Latency in Human Immunodeficiency Virus Type 1 Infection: No Easy Answers

In summary, HIV-1 latency represents a formidable therapeutic challenge for which there are no easy answers. As a result of viral tropism for activated CD4+ T cells and the reversion of some of these cells to a profoundly quiescent and long-lived memory state, the virus can persist through the same mechanisms responsible for the most fundamental characteristic of the immune system, immunologic memory. The dependence of viral gene expression on host factors that are inactive in resting T cells means that viral gene expression can be largely or completely extinguished in latently infected cells. In the absence of virus gene expression, latently infected cells will differ from their uninfected counterparts by only the presence of 10 kb of viral DNA integrated into a host cell chromosome. In this case, the virus is persisting as genetic information in a stably integrated form in rare memory cells that cannot be distinguished from their uninfected counterparts. It is difficult to envision any targeting mechanism that will allow specific elimination of this reservoir. Optimism stems from the fact that antiretroviral drugs come very close to stopping the active replication of the virus, with its attendant damage to the immune system. In some patients on HAART, the evolution of drug-resistant viruses, which is the principal cause of treatment failure, is largely halted. The development of nontoxic, convenient, and affordable combinations of antiretroviral drugs may allow infected individuals to live a normal life despite the indefinite persistence of latent HIV-1 in resting memory CD4+ T cells.