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Query: UMLS:C0019693 (HIV)
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The genetic diversity of HIV-1 strains in Chad was documented with a total of 107 samples from patients attending the general hospital in N'Djamena, the capital city of Chad. The genetic subtypes were identified in the V3-V5 env and p24 gag regions by sequence and phylogenetic tree analyses. Of the 107 strains, 78 had the same subtype/CRF designation between env and gag. Four subtypes and three CRFs were found to cocirculate: subtype A, 20.5%; subtype D, 18.7%; CRF02_AG, 13.1%; CRF11_cpx, 13.1%; subtype G, 3.7%; CRF01_AE, 2.8%; and subtype F1, 0.9%. The remaining 29 strains (27%) had discordant subtypes or CRF designations between env and gag; in 15 of these 29 strains, a CRF was involved in the recombination event, and 10 were subtype G in gag and subtype A in env, forming a separate subcluster within subtypes G and A. Subtype D strains represent almost 20% of the HIV-1 strains circulating in Chad and form a separate subcluster in gag and env. Nearly full-length genome sequencing for two such strains (99TCD-MN011 and 99TCD-MN012) revealed that they represent nonrecombinant subtype D variants. Compared with neighboring countries, the genetic subtype distribution of HIV-1 strains in Chad is unique for several reasons: lower prevalence of CRF02, high prevalence of CRF11 and subtype D, and absence of CRF06. These data clearly show that subtype distribution is very heterogeneous in Africa, probably the result of different founder effects.
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PMID:High genetic diversity of HIV-1 strains in Chad, West Central Africa. 1279 61

HIV infection is associated with several renal syndromes, including acute renal failure. Chronic renal failure directly linked to HIV infection includes thrombotic microangiopathic renal diseases, immune-mediated glomerulonephritides, and HIV-associated nephropathy. A renal biopsy may be necessary for diagnosis. The development of HIV-associated nephropathy has been definitively linked to renal cellular infection, but the disease affects only a minority of patients, typically men of African descent. Therefore, factors determining disease expression in infected patients must now be emphasized. The pathogenic mechanisms involved in HIV-associated renal disease remain obscure. Genetic factors, as well as renal cellular responses, mediated by HIV proteins (including an immune-activated microenvironment) capable of presenting antigen in susceptible hosts probably explain most cases. HIV-associated nephropathy has a characteristic pathologic phenotype, including glomerular, tubular, and interstitial changes, and ultrastructural findings. Infection of the glomerular epithelial cell, or podocyte, and consequent structural and biochemical changes may be pivotal in pathogenesis. The HIV-1 transgenic mouse is an important model for understanding disease pathogenesis, particularly the role of HIV proteins in mediating renal tissue injury. Rigorously controlled randomized trials have not evaluated treatment, but corticosteroids and angiotensin-converting enzyme inhibitors have been used. Highly active antiretroviral therapy seems to have decreased the incidence of end-stage renal disease related to HIV infection and, in case reports, to have improved renal functional and pathologic outcomes of HIV-associated nephropathy. Outcomes in patients undergoing hemodialysis and peritoneal dialysis have improved, and current research focuses on renal transplantation for treatment of HIV-infected patients.
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PMID:Pathogenesis and treatment of HIV-associated renal diseases: lessons from clinical and animal studies, molecular pathologic correlations, and genetic investigations. 1289 89

