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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Despite widespread public awareness in Kenya about the HIV/AIDS epidemic, most policy makers in government and other sectors as of 1994 chose not to adopt and implement HIV/AIDS prevention and control policies. Since then, however, the HIV/AIDS policy situation has changed in many ways. Officials now hope to see practical policies adopted and implemented. The government is preparing a national HIV/AIDS policy and has sought input from a broad range of technical, legal, ethical, and policy opinion makers. With support from the AIDS Control and Prevention (AIDSCAP) Project, MAP International facilitated policy-oriented discussions among church leaders, while the Kenya AIDS Nongovernmental Organizations Consortium solicited the experiences and views of local constituents during a series of district and provincial policy workshops. These and other efforts to shape HIV/AIDS policy include improvements in the policy climate in Kenya, better mechanisms for strengthening HIV/AIDS prevention and care, and some specific changes in policy. Policy development, the policy climate, improved mechanisms, and policy change are discussed.
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PMID:Influencing HIV / AIDS policy in Kenya: NGOs build consensus. Policy profile. 1234 96

By the end of 1998, 33.4 million people worldwide were infected with HIV, 10% more than in 1997, and there were 2.5 million AIDS-related deaths. New estimates by the UN AIDS organization, UNAIDS, and the World Health Organization show that practically every country in the world has been affected by the pandemic. HIV prevalence in eastern Europe, Latin America, and the Caribbean currently appears to be concentrated in, but not limited to, marginalized groups. MAP (Monitoring the AIDS Pandemic), a network of experts with more than 120 members in 40 countries around the world, has estimated that more than 1.6 million people are living with HIV/AIDS in Latin America and the Caribbean, or 5.4% of all HIV/AIDS cases worldwide in January 1998. Infection trends in the area differ both between and within countries. HIV in the region does, however, appear to be mainly in socially and economically marginalized populations, and is most noticeable among men who have sex with men and IV drug users. Evidence also exists that HIV is increasingly spreading among the poor and illiterate segments of society. Infection rates are rising among women, showing that heterosexual transmission is becoming more important. The Caribbean Regional Network of People Living with HIV/AIDS was created out of a 3-day consultation in Port of Spain, Trinidad, sponsored by a number of international organizations. That the number of HIV-positive people in the region is increasing should not be taken lightly.
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PMID:HIV / AIDS in the Caribbean. 1234 1

Chemokines and chemokine receptors play a crucial role in the trafficking of leukocyte populations across the body, and are involved in the development of a large variety of human diseases. CCR5 is the main coreceptor used by macrophage (M)-tropic strains of human immunodeficiency virus type 1 (HIV-1) and HIV-2, which are responsible for viral transmission. CCR5 therefore plays an essential role in HIV pathogenesis. A number of inflammatory CC-chemokines, including MIP-1 alpha, MIP-1 beta, RANTES, MCP-2, and HCC-1[9-74] act as CCR5 agonists, while MCP-3 is a natural antagonist of the receptor. CCR5 is mainly expressed in memory T-cells, macrophages, and immature dendritic cells, and is upregulated by proinflammatory cytokines. It is coupled to the Gi class of heterotrimeric G-proteins, and inhibits cAMP production, stimulates Ca2+ release, and activates PI3-kinase and MAP kinases, as well as other tyrosine kinase cascades. A mutant allele of CCR5, CCR5 delta 32 is frequent in populations of European origin, and encodes a nonfunctional truncated protein that is not transported to the cell surface. Homozygotes for the delta 32 allele exhibit a strong, although incomplete, resistance to HIV infection, whereas heterozygotes display delayed progression to acquired immunodeficiency syndrome (AIDS). Many other alleles, affecting the primary structure of CCR5 or its promoter have been described, some of which lead to nonfunctional receptors or otherwise influence AIDS progression. CCR5 is considered as a drug target in the field of HIV, but also in a growing number of inflammatory diseases. Modified chemokines, monoclonal antibodies and small chemical antagonists, as well as a number of gene therapy approaches have been developed in this frame.
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PMID:CCR5 and HIV infection. 1240 6

