Thus IGFBP-3 would be upstream to TNFa in the pathway regulating insulin signal transduction. In support of this notion, studies using other organs report a strong association between TNFa and dysfunctional insulin signal transduction through activation of SOCS3 or phosphorylation of IRS-1Ser307. A key outcome of insulin receptor signal transduction is activation of the anti-apoptotic factor, Akt, and decreased apoptosis. We have previously reported that Compound 49b restored IGFBP-3 levels in diabetic animals, reduced apoptosis in the retina, and increased phosphorylation of Akt. We now show that increasing IGFBP-3 through an intravitreal injection of IGFBP-3 NB can directly reduce apoptotic markers, while increasing two anti-apoptotic markers, including Akt and Bcl-xL. While this study did not measure apoptosis in particular cell types, we believe that the reduced apoptosis is likely occurring in retinal endothelial cells as we have previously reported that IGFBP-3 is key to retinal endothelial cell survival. This reduction in apoptosis was associated with improvement of the ERG in the treated eye. It is unclear whether the improvement was a direct or indirect effect, since the ERG improvement occurred so rapidly after treatment. Additionally, since ERG does not directly test retinal degeneration, further work would be required to validate the retinal changes resulting in altered ERG responses. Nonetheless, the finding warrants further study and highlights the Benzoylpaeoniflorin potential Evodiamine importance of IGFBP-3 in protection/maintenance of retinal function. While we cannot rule out actions of IGF-1 receptor signaling in the observed changes, the use of the IGFBP-3 NB strongly suggests that IGFBP-3 is acting independent of changes in IGF-1. In conclusion, our data demonstrate that an intravitreal injection of IGFBP3 NB is able to reduce TNFa levels in diabetic rats. This reduction in TNFa is associated with reduced SOCS3, IRS-1Ser307, and IRTyr960 levels in retinal lysates from the treated eye. IGFBP-3 NB injected eyes had reduced apoptosis markers, likely associated with maintenance of insulin receptor signaling, indicated by phosphorylation of the insulin receptor. Additionally, IGFBP-3 NB treatment of diabetic rats improved the ERG measured at 4 days after intravitreal injection. These findings support the hypothesis that insulin signaling pathways in retina play a key role in maintaining retinal function and that diabetic insult targets these pathways to produce the diabetic retinopathy phenotype. In the Primo-SHM trial, a multicenter randomized trial comparing no treatment with 24- or 60-weeks of combination antiretroviral therapy during primary HIV-infection, we recently demonstrated that temporary early cART lowered the viral setpoint and deferred the need for reinitiation of cART during chronic HIV-infection. Two other randomized studies also observed a modest delay 
in disease progression after a short course of cART in PHI. However, an important concern of temporary early cART, and of structured treatment interruptions in general, is the risk of developing drug resistance mutations after TI, especially in the case of NNRTIbased regimens, which compromise future treatment options. The aim of this study was to assess the effect of temporary cART during PHI on the subsequent virologic.