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HIV Strains (hiv + strain)
Selected AbstractsHIV-1 proviral resistance mutations: usefulness in clinical practiceHIV MEDICINE, Issue 8 2010B Kabamba-Mukadi Objectives Transmitted HIV strains may harbour drug resistance mutations. HIV-1 drug resistance mutations are currently detected in plasma viral RNA. HIV-1 proviral DNA could be an alternative marker, as it persists in infected cells. Methods This was a prospective study assessing the prevalence and persistence of HIV-1 drug resistance mutations in DNA from CD4 cells before and after protease inhibitor (PI)- or nonnucleoside reverse transcriptase inhibitor (NNRTI)-based therapy initiation in 69 drug-naïve patients. Results Before therapy, 90 and 66% of detected mutations were present in CD4 cells and plasma, respectively. We detected seven key mutations, and four of these (M184M/V, M184M/I, K103K/N and M46M/I) were only found in the cells. When treatment was started, 40 patients were followed; the mutations detected at the naïve stage remained present for at least 1 year. Under successful treatment, new key mutations emerged in CD4 cells (M184I, M184M/I and Y188Y/H). Conclusions The proportion of mutations detected in the DNA was statistically significantly higher than that detected in standard RNA genotyping, and these mutations persisted for at least 1 year irrespective of therapy. The pre-existence of resistance mutations did not jeopardise treatment outcome when the drug concerned was not included in the regimen. Analysis of HIV-1 DNA could be useful in chronic infections or when switching therapy in patients with undetectable viraemia. [source] Antiviral activity of low-dose alovudine in antiretroviral-experienced patients: results from a 4-week randomized, double-blind, placebo-controlled dose-ranging trial,HIV MEDICINE, Issue 3 2007J Ghosn Background Alovudine inhibits replication of highly nucleoside reverse transcriptase inhibitor (NRTI)-resistant HIV strains in vitro. However, dose-dependent safety concerns resulted in its initial development being halted. Recently, a 4-week course of alovudine 7.5 mg/day added to a stavudine-free failing regimen yielded a significant decrease in viral load by ,1.88 log10 HIV-1 RNA copies/mL. The magnitude of the reduction in viral load suggested that lower doses might still be effective while offering adequate safety during long-term use. Objective To determine whether lower dosages of alovudine still provide significant antiviral activity in patients with broad NRTI resistance. Methods A randomized, double-blind, placebo-controlled trial investigating three doses of alovudine (0.5, 1 and 2 mg) or placebo added for 4 weeks to a failing regimen in patients with evidence of NRTI-resistant HIV strains [,2 thymidine-associated mutations (TAMs)]. The primary endpoint was the mean viral load reduction between baseline and week 4. Results Seventy-two patients were enrolled in the study: 21, 13, 18 and 20 in the placebo and 0.5, 1 and 2 mg arms, respectively. Baseline median CD4 count and viral load were 298 cells/,L (range 44,692 cells/,L) and 3.9 log10 copies/mL (range 2.5,5.2 log10 copies/mL), respectively. Baseline viral isolates harboured a median of four TAMs. Alovudine was added to a median four-drug failing regimen. At week 4, compared with placebo, mean viral load changes were ,0.42 log10 [95% confidence interval (CI) ,0.67 to ,0.18] and ,0.30 log10 (,0.55 to ,0.06) in the 2 and 1 mg arms, respectively. There was no significant change in CD4 cell count. Alovudine was well tolerated. Conclusion: A 4-week course of alovudine 2 mg/day provided a modest but significant viral load reduction in patients harbouring viruses with a median of four TAMs. [source] Inhibition of DC-SIGN-mediated trans infection of T cells by mannose-binding lectinIMMUNOLOGY, Issue 1 2003Gregory T. Spear Summary Some dendritic cells (DC) express a cell-surface lectin called ,dendritic cell-specific intracellular adhesion molecule 3 (ICAM-3)-grabbing non-integrin' (DC-SIGN). DC-SIGN has been shown to mediate a type of infection called ,trans' infection, where DC bind human immunodeficiency virus (HIV) and efficiently transfer the virus to T cells. We investigated the possibility that mannose-binding lectin (MBL), a soluble lectin that functions as a recognition