Unexpected coreceptor usage of primary human immunodeficiency virus type 1isolates from viremic patients under highly active antiretroviral therapy

Recently, combinations of antiretroviral drugs (highly active antiretrovira l therapy [HAART]) have led to a dramatic reduction of human immunodeficien cy virus type 1 (HIV-1)-related clinical symptoms. Success of treatment is defined as almost complete suppression of plasma viremia, although in a siz able fraction of patients this goal is not achieved. We characterized prima ry HIV-1 isolates from 2 cohorts of patients in which HAART failed in terms of viral suppression. One cohort showed clinical benefit and stable or inc reasing CD4(+) T cell numbers despite high viral load. The second viremic c ohort had no CD4(+) T cell recovery and exhibited typical AIDS-related symp toms. Primary isolates from HAART patients with minor clinical symptoms use d CXCR4 as the most relevant receptor on primary cells, Thus, for the first time, it is shown that patients improving clinically under HAART harbor re latively high viral loads with viruses preferring CXCR4 as coreceptor.