Mucosal secretory IgA is considered to have an important role in the prevention of human immunodeficiency virus type 1 (HIV-1) transmission through sexual intercourse. Therefore, substances that induce HIV-1-specific IgA antibody in the genital tract may become promising candidates for prophylactic vaccine against HIV-1 infection. We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and gp120 antigens on their surface and that intravaginal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody in mice. In this study, various strategies for immunization with HIV-NS were undertaken to induce HIV-1-specific IgA response in the mouse genital tract. HIV-NS were administered intravaginally, orally, intranasally or intraperitoneally to mice. Progesterone treatment enhanced the anti-HIV-1 IgA response to intravaginal immunization significantly, but intranasal immunization with HIV-NS was more effective compared with other immunization routes in terms of vaginal IgA response. In addition, vaginal washes from intranasally immunized mice were capable of neutralizing HIV-1(IIIB). Thus, application of HIV-NS is a practical approach to promote HIV-1-specific IgA response by the vaginal mucosa in the mouse and intranasal appears to be an effective immunization route in this animal model. Intranasal immunization with HIV-NS should be further pursued for its potential as an HIV-1 prophylactic vaccine.
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PMID:Mucosal immunization with inactivated HIV-1-capturing nanospheres induces a significant HIV-1-specific vaginal antibody response in mice. 1268 3

While HIV has subverted the chemokine receptors CCR5 and CXCR4 for its own use as an entry co-receptor, their normal functions are to transduce signals in response to extracellular ligands. Our lab is interested in understanding how HIV-1 glycoprotein 120 (gp120) may activate intracellular signals through these receptors in primary human macrophages, and how these responses may contribute to pathogenesis. Our studies demonstrate HIV-1 gp120 elicits several different types of signals in macrophages through CXCR4 and CCR5, including calcium elevations, ionic channel activation, non-receptor protein tyrosine kinase activation, and activation of MAP kinases. Receptor activation is triggered by both monomeric gp120 and whole HIV virus. Furthermore, gp120 elicits a number of functional responses in macrophages, such as secretion of chemokines and other soluble products, and we demonstrate that specific pathways linked to the chemokine receptors are responsible. These studies help illuminate the pathways through which chemokine receptors are coupled in primary macrophages, and provide a mechanistic basis for effects that HIV has on macrophage function. These signaling responses may play a role in the pathogenesis of organ dysfunction such as HIV encephalopathy and lymphocytic interstitial pneumonitis where macrophages are the principal infected cell type and inappropriate immune activation plays a central role.
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PMID:HIV-1 Env-chemokine receptor interactions in primary human macrophages: entry and beyond. 1284 69

InKine Pharmaceutical Co. is developing an oral compound, CBP 1011, for the treatment of immune thrombocytopenic purpura (ITP) [Hematrol] and for the treatment of inflammatory bowel disorders, ulcerative colitis and Crohn's disease (Colirest). This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. CBP 1011 or medroxyprogesterone, is a progesterone agonist and inhibits pro-inflammatory mediators such as interleukin-6 and tumour necrosis factor (TNF). CBP 1011 was originally developed by CorBec Pharmaceuticals, which in 1997 was aquired by Panax and then intergrated into InKine Pharmaceuticals. According to a company spokesperson, InKline is pursuing outlicensing opportunities for Hematrol since the company's current commercial focus is on gastrointestinal products. In June 2000, InKine announced the completion of a study comparing the bioavailability of a commercially viable tablet formulation of CBP 1011 to the original capsule formulation that is currently being used in the company's phase III studies in patients with idiopathic thrombocytopenic purpura. Preliminary results from this study indicate that the bioavailability of the tablet formulation does not differ significantly from that of the capsule formulation. The trial enrolled ITP patients (i) who are HIV positive, (ii) who are chronic ITP sufferers despite having had a splenectomy, (iii) who are older, or (iv) who have less severe thrombocytopenia. In preclinical trials, CBP 1011 was shown to decrease lymphocyte infiltration into the bowel compared with the control. Studies also show that it possibly offers safety benefits over steroid therapies. In June 2001, InKine commenced enrolment for a pivotal phase III trial in the treatment of Crohn's disease. This randomised, double-blind trial will enrol approximately 250 patients and will compare two doses of CBP 1011 (400 and 1000mg) with placebo. In April 2003, the US Patent and Trademark Office granted InKine Pharmaceutical a 'Notice of Allowance' for the 'Method of Treating Inflammatory Conditions with Progesterone or Progesterone Analogs'. This patent for medroxyprogesterone (Colirest) provides InKine patent protection for the use of Colirest in treating patients with Crohn's disease, ulcerative colitis, proctitis, microscopic colitis, allergic eosinophilic gastroenteritis, food allergies, drug-induced oesophagitis, coeliac disease, recurrent polyps and haemorrhoids. The patent protection also covers Colirest in a variety of delivery forms such as tablet, enema, suppository, foam, gel, ointment and suspension.
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PMID:CBP 1011: Colirest, Hematrol. 1284 89

