Showing 11 ideas for tag "hiv"

Goal 1: Promote Human Health

The Human Virome and Host Interactions in Heart, Lung, and Blood

What are the unknown elements of the human virome, and what host-virome interactions affect the heart, lung, and blood health and diseases?

A major challenge has been the need for in vitro culture systems and animal models for studying the virome, which is a significant limitation that has forced current studies of the virome to be mostly descriptive. NHLBI has supported one research group to identify human virome and... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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• The virome contains the most abundant and fastest mutating genetic elements on Earth. The human virome is constituted of viruses that infect host cells, virus-derived elements in our chromosomes, and viruses that infect the broad array of other types of organisms that inhabit us. The virome may influence the host in profound ways independent of classical viral disease. The immune system is continuously stimulated by chronic systemic viruses and this aspect of host-microbiome interactions appears specific to the virome. The virome is considered one of the drivers of idiopathic systemic inflammation that has been linked to many of the most severe public health threats, including cardiovascular diseases. Disruptions in immunity by immunosuppressing events can undoubtedly alter the interactions of the virome with the host. However, little research has been done in all of these aspects other than limited descriptive studies to identify the presence or composition of the human virome. The NHLBI Microbiome Working Group in June 2014 clearly identified under-representation of studies of the human virome. Identification and characterization of unknown viral elements of the human virome and research on the interactions with the host will allow exploration of their impact on heart, lung and blood health and diseases, including impact in the presence of immunosuppression with the host such as in AIDS or HIV infection.

Feasibility and challenges of addressing this CQ or CC

This initiative is feasible because of new technologies that have been developed recently such as the deep sequencing techniques. The initiative is also timely in that research supported by the NIH Human Microbiome Program and other programs has allowed us to better understand microbiome, especially bacteria in and on humans, and we began to realize the magnitude of the virome. This initiative will attract more investigators to not only identify more elements of the virome but more importantly to understand the roles of the human virome in heart, lung and blood health and diseases, and eventually to help develop diagnostic and intervention strategies.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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29 up votes
16 down votes
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Goal 3: Advance Translational Research

Implementation Research to Improve Global Availability of Safe Blood Transfusions

What well-developed principles and lessons learned can be employed to improve the safety and availability of blood transfusions in developing countries?

The WHO Global Status Report 2013, many research reports, and a recent assessment of burdens of transfusion transmissible infections with HIV, HBV and HCV identified several critical challenges: 1) Significant proportions of blood collections in a large number of countries... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

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Significant progress has been made globally in providing adequate supply of safe blood for clinical transfusion thanks to efforts by many, including the US PEPFAR and research supported by NIH such as the REDS programs. Nevertheless, there remains a lack of blood for transfusion and paid blood donations are still collected in many countries. A total of 25 countries were not able to screen all donated blood for one or more of infections with human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV) and syphilis in 2011. As many as 24% of blood donations in low-income countries were not screened following basic quality procedures which include documented standard operating procedures and participation in an external quality assurance scheme. (WHO: Global Status Report 2013). Implementation research to identify cost-effective and sustainable ways to improve blood supplies in the developing world can help reduce blood shortage while enhancing safety by eliminating transfusion transmission of HIV, HBV and HCV.

Feasibility and challenges of addressing this CQ or CC

Research, including studies supported by the NHLBI REDS, REDS-II, and REDS-III programs, has identified major gaps in global blood supply and reasons for such gaps. International programs, especially PEPFAR, have gained valuable experience implementing quality systems. The time has come to conduct research to optimize the implementation, that is, to find out how to improve global supply of safe blood for transfusion more efficiently in local settings and in a more sustainable manner.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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7 net votes
20 up votes
13 down votes
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Goal 2: Reduce Human Disease

Influence of the Gut Microbiome on Pulmonary Immunity in HIV-Infected Individuals

It has become increasingly clear that gut microbiota have a tremendous impact on human health and disease. While it is well known that commensal gut bacteria are crucial in maintaining immune homeostasis in the intestine, there is also evidence of indirect effects on the lung. Multiple studies have shown that alterations in gut microbiota can lead to severe defects in pulmonary immune responses and reduced ability to... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

