25 years of HIV-1 research – progress and perspectives

The first cases of acquired immunodeficiency syndrome (AIDS) were described in homosexual men in the US in 1981 [1]. Several years later in 1983 and 1984, respectively, French and American scientists confirmed that the causative agent for AIDS was a retrovirus, the human immunodeficiency virus (HIV) [2-4]. Today, 25 years after the isolation of HIV-1, approximately 25 million individuals have died from AIDS, a number exceeding by 60 times the total number of American casualties in World War II; and over 33 million people globally are infected and living with HIV-1. In 2007, 2.7 million individuals became newly infected with HIV-1, and 2 million AIDS deaths occurred [5]. Regrettably, half of all people who are infected with HIV acquire the infection before the age of 25 years, and are killed by AIDS before they turn 35. More than 95% of new HIV-1 infections arise in low and middle income nations, populations least likely to have access to antiretroviral therapy. In the face of these daunting statistics and an unabated pandemic, we look back on progress achieved in HIV-1 research, treatment, and policies, and look forward to the challenges that confront AIDS scientists, clinicians and decision-makers for the next 25 years.The basic research of HIV has made great strides over the past quarter century. Key discoveries, reviewed here in brief, have clarified the intricate steps used by the virus from entry into and exit from the cell (Figure 1). HIV-1 is an enveloped virus with glycoproteins on its surface [6,7], responsible for viral entry into cells. The cell's primary receptor for the virus is the CD4 molecule, and its co-receptors are members of a family of chemokine receptors [8,9]. Using the different co-receptors, HIV-1 can differentially infect T-lymphocytes and/or macrophages [10,11].Entry of the virus into the cytoplasm initiates the disassembly of the HIV core. At this juncture, the virus can be susceptible to intrinsic cellular antiviral mechanisms which incl