OBJECTIVE: In the pre-HAART period, HIV-1 patients were greatly at risk for cytomegalovirus (CMV) disease. In HAART-treated patients, the incidence of CMV disease has decreased dramatically and the timing and presentation of CMV infection may be different. Also the relevance of different CMV genotypes is part of debate. DESIGN AND METHODS: A total of 132 antiretroviral naive patients starting HAART were selected for a 2-year follow-up study in the Netherlands. RESULTS: In 105 (80%) patients, CMV DNA were less than 100 copies/ml in all plasma samples during follow-up. In 27 (20%) patients, a detectable CMV load was found during follow-up. In seven patients, the initial decrease in HIV-1 loads during HAART was accompanied by an increase in CMV loads. Of 1348 plasma samples, only 50 (3.7%) samples were positive with a CMV load more of than 100 copies/ml plasma. CMV loads more than 1000 copies/ml were found only in samples with CD4 levels less than 250 x 10 cells/l and with detectable HIV-1 loads. CMV glycoprotein B (gB) typing was possible in 19 patients. Among these patients, including four patients with triple CMV infection and seven patients with double infection, the most prevalent genotype was gB3 (16x) followed by gB2 (9x), gB1 (5x) and gB4 (4x). CONCLUSION: CMV disease during HAART is very unlikely as soon as the HIV-1 viral load becomes undetectable (<50 copies/ml) and/or CD4 cell levels are restored to more than 250 x 10 cells/l. Within Dutch HAART treated patients, infection with CMV gB3 is most prevalent, but also double or triple infection with other CMV gB strains are common.