From the University of California, San Francisco, and San Francisco General Hospital.
Edited by Ronna Henry Siegel, MD, JAMA Fishbein Fellow.
ALTHOUGH progress against the human immunodeficiency virus (HIV) over
the past year has been real and dramatic, the limitations of current antiretroviral
therapy are now beginning to be appreciated. In this brief assessment of HIV
treatment, we focus on recent advances in antiretroviral therapy, new insights
into the pathogenesis of HIV disease, and the implications for clinical practice.
In 1996, scientists began to explore the feasibility of HIV eradication
in infected patients. This provocative speculation was based on the assumption
that cellular reservoirs of HIV have a short half-life and that they are reached
by current drugs. Theoretically, if aggressive interventions could completely
prevent de novo infection of cells, then therapy could be safely discontinued
after all currently infected cells had died. Mathematical models predicted
that this goal could be achieved in 1 to 3 years, especially for patients
who initiated therapy during acute, primary infection. This optimism has been
challenged by several recent observations, including reports that a small
proportion of resting CD4 memory cells from treated patients with undetectable
plasma HIV RNA levels harbor integrated replication competent HIV proviral
DNA, and that the half-life of these cells may be on the order of months to
Volberding PA, Deeks SG. Antiretroviral Therapy for HIV InfectionPromises and Problems. JAMA. 1998;279(17):1343-1344. doi:10.1001/jama.279.17.1343