New developments in the biology and treatment of HIV
- *Infectious Disease Laboratory, Salk Institute, 10010 North Torrey Pines Road, La Jolla, CA 92037; †Aaron Diamond AIDS Research Center, 455 1st Avenue, 7th Floor, New York, NY 10016; and ‡Merck Research Laboratories, Antiviral and Vaccine Research, 770 Summeytown Pike, WP16-225, West Point, PA 19486
The last 2 years have seen tremendous advances in the ability to treat HIV type 1 (HIV-1) infection, fueled in part by new discoveries on the biology of the virus. Many patients have gained years of life thanks to the introduction of new treatment regimens. Nonetheless, much remains to be accomplished. The newer anti-HIV-1 regimens do not fully eliminate the virus infection, thereby requiring lifelong treatment. Although the new therapies have had considerable impact in the developed world, they are difficult to apply in the developing world where HIV-1 infection is the most devastating. In addition, the emergence of viral variants resistant to the available treatments drives the need to discover new therapeutic agents. Here we describe the advances that have led to the dramatically improved therapy and discuss recent findings in HIV-1 biology that may lead to new anti-viral agents.
HIV-1 Infection and AIDS
Until about 2 years ago, medical science could offer little to alter the course of HIV-1 infection. After initial transmission of HIV, viral particles accumulate in blood to high levels within a few weeks, but levels then fall concomitant with the onset of the host immune response. Thereafter, the disease usually remains quiescent for a prolonged period, often for years or even decades, a phase termed clinical latency.
During this period, the number of cells bearing the CD4 protein on their surfaces (CD4+ cells) declines at a slow rate because of killing by HIV. The CD4 protein itself is an essential element of signaling pathways regulating immune responses to infection. CD4+ cells are important components of the immune system. Many CD4+ cells circulate in blood and are normally present at about 1,000 per microliter of blood plasma. HIV replicates in CD4+ cells, killing them in the process. Over time the number of CD4+ cells …
