Among rural populations in Cameroon, HIV-1 prevalence is low and the genetic diversity broad. An unusual population-level genetic background may modulate this pattern of HIV infection. We examined HIV-1 prevalence, CCR5Δ32 and CCR5 promoter −2459 G genotype frequency among 1390 rural inhabitants. No individual was identified with the CCR5Δ32 allele, but homozygotes for the CCR5 promoter variant −2459G (27.5%) were relatively common. A seroprevalence of 3.1% of HIV-1 was reported.