molecule in innate immunity and that binds to HIV, could block trans infection mediated by DC-SIGN. Binding studies with glycoprotein (gp)120/gp41-positive and -negative virus preparations suggested that DC-SIGN and MBL bind primarily to glycans on gp120/gp41, as opposed to glycans on host-cell-derived proteins, indicating a close overlap in the binding site of the two lectins and supporting the notion that MBL could prevent binding of HIV to DC-SIGN. Preincubation of X4, R5 or dual-tropic HIV strains with MBL prevented DC-SIGN-mediated trans infection of T cells. The mechanism of MBL blocking trans infection of T cells was at least partly caused by blocking of virus binding to DC-SIGN positive cells. This study shows that MBL prevents DC-SIGN-mediated trans infection of T cells in vitro and suggests that in infected persons, MBL may inhibit DC-SIGN-mediated uptake and spread of HIV. [source] Changes in circulation of B and non-B HIV strains: Spotlight on a reference centre for infectious diseases in Northern ItalyJOURNAL OF MEDICAL VIROLOGY, Issue 6 2008Fausto Baldanti Abstract Stored demographic data and HIV RT and protease sequences of 877 HIV patients attending for the first time the HIV/AIDS outpatient clinics of a reference Infectious Diseases centre in Northern Italy between 1999 and 2006 were stratified by 3-year spanning periods according to date of HIV infection. In the period 1980,1982, new infections were entirely caused by HIV-1 subtype B strains and were all diagnosed in injection drug users, 88.9% of whom were males. Injection drug users accounted for 12.8% of new infections in 2004,2006. The frequency of heterosexually-transmitted infections consistently increased until 2000 (from almost none to 51.5%) remaining stable afterwards. About half of heterosexual patients were females. HIV infections among homosexual men increased from 0% in 1980,1982 to 15,21% between 1998 and 2006. Overall, the frequency of non-B subtypes HIV strains increased from 0% in 1980,1982 to 20.3% in 2004,2006 with a greater impact in heterosexuals (from 0% in 1980,1982 to 30.5% in 2004,2006). In conclusion, a picture of the changing scenario of circulating HIV types and subtypes in a reference Infectious Diseases centre in Northern Italy over the past 26 years is provided. A progressive modification in risk factors for HIV infection and a significant increase in the frequency of non-B HIV strains were observed. J. Med. Virol. 80:947,952, 2008. © 2008 Wiley-Liss, Inc. [source] Global epidemiology of HIV,JOURNAL OF MEDICAL VIROLOGY, Issue S1 2006Francine E. McCutchan Abstract HIV is among the most generically variable of human pathogens. A comprehensive and detailed description of HIV strains in the pandemic is an important foundation for diagnosis, treatment, and prevention. The current sequence database for HIV includes almost 800 complete genome sequences, documenting HIV-1 groups M, O, and N, and HIV-2. Among HIV-1 group M strains, responsible for the vast majority of HIV infections worldwide, 743 sequences represent 9 genetic subtypes, 16 circulating recombinant forms (CRF) that are spreading in populations, and a variety of unique recombinant forms (URF), identified so far only from a single individual. The global distribution of HIV is complex and dynamic with regional epidemics harboring only a subset of the global diversity. HIV strains differ enormously in terms of global prevalence. Six strains account for the majority of HIV infections: HIV-1 subtypes A, B, C, D, and two of the CRF, CRF01-AE and CRF02_AG, respectively. Many of the known subtypes and recombinant forms are currently rare in the epidemic, but could spread more widely if favorable conditions arise. HIV-2 is largely restricted to West Africa at relatively low prevalence there. Groups O and N of HIV-1 are very rare in the pandemic. The goal of universal coverage of HIV-1 strains by diagnostic tests can be met by minimizing false negative test rates for the six globally prevalent HIV-1 group M strains and HIV-2, and by evaluating systematically coverage of rare subtypes and recombinant forms. J. Med. Virol. 