Progressive immunodeficiency in HIV infection is paralleled by a decrease in IL-12 production, a cytokine crucial for cellular immune function. Here we examine the molecular mechanisms by which HIV infection suppresses IL-12 p40 expression. HIV infection of THP-1 myeloid cells resulted in decreased LPS-induced nuclear factor binding to the NF-kappaB, AP-1, and Sp1 sites of the IL-12 p40 promoter. By site-directed mutagenesis we determined that each of these sites was necessary for transcriptional activation of the IL-12 p40 promoter. Binding of NF-kappaB p50, c-Rel, p65, Sp1, Sp3, c-Fos, and c-Jun proteins to their cognate nuclear factor binding sites was somewhat impaired by HV infection, although a role for other as yet unidentified factors cannot be dismissed. The cellular levels of these transcription factors were unaffected by HIV infection, with the exception of a decrease in expression of NF-kappaB p65, consistent with the observed decrease in its binding to the IL-12 p40 promoter following HIV infection. Analysis of regulation of upstream LPS-induced MAP kinases demonstrated impaired phosphorylation of JNK and p38 MAPK, and suppressed phosphorylation and degradation of IkappaBalpha following HIV infection. These results suggest that alterations in nuclear factor binding to numerous sites in the IL-12 p40 promoter, together may contribute to the suppression in IL-12 p40 transcription previously reported. These effects on nuclear factor binding may be a direct effect of HIV infection on the IL-12 p40 promoter, or may occur indirectly as a consequence of altered MAP kinase activation.
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PMID:Disruption of MAP kinase activation and nuclear factor binding to the IL-12 p40 promoter in HIV-infected myeloid cells. 1527 Aug 50

CXCR4, the specific receptor for the chemokine SDF-1 alpha that also binds CXCR4-using HIV gp120s, affects survival of different cell types, including neurons. However, current data show that the outcome of CXCR4 activation on neuronal survival may vary depending on the ligand and/or the cellular conditions. In this study, we have systematically compared the effects of SDF-1 alpha and gp120(IIIB) (with or without CD4) on several intracellular pathways involved in cell survival, including MAP kinases and Akt-dependent pathways. Our data show that gp120(IIIB) and SDF-1 alpha are both potent activators of MAP kinases in neuronal and non-neuronal cells, though the kinetic of these responses is slightly different. Furthermore, unlike SDF-1 alpha, and independently of CD4, gp120(IIIB) is unable to stimulate Akt and some of its antiapoptotic targets (NF-kappa B and MDM2)--despite its ability to activate other signaling pathways in the same conditions. Finally, the viral protein is more efficient in recruiting some effectors (e.g., JNK) than others in comparison with SDF-1 alpha (EC(50) = 0.1 vs. 0.6 nM). We conclude that the intrinsic efficacy of the two ligands is significantly different and is pathway dependent. These findings have important implications for our understanding of CXCR4-mediated responses in the CNS, as well as the role of this coreceptor in HIV neuropathogenesis.
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PMID:Apoptotic and antiapoptotic effects of CXCR4: is it a matter of intrinsic efficacy? Implications for HIV neuropathogenesis. 1558 97

The impact of demographic characteristics, phase of the menstrual cycle, use of hormonal contraceptives, and concomitant lower genital-tract infections on cervicovaginal inflammatory cells was assessed in 967 women, 654 of whom were infected with human immunodeficiency virus type 1 (HIV-1). Cervicovaginal lavage (CVL) fluid was evaluated for total white blood cell (WBC), polymorphonuclear leukocyte, and monocyte counts. HIV-1 infection was not associated with statistically significant differences in numbers of inflammatory cells in CVL fluid except in 1 group--HIV-1-infected women with Chlamydia trachomatis infection had a 0.43 log(10) higher WBC count than their HIV-uninfected, chlamydia-positive counterparts (P=.04). Younger age and use of progesterone-based hormonal contraceptives were independently associated with increased numbers of inflammatory cells in CVL fluid. A 0.15-0.2 log(10) increase in inflammatory cells was seen in black versus white and Hispanic women after adjustment for known potential confounders. Progesterone-based contraceptives, younger age, and race have an independent effect on cervicovaginal inflammatory cells.
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PMID:Influence of sex hormones, HIV status, and concomitant sexually transmitted infection on cervicovaginal inflammation. 1563 94

HIV Tat has been known to have multiple regulatory roles including replication of HIV and modulation of cellular kinases. We investigated whether signaling kinase PKR plays a critical role in mediating Tat-induced cytokine dysregulation. We showed Tat induction of IL-10 dysregulation is associated with PKR activation. To examine the mechanism involved, inhibition of PKR activity abrogated the Tat-induced cytokine induction. We next identified that the MAP kinases including ERK-1/2 and p38 are downstream of PKR in these Tat-induced pathways. Thus, PKR may play a critical role in mediating the subversive effects of HIV Tat resulting in IL-10 induction.
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PMID:Mechanisms for HIV Tat upregulation of IL-10 and other cytokine expression: kinase signaling and PKR-mediated immune response. 1590 45


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