EgravirFigure 3 Association of viral load decrease with raltegravir treatment of SIVmacEgravirFigure 3 Association of

EgravirFigure 3 Association of viral load decrease with raltegravir treatment of SIVmac
EgravirFigure 3 Association of viral load decrease with raltegravir treatment of SIVmac251-infected animals (Group 2). SIVmac251infected rhesus macaques (Macaca mulatta) received 100 mg of raltegravir twice daily with food (bid). Monotherapy was continued for ten days. Comparison between pre- and post-raltegravir viral load measurements was done. Viral load values at Day 0, Day 7 and Day 10 were compared with viral loads at 27 and 166 days prior to treatment start. Significant differences (P < 0.05; Bonferroni's test following repeated-measures ANOVA; shown in the graph by the red asterisks) were found between both the values at 166 and 27 days prior to treatment start and the values at Day 7 and Day 10 of treatment. No significant differences, instead, were found between the values at 166 days, or 27 days, prior to treatment, and the values at Day 0. The dashed line parallel to the x axis marks the detection threshold of the technique adopted.monotherapy. This animal was the only component of Group 2 to show a low viral load (i.e., 1,520 copies/ml) before treatment was initiated. To further support the contribution of raltegravir treatment to the viral load decline in this subject, treatment was stopped and viral load was followed up. Results showed that a rebound in viral load occurred following treatment suspension (4,520 viral RNA copies/ml; value at two weeks from suspension).SIVmac251 proviral DNA persists during ART in peripheral blood mononuclear cells of the non-human primatesTo evaluate whether copies of SIVmac251 proviral DNA persisted during ART despite suppression of viral load to undetectable levels, we measured proviral DNA copy numbers in PBMCs of the non-human primates prior to starting dosing and after 52 days of therapy. Results showed that proviral DNA was maintained stable during the treatment period analyzed. The difference between the proviral DNA levels at the two time points analyzed was not statistically significant (P > 0.05; WilcoxonLewis et al. Retrovirology 2010, 7:21 http://www.retrovirology.com/content/7/1/Page 7 ofFigure 4 Persistence of proviral DNA during therapy (Group 1). Proviral DNA was measured by a quantitative PCR technique at start of treatment with antiretroviral PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28404814 drugs, and at 52 days of therapy.signed rank test) (Fig. 4). We concluded that ART regimens consisting of two NRTIs/NtRTIs plus raltegravir maintains stably suppressed SIVmac251 viral load, but not the proviral DNA, in non-human primates.DiscussionSusceptibility of SIVmac251 to raltegravirThe results of the present study show that raltegravir inhibits SIVmac251 replication both in tissue culture and in vivo. The result is comparable to those of previous susceptibility studies using wild-type HIV-1 and HIV-2 [25,30] and is supported by similar assays conducted in the present study using HIV-1 and HIV-2 as positive controls for viral replication inhibition. The PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/27735993 EC50 of raltegravir found by Hombrouck et al. [25] in the MTT-based assays for HIV-1 IIIB cythopathic effects is slightly lower than that obtained in the present study. Differences between our results and those of Hombrouck et al. can be N-hexanoic-Try-Ile-(6)-amino hexanoic amide supplier attributed to the differences in the experimental protocols such as the higher MOI of HIV1 used in the present study. Similarly, the higher EC50 of raltegravir for HIV-2 reported in a previous study of Roquebert et al. using HIV-2 ROD can be explained by the fact that these authors adopted a different method for viral quantification, i.e. a quant.