HIV-infected individuals are at significant risk of developing and dying from infectious and non-infectious pulmonary complications. Alteration of gut microbiota have been shown to have dramatic effects on pulmonary immunity and severity of lung infections. For instance, multiple studies have indicated that probiotic treatment with certain Lactobacillus and Bifidobacterium strains results in reduced incidence and severity of upper respiratory tract infections in children. Similarly, a recent study showed that treatment with the minimally absorbed antibiotic neomycin was associated with alterations in gut microbiota composition and concomitant reduced pulmonary immunity and the inability to control Influenza infection in mice. It was recently described that HIV infection is associated with a dramatic alteration in gut microbiota and that these changes persist with antiretroviral therapy (ART). Thus, it is important to understand how these alterations may effect lung immunity, since the majority of HIV-infected individuals develop pulmonary infections. Furthermore, gut microbiota contribute to development of non-infectious complications such as atherosclerosis, metabolic disease, obesity and diabetes. It is thus highly plausible that the gut microbiota may also play a role in the development of non-infectious complications of the lung such as Chronic Obstructive Pulmonary Disease and Pulmonary Hypertension, the rates of which are elevated in HIV-infected individuals.

Feasibility and challenges of addressing this CQ or CC

A better understanding of how alterations in gut microbiota associated with HIV infection affects pulmonary infectious and noninfectious complication could lead to therapies to protect this “at risk” group. Furthermore, manipulation of the gut microbiota in HIV-infected individuals using pro- and/or pre-biotics, antibiotics or diet modification to a composition that is associated with increased pulmonary immunity, reduced infections and lung complications are all low risk therapeutic strategies that could substantially improve lung heath in these individuals.

Name of idea submitter and other team members who worked on this idea Brent Palmer (NHLBI-INHALD group member) and Catherine Lozupone

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7 up votes
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Goal 2: Reduce Human Disease

Interactions between anticoagulant therapy and antiretroviral drugs

Cardiovascular pathology has become a major problem in the management of the HIV-infected patient during the ART era. A large number of HIV patients will receive anticoagulants drugs for secondary prevention of cardiovascular disease. It is therefore critical to understand the interactions between antiretroviral therapy and anticoagulant therapy to safely treat HIV patients.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

With over 50% of HIV-infected patients in the US anticipated to be > 50 years of age by 2015, the overall risk of CVD will be significantly higher and could become the main challenge for the management of chronic HIV infection. A large number of HIV-infected patients with CVD will therefore need treatment for primary and secondary prevention of atherothrombotic events. The secondary prevention of CVD almost invariably includes prescription of one or multiple anticoagulants drugs. It is therefore conceivable that anticoagulant therapies will be frequently associated with ART for the management of HIV patients, which already developed CVD. The interactions between these therapies are not well studied and are critical for the management of the HIV-infected patients.

Feasibility and challenges of addressing this CQ or CC

Feasibility: 1) retrospective studies on a large number of HIV patients that had cardiovascular events and were treated with antiretroviral drugs; 2) prospective studies comparing different antiretroviral regimens associated with the most current anticoagulant therapy recommended for secondary prevention of CV disease; 3) use of animal models of AIDS for testing new anticoagulants and the interaction with the antiretroviral drugs.

Name of idea submitter and other team members who worked on this idea Ivona Pandrea

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5 up votes
3 down votes
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Goal 3: Advance Translational Research

Leveraging PEPFAR infrastructure for CVDs

How do we go about leveraging existing infrastructure, such as PEPFAR, to reduce the risk of HLBS diseases among HIV patients and other vulnerable populations?

