HIV-1 eradication strategies: Design and assessment

PURPOSE OF REVIEW: Recent developments have generated renewed interest in the possibility of curing HIV-1 infection. This review describes some of the practical challenges that will need to be overcome if curative strategies are to be successful. RECENT FINDINGS: The latent reservoir for HIV-1 in resting memory CD4 T cells is the major barrier to curing the infection. The most widely discussed approach to curing the infection involves finding agents that reverse latency in resting CD4 T cells, with the assumption that the cells will then die from viral cytopathic effects or be lysed by host cytolytic T lymphocytes (CTLs). A major challenge is the development of in-vitro models that can be used to explore mechanisms and identify latency-reversing agents (LRAs). Although several models have been developed, including primary cell models, none of them may fully capture the quiescent state of the cells that harbour latent HIV-1 in vivo. An additional problem is that LRAs that do not cause T-cell activation may not lead to the death of infected cells. Finally, measuring the effects of LRAs in vivo is complicated by the lack of correlation between different assays for the latent reservoir. SUMMARY: Progress on these practical issues is essential to finding a cure.