This journal article argues that people living with HIV/AIDS (PLWHA) have weakened physiological responses and are immunologically vulnerable to pathogens and stressors in their environment, putting them at a health disadvantage in climate-based rising temperatures, water scarcity, air pollution, potential water- and vector-borne disease outbreaks, and habitat redistributions. It is argued that coupled with HIV/AIDS, climate change threatens ecological biodiversity via a larger-scale socioeconomic recourse to natural resources. Corresponding human and environmental activity shape conditions conducive to exacerbating high rates of HIV/AIDS. In South Africa, this epidemic is forming a ‘syndemic’ with tuberculosis (TB), which has come to include multidrug-resistant TB (MDR-TB) and extremely drug-resistant TB (XDR-TB) strains. The paper argues that, because of high convergence rates, one epidemic cannot be addressed without understanding the other.