IV latency in vivo. Specifically, we have demonstrated that a combination of wellcharacterized human antiretroviral drugs is capable of effectively controlling viral replication. We demonstrated the presence of latently infected resting human CD4 T cells in ART treated BLT mice that can be induced ex vivo Cytisine to produce HIV. In these experiments, we observed that the frequency of infected resting human CD4 T cells present in tissues from BLT mice is within the range observed circulating in patients undergoing suppressive ART. Overall these results demonstrate that humanized BLT mice are an attractive model for testing the in vivo efficacy of novel HIV eradication strategies.
ACKNOWLEDGMENTS This work was supported in part by National Institutes of Health grants AI096113, AI073146, AI071940, AI082608, AI082637 , AI081613 , and 5T32AI005284 , the UNC Center for AIDS Research grant P30 AI50410, a Foundation for AIDS Research Fellowship , the Augustinus Foundation, the Danish AIDS Caspase Pathway Foundation, Danielsen’s Foundation , and a Research Fellowship of the Japan Society for the Promotion of Science . The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. We thank I. Chen for providing the JR CSF plasmid via the AIDS Research and Reference Reagent Program and former and current lab members and veterinary technicians at UNC Division of Laboratory Animal Medicine for their assistance with aspects of this work.HIV epidemic in sub Saharan Africa, which would be tragic.
Conversely, limiting one of the most highly used eff ective methods of contraception in sub Saharan Africa would probably contribute to reased maternal mortality and morbidity and more low birthweight babies and orphans an equally tragic result. The time to provide a more defi nitive answer to this crucial public paraffin health question is now; the donor community should support a randomised trial of hormonal contraception and HIV acquisition.Combination antiretroviral treatment has transformed HIV infection from a deadly disease to a chronic one.1,2 Long term suppression of viraemia requires patients’ commitment to take antiretroviral drugs on a daily basis for the rest of their lives. Although more than 25 antiretroviral drugs have been approved for clinical use, novel and better treatment options are needed for individuals in whom existing regimens fail because of antiviral resistance or side eff ects.
HIV integrase inhibitors are potent antivirals that induce a rapid and durable decrease in viral load.3 Raltegravir and elvitegravir are members of this class of drug. Regimens based on a twice daily dose of raltegravir are recommended for management of both treatmentexperienced and treatment naive HIV infected patients; once daily dosing of raltegravir is not recommended.4 Elvitegravir is an investigational drug that is suitable for once daily dosing when combined with a pharmacokinetic booster.5 Furthermore, a next generation integrase inhibitor, dolutegravir, which can be used without a protease inhibitor booster, is under investigation in the SPRING 16 and VIKING7 clinical trials. Moreover, dolutegravir can be taken once a day without a protease inhibitor booster, and it seems to display a higher genetic barrier to resistance.