background and extend their potential for research in specified health-related areas. |
Regulation of Glycoprotein Synthesis @ University of Pennsylvania |
0.907 |
1996 — 2000 |
Eshleman, Susan H |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
V3 Region Diversity in Hiv Vertical Transmission: Uganda @ Johns Hopkins University
Description (adapted from the Abstract): This Principal Investigator proposes to study the third variable (V3) region of gp120 to identify determinants which may influence vertical transmission of HIV-1 from a mother to her infant. The pattern of glycosylation of the V3 region of HIV-1 variants may be particularly important in this setting and special attention will be directed to this. The proposed studies will test the hypothesis that the genotype and glycosylation pattern in the V3 region of gp120 are important determinants of HIV-1 vertical transmission. The specific aims are to: (1) Clone and sequence V3 region cDNAs from RNA of HIV-1 variants in Ugandan mother-infant pairs that were participants in NIH/WHO studies of pediatric HIV-1 vertical transmission. By these assays the Investigator will characterize the extent of genetic diversity among HIV-1 variants in pregnant Ugandan women and children, and will determine the genotypic relatedness between the viral populations in these persons. Statistical methods will be used to increase the probability that the viral profiles obtained from DNA sequence analysis accurately reflect the profiles of HIV-1 variants in each mother and infant studied. The PCR amplification will be subdivided into 10 aliquots for each sample and 100 clones will be sequences. (2) Determine the pattern of N-linked glycosylation in the V3 region of the variants in each subject using a novel glycosylation assay. (3) analyze data generated in Specific Aims #1 and #2 to identify genotypic features important in HIV-1 vertical transmission. (4) Use heteroduplex assays to define further the role of V3 region genotype in HIV-1 vertical transmission.
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0.955 |
2002 — 2005 |
Eshleman, Susan H |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Drug Resistance in Non-Subtype B Hiv-1 @ Johns Hopkins University
[unreadable] DESCRIPTION (Provided by applicant): Resistance to antiretroviral drugs can limit the efficacy of regimens for prevention and treatment of HIV-I infection. A wealth of studies have analyzed HIV-1 drug resistance in subtype B, the most common HIV-1 subtype in the U.S. However, remarkably little is known about drug resistance in other subtypes, even though non-B subtypes account for the overwhelming majority of HIV-1 infections worldwide. Research on drug resistance in non-subtype B HIV-1 is becoming increasingly important for two reasons: (1) the prevalence of non-subtype B is increasing in the U.S. and other countries where antiretroviral drugs are widely used, and (2) the availability and use of antiretroviral drugs is growing in countries where non-subtype B HIV-1 is prevalent. This proposal will test the hypothesis that resistance of HIV-1 to antiretroviral drugs is influenced by HIV-I subtype. These experiments will be performed in the context of the Ugandan HIVNET 012 trial, which demonstrated that single dose nevirapine (NVP) prophylaxis can prevent HIV-1 mother-to-child transmission. That regimen is now being implemented in resource-poor countries around the world. We found that NVP resistance (NVPR) arose in 24% of women in HIVNET 012 6-8 weeks after NVP administration. Furthermore, we found that the rate of NVPR 6-8 weeks after NVP is significantly higher in women with subtype D than A (35/98=36% vs. 24/149=16%, respectively, p=0.0004). Emergence of NVPR in this setting could limit the efficacy of NVP prophylaxis in future pregnancies, and could limit treatment options for women and infants. NVPR could also spread in the population, decreasing the efficacy of NVP prophylaxis over time. In this proposal, we will further define the virologic factors that influence emergence and fading of NVPR following NVP prophylaxis in women with subtype A and D infection.The Specific Aims of this proposal are:Aim 1: Compare HIV-1 sequences from women in HIVNET 012 before and after single dose NVP to define the genetic correlates of NVPR in subtype A and D.Aim 2: Compare the emergence and fading of NVPR in women in HIVNET 012 with subtype A vs. D.Aim 3: Compare the antiretroviral drug susceptibility of subtype A and D HIV-1 variants in the presence and absence of NVPR mutations.Aim 4: Compare the fitness of subtype A vs. D HIV-I variants in the presence and absence of NVPR mutations. Information gained from this proposal will enhance our understanding of the impact of HIV-I subtype on antiretroviral drug resistance, and will help optimize antiretmviral regimens for prevention and treatment of HIV-1 infection.