HIV-1 subtype B and CRF01_AE have been in circulation in Thailand and Southeast Asia for more than a decade. Initially separated by risk group, the two strains are increasingly intermixed, and two recombinant strains of essentially reciprocal structure have been recently reported. Here we identify additional CRF_01B recombinants and provide the evidence that HIV-1 strains now pass freely between the two high-risk populations. HIV isolates that showed discordance between CRF01_AE and subtype B in multi-region genotyping assays were selected for the study. They were drawn from 3 different cohorts in Thailand representing different risk behaviors and demographic characteristics: a drug user cohort in the north, a family planning clinic attendee cohort in the southeast, and a cohort study of the mucosal virology and immunology of HIV-1 infection in Thailand. The DNA from these isolates was PCR amplified to recover the full HIV-1 genome and subjected to sequencing and phylogenetic analysis. We establish that one particular CRF_01B recombinant, with the external envelope of subtype B and the rest of the genome from CRF01_AE, is circulating widely in Thailand. Termed CRF15_01B (also referred to as CRF15), the strain was primarily heterosexually transmitted, although injecting drug use (IDU) also played a role. In aggregate data from the studies, CRF15 constituted 1.7% of all HIV-1 infections (95% confidence interval 0.5-4.4%) and was dispersed widely in the country. The previously separate heterosexual and IDU epidemics have apparently been bridged by a new CRF. The entry of CRF15 into the mainstream of the epidemic signals new complexity in the long stable molecular picture in Thailand. These recombinants must be considered in ongoing or projected efficacy evaluations of HIV-1 vaccines and antiviral therapies.
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PMID:A new circulating recombinant form, CRF15_01B, reinforces the linkage between IDU and heterosexual epidemics in Thailand. 1290 33

Dual infection with HIV-1 and HIV-2 can occur in locales where these viruses co-circulate, most commonly in West Africa. Although dual seropositivity is common in this region, the true rate of dual infection remains unclear. In addition, whether unique HIV-1 subtypes are circulating in dually infected individuals is unknown. A cohort of 47 HIV-1 and HIV-2 dually seropositive individuals from Senegal, West Africa was screened for the presence of HIV-1 and HIV-2 gag and env PBMC viral DNA sequences using PCR. Of the 47 dual HIV-1/HIV-2 seropositive individuals tested, 19 (40.4%) had infection with both HIV-1 and HIV-2 confirmed by genetic sequence analysis, whereas only HIV-1 or HIV-2 was confirmed in 17 (36.2%) or 9 (19.1%), respectively. The majority of HIV-1 subtypes found were CRF-02 and A, although subtypes D, C, G, J and B were also found, reflecting the subtypes known to be circulating in Senegal. There was no significant difference in HIV-1 subtype distribution between individuals with confirmed dual infection and patients in this study with dual seropositivity but lacking HIV-2, or with HIV-1 infected patients within the general population in Senegal, although the study was underpowered to detect anything but large differences. The prevalence of HIV-1/HIV-2 dual infection appears to be significantly less than that of dually seropositive individuals and this likely reflects cross-reactive serology. The common HIV-1 subtypes prevalent in West Africa (CRF-02 and subtype A) have a similar distribution to those found in our cohort of dually infected and dually seropositive subjects.
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PMID:Molecular epidemiology of dual HIV-1/HIV-2 seropositive adults from Senegal, West Africa. 1290 35

HIV-1 CRF.AE-01 (formerly subtype E) infection is highly prevalent in Southeast Asia. Despite success with public health measures, the development of an effective CRF01.AE vaccine is critical to the control of this epidemic. Sera from the open-label arms of the first clinical trial of a bivalent HIV gp120 SF2/CM235 (subtypes B and CRF.AE-01, respectively) vaccine were evaluated for the presence of gp120-specific binding (BAb) and neutralizing antibody (NAb). Twelve pre- and postvaccination sera pairs were tested for CM235 BAb; anti-gp120 CM235 BAb was found in all postvaccination samples. The 12 pre- and postvaccination (1 month after third vaccination) serum pairs were evaluated in several neutralization formats: heterologous T cell line adapted (TCLA) NP03/H9, homologous CM235/PBMC, CM235/dendritic cell, and CM235M4-C4.6/A3R5. A3R5 is a CCR5+ T cell line, and CM235M4-C4.6 is the homologous CM235 virus adapted to growth in A3R5 cells. All volunteers developed BAb, but meaningful NAb was not demonstrable against primary isolate CM235. Using the TCLA CRF01.AE virus NP03 in H9 cells, 9 of 12 persons had NAb with a geometric mean titer (GMT) of 46. The CM235M4-C4.6 virus in A3R5 cells also detected NAb in 9 of 12 persons, with a GMT of 41. CM235M4-C4.6/A3R5 detected NAb in two persons with negligible NAb to NP03/H9 and vice versa. Whether the NAb detected by the CM235M4-C4.6/A3R5 system is qualitatively different from those in more traditional NP03/H9 assays will require further study.
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PMID:Specific antibody responses to vaccination with bivalent CM235/SF2 gp120: detection of homologous and heterologous neutralizing antibody to subtype E (CRF01.AE) HIV type 1. 1458 11

