Host genetic variation modifying HIV-1 acquisition risk can inform development of HIV-1 prevention strategies. However, associations between rare or intermediate-frequency variants and HIV-1 acquisition are not well studied. We tested for the association between variation in genic regions and extreme HIV-1 acquisition phenotypes in 100 sub-Saharan Africans with whole genome sequencing data. Missense variants in immunoglobulin-like regions of CD101 and, among women, one missense/5' UTR variant in UBE2V1, were associated with increased HIV-1 acquisition risk (p = 1.9x10-4 and p = 3.7x10-3, respectively, for replication). Both of these genes are known to impact host inflammatory pathways. Effect sizes increased with exposure to HIV-1 after adjusting for the independent effect of increasing exposure on acquisition risk.