Dynamics of the pool of infected resting CD4 HLA-DR- T lymphocytes in patients who started a triple class five-drug antiretroviral regimen during primary HIV-1 infection.

Starting standard antiretroviral therapy within 10 days after the onset of a primary HIV-1 infection cannot prevent the establishment of a reservoir of HIV-1-infected memory CD4 T cells. Here we studied the reservoir of HIV-1-infected memory CD4 T cells in four patients who started a triple class, five-drug regimen during primary HIV-1 infection. There was a strong correlation between the proportion of productively infected CD4 HLA-DR- T lymphocytes and plasma HIV-1 RNA levels (r=0.

Persistence of viral HLA-DR- CD4 T-cell reservoir during prolonged treatment of HIV-1 infection with a five-drug regimen.

During sustained suppression of plasma viraemia using a standard triple-drug regimen, replication-competent HIV-1 can still be recovered from resting memory CD4 T cells. In an attempt to accelerate the clearance of this pool of infected CD4 T cells, eight antiretroviral therapy-naive HIV-1-infected patients were treated with a five-drug regimen. While plasma HIV-1 RNA levels generally remained below the level of detection (< 5 copies/ml), replication competent HIV-1 was isolated from HLA-DR- CD4 T cells from all patients on multiple occasions throughout treatment.

Both R5 and X4 human immunodeficiency virus type 1 variants persist during prolonged therapy with five antiretroviral drugs.

A viral reservoir of human immunodeficiency virus type 1 (HIV-1)-infected, resting CD4(+) T cells persists despite suppression of plasma viremia by combination antiretroviral therapy. In a longitudinal analysis of three patients treated with a five-drug regimen, both R5 and X4 HIV-1 variants persisted in the cellular reservoir for up to 3 years.

Differential coreceptor expression allows for independent evolution of non-syncytium-inducing and syncytium-inducing HIV-1.

We demonstrated previously that CD45RA(+) CD4(+) T cells are infected primarily by syncytium-inducing (SI) HIV-1 variants, whereas CD45RO(+) CD4(+) T cells harbor both non-SI (NSI) and SI HIV-1 variants. Here, we studied evolution of tropism for CD45RA(+) and CD45RO(+) CD4(+) cells, coreceptor usage, and molecular phylogeny of coexisting NSI and SI HIV-1 clones that were isolated from four patients in the period spanning SI conversion. NSI variants were CCR5-restricted and could be isolated throughout infection from CD45RO(+) CD4(+) cells.