HIV has increasingly become an infection of poverty. Adequate HIV transmission knowledge among HIV-positive patients is necessary to reduce the risk of secondary infection and protect those who are uninfected from transmission. This study was conducted among individuals enrolled in a program that serves impoverished HIV patients in the Boston area. Although the mean HIV transmission knowledge score was 80% for this group, a significant proportion of patients demonstrated limitations in knowledge of HIV transmission. Highly vulnerable patients, such as those who reported not accessing HIV medications, a history of sexual abuse, or problems getting clothing, had lower levels of HIV knowledge. This paper hopes to alert providers that their most vulnerable patients may be at an increased risk of re-infection or transmission due to limited HIV knowledge. Programs that serve HIV-positive patients coping with poverty and other serious problems need to ensure adequate knowledge of HIV transmission to reduce the overall burden of HIV in resource-poor settings.