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0.955 |
2006 — 2013 |
Eshleman, Susan H |
U01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. UM1Activity Code Description: To support cooperative agreements involving large-scale research activities with complicated structures that cannot be appropriately categorized into an available single component activity code, e.g. clinical networks, research programs or consortium. The components represent a variety of supporting functions and are not independent of each component. Substantial federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of the award. The performance period may extend up to seven years but only through the established deviation request process. ICs desiring to use this activity code for programs greater than 5 years must receive OPERA prior approval through the deviation request process. |
Hiv Prevention Trials Network: Network Laboratory @ Johns Hopkins University
The mission of the HIV Prevention Trials Network (HPTN) is to discover and develop interventions that can be used globally to prevent sexual and/or parenteral transmission of HIV. Our research encompasses the testing of novel biomedical and behavioral approaches. We seek HIV prevention strategies that are effective, safe, feasible, and sustainable, even in resource-limited settings. The incumbent HPTN has built field site research capacity in 16 developing countries. In the International HIVNET and the HPTN, we have recruited 31,250 HIV uninfected (principally) and infected persons into 38 trials (19,500 by the incumbent HPTN since 1999). Subjects are almost exclusively high risk, including adolescents and acutely infected persons. Focusing on resource-constrained countries in Africa, Asia, So. America, and E. Europe, as well as high incidence populations in the U.S., our highest impact trials have literally changed global public health practice, as with HIVNET 012 for the prevention of mother-to-infant HIV transmission. We are dividing the current HPTN agenda into three parts, our perinatal group partnering to create IMPAACT and the microbicide group spearheading MTN. Hence, the new HPTN focus is fourfold: (1) antiretroviral therapy and co-infection therapy for viral load reduction and prevention of HIV transmission; (2) treatment of sexually transmitted infections (STI) to lower HIV transmission risk; (3) treatment of substance abuse and addiction, including injection drug use and stimulants (cocaine and methamphetamines) to reduce HIV transmission; and (4) behavioral risk reduction with biological endpoints. We use randomized controlled trials with HIV incidence endpoints in uninfected persons. For prevention research among acutely and chronically HIV- infected persons, we study incidence of non-HIV STIs, lowering of HIV viral load, and/or HIV incidence in sexual or needle-sharing partners. We propose to complete five ongoing HPTN trials and to transition an additional six ongoing HPTN trials to IMPAACT and MTN networks, if funded. We present eight new trial concepts, five for prevention of HIV infection, one for detection and intervention among acutely infected persons (pre-seroconversion), and two focused on prevention among HIV-seropositive persons. Our risk populations include high risk heterosexuals, men who have sex with men, substance abusers, and, for selected trials, their sexual or needle-sharing partners. Our proposed affiliated Clinical Trials Units serve at- risk populations on five continents, especially sub-Saharan Africa and the U.S. The HPTN Leadership Group is experienced and diverse and includes experienced ethics experts and community leaders. HPTN governance is designed to develop and complete trials efficiently. We emphasize concepts of high potential public health impact, focusing on existing technologies that can be brought immediately into practice. Therefore, our agenda is complementary to long-term investments (finding a cure, vaccine, or microbicide).
