One hundred twenty-three subjects with documented HIV-1 primary infection were followed for over a year; 96 received highly active antiretroviral therapy (HAART) at recruitment; 27 declined treatment. Fifty uninfected subjects served as baseline controls. HIV-1 viral load, CD4 and CD8 T cell numbers, and serologic changes to Epstein-Barr virus (EBV), human herpesvirus 6 (HHV-6), human herpesvirus 8 (HHV-8), and cytomegalovirus (CMV) were monitored. Although responses to HAART varied, herpesvirus reactivation frequencies did not differ relative to HIV-1 virologic responses. Forty-seven subjects had reactivations to a single herpesvirus type and 12 subjects to > or =2 types; no single herpesvirus dominated. Antibody seroprevalence to EBV, HHV-6, and CMV were similar but HHV-8 infection was twice as prevalent in HIV-1-infected vs. uninfected individuals. Notably, lower HIV-1 viremia (7,313 vs. 55,548 geometric mean RNA copies/ml) at baseline was significantly associated with HHV-8 seropositivity (p < 0.004).