Modelling HIV and MTB Co-Infection Including Combined Treatment Strategies

Santosh Ramkissoon,Alan P. Matthews,Henry G. Mwambi,Edward Goldstein

doi:10.1371/journal.pone.0049492

Abstract

A new host-pathogen model is described that simulates HIV-MTB co-infection and treatment, with the objective of testing treatment strategies. The model includes CD4+ and CD8+ T cells, resting and activated macrophages, HIV and Mycobacterium tuberculosis (MTB). For TB presentation at various stages of HIV disease in a co-infected individual, combined treatment strategies were tested with different relative timings of treatment for each infection. The stages were early HIV disease, late HIV disease and AIDS. The main strategies were TB treatment followed by anti-retroviral therapy (ART) after delays of 15 days, 2 months and 6 months. ART followed by TB treatment was an additional strategy that was tested. Treatment was simulated with and without drug interaction. Simulation results were that TB treatment first followed by ART after a stage-dependent delay has the best outcome. During early HIV disease a 6 month delay is acceptable. During late HIV disease, a 2 month delay is best. During AIDS it is better to start ART after 15 days. However, drug interaction works against the benefits of early ART. These results agree with expert reviews and clinical trials.

Highlights

In many developing countries, most notably in Africa where the HIV epidemic is severe, individuals infected with HIV are initiated on anti-retroviral therapy (ART) only when their CD4+ T cell count is below 200 per mm3
After ART the recovery of the immune system may result in Immune Reconstitution Inflammatory Syndrome (IRIS) which is especially problematic for an individual with TB
Time t is measured in years, with HIV infection started at t = 0 by setting viral load V = 0.1 mm23

Summary

Introduction

Most notably in Africa where the HIV epidemic is severe, individuals infected with HIV (human immunodeficiency virus) are initiated on ART (antiretroviral therapy) only when their CD4+ T cell count is below 200 per mm. Most notably in Africa where the HIV epidemic is severe, individuals infected with HIV (human immunodeficiency virus) are initiated on ART (antiretroviral therapy) only when their CD4+ T cell count is below 200 per mm3 At this stage an HIV-infected individual is likely to be co-infected with Mycobacterium tuberculosis (MTB) due to a new MTB infection or latent MTB re-activated due to a weakened immune system. Severe side effects may compromise strict adherence to the drug regime resulting in sub-optimal treatment and development of drug-resistant strains of both MTB and HIV, and accelerated progression of both diseases. After ART the recovery of the immune system may result in Immune Reconstitution Inflammatory Syndrome (IRIS) which is especially problematic for an individual with TB

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