Several human monoclonal antibodies can neutralize a range of human immunodeficiency virus type 1 (HIV-1) primary isolates but their potency and related ability to suppress generation of HIV-1 escape mutants is significantly lower than the activity of antiretroviral drugs currently in clinical use. Recently, a human Fab, X5, was identified and found to neutralize primary isolates from different clades. Further improvement of the potency and breadth of HIV-1 neutralization by this antibody could be critical for its potential use in the treatment of HIV-1-infected patients. However, increasing potency of an antibody by selection from libraries may lead to a decrease in the breadth of neutralization. In an attempt to solve this problem, we subjected a random mutagenesis library of the scFv X5 to sequential rounds of selection on non-homologous HIV-1 envelope glycoproteins (Envs) dubbed sequential antigen panning (SAP). By using SAP, we identified two scFv antibodies, m6 and m9, that were tested with a panel of 33 diverse primary HIV-1 infectious isolates in an assay based on a reporter cell-line expressing high levels of CD4, CCR5 and CXCR4. The IC(50) was less than 50 microg/ml for 21 (m6) and 19 (m9) out of 29 isolates from group M (subtypes A-C, F, G and CRF-01AE) and one isolate from group N; three isolates from group O were not significantly inhibited at 50 microg/ml. The average IC(50) values for the two antibodies were significantly (p<0.001, n=29) lower compared to scFv X5. Their inhibitory activity does not appear to be related to the HIV-1 subtype, coreceptor usage or the disease stage. m9 inhibited infection of peripheral blood mononuclear cells by the primary isolates JRCSF, 89.6 and BR020 with IC(90) of 4, 6 and 25 microg/ml, respectively; for a single-round infection by pseudovirus, the IC(90) for JRSCF, 89.6, YU2 and HXBc2 was 15, 5, 15 and 5 microg/ml, respectively. In these two assays the IC(90) for m9 was, on average, two- to threefold lower than for scFv X5. These results demonstrate that both the potency and the breadth of HIV-1 neutralization of one of the few known potent broadly cross-reactive human monoclonal antibodies, scFv X5, could be improved significantly. However, only experiments in animal models and clinical trials in humans will show whether these new scFvs and the approach for their identification have potential in the development of prophylactics and therapeutics for HIV-1 infections.
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PMID:Improved breadth and potency of an HIV-1-neutralizing human single-chain antibody by random mutagenesis and sequential antigen panning. 1465 51

The introduction of recombinant human erythropoietin (RHuEPO) has dramatically changed the therapeutic approach to the anemia of chronic renal failure. Clinical studies have also demonstrated that RHuEPO is effectiveness in various non-uremic conditions, such as anemia associated with onco-hematological disorders, prematurity, HIV infection and to reduce the exposure to allogeneic blood in surgical patients. In this review, we briefly analyze the main clinical applications of RHuEPO, with particular attention to the potential complications deriving from its use.
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PMID:[Clinical use of erythropoietin]. 1514 48

