Roger J Pomerantz; David L Horn


Nat Med. 2003;9(7) 

In This Article

Abstract and Introduction

Antiretroviral therapy, where available, has transformed HIV-1 disease into a treatable and somewhat chronic infection. This article summarizes the accomplishments thus far and what lies ahead in our struggle to improve the treatment of, and possibly eliminate, HIV-1 infection.


In the 20 years since the isolation of HIV-1, modern drug discovery and development have transformed HIV-1 disease into a treatable, chronic infectious disease ( Table 1 ), although issues of resistance to current therapy and viral reservoirs remain. The speed of the US Food and Drug Administration (FDA) approval of new agents ( Table 2 ) and the pace of drug development, with the likely introduction of therapeutics targeting different components of the HIV-1 replication cycle, have quickened (Fig. 1). It is therefore an opportune time to reflect on what has been accomplished and how far we must go.

Figure 1.

HIV-1 life cycle. Text in red refers to targets inhibited by existing agents approved by the FDA. Text in blue refers to targets that are inhibited by agents that are likely to be available in the near future. After binding and fusing to the surface of the host cell, the HIV-1 core enters the host cell. Reverse transcriptase synthesizes proviral double-stranded DNA, which is transported to the nucleus. Integration occurs and the ensuing provirus expresses viral RNA that will synthesize viral proteins using the host's ribosomes. New virions are created by assembly and budding through the infected cell membrane and subsequent maturation due to the actions of protease. This figure is modified from Ref. 87.