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Alveolar macrophages (AMs) are the most abundant cell type in the lung airspace and are a primary line of defense against airborne pathogens. AMs from people with untreated HIV have impaired function which is believed to contribute to the increased susceptibility to active tuberculosis (TB) seen in this population. The lung is an early site of HIV replication and HIV RNA and DNA have been detected in AMs in the initial stages of infection, even though HIV at this stage does not enter macrophages efficiently in vitro. The mechanism of entry of HIV into AMs is unknown, and so are the impacts of untreated HIV infection on macrophage susceptibility to active TB. We performed bronchoscopy in HIV-infected antiretroviral therapy (ART)-naïve or uninfected control subjects living in South Africa. We isolated primary HIV envelope RNA sequences from AMs and plasma and used them to produce replication-competent …