Antibody responses in primary HIV-1 infection.
OBJECTIVE
HIV-1 establishes persistent infections characterized by high levels of viral replication. This finding is remarkable given the presence of apparently vigorous HIV-specific cellular and humoral immune responses. We review the dynamics of antibody responses and viral escape from these responses during primary HIV-1 infection.


RESULTS
Many B cell dysfunctions appear early in HIV-1 infection, and compromise humoral responses to HIV-1 and other pathogens. The rate of viral escape from autologous neutralization varies greatly between individuals with primary HIV-1 infection, and is on average higher than the rate of escape in chronically infected individuals. Mutations, changes in glycosylation and insertions and deletions in the viral envelope may all contribute to viral escape. There may be differences in neutralization sensitivity and evolution of neutralization escape between different HIV-1 subtypes. Although several broadly neutralizing monoclonal antibodies have been identified, the factors that contribute to the development of broad heterologous responses remain unclear.


CONCLUSIONS
The rapid escape of HIV-1 in response to neutralizing antibodies and the plethora of B cell dysfunctions that occur during HIV infection pose significant obstacles to the design of an effective HIV-1 vaccine. The study of large cohorts of individuals enrolled during primary HIV-1 infection using high-throughput immunoassays, sequencing of the virus and the host, and new statistical tools may help to elucidate the pathways of viral escape, to elicit broadly neutralizing antibody responses, and to suggest means of minimizing the impact of HIV-1 on humoral immunity.
Department of Pathology, University of California, San Diego, California, USA. sdfrost@ucsd.edu
Simon D W
SD
Frost
Alexandra
A
Trkola
Huldrych F
HF
Günthard
Douglas D
DD
Richman