Virologic determinants of success after structured treatment interruptions of antiretrovirals in acute HIV-1 infection.

BACKGROUND: Latently infected resting memory CD4 T cells are thought to be the major reservoir that contributes to rebound viremia after cessation of antiretrovirals (ARVs). Commencing ARVs during primary HIV-1 infection (PHI) may limit the size of the latent pool and lead to improved control of viral replication during structured treatment interruption (STI). METHODS: Individuals with PHI (n = 59) were randomized to receive ARVs with or without hydroxyurea. After STI, a good response was defined as maintenance of HIV-1 RNA <5000 copies/mL for 24 weeks off therapy. In a detailed prospective virologic substudy (n = 19), integrated HIV-1 DNA, total HIV-1 DNA, and cell-associated HIV-1 unspliced (US) RNA were quantified using a real-time polymerase chain reaction assay. RESULTS: The plasma HIV-1 RNA 12 weeks after the initiation of ARVs was significantly lower in good responders (n = 7) compared with poor responders (n = 12) (P = 0.005). There were no significant differences between good and poor responders in integrated HIV-1 DNA, HIV-1 DNA, and HIV-1 US RNA. Integrated HIV-1 DNA before initiation of ARVs was strongly correlated with plasma HIV-1 RNA at week 12 (P = 0.006, r = 0.81). CONCLUSION: HIV-1 RNA measured 12 weeks after initiation of ARV was the only virologic variable associated with viral rebound after treatment interruption in PHI.

[The effect of specific virus delivering of Langerhans cell for the M-tropic HIV infection].

OBJECTIVE: To observe the cellular mechanism of via skin infection of Microphage tropic (M-tropic) HIV and further differentiate the infection of M-tropic and T-tropic HIV. METHODS: DNA clone of AD8 and NL43 was respectively transfected to skin by Gene Gun, The expression of virus in the epidermal cells was observed by flow-cytometry and fluoroscope. Emigrating cells were Mac-sorted into CD80+ and CD80-. The infection of CD4+ T lymphocytes by HIV from emigrating cells were further assessed by PCR and RT assay. RESULTS: Through direct transfection of skin by Gene Gun, emigrating cells from skin showed transfection of AD8 and NL43 and the gag gene can be amplified from the cells. Only AD8 transfected emigrating cells can further infect CD4+ T lymphocyte. Gag can be amplified and reverse transcriptase can be expressed from these CD4+ T cells; NL43 transfected emigrating cells can not infect CD4+ T lymphocyte. No gag can be amplified and no reverse transcriptase can be expressed. AD8 transfected and 1/2 log diluted CD80+ cells can infect CD4+ T lymphocyte. Even after 4 dilutions, there are still a lot of CD4+ T cells, gag can be amplified and a large amount of reverse transcriptase was expressed that is double or triple of controls. AD8 infected CD80-cells co-cultured with CD4+ T cells showed gag amplification only in first dilution and reverse transcriptase is also expressed. Gag can not be amplified by further dilution. NL43 infected CD80+ or CD80- emigrating cells co-cultured with CD4+ T cells did not show gag amplification and did not express reverse transcriptase. CONCLUSION: Direct AD8 transfected CD80+ emigrating epidermal cells can specifically infect CD4+ T lymphocyte. This specificity not only depends on affinitive combination of HIV receptor on cell surface, but also on the specific virus delivering of AD8 transfected CD80+ cells that infect the CD4+ T cells. That means even without the receptor, CD80+ cells only deliver transfected AD8 but not NL43. So, it can be said that the specificity of the virus receptor is not the only clue of HIV infection.