HIV-1 infection disproportionately affects women in sub-Saharan Africa, where areas of high HIV-1 prevalence and Schistosoma haematobium endemicity largely overlap. Female genital schistosomiasis (FGS), caused most frequently by S. haematobium egg deposition in the genital tract, has been associated with prevalent HIV-1 infection in cross-sectional studies. The presence of S. haematobium eggs in genital tissue is also associated with vascularization and the accumulation of CD4+ lymphocytes and macrophages, making the granuloma-associated environment a potential contributor to HIV-1 vulnerability. In addition to modulation of the local cervicovaginal environment, FGS has also been associated with a higher frequency of systemic CD4 T-cells expressing the chemokine receptor CCR5. Tissue-entrapped eggs are also associated with clinically visible FGS-associated manifestations in the cervicovaginal mucosa. FGS lesions may breach the intact cervicovaginal immune barrier and are hypothesized to provide an entry point for HIV-1 infection. However, the underlying mechanism for potential HIV-1 vulnerability in FGS has not been fully characterized and requires further investigation.