Co-Infection with TB and HIV: Converging Epidemics, Clinical Challenges, and Microbial Synergy

Huante, Matthew B.; Nusbaum, Rebecca J.; Endsley, Janice J.

doi:10.1007/978-3-030-25381-3_7

Cited by 8 publications

(2 citation statements)

References 219 publications

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“…J. Endsley has employed the BLT humanized mouse model for studying the complex molecular and immunological interactions of HIV/TB co-infection [ 31 - 33 ]. BLT mice develop poorly organized necrotic granulomas in response to Mtb infection.…”

Section: Session 3: Mycobacterium Tuberculosis (Mtmentioning

confidence: 99%

Small Animal Models for Human Immunodeficiency Virus (HIV), Hepatitis B, and Tuberculosis: Proceedings of an NIAID Workshop

Akkina

Barber

Bility

et al. 2020

CHR

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The main advantage of animal models of infectious diseases over in vitro studies is the gain in the understanding of the complex dynamics between the immune system and the pathogen. While small animal models have practical advantages over large animal models, it is crucial to be aware of their limitations. Although the small animal model at least needs to be susceptible to the pathogen under study to obtain meaningful data, key elements of pathogenesis should also be reflected when compared to humans. Well-designed small animal models for HIV, hepatitis viruses and tuberculosis require, additionally, a thorough understanding of the similarities and differences in the immune responses between humans and small animals and should incorporate that knowledge into the goals of the study. To discuss these considerations, the NIAID hosted a workshop on ‘Small Animal Models for HIV, Hepatitis B, and Tuberculosis’ on May 30, 2019. Highlights of the workshop are outlined below.

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Section: Session 3: Mycobacterium Tuberculosis (Mtmentioning

confidence: 99%

Small Animal Models for Human Immunodeficiency Virus (HIV), Hepatitis B, and Tuberculosis: Proceedings of an NIAID Workshop

Akkina

Barber

Bility

et al. 2020

CHR

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“…In endemic regions, the potential for HIV-associated factors to impact treatment is even greater for those undergoing drug therapy for multi-drug resistant TB due the 18-24 month treatment period (Falzon et al, 2017). The strong association between TB and HIV includes biological mechanisms of pathogen synergy as well as many non-biological factors (e.g., socioeconomic) and clinical issues as recently reviewed (Huante et al, 2019). A greater understanding of the complex interplay between Mtb and HIV in the setting of in vivo drug treatment is needed to inform development of new approaches to reduce TB relapse.…”

Section: Introductionmentioning

confidence: 99%

Small Animal Model of Post-chemotherapy Tuberculosis Relapse in the Setting of HIV Co-infection

Huante

Saito

Nusbaum

et al. 2020

Front. Cell. Infect. Microbiol.

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Tuberculosis relapse following drug treatment of active disease is an important global public health problem due to the poorer clinical outcomes and increased risk of drug resistance development. Concurrent infection with HIV, including in those receiving anti-retroviral therapy (ART), is an important risk factor for relapse and expansion of drug resistant Mycobacterium tuberculosis (Mtb) isolates. A greater understanding of the HIV-associated factors driving TB relapse is important for development of interventions that support immune containment and complement drug therapy. We employed the humanized mouse to develop a new model of post-chemotherapy TB relapse in the setting of HIV infection. Paucibacillary TB infection was observed following treatment with Rifampin and Isoniazid and subsequent infection with HIV-1 was associated with increased Mtb burden in the post-drug phase. Organized granulomas were observed during development of acute TB and appeared to resolve following TB drug therapy. At relapse, granulomatous pathology in the lung was infrequent and mycobacteria were most often observed in the interstitium and at sites of diffuse inflammation. Compared to animals with HIV mono-infection, higher viral replication was observed in the lung and liver, but not in the periphery, of animals with post-drug TB relapse. The results demonstrate a potential role for the humanized mouse as an experimental model of TB relapse in the setting of HIV. Long term, the model could facilitate discovery of disease mechanisms and development of clinical interventions.

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Computational design of MmpL3 inhibitors for tuberculosis therapy

et al. 2022

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Co-Infection with TB and HIV: Converging Epidemics, Clinical Challenges, and Microbial Synergy

Cited by 8 publications

References 219 publications

Small Animal Models for Human Immunodeficiency Virus (HIV), Hepatitis B, and Tuberculosis: Proceedings of an NIAID Workshop

Small Animal Models for Human Immunodeficiency Virus (HIV), Hepatitis B, and Tuberculosis: Proceedings of an NIAID Workshop

Small Animal Model of Post-chemotherapy Tuberculosis Relapse in the Setting of HIV Co-infection

Computational design of MmpL3 inhibitors for tuberculosis therapy

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