• Common goals and deliverables between NHLBI and partners will need to be identified
• The best return on investment of NHLBI funds will need to be determined
• Feasible T4 translation interventions in PEPFAR funded studies utilizing HIV populations with HLBS... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

• Decrease the burden of heart, lung, blood, and sleep diseases in studies funded by PEPFAR in HIV populations
• Lessons learned could be expanded to HIV populations outside of Africa
• T4 translation interventions in these populations could help reduce risk factors for heart, lung, blood, and sleep diseases leading to better health outcomes

Feasibility and challenges of addressing this CQ or CC

• PEPFAR has identified and recruited existing HIV populations in Africa which can be leveraged by NHLBI for heart, lung, blood, and sleep chronic disease research
• Infrastructure that has received PEPFAR investments can also be leveraged to undertake T4 translation interventions

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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Goal 3: Advance Translational Research

Translational Research for HIV/AIDS and HLB Health and Diseases

What are the best inroads for the NHLBI to support innovative approaches in the next 5-10 years, especially blood cell therapies based on hematopoietic stem cell and novel gene therapy approaches to control or even cure HIV infection?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

HIV control or possibly even HIV cure could result from developing novel cell therapies, especially hematopoietic stem cell (HSC) transplants, and might also result from early use of antiretroviral therapy in acutely HIV-infected individuals.
• Transplantation of HSC including engineered cells has the potential to eradicate HIV reservoirs for HIV cure: the Berlin patient treated with HSC transplant remains free of HIV and is still the only patient cured of HIV infection as of today;
• Identification of acute HIV infections through routine blood donor screening and early anti-retroviral therapy for identified HIV-infected donors can limit or even prevent the establishment of HIV reservoirs.

Feasibility and challenges of addressing this CQ or CC

• The Berlin patient has provided the proof of concept that HIV infection can be eradicated, that is, sterilizing cure can be achieved, through HSC transplantation in combination with other therapies;
• Recent studies have shown that early identification of HIV infection and treatment of infected individuals with anti-retroviral therapy as soon as possible can significantly limit the size of the HIV reservoirs even if such early treatment may not be able to completely prevent the establishment of HIV reservoirs; routine blood donor screening for both anti-HIV antibodies and HIV RNA among blood donors offers unique opportunities to identify acute HIV infections.

 

For HIV cure, the challenges include:

• Generation of HIV-resistant HSCs in adequate quantity for transplantation;

• Efficiency of homing and expansion of HIV-resistant HSC transplants;

• Efficiency in replacing HIV-infected cells, including CD4+ resting cells as the major HIV reservoirs, with HIV-resistant HSCs following transplantation;

• Efficiency in immune reconstitution by HSC transplants;

• Safety of HSC transplantation with needed GVHD to eliminate HIV-infected resting T cells while avoiding irreversible damage to the host.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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15 up votes
31 down votes
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Goal 2: Reduce Human Disease

Basic Research for HIV/AIDS and HLB Health and Diseases

What HIV/AIDS-related basic research can NHLBI support in the next 5-10 years to investigate the fundamental mechanisms of HIV-related heart, lung, and/or blood (HLB) diseases alone and in the context of antiretroviral therapy (ART) to improve heart, lung, and blood health outcomes in HIV infections as well as the fundamental mechanisms of hematopoietic stem cell transplantation in potential elimination or eradication... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Widespread availability of effective antiretroviral therapy (ART) has changed the epidemiology of AIDS. HIV-infected patients on ART can expect to live for many decades, but now chronic diseases are increasingly replacing acute infections as important causes of morbidity and death. A growing body of evidence suggests that HIV may alter and/or accelerate the natural history of fundamental processes underlying atherosclerosis, pulmonary arterial hypertension (PAH), chronic obstructive pulmonary disease (COPD), pulmonary co-infections, anemia, coagulation, thrombotic disorders, and immune senescence.

 

 

However, the mechanisms by which HIV and ART may modify these processes have not been fully elucidated, primarily because of the multiple direct and indirect pathways by which HIV and ART induce cellular dysfunction. Advancing knowledge of which cell types are affected by HIV (and serve as reservoirs), as well as increased understanding of the vital interactions between HIV and the host cells as well as interactions between HIV and other elements of the human virome and the broader microbiome is essential to elucidating the pathogenesis of HIV-related HLB diseases.
The use of basic research models will complement and extend the results of clinical studies.

