Review Article | Published:

Pathogenesis of HIV-1 and Mycobacterium tuberculosis co-infection

Nature Reviews Microbiology volume 16, pages 8090 (2018) | Download Citation


Co-infection with Mycobacterium tuberculosis is the leading cause of death in individuals infected with HIV-1. It has long been known that HIV-1 infection alters the course of M. tuberculosis infection and substantially increases the risk of active tuberculosis (TB). It has also become clear that TB increases levels of HIV-1 replication, propagation and genetic diversity. Therefore, co-infection provides reciprocal advantages to both pathogens. In this Review, we describe the epidemiological associations between the two pathogens, selected interactions of each pathogen with the host and our current understanding of how they affect the pathogenesis of TB and HIV-1/AIDS in individuals with co-infections. We evaluate the mechanisms and consequences of HIV-1 depletion of T cells on immune responses to M. tuberculosis. We also discuss the effect of HIV-1 infection on the control of M. tuberculosis by macrophages through phagocytosis, autophagy and cell death, and we propose models by which dysregulated inflammatory responses drive the pathogenesis of TB and HIV-1/AIDS.

Key points

  • There were 1.14 million new cases of HIV-1 and tuberculosis (TB) co-infection and 400,000 deaths that were attributed to co-infection in 2015.

  • The risk of TB increases by 2–5-fold in early HIV-1 infection and by more than 20-fold in advanced HIV-1 disease. The risk of TB remains increased by approximately fourfold in patients infected with HIV-1 treated with antiretroviral therapy (ART).

  • HIV-1 infects CD4+ T cells and macrophages. Mycobacterium tuberculosis primarily infects macrophages, which require CD4+ T cells to augment intracellular clearance of microbial pathogens. Hence, the depletion of CD4+ T cells that is associated with HIV-1 infection is thought to have a major role in the increased risk of TB in individuals infected with HIV-1.

  • Co-infection of HIV-1 and M. tuberculosis at the level of individual macrophages may also occur but has not been demonstrated in vivo. This is important because experimental models show that HIV-1 infection of macrophages can attenuate phagocytosis and intracellular killing by the autophagy pathway.

  • Progressive HIV-1 disease and TB are both characterized by chronic inflammation driven by the failure to clear either pathogen. The chronic nature of these responses may undermine host protection by promoting an immunoregulatory phenotype that is characterized by attenuated T cell responses.

  • Advanced HIV-1 infection is associated with reduced immunopathology of TB co-infection, but the introduction of ART can exacerbate the immunopathology of TB, giving rise to immune reconstitution inflammatory syndrome (IRIS). This reflects recovery of innate immune inflammatory responses to M. tuberculosis, which may be exacerbated by the recirculation of M. tuberculosis-reactive T cells and failure of the normal homeostatic control of inflammatory responses.

  • The pro-inflammatory response to M. tuberculosis may exacerbate HIV-1/AIDS disease progression by increasing virus propagation through increased transcription and cell–cell transmission.

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L.C.K.B. was funded by a Medical Research Council Doctoral Training Award through the University College London MB PhD programme. M.N. is supported by a Wellcome Trust Investigator Award and National Institute of Health Research Biomedical Research Centre Funding to University College Hospitals National Health Service (NHS) Foundation Trust and University College London.

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  1. Division of Infection & Immunity, Cruciform Building, University College London, WC1E 6BT, London, UK.

    • Lucy C. K. Bell
    •  & Mahdad Noursadeghi


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L.C.K.B. and M.N. contributed to researching data for article. L.C.K.B. and M.N. substantially contributed to the discussion of content. L.C.K.B. and M.N. wrote the article. L.C.K.B. and M.N. reviewed and edited the manuscript before submission.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Mahdad Noursadeghi.


Acid-fast bacillus

A bacterium that is resistant to decolourization during laboratory staining procedures, which is a recognized property of mycobacteria. This arises due to the high mycolic acid content of the bacterial cell wall. Several diagnostic tests for tuberculosis rely on this property, including Ziehl–Neelsen staining.

Independent risk factor

A variable that improves the prediction of outcome in a statistical model that already includes other variables.

Lung apices

The upper lobe of each lung.

Pleural effusions

Accumulations of fluid in the pleural cavity, the anatomical compartment that surrounds the lungs. This can arise due to a range of causes, one of which is infections such as tuberculosis.


Anatomical locations beyond the thoracic cavity or lung.


Circulation of mycobacteria in the bloodstream, identified by culture of blood.


A genetically heterogenous population arising from a process of mutation and selection.

Viral rebound

Development of a detectable plasma viral load in an individual with HIV-1 following a period of virological suppression, typically associated with an interruption in antiretroviral therapy or the development of drug resistance.

Sentinel cells

Tissue-resident cells that initiate a host immune response.

T helper17 cells

CD4+ T helper cell subset that produces interleukin-17 (IL-17) on stimulation, which in turn has a canonical role in augmenting neutrophil responses to infection.

Resting T cells

T cells that have not been activated by binding of their cognate antigen to the T cell receptor or stimulation by mitogens.


Multimeric molecular complexes formed during innate immune signalling that activate caspase enzymes, control maturation of the pro-inflammatory cytokines interleukin-1β (IL-1β) and IL-18 and may lead to cell death via pyroptosis.


A specific cell death pathway triggered by activation of caspase 1.

Immune senescence

The observable decline in immune function associated with ageing.


Mechanisms by which the immune system self-regulates via negative feedback loops, for example, the production of immunosuppressive cytokines.


A cytoplasmic vesicle formed as a result of the cellular uptake of particles >0.75 μm in diameter.

Granulomatous pathology

Chronic inflammatory foci within tissues, primarily made up of a core of activated macrophages surrounded by CD4+ T cells.


The process by which dead or dying cells are cleared by phagocytosis.

Pulmonary cavitation

Formation of large airspaces in the lung parenchyma due to tissue destruction.

Pro-inflammatory cytokines

Extracellular signalling molecules secreted chiefly by immune cells, which induce cell-surface receptors to trigger inflammatory processes.


The antigenic epitopes most commonly targeted by the adaptive immune response.

Tuberculin skin test

(TST). Intradermal injection of a standardized preparation of a purified protein derivative of killed and homogenized Mycobacterium tuberculosis.

Necrotic granulomas

Granulomatous inflammation sites with a core of dead cells.

Bacillary load

The measurable quantity of bacteria within a host organism or sample.

Long terminal repeat

(LTR). Repetitive non-coding sequences at each end of the HIV-1 proviral DNA, which are formed during reverse transcription and have important roles in integration and regulation of viral gene expression.

Giant cells

Multinucleated cells derived from macrophages, typically found within granulomatous inflammation.

Sympatric speciation

The evolutionary process by which one species adapts to another with which it overlaps geographically.

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