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This thesis consists of a series of publications that address the emerging public health issues in the field of HIV/AIDS among men who have sex with men (MSM) in China. Men who have sex with men (MSM) in China are a population group particularly susceptible to HIV transmission and other sexually transmitted infections (STIs) but at the same time they are a hidden population due to social discrimination in Chinese society. The objectives of this thesis were to understand the past and current pattern of HIV epidemic and related risk behaviours of MSM, and estimate the HIV incidence among MSM in China through a modelling approach. This study first commenced with systematic reviews of all available Chinese and English literature and a series of meta-analyses to provide the best combined evidence on the trends of HIV epidemic and high-risk behavioural patterns in Chinese MSM. The second section of this study involved two empirical studies to investigate the HIV disease burden and behaviours among MSM particularly in a rural Chinese setting. Qualitative approach was used to explore the pattern and underlying causes of high-risk sexual practices and multiple sexual identities among MSM. Lastly, based on a mathematical model, this study examined the likelihood of HIV transmission (e.g. HIV incidence) through homosexual intercourses among MSM. As bisexual behaviour is also common among Chinese MSM, this model was then extended to examine HIV transmission to their female sex partners. This study represents an unprecedented and comprehensive integration of China’s HIV epidemiological and behavioural data. It provides strong evidence that HIV epidemic among MSM has been increased rapidly and became the dominant mode of HIV transmission in China. The HIV epidemic in China has clearly entered a new phase of transmission and will demand appropriate changes in its health policies and prevention strategies.

In order to survive in its host, M. tuberculosis must be able to survive and thrive in the in vivo milieu. M. tuberculosis has evolved many virulence factors to deal with the host response to infection. One important element is the MmpL family of proteins. Several of the MmpLs are required for virulence. The mmpL4- mutant has the most severe defect of all the mmpL- mutants, but the cause of the defect is unknown. Interestingly, the in the absence of interferon-γ, the mmpL4- mutant has no virulence defect, suggesting that the function of MmpL4 is to counteract a host immune response. Our work has revealed that MmpL4, an RND-like efflux pump, is required for virulence by conferring resistance to 4-cholestene-3-one (4c3), a toxic metabolite of cholesterol metabolism. Interestingly, both MmpL4 and cholesterol metabolism are only required when the host interferon-γ signaling pathway is intact. MmpL4 is a member of a family of related lipid transporters called the MmpLs (Mycobacterial Membrane Protein - Large). This family is homologous to the RND family of transporters found across all kingdoms of life. Several members of the MmpLs have been shown to secrete specific lipids important for virulence. We initially believed this to be the case for MmpL4, but repeated attempts to identify differences in lipid composition in MmpL4- mutant cells were fruitless. We discovered that MmpL4 is only required when host interferon-γ signaling is intact and that this is due to increased toxicity of the mmpL4-γ mutants to 4c3. In addition to 4c3, mmpL4- cells are more sensitive to a variety of xenophobic compounds, raising the possibility that MmpL4 secretes other toxic compounds M. tuberculosis encounters in the host