Feasibility and challenges of addressing this CQ or CC

For HIV infection and heart, lung, and blood health and diseases:
• NHLBI investments in this aspect, including the three RFAs in 2014-2015, two on basic research and one on clinical research, have laid good foundation.
• Collaborations between HIV investigators and HLB investigators that have been facilitated by the NHLBI investments including the three RFAs.
• The Berlin patient has provided the proof of concept that HIV infection can be eradicated, that is, sterilizing cure can be achieved, through HSC transplantation in combination with other therapies.
• New technologies that have been developed recently, such as the deep sequencing techniques and research supported by the NIH Human Microbiome Program and other programs have allowed us to better understand microbiome, especially bacteria in and on humans, and we began to realize the magnitude of the human virome.

?

For HLB comorbidities of HIV infection, the challenges include:

• Closer collaboration between HIV investigators and HLB investigators;

• Leverage of resources available both in HIV research and in HLB research.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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-22 net votes
14 up votes
36 down votes
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Goal 2: Reduce Human Disease

Clinical Research for HIV/AIDS and HLB Health and Diseases

What HIV/AIDS-related clinical research can NHLBI support in the next 5-10 years on the prevention, diagnosis, and treatment of HIV-related heart, lung, and/or blood (HLB) diseases in adults and children to improve heart, lung, and blood health outcomes in HIV infections?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Remarkable progress in anti-retroviral therapy (ART) has increased survival in the HIV population and significantly reduced mother-to-child transmission of HIV both in resource-rich and resource-limited settings. However, this enhanced longevity is now associated with an increasing burden of chronic diseases, such as coronary artery disease (CAD), chronic obstructive pulmonary disease (COPD), and chronic anemia. In patients with HIV, there may be a complex interplay between the processes of inflammation, traditional risk factors, and the adverse effects of ART. Additionally, the long-term effects of in utero exposure to HIV and antiretroviral drugs in HIV-exposed but uninfected children on HLB diseases is unknown.
Furthermore, HIV control or possibly even HIV cure could result from developing novel cell therapies, especially hematopoietic stem cell (HSC) transplants, and might also result from early use of antiretroviral therapy in acutely HIV-infected individuals. Finally, other unique NHLBI research activities and resources could be leveraged for HIV/AIDS-related research.

Feasibility and challenges of addressing this CQ or CC

• Collaborations between HIV and HLB investigators that have been facilitated by the NHLBI investments, including three RFAs.

• The Berlin patient has provided the proof of concept that HIV infection can be eradicated, that is, sterilizing cure can be achieved, through HSC transplantation in combination with other therapies;

• Recent studies have shown that early identification of HIV infection and treatment of infected individuals with anti-retroviral therapy as soon as possible can significantly limit the size of the HIV reservoirs even if such early treatment may not be able to completely prevent the establishment of HIV reservoirs; routine blood donor screening for both anti-HIV antibodies and HIV RNA among blood donors offers unique opportunities to identify acute HIV infections.

• For other NHLBI research activities and resources that could be leveraged: data and specimens are available in the NHLBI repositories as well as repositories of NHLBI investigators.

 

For HLB comorbidities of HIV infection, the challenges include:

• Closer collaboration and leverage of resources available

For HIV cure, the challenges include:

• Generation of HIV-resistant HSCs in adequate quantity for transplantation;

• Efficiency of homing and expansion of HIV-resistant HSC transplants, replacing HIV-infected cells, and immune reconstitution by HSC transplants

• Safety of HSC transplantation with needed GVHD to eliminate HIV-infected resting T cells

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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33 down votes
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Goal 3: Advance Translational Research

New treatment for HIV and HIV-related lymphoma trending idea

Highly active antiretroviral therapy (HAART), while clearly invaluable, does not halt growth or proliferation of HL, in fact, while AIDS-defining malignancies like Kaposi’s sarcoma (KS) and non-Hodgkin’s lymphoma (NHL) have declined thanks to HAART, the incidence of HL in HIV patients has actually increased, from 14 times higher than that of non-HIV patients in the pre-HAART era to 32 times higher in the HAART era. Typical... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Today, approximately 10% (over 3.5 million worldwide) of HIV-infected patients develop lymphoma. The societal cost of HIV-related HL is particularly steep. HL patients are typically young (20s-30s), likely to actively spread virus, and without treatment, represent years of lost productivity.

