Current progress of China’s free ART program

INTRODUCTION At the end of 2003, there were an estimated 840,000 people in China infected with HIV, among whom 80,000 were in need of antiretroviral therapy (ART) [1]. Since 1999, the annual rate of increase in reported HIV infec- tions has been around 30%, with growing numbers of females becoming infected [1]. The transmission of HIV/ AIDS in China has been through intravenous drug use (43. 2%) in the south, southwest, and western provinces; prior commercial blood and plasma selli…     

Translocated microbiome composition determines immunological outcome in treated HIV infection

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1225例HIV/AIDS患者流行病学特征分析

目的:了解来陕西地区就诊的人类免疫缺陷病毒/艾滋病(Human immunodeficiency virus/Acquired immuno deficiency syndrome,HIV/AIDS)患者感染状况、流行特征。方法:收集来我院就诊的HIV/AIDS患者的基本信息,对其流行病学资料统计分析。结果:在调查的1225例HIV/AIDS患者中,男性占83.51%,平均年龄为(35.55±11.61)岁,50.98%为农民,小学及以下学历占33.55%,经血液途径感染250例,经性传播途径感染916例,其中同性性传播337例,经母婴垂直传播16例,就诊时CD4+T淋巴细胞计数平均值为(222.82±190.49)个/μL,56%的HIV/AIDS患者采用的抗病毒方案为齐多夫定(Zidovudine,AZT)/替诺福韦(Tenofovir Disoproxil Fumarate,TDF)+拉米夫定(Lamivudine,3TC)+依非韦伦(Efavirenz,EFV)方案。结论:陕西地区HIV/AIDS感染人数呈上升趋势,且年轻化加剧,同性性传播比例大幅增加。虽然治疗较为及时,应进一步在高危人群中积极宣传防艾知识与措施。     

A Mother-to-Child Transmission Study in Nigeria: The Impact of Maternal HIV Infection and HAART on Plasma Immunoglobulins,Cytokine Profiles and Infant Outcome

Prevention of mother-to-child transmission (PMTCT) of HIV with highly active antiretroviral therapy (HARRT) allows the HIV~+ pregnant mothers to have vaginal delivery and breastfeed.Here we investigated the maternal plasma immunoglobulin,cytokine secretion and the outcome of the exposed infants among the HIV~+ HAART treated pregnan women in Nigeria.In this study,different plasma immunoglobulins and cytokines were measured in the HIV~+ HAART treated pregnant mothers.Pooled culture supernatants of B and T lymphocytes showed lower levels of IFN-γ,IL-10 and IL-4.There were lower IFN-γ and IL-10 secretions at 1st trimester;however,IL-10 continued to be lower throughout 2nd and 3rd trimesters.TNF-α secretion significantly decreased as pregnancy progressed to term.There were high plasma IgG and low IgM in the HIV~+ HAART treated pregnant women.Plasma IgG was high during 1st and 3rd trimesters.After one year of follow up,all the exposed children were seronegative for HIV-1 and HIV-2.Vaginal delivery and breastfeeding among HIV~+ HAART treated mothers have shown to be safe.The use of HAART by the infected mothers and the use of septrin and niverapin by the exposed infants prevented mother to-child transmission of HIV.     

Methods Development for Blood Borne Macrophage Carriage of Nanoformulated Antiretroviral Drugs

Nanoformulated drugs can improve pharmacodynamics and bioavailability while serving also to reduce drug toxicities for antiretroviral (ART) medicines. To this end, our laboratory has applied the principles of nanomedicine to simplify ART regimens and as such reduce toxicities while improving compliance and drug pharmacokinetics. Simple and reliable methods for manufacturing nanoformulated ART (nanoART) are shown. Particles of pure drug are encapsulated by a thin layer of surfactant lipid coating and produced by fractionating larger drug crystals into smaller ones by either wet milling or high-pressure homogenization. In an alternative method free drug is suspended in a droplet of a polymer. Herein, drug is dissolved within a polymer then agitated by ultrasonication until individual nanosized droplets are formed. Dynamic light scattering and microscopic examination characterize the physical properties of the particles (particle size, charge and shape). Their biologic properties (cell uptake and retention, cytotoxicity and antiretroviral efficacy) are determined with human monocyte-derived macrophages (MDM). MDM are derived from human peripheral blood monocytes isolated from leukopacks using centrifugal elutriation for purification. Such blood-borne macrophages may be used as cellular transporters for nanoART distribution to human immunodeficiency virus (HIV) infected organs. We posit that the repackaging of clinically available antiretroviral medications into nanoparticles for HIV-1 treatments may improve compliance and positively affect disease outcomes.     

Nicotine and cotinine increases the brain penetration of saquinavir in rat

Endothelial tight junctions and efflux transporters of the blood-brain barrier (BBB) significantly limit brain accumulation of many drugs, including protease inhibitors such as saquinavir. The cholinergic agonist nicotine is one of the most commonly used drugs in the world and the incidence is even higher in the human immune deficiency virus population (～ 70%). We examined the ability of nicotine and its primary metabolite cotinine to modify brain uptake of saquinavir in rats. Both nicotine and cotinine at pharmacological concentrations matching those in smokers, increased brain saquinavir uptake by two fold. Co-perfusion with nicotinic receptor antagonists and passive permeability markers showed that the effect was not caused by receptor activation or BBB permeability disruption. Transport inhibition studies demonstrated that brain saquinavir uptake is limited by multiple efflux transporters, P-glycoprotein (P-gp), breast cancer resistance protein and multidrug resistance-associated protein. In situ perfusion and in vitro experiments using a classical P-gp substrate rhodamine 123 linked the effect of nicotine to inhibition of BBB P-gp transport. The effect was confirmed in vivo in chronic 14 day nicotine administration animals. These data suggest nicotine increases antiretroviral drug exposure to brain and may represent a significant in vivo drug-drug interaction at the BBB. Although this may slightly benefit CNS antiretroviral efficacy, it may also expose the brain to potential serious neurotoxicity.