There indeed seems to be a new mood of optimism in researchers and clinicians studying HIVs and patients infected with these viruses. A new understanding of the virology, biology, and therapy of HIV-1 includes the following: (1) The level of HIV-1 viremia, as measured by the HIV-1 plasma RNA, is a critical determinant of the time to development of AIDS and death. (2) Lessons from nonprogressors or long-term survivors, who do not develop AIDS or immune impairment despite their long-term infection, show clearly that the HIV-1 replication is significantly lower (4 to 20 times) than in people with progressive disease, and there is a vigorous and specific immune response against HIV-1. (3) Reducing viremia with antiretroviral drugs can delay the onset of AIDS and prolong survival. (4) Combination drug therapies, including an RT inhibitor and a PR inhibitor, can lower viremia to undetectable levels and delay the development of drug-resistant HIV-1. (5) HIV-1 subgroups have marked geographically distinct distributions, which may specify the routes of infection in different populations at risk.