Feasibility and challenges of addressing this CQ or CC

To this end, it is important to gather a team of collaborators from the fields of immunology, cancer, immunotherapy, and HIV. Through these combined expertise, we hope to lay the groundwork for novel, life-saving therapy for patients with HL in the problematic context of HIV viral infection.

Name of idea submitter and other team members who worked on this idea Dongfang Liu

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34 down votes
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Goal 2: Reduce Human Disease

Persistent Burden of HIV Infection on Lung Health in the U.S. and Globally

Despite the advent of HAART the lung and vascular compartment continue to bear the brunt of complications associated with HIV infection. Potential causes include the establishment of HIV latency in the lung, inability of current therapeutic agents to treat latent reservoirs, inadequate immune reconstitution in the lung, and persistent impairment of normal lung homeostasis after treatment (i.e. persistent alterations... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Lung disease remains a major contributor to HIV morbidity in the HAART era. In fact, the lung continues to bear the burden of chronic HIV complications. The cause of this is likely multifactorial, including:

  1. Persistence of HIV reservoirs. The lung is populated by long lived cells which makes them uniquely situated to serving as reservoirs. A better understanding of viral latency in the lung is needed.

  2. Inadequate immune reconstitution. This can lead to persistent increased risk to chronic infections and poor tumor surveillance. It is well recognized that earlier initiation of antiretroviral therapy, rather than waiting till immune exhaustion, leads to better immune reconstitution. Thus to improve lung immune reconstitution will need better approaches to diagnosing HIV early. Furthermore, studies are needed to better define when adequate lung immune reconstitution has occurred.

  3. Persistent abnormalities in normal lung homeostasis. Despite the absence of detectable replicating HIV in the lung there appears to be persistent alterations in the lung inflammatory state. Abnormalities in the lung microbiome and virome could also remain. Lastly, risk factors that may have contributed to HIV infection and lung disease in the first place (i.e. smoking, IVDU) persist in patients on therapy. Contributions of these risk factors towards lung disease in the HIV-infected population are sorely needed.

Feasibility and challenges of addressing this CQ or CC

Given the continued large burden of the HIV population in the U.S. and globally these studies are certainly feasible. One of the biggest challenges will be the identification of an appropriate control nonHIV-infected cohort that shares the same risk factors (i.e. smoking, IVDU) as the HIV-infected population. Historically this has been problematic given the known demographic differences in the HIV population (i.e. increased prevalence of smoking, greater male to female ratio, differences in other HIV risk factors). The second major challenge is the recognition that the new spectrum of lung complications in HIV-infection are chronic in nature and thus will require long term longitudinal studies to adequately assess the critical questions raised here. Finally, it must be recognized that the greatest burden of HIV infection lies outside our borders in third world countries. In addition to the high prevalence of HIV infection in these regions, the major infections complications, which have been largely controlled in the U.S. through early antiretroviral therapy, continue to play a major role in HIV morbidity and mortality. Thus one cannot forget that first and foremost untreated HIV infection leads to profound immunosuppression with an associated increased risk of usual and opportunistic infections.

Name of idea submitter and other team members who worked on this idea Homer L. Twigg III on behalf of the INHALD Consortium

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Goal 2: Reduce Human Disease

CVD as a comorbidity of HIV-1 Infection

Even in cART treated HIV-1 infected subjects, development of CVD is a major co-morbidity. Research is needed to evaluate the role of various biomarkers as well as anti-retrovirals .Role of ethnicity and gender also seems to be important. Since these persons are rather younger, Framingham concept may not applicable.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

there are about one million HIV-1 infected individuals in the U.S. more than 50% of them are at a risk to develop CVD despite their infection under control. If the risk factors are known, intervention can be introduced.

Feasibility and challenges of addressing this CQ or CC

Very much doable. It may be carried across the United States so that role of environments, ethnicity and dietary practices may also be taken into consideration.

Name of idea submitter and other team members who worked on this idea Mahendra Kumar, Debrah Jones Weiss

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11 up votes
14 down votes
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