Background. Disease progression and transmission of human immunodeficiency virus (HIV) type 2 are attenuated, compared with HIV-1, which is consistent with the lower plasma viral loads observed in HIV-2 infection. Although numerous studies have characterized the intrapatient evolution of viral sequences during HIV-1 infection, prospective studies examining intrapatient evolution during HIV-2 infection have been limited.Methods. We examined viral sequence evolution in the C2V3C3 region of the viral env gene in 8 HIV-2-infected individuals from Dakar, Senegal, over the course of approximately 10 years. To compare results with HIV-1 infection, we reanalyzed data from our previous study that prospectively examined intrapatient viral evolution in HIV-1-infected individuals from the same population.Results. HIV-2 sequences from early and late time points were phylogenetically intermixed for all subjects. No distinct trends were observed in terms of increases or decreases in fragment size or the number of N-linked glycosylation sites, and ratios of synonymous substitutions per synonymous site to nonsynonymous substitutions per nonsynonymous site suggested selection to be neutral or negative. In homologous env C2V3 sequences, rates of viral divergence and diversification were slower in individuals infected with HIV-2 than in those infected with HIV-1.Conclusions. Viral evolution occurs slowly in HIV-2 infection, which is consistent with the slow disease progression of HIV-2 and supports the notion that viral evolution may be a relevant correlate for disease progression.