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0.955 |
2009 — 2010 |
Eshleman, Susan H |
R03Activity Code Description: To provide research support specifically limited in time and amount for studies in categorical program areas. Small grants provide flexibility for initiating studies which are generally for preliminary short-term projects and are non-renewable. |
Resistance in Hiv-Infected Infants After Extended Arv Prophylaxis: Pepi-Malawi @ Johns Hopkins University
DESCRIPTION (provided by applicant): Many resource-poor countries must rely on simplified antiretroviral (ARV) regimens to prevent HIV mother-to- child transmission (MTCT). Unfortunately, these regimens are not fully effective and offer little protection against HIV transmission by breastfeeding, which accounts for at least 1/3 of all pediatric HIV infections. This situation is likely to improve, since two recent studies show that the risk of post-natal HIV transmission can be greatly reduced by providing breastfeeding infants with extended daily prophylaxis with nevirapine (NVP) or NVP plus zidovudine (ZDV). Therefore, extended NVP is likely to become a key component in regimens used to prevent MTCT in resource-poor countries where breastfeeding is critical for infant health. Unfortunately, data from one study shows that when infants are HIV-infected despite prophylaxis, those who received single dose NVP (sdNVP) plus up to 6 weeks of daily NVP had higher rates of NVP resistance than infants who received sdNVP alone;NVP resistance was also more likely to persist over time in infants who received the extended NVP regimen. In resource-poor settings, most first-line ARV treatment regimens for HIV-infected children include NVP. Therefore, the presence of NVP-resistant HIV strains in infants who received extended NVP prophylaxis may significantly reduce their chance of future ARV treatment success. The hypothesis of the proposed studies is that the addition of extended ZDV to extended NVP prophylaxis will reduce emergence and persistence of NVP resistance in breastfeeding infants who become HIV-infected despite having received prophylaxis. We will test this hypothesis by analyzing samples and data from the Post-Exposure Prophylaxis of Infants in Malawi trial (PEPI-Malawi). In PEPI-Malawi, most women received sdNVP in labor, and 3,352 infants were randomized to one of three study arms: (1) the control arm [sdNVP plus 1 week of daily ZDV], (2) the extended NVP arm [control regimen plus daily NVP to 14 weeks of age], or (3) the extended NVP/ZDV arm [control regimen plus daily NVP and daily ZDV to 14 weeks of age]. At 9 months, the estimated risk of post- natal HIV transmission among infants who were HIV-uninfected at birth was 10.6% in the control arm, 5.2% in the extended NVP arm (p<0.001), and 6.4% in the extended NVP/ZDV arm (p=0.002). The reduction in HIV transmission in the extended NVP and extended NVP/ZDV arms was still observed at 24 months. In the proposed studies, we will analyze emergence and persistence of NVP resistance in infants in PEPI-Malawi who were HIV-uninfected at birth, but became HIV-infected by 14 weeks of age. We will compare NVP resistance in the extended NVP arm and the extended NVP/ZDV arm, and will identify factors that influence emergence and persistence of NVP resistance in infants. We will also assess whether NVP resistance influences infant health. This information will facilitate the design and implementation of programs for prevention of post-natal MTCT in Africa and elsewhere. PUBLIC HEALTH RELEVANCE: These studies will evaluate antiretroviral drug regimens that reduce the risk of HIV transmission during breastfeeding. These studies will facilitate the design and implementation of programs for prevention of HIV mother-to-child transmission in resource-poor settings.
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0.955 |
2010 — 2013 |
Eshleman, Susan H |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Impact of Maternal Haart On Hiv-Infected Breastfeeding Infants: Malawi @ Johns Hopkins University
DESCRIPTION (provided by applicant): In many settings in Africa, women with unknown HIV status present late in pregnancy or in labor, and the postpartum period represents a major entry point for counseling, testing, and assessment for antiretroviral (ARV) treatment. ARV use in pregnant and breastfeeding women has clear benefits for mothers and infants. Furthermore, if an infant is already HIV-infected, breastfeeding is seen as posing no risk to the infant, and women are strongly encouraged to continue breastfeeding to maximize survival of the infant. However, use of highly active antiretroviral therapy (HAART) in breastfeeding women may induce ARV resistance in some HIV-infected infants, either through transfer of ARV-resistant strains from the mother to the infant, or by exposing the infant to biologically significant but sub-therapeutic amounts of ARV drugs, leading to selection of ARV-resistant HIV in infants who are already infected with ARV-susceptible HIV. Development of ARV resistance to more than one class of ARV drugs (multi-class resistance) in HIV-infected infants is likely to significantly reduce their chance of responding to life-saving ARV therapy. The hypothesis of this study is that maternal HAART induces multi-class ARV resistance in the majority of HIV-infected breastfeeding infants. This hypothesis will be tested using samples and data from the Post-Exposure Prophylaxis of Infants (PEPI) trial that was conducted in Blantyre, Malawi. In PEPI, approximately 90 women