Home About us Contact
|
Home About us Contact | ||
|
|
||
HIV-1 Strains (hiv-1 + strain)
Selected AbstractsEffective program against mother-to-child transmission of HIV at Saint Camille Medical Centre in Burkina FasoJOURNAL OF MEDICAL VIROLOGY, Issue 7 2007J. Simpore Abstract The present research was aimed to prevent mother-to-child transmission of HIV; to use RT-PCR in order to detect, 6 months after birth, infected children; and to test the antiretroviral resistance of both children and mothers in order to offer them a suitable therapy. At the Saint Camille Medical Centre, 3,127 pregnant women (aged 15,44 years) accepted to be enrolled in the mother-to-child transmission prevention protocol that envisages: (i) Voluntary Counselling and Testing for all the pregnant women; (ii) Antiretroviral therapy for HIV positive pregnant women and for their newborns; (iii) either powdered milk feeding or short breast-feeding and RT-PCR test for their children; (iv) finally, pol gene sequencing and antiretroviral resistance identifications among HIV positive mothers and children. