The Effects Of Early Drug Therapy On Virus Replication And Inflammation In Tissues Based On The AIDS Macaques Model

Human immunodeficiency virus(HIV)is the causative pathogen of acquired immune deficiency syndrome(AIDS),which has become a serious social problem endangering health.Viral reservoirs remains a major obstacle to curing HIV.The early highly active antiretroviral therapy(HAART)could reduce the scale of viral reservoirs.The early HAART refers to initiate HAART in the acute phase or early stage of HIV.HAART initiated very early during infection could prevent the loss of CD4+ T cells from the gut and may delay the onset of the disease.While HIV reservoirs are also set up during acute infection,few studies have focused on the effect of early HAART on Peripheral blood mononuclear(PBMC)and different tissues viral replication and reservoirs.Based on this,night 8~10 year old young adult male rhesus macaques of Chinese origin were used in this study.Six animals were inoculated intravenously with SIVmac239.Three animals of six were treated with Tenofovir disoproxil fumarate(TDF),Emtricitibine(FTC)and Raltegravir(RAL).The treatment was initiated three days post infection.We established the methods of viral reservoirs and investigated the impact of early HAART on viral replication of PBMC and the scale and distribution of tissues reservoirs.The marker of viral reservoirs,including total SIV-DNA,2-LTR SIV-DNA and SIV-RNA.Using total SIV-DNA to asses the scale of tissue reservoirs and SIV RNA to evaluate viral production and 2-LTR have been suggested to accumulate in recently infected target cells.We found TDF,FTC and RAL combination could reduce the size of viral reservoirs and alter the distribution of viral reservoirs,but it could not prevent PBMC and tissues produce new viral particles.Liver and lymph node may be served as the critical site of viral reservoir,they had the highest levels of total SIV-DNA.When initiated HAART,they still ongoing infection and produced virus.In addition,several studies reported the magnitude of the viral reservoirs is strongly associated with the residual levels of immune activation that persists during ART,suggesting that HIV persistence and residual inflanmmation are interdependent.We choosed mesenteric and inguinal lymph node to explore the expression levels of inflammatory factor and chemokines.The result showed that early HAART was able to improve inflanmmation but may not completely restore the normal level.