who initiated HAART postpartum had infants who were HIV-infected. Women and infants in PEPI received ARV drugs for prevention of mother-to-child transmission of HIV (pMTCT). Most women (~70%) received single dose nevirapine (sdNVP). All infants received sdNVP and 1 week of zidovudine (control regimen). Infants were then randomized at birth to receive either the control regimen alone, or the control regimen plus up to 14 weeks of extended daily NVP or extended daily NVP plus extended daily ZDV. These regimens were stopped immediately in infants with confirmed HIV infection. Because these pMTCT regimens are known to cause selection of NVP-resistant HIV in some women and some HIV-infected infants, exposure to pMTCT regimens will be considered in our analysis. The Specific Aims of this proposal are: Aim 1: Test whether initiation of maternal HAART postpartum is associated with emergence of multi-class resistance in HIV- infected breastfeeding infants. Aim 2: Analyze HIV viral load, ARV drug levels, and HIV drug resistance in breast milk samples from women on HAART. These studies will quantify the prevalence of multi-class resistance in infant plasma and breast milk after maternal HAART initiation, and will identify factors associated with development of multi-class resistance in HIV-infected breastfeeding infants. These studies will also assess whether infants in this setting are more likely to acquire multi-class resistance from transmission of resistant HIV from the mother (selected from her HAART regimen), or from exposure to ARV drugs in breast milk. This information will facilitate the design and implementation of strategies for HIV prevention and treatment in resource-constrained settings. PUBLIC HEALTH RELEVANCE: In resource-limited settings, many HIV-infected women are diagnosed with HIV infection during pregnancy or shortly after delivery, and many begin HIV treatment with antiretroviral drugs while they are still breastfeeding. We will determine whether initiation of treatment in breastfeeding women poses any risk to breastfeeding infants who are HIV-infected, by inducing resistance to antiretroviral drugs in the infant's virus.
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0.955 |
2011 — 2014 |
Brookmeyer, Ronald S (co-PI) [⬀] Eshleman, Susan H |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Laboratory and Statistical Development of Cross-Sectional Hiv Incidence Assays @ Johns Hopkins University
DESCRIPTION (provided by applicant): HIV incidence is the rate at which new HIV infections occur in populations. While HIV prevalence measures overall disease burden, HIV incidence tracks the leading edge of the HIV/AIDS epidemic. Accurate HIV incidence estimates are critical for monitoring the HIV/AIDS epidemic, identifying populations at high risk of HIV acquisition, targeting prevention efforts, and designing and evaluating HIV prevention trials. Current methods for cross-sectional HIV incidence determination are insufficiently accurate. Our goal is to develop and validate accurate, cost-effective methods for cross-sectional HIV incidence determination. Our hypothesis is that diverse laboratory assays and robust statistical modeling can be combined to improve the accuracy of cross-sectional HIV incidence estimates. We will focus on analysis of HIV incidence in both subtype B (the major subtype driving the HIV/AIDS epidemic in the United States) and subtype C (the major subtype driving the HIV/AIDS epidemic in sub-Saharan Africa);other subtypes prevalent in sub-Saharan Africa will also be analyzed. The Specific Aims of the project are: Aim 1: Continue to build a repository of diverse, well-characterized samples with information on the duration of HIV infection. Analyze the samples using serologic HIV incidence assays. Aim 2: Further develop and validate a novel high resolution melting (HRM) assay for HIV diversity. Determine whether HIV diversity can be used as a biomarker to differentiate between individuals with recent vs. chronic HIV infection. Aim 3: Use statistical analysis and mathematical modeling to assess the accuracy of methods for HIV incidence determination. Apply those approaches to data from Aim 1 (CD4 cell count, HIV viral load, and data from serologic assays) and Aim 2 (data from the HRM assay) to identify methods for HIV incidence determination that perform well in a wide variety of settings, and to assess their relative costs. Our repository will include samples from at least 19 completed clinical trials, cohort studies, and research projects representing key geographic, demographic, and clinically-relevant populations. Over 10,000 of the samples are already in hand. We will integrate laboratory science with statistical analysis and mathematical modeling in all phases of the project, and will evaluate a broad range of design parameters, including use of individual assays versus multi-assay algorithms, use of different assay cutoffs, and sequential ordering of assays. We believe that this comprehensive approach will lead to identification of accurate and cost-effective methods for cross-sectional HIV incidence determination. ) ) PUBLIC HEALTH RELEVANCE: This project will evaluate and optimize methods that can be used to determine HIV incidence (the rate of new HIV infections) from cross sectional surveys of single blood samples collected from individuals. These methods are needed to monitor the HIV/AIDS epidemic, to identify populations at high risk of HIV infection, to target HIV prevention efforts, and to design and evaluate HIV prevention trials.
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1 |
2014 — 2020 |
Eshleman, Susan H |
UM1Activity Code Description: To support cooperative agreements involving large-scale research activities with complicated structures that cannot be appropriately categorized into an available single component activity code, e.g. clinical networks, research programs or consortium. The components represent a variety of supporting functions and are not independent of each component. Substantial federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of the award. The performance period may extend up to seven years but only through the established deviation request process. ICs desiring to use this activity code for programs greater than 5 years must receive OPERA prior approval through the deviation request process. |
Lc: Hiv Prevention Trials Network @ Johns Hopkins University
DESCRIPTION (provided by applicant): With 13 years of experience and an outstanding record of performance, the HIV Prevention Trials Network (HPTN) Laboratory Center (LC) is optimally positioned to support the HPTN in 2013 and beyond. As part of the HPTN Leadership Group, the LC will help shape the network's scientific agenda. The HPTN LC will oversee laboratory activities at study sites; perform Quality Control/Quality Assurance (QA/QC) and specialized testing for HPTN protocols; evaluate and validate assays for use in HPTN protocols; develop novel assays to achieve study objectives; and perform ancillary studies related to HIV prevention. The HPTN LC has comprehensive QA/QC, Virology, and Pharmacology Cores, with Support Laboratories in other key areas (Sexually Transmitted Diseases, Microbiology, Immunology, and Toxicology). The HPTN LC has extensive experience supporting HIV prevention trials in the United States, South America, Asia, and Africa and has led efforts to harmonize laboratory procedures across networks and in other groups. The HPTN LC has supported HPTN protocols evaluating behavioral, biomedical, and structural interventions for HIV prevention, often delivered in combination in a wide range of settings and non-traditional venues. This includes observational, Phase I, Phase II and Phase III studies, with interventions delivered to HIV uninfected individuals, HIV-infected individuals, couples, cohorts, and communities. HPTN study populations include adolescents, women, men who have sex with men, serodiscordant couples, injection drug users, and individuals with acute HIV infection, with some trials enrolling >50,000 participants. The Specific Aims of the HPTN LC are: Aim 1: To provide leadership, expertise, and laboratory support to the HPTN; Aim 2: To support site laboratories and ensure the quality of HPTN laboratory results; Aim 3: To advance HIV prevention science through assay development and biomedical research. A strong and effective LC is particularly important in the HPTN because of the vast international scope, diversity, and complexity of HIV prevention trials. This award will enable the HPTN to continue its mission to identify effective strategies for HIV prevention that will help end the HIV/AIDS epidemic. RELEVANCE: The goal of HIV Prevention Trials Network (HPTN) is to identify effective strategies for HIV prevention. The HPTN Laboratory Center (LC) is part of the HPTN leadership group. HPTN LC investigators will oversee laboratory testing performed at study sites, analyze samples collected in HPTN studies, develop novel laboratory assays, and perform laboratory-related research relevant to HIV prevention.
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1 |
2017 — 2021 |
Eshleman, Susan H |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Hiv Incidence Testing in An Evolving Epidemic: Identification of Accurate Multi-Assay Algorithms That Include Serosignatures From a Novel Antibody Profiling System. @ Johns Hopkins University
PROJECT SUMMARY Accurate HIV incidence estimates are critical for monitoring the HIV/AIDS epidemic and evaluating interventions for HIV prevention. We have developed multi-assay algorithms (MAAs) that provide accurate incidence estimates. However, there are new challenges in this field of research. With increasing use of antiretroviral drugs for HIV treatment and prevention and a push towards early treatment initiation, more individuals, including those with recent infection, will be virally suppressed. This will impact cross-sectional incidence testing: higher rates of viral suppression will increase misclassification with standard serologic incidence assays; low viral load (VL) will no longer serve as biomarker for non-recent infection; and use of HIV diversity assays for incidence testing will be problematic, since it may not be possible to analyze samples with low VLs. Our hypothesis is that well-characterized samples, novel assays, and statistical modeling can be used to develop methods that provide accurate cross-sectional incidence estimates in the evolving landscape of HIV treatment and prevention. The Specific Aims of this project are: Aim 1: Expand a repository of well-characterized samples with information on the duration of HIV infection; use these samples to evaluate performance of HIV incidence assays. Our repository includes >17,000 samples from individuals with known duration of infection. We will continue to expand this repository, focusing on key populations and settings with high rates of viral suppression. These samples repository will be used to evaluate serologic HIV incidence assays. Aim 2: Use massively multiplexed VirScan assay to identify serosignatures that discriminate between recent and non-recent HIV infection. VirScan uses phage display, immuno-precipitation, and next generation sequencing to measure antibody reactivity to >3,300 HIV peptides. We will test samples from Aim 1 with VirScan and will use the data to identify ?serosignatures? that distinguish between recent and non-recent infection, independent of VL. We will also use VirScan data to develop multi-peptide immunoassays (EIAs). Aim 3: Develop MAAs for HIV incidence estimation and validate the top-performing MAAs using independent sample sets from cohort studies and clinical trials with known HIV incidence. Data from Aims 1 and 2 will be used to identify MAAs that maximize accuracy and minimize cost of cross-sectional incidence testing. The performance of MAAs and VirScan-based EIAs will be validated by comparing incidence estimates obtained with these methods to those observed in longitudinal follow-up in cohorts and clinical trials. Based on our prior work and preliminary data, we believe that these studies will identify accurate, cost- effective methods for cross-sectional HIV incidence estimation for use in diverse populations and settings. This work will have direct public health benefit, providing improved methods for surveillance of the HIV/AIDS epidemic, targeting prevention interventions, and design and evaluation of HIV prevention trials.
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1 |
2020 |
Eshleman, Susan H |
UM1Activity Code Description: To support cooperative agreements involving large-scale research activities with complicated structures that cannot be appropriately categorized into an available single component activity code, e.g. clinical networks, research programs or consortium. The components represent a variety of supporting functions and are not independent of each component. Substantial federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of the award. The performance period may extend up to seven years but only through the established deviation request process. ICs desiring to use this activity code for programs greater than 5 years must receive OPERA prior approval through the deviation request process. |
Lc: Hiv Prevention Trials Network - Laboratory Support For the Sars-Cov-2 Seroprevalence Study (Covpn 5002) @ Johns Hopkins University
PROJECT SUMMARY This project will provide laboratory support for a large, cross-sectional COVID-19 seroprevalence study that will be conducted in 23-25 communities in the United States: the SARS-CoV-2 Seroprevalence Study (COVID-19 Prevention Trials Network [CoVPN] 5002). The CoVPN 5002 study will include collection of data and specimens from up to 98,000 persons, including persons living in nursing homes and assisted living facilities, persons attending clinics, and persons living in study communities. The study will include children (ages 2 months and older) and adults. Participants will be tested for COVID-19 in real time using SARS-CoV-2 RNA assays. Seroprevalence will be assessed retrospectively using stored specimens from all participants using a sensitive and specific SARS-CoV-2 IgG assay (Abbott ARCHITECT COVID-19 IgG test). A subset of specimens from CoVPN 5002 will also be used to evaluate the performance of diagnostic and serologic SARS-CoV-2 assays using alternate specimen types (saliva and dried blood spots). Collection of these sample types is simpler and less invasive than collection of nasal swabs or collection of blood samples by phlebotomy. This project will also use of specialized assays to evaluate the serologic response to SARS-CoV-2. This will include use of a massively multiplexed antibody profiling assay (CoronaScan) to measure antibody binding to SARS-CoV-2 peptides spanning the viral genome. This analysis will provide information on the fine specificity of the antibody response to SARS-CoV-2 and reactivity to other coronaviruses and other viruses that cause respiratory illnesses. This testing may also identify participants who have false positive or false negative test results using the ARCHITECT COVID-19 IgG test. Specimens that have antibodies to the SARS-CoV-2 spike protein (identified using the CoronaScan assay) will be further assessed using a phenotypic recombinant viral neutralization assay (PhenoSense Anti-SARS-CoV-2 Neutralizing Antibody Assay). This analysis may identify viral epitopes associated with viral neutralization and may also identify demographic and clinical factors associated with the presence of neutralizing antibodies. Specimens from CoVPN 5002 will also be used for further development and evaluation of a novel, massively multiplexed pathogen detection assay, cRASL-Seq, that does not require RNA extraction. Findings from this research will inform the design of clinical trials for SARS-CoV-2 prevention and treatment by providing information about the seroprevalence of COVID-19 in diverse geographic regions and participants groups, including asymptomatic and symptomatic individuals, children and adults in the general population, and adults at increased risk for COVID-19.