78:S7,S12, 2006. © 2006 Wiley-Liss, Inc. [source] Alcohol Suppresses IL-2,Induced CC Chemokine Production by Natural Killer CellsALCOHOLISM, Issue 9 2005Ting Zhang Background: Natural killer (NK) cells are a critical component of the host innate immune system. We investigated whether alcohol impairs NK cell function, particularly production of CC chemokines induced by interleukin (IL)-2, the natural ligands for CCR5 receptor. Methods: Primary NK cells and NK cell line (YTS) were cultured with or without alcohol (10 to 80 mM) for three hours. The culture supernatants were then harvested and used to treat human peripheral blood monocyte-derived macrophages and a HeLa cell line, which expresses CD4, CCR5, and CXCR4 receptors (MAGI cells). CC chemokine expression by YTS and primary NK cells treated with or without alcohol was analyzed with the real-time RT-PCR and ELISA. Ca2+i and Western blot assays were used to determine calcium-mediated intracellular signaling pathway and NF-,B p65 expression. HIV strains (Bal and UG024) were used to infect macrophages and MAGI cells. In addition, ADA (macrophage-tropic strain) and murine leukemia virus (MLV) envelope-pseudotyped HIV infection was carried out in macrophages. HIV infectivity was determined by HIV reverse transcriptase (RT) and ,-galactosidase activity assays. Results: Alcohol inhibited IL-2,induced CC chemokine (CCL3 and CCL4) expression by NK cells. Functional tests demonstrated that this reduced expression of CC chemokines was associated with diminished anti-HIV ability of NK cells. Alcohol also reduced the ability of NK cells to response to CCL3-mediated chemotaxis. Alcohol inhibited IL-2,induced NF-,B p65 protein expression and calcium mobilization by NK cells. Conclusions: Alcohol, through the inhibition of IL-2,induced NF-,B p65 protein expression and intracellular calcium mobilization, suppressed NK cell production of CC chemokines. This suppression of CC chemokine production was associated with diminished anti-HIV activity of NK cells. Thus, by inhibiting NK cell,mediated innate immunity against HIV, alcohol consumption may have a cofactor role in the immunopathogenesis of HIV disease. [source] Synthesis and Studies of New 2-(Coumarin-4-yloxy)-4,6-(substituted)-s-Triazine Derivatives as Potential Anti-HIV AgentsARCHIV DER PHARMAZIE, Issue 5 2009Dharmesh H. Mahajan Abstract Novel 2-(coumarin-4-yloxy)-4,6-(substituted)-s-triazine derivatives i. e., diaryltriazine (DATA) are reported as novel non-nucleoside reverse transcriptase inhibitors (NNRTIs), were synthesized and their activities against human immunodeficiency virus HIV-1 (III-B), HIV-2 (ROD), and the double RT mutant HIV-1 (K103N and Y181C) were assessed. Modifications at positions 4 and 6 of the coumarinyl-triazine scaffold generated interesting derivatives displaying good to moderate anti-HIV activity against selected HIV strains as compared to nevirapine and efavirenz. The synthesized compounds were characterized by FTIR, 1H-NMR, and mass spectral data together with elemental analysis. [source] On the origin and evolution of the human immunodeficiency virus (HIV)BIOLOGICAL REVIEWS, Issue 2 2001EDWARD C. HOLMES ABSTRACT The human AIDS viruses , HIV-1 and HIV-2 , impose major burdens on the health and economic status of many developing countries. Surveys of other animal species have revealed that related viruses , the SIVs , are widespread in a large number of African simian primates where they do not appear to cause disease. Phylogenetic analyses indicate that these SIVs are the reservoirs for the human viruses, with SIVsm from the sooty mangabey monkey the most likely source of HIV-2, and SIVcpz from the common chimpanzee the progenitor population for HIV-1. Although it is clear that AIDS has a zoonotic origin, it is less certain when HIV-1 and HIV-2 first entered human populations and whether cross-species viral transmission is common among primates. Within infected individuals the process of HIV evolution takes the form of an arms race, with the virus continually fixing mutations by natural selection which allow it to escape from host immune responses. The arms race is less intense in SIV-infected monkeys, where a weaker immune response generates less selective pressure on the virus. Such a difference in virus-host interaction, along with a broadening of co-receptor usage such that HIV strains are able to infect cells with both CCR5 and CXCR4 chemokine receptors, may explain the increased virulence of HIV in humans compared to SIV in other primates. [source] | |||||||||||||