HIV This Week

Cadogan M, Dalgleish AG. HIV immunopathogenesis and strategies for intervention. Lancet Infect Dis. 2008;8(11):675-84

Therapeutic options aimed at tackling the HIV pandemic face many obstacles. The lack of readily accessible and affordable therapies means that most of those affected go untreated. The array of escape mechanisms used by HIV has undermined the efficiency of many antiviral products and continually represents a barrier to the development of an effective vaccine. Recent developments have seen a shift away from a cytopathic viral model of HIV pathogenesis towards the crucial role of immunopathogenic features-notably generalised immune activation-in the development of AIDS. As conventional vaccine strategies have sought to promote viral neutralisation and suppressive cellular responses, novel strategies that aim to address HIV immunopathogenesis should be sought. We review current opinion on HIV-induced pathogenic immune activation and strategies aimed at eliminating HIV, including a potential role for non-neutralising antibodies as part of a therapeutic vaccine option.

Editors’ note: Current HIV treatment focuses on interrupting the viral life-cycle using long-term reduction of viral load as a measure of success. Despite complete viral suppression, chronic generalised immune activation can persist with resultant progression to AIDS. Although HIV is well adapted to humans, taking advantage of cellular machinery for replication and transmission while using a number of immune evasion strategies, it provokes immune activation. This inadvertently benefits HIV because activated lymphocytes are its preferential targets. After reading this review, which has good tables and coloured graphics of virus-lymphocyte interactions, you will be hard pressed not to be convinced that more effort should be devoted to understanding and minimising HIV immunopathogenesis.