Viral evolution and escape during primary human immunodeficiency virus-1 infection: implications for vaccine design

Purpose of review The ability of human immunodeficiency virus to mutate rapidly to evade host immune pressures is a key hurdle limiting the control of human immunodeficiency virus-1 by cellular immune responses. Viral escape from CD8(+) T-cell recognition continues to be studied extensively, and emerging data provide greater appreciation of the affect of these mutations on the virus. These data may help identify key immune responses capable of suppressing viral replication. This goal remains critical, as current vaccines are unlikely to produce protective T-cell immunity. Recent findings Recent studies provide greater understanding of the propensity for transmitted mutations to revert, and of the ability of CD8(+) T-cell escape mutations to impact viral replication capacity and protein structure. These observations reveal important constraints on virus evolution and sequence diversity. Data are also accumulating for the ability of the immune system to mount de-novo CD8(+) T-cell responses against escape variants, revealing an underappreciated complexity of the process of viral escape. Summary Understanding the limits of sequence variation and the impact of immune escape mutations on viral fitness, particularly during acute infection, will be critical to guide the design of contemporary vaccines or therapeutics attempting to force human immunodeficiency viruses to become less fit.