Fig. 4. Predominance of negative epistasis between beneficial HIV-1 mutations.

a, Comparison of inferred epistatic interactions, ${\widehat{\mathit{s}}}_{ij}$, and the corresponding sum of individual selection coefficients, ${\widehat{\mathit{s}}}_i+{\widehat{\mathit{s}}}_j$, in a typical case (700010077-3; see Supplementary Fig. 2 for all individuals). Generically, we find negative correlations between inferred epistatic interactions and selection coefficients. CTL escape mutations are typically found to be both strongly beneficial and to have negative epistatic interactions with other escape mutations. b, Distribution of inferred epistatic interactions across all individuals. Most terms are near zero, but a few epistatic interactions are significantly negative.