During chronic infection, HIV-1 engages in a rapid coevolutionary arms race
with the host's adaptive immune system. While it is clear that HIV exerts
strong selection on the adaptive immune system, the characteristics of the
somatic evolution that shape the immune response are still unknown. Traditional
population genetics methods fail to distinguish chronic immune response from
healthy repertoire evolution. Here, we infer the evolutionary modes of B-cell
repertoires and identify complex dynamics with a constant production of better
B-cell receptor mutants that compete, maintaining large clonal diversity and
potentially slowing down adaptation. A substantial fraction of mutations that
rise to high frequencies in pathogen engaging CDRs of B-cell receptors (BCRs)
are beneficial, in contrast to many such changes in structurally relevant
frameworks that are deleterious and circulate by hitchhiking. We identify a
pattern where BCRs in patients who experience larger viral expansions undergo
stronger selection with a rapid turnover of beneficial mutations due to clonal
interference in their CDR3 regions. Using population genetics modeling, we show
that the extinction of these beneficial mutations can be attributed to the rise
of competing beneficial alleles and clonal interference. The picture is of a
dynamic repertoire, where better clones may be outcompeted by new mutants
before they fix