Different HIV strains in one individual that recombine (red/blue overlap) at immune-targeted sites escape T cell attack.

Most HIV-infected individuals initially develop a strong CD8⁺ T cell response against multiple epitopes, including those found within HIV's Gag and Env proteins, some of which eventually develop escape mutations. In one HIV-infected individual, the authors found, new CD8⁺ T cells quickly developed against such mutated epitopes while the original T cells waned. Viral levels remained low in the patient, suggesting that the variant-specific T cells controlled the mutant HIV strain.

But this control was broken by an apparent second infection in the individual. Soon after it entered the host, the second strain recombined with the first. In the resulting strain, the authors found switched sequences at the immune-targeted Gag and Env sites. The switch provided the new strain with the original version of the first, before the escape mutations occurred. This allowed viral levels to reach an all-time high by facilitating viral escape from the CD8⁺ T cell responses that were dominant prior to the second infection. The second strain might distinguish between available strains and choose the right one for recombination. More likely, however, viruses lucky enough to acquire the right bits of Gag or Env might simply be spared by the weakened T cell response.

CD8⁺ T cells were eventually regenerated against the switched epitopes, and viral levels decreased. But this control was also short lived; a second recombination event at the same regions—this time with the mutated version of the first strain—raised viral levels. The findings suggest that, like escape mutations, recombination is a trick that HIV uses to stay a step ahead of the immune system.