The immune response to HIV

HIV infects CD4+ T lymphocytes and, to a lesser extent, other cells expressing the CD4 molecule such as macrophages and dendritic cells. Chronic infection is characterized by progressive loss of CD4 T cells in the face of a vigorous but ultimately ineffective immune response. At a critical threshold of < 200 CD4+ T cells/µl in the circulation, infected individuals have a markedly increased risk of developing opportunistic infections and cancers. Over the last 20 years, extensive studies of HIV-infected persons and of simian immunodeficiency virus-infected monkeys have helped to elucidate the mechanisms underlying the failure of the immune system to clear these retroviruses. A delayed and ineffectual neutralizing antibody response permits establishment of persistent infection; incomplete suppression of virus replication by cellular immune responses, probably because of early loss of CD4 T cell help, allows virus escape mutants to emerge. The lack of an immune correlate of protection is a major obstacle to the development of an effective prophylactic vaccine. However, this remains an urgent priority, because readily available preventive strategies have not been adequate to contain the global epidemic, and current antiretroviral drugs control, but do not eradicate HIV infection. It is hoped that this goal will be attained through a better understanding of the immune response to HIV.