The molecular diversity and demographic characteristics among 976 anti-HIV-1-positive heterosexuals attending 15 sexually transmitted infection (STI) clinics participating in an unlinked anonymous HIV prevalence serosurvey in England and Wales during 1997-2000 were investigated. Subtypes were assigned by heteroduplex mobility assay or sequencing of the p17/p24 region of gag and the V3/V4 region of env and by sequencing of the protease gene. Overall, there was no significant change in the subtype distribution, with subtype C accounting for the majority (32%) of subtyped infections. Subtypes B (29%), A (12%), circulating recombinant forms (CRFs, 9%), unique recombinant forms (URFs, 8%), and subtypes D-H (8%) were also detected. Thirty-nine percent of infections in men were with subtype B, whereas subtype C was most common (38%) in women. Logistic regression analyses showed the relative risk (RR) of infection with a non-B subtype, compared with subtype B, to be greater in African-born individuals (RR = 28.9, P < 0.01), among newly diagnosed infections (RR = 3.4, P < 0.01), and in women (RR = 2.4, P < 0.01). These findings indicate a high level of genetic diversity among HIV-infected heterosexual STI clinic attendees in England and Wales. Recently, subtype C has become most prevalent, particularly in younger age groups, suggesting recent acquisition of this viral strain. The high proportion of non-B, CRF, and URF infections among UK-born individuals is consistent with mixing between migrants and UK-born individuals in England and Wales. As migration patterns change, continued monitoring of HIV genetic diversity will aid understanding of transmission patterns.
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PMID:Surveillance of HIV-1 subtypes among heterosexuals in England and Wales, 1997-2000. 1524 63

More than 1,100 transplants have been performed at WFUBMC, including 60 pediatric transplants and 40 pancreas transplants. The one-year living donor kidney graft survival rate exceeds 90% and the 2 year deceased donor kidney graft survival rate exceeds 80%. The current active waiting list includes more than 300 candidates. Despite more transplants being performed, we continue to under-serve our referral area, which has among the highest rates of hypertension, diabetes, and end stage renal disease in the country. The AOTP has experienced a period of rapid growth over the past 2 years based upon sharing of zero HLA antigen-mismatched kidneys, use of ECD kidneys, liberalization of donor and recipient selection criteria, and the continued development of the pancreas transplant and laparoscopic donor nephrectomy programs. The pancreas transplant program will continue to grow as the waiting list enlarges and matures, with a 200% increase in activity expected within the next few years. The LDKT program will expand as more emphasis is placed on our pretransplant practice, including the more liberal application of laparoscopic donor nephrectomy, which has now become a standard procedure at our WFUBMC is involved in a number of clinical research projects studying new immunosuppressive agents and regimens. In this chapter, we have presented our recent experience with KTX in the elderly, ECD kidneys, alternate day Thymoglobulin administration, valganciclovir prophylaxis, SRL conversion using daclizumab bridge therapy, and pancreas transplantation with portal-enteric drainage. We plan to initiate a number of new protocols in the immediate future, including desensitization of the highly sensitized patient, ABO incompatible transplantation, transplantation of the HIV-positive patient, steroid withdrawal and avoidance regimens, living kidney donation from the anonymous altruistic donor, paired kidney exchanges from living donors, and islet transplantation. WFUBMC remains the most active donor hospital in North Carolina, and a non-heart beating donor protocol has been successfully initiated at our facility. Although much has been accomplished, a number of challenges remain. We look forward to building on our accomplishments, confronting the challenges, and achieving a level of excellence that could only be attained by mutual commitment from a dedicated, multidisciplinary team.
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PMID:Kidney and pancreas transplantation at Wake Forest University Baptist Medical Center. 1538 15

According to UNAIDS data there are 40 millions of HIV infected people in the world. 7880 people are infected with HIV (official statistics) in Poland. Because of improvement of dialysis accessibility in Poland there is no limitations of qualification for dialysis for HIV infected patients. In this article authors present general information about HIV infection (epidemiology, diagnostic, clinical picture and treatment), post exposure management and prophylaxis in dialysis centers. We present also algorithms of management with patient with acute/chronic renal failure in dependence on result of HIV test.
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PMID:[Problem of HIV-infected patients receiving dialysis]. 1551 30

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