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1 |
2021 |
Eshleman, Susan H |
UM1Activity Code Description: To support cooperative agreements involving large-scale research activities with complicated structures that cannot be appropriately categorized into an available single component activity code, e.g. clinical networks, research programs or consortium. The components represent a variety of supporting functions and are not independent of each component. Substantial federal programmatic staff involvement is intended to assist investigators during performance of the research activities, as defined in the terms and conditions of the award. The performance period may extend up to seven years but only through the established deviation request process. ICs desiring to use this activity code for programs greater than 5 years must receive OPERA prior approval through the deviation request process. |
Lc: Hiv Prevention Trials Network @ Johns Hopkins University
PROJECT SUMMARY With 20 years of experience and an outstanding record of performance, the HIV Prevention Trials Network (HPTN) Laboratory Center (LC) is optimally positioned to support the HPTN in 2020 and beyond. As part of the HPTN leadership group, the HPTN LC will help shape the network?s scientific agenda. The HPTN LC will oversee laboratory activities at study sites; perform Quality Assurance/Quality Control (QA/QC) and specialized testing for HPTN protocols; evaluate and validate assays for use in HPTN studies; develop novel assays to achieve study objectives; and perform ancillary studies related to HIV prevention. The HPTN LC has an Administrative Core, a Protocol Operations Core, and five laboratory Cores (Virology, Pharmacology, Co-Infections, Toxicology, Immunology). The HPTN LC also has an Early Product Development Working Group and a working group for Point-of-Care Testing and Remote Technologies. The HPTN LC has extensive experience supporting HIV protocols in the United States (US), Latin America, Africa, and Asia, with recent work in Eastern Europe. The HPTN LC includes seven Protocol Specialists with >100 combined years of experience supporting HPTN studies. The HPTN LC has led efforts to harmonize laboratory procedures across other networks and groups, and collaborates extensively with academic, government, and industry partners. The HPTN LC has supported protocols evaluating biomedical, behavioral, and structural interventions for HIV prevention, often delivered in combination in a wide range of settings and venues. This includes vanguard studies, observational studies, and Phase 1, 2, and 3 clinical trials, with interventions delivered to HIV-uninfected individuals, HIV-infected individuals, couples, cohorts, and communities. HPTN study populations include adolescents, women, men who have sex with men, transgender women, persons who inject drugs, and other groups at risk, with some trials enrolling >40,000 participants. The HPTN LC has performed numerous studies under Investigational New Drug (IND) applications for the US Food and Drug Administration. The HPTN LC?s Quality Management Team includes a Regulatory Affairs Officer who will ensure compliance with institutional, state, federal, and other regulatory requirements. Under the new award, the HPTN will evaluate new products for HIV pre-exposure prophylaxis, including new drugs, new drug delivery systems, multipurpose technologies, and broadly neutralizing antibodies; the HPTN will also perform integrated strategy studies that combine biomedical and socio-behavioral interventions for HIV prevention. The Specific Aims of the HPTN LC are: Aim 1: To provide leadership, expertise, and laboratory support to the HPTN; Aim 2: To support site laboratories and ensure the quality of HPTN laboratory results; and Aim 3: To advance HIV prevention science through assay development and biomedical research. A strong and effective HPTN LC is particularly important in the HPTN because of the vast international scope, diversity, and complexity of HIV prevention trials. This award will enable the HPTN to continue its mission to identify effective strategies for HIV prevention that will help end the HIV/AIDS epidemic.
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