OBJECTIVE: The recovery of CD4 target cells following antiretroviral therapy may facilitate virus production and escape from antiretroviral suppression. To address this hypothesis, we directly examined whether the CD4 target cell number increases viral production in the presence of suboptimal therapy. DESIGN: The effect of the CD4 T cell number on HIV-1 replication with a suboptimal dose of zidovudine was studied in vitro. METHODS: Varying numbers of CD4 T cells were infected with HIV-1 and treated with 1 nM zidovudine. Virus production was measured by p24 antigen capture enzyme-linked immunosorbent assay. Partial sequencing of HIV-1 pol was performed to assess zidovudine-resistant mutations. RESULTS: Wild type virus production was found to increase eightfold in cultures with 100 x 10(4) cells compared with cultures with 10 x 10(4) cells. The IC90 of zidovudine was 4 logs higher in cultures with 16 x 10(4) cells compared with cultures with 1 x 10(4) cells. No zidovudine-resistant mutations were found. CONCLUSION: Target cell availability may play a direct role in wild type HIV-1 resurgence following therapy.
OBJECTIVE: The recovery of CD4 target cells following antiretroviral therapy may facilitate virus production and escape from antiretroviral suppression. To address this hypothesis, we directly examined whether the CD4 target cell number increases viral production in the presence of suboptimal therapy. DESIGN: The effect of the CD4 T cell number on HIV-1 replication with a suboptimal dose of zidovudine was studied in vitro. METHODS: Varying numbers of CD4 T cells were infected with HIV-1 and treated with 1 nM zidovudine. Virus production was measured by p24 antigen capture enzyme-linked immunosorbent assay. Partial sequencing of HIV-1 pol was performed to assess zidovudine-resistant mutations. RESULTS: Wild type virus production was found to increase eightfold in cultures with 100 x 10(4) cells compared with cultures with 10 x 10(4) cells. The IC90 of zidovudine was 4 logs higher in cultures with 16 x 10(4) cells compared with cultures with 1 x 10(4) cells. No zidovudine-resistant mutations were found. CONCLUSION: Target cell availability may play a direct role in wild type HIV-1 resurgence following therapy.
Authors: Zhi-Qiang Zhang; Stephen W Wietgrefe; Qingsheng Li; Marta Dykhuizen Shore; Lijie Duan; Cavan Reilly; Jeffrey D Lifson; Ashley T Haase Journal: Proc Natl Acad Sci U S A Date: 2004-04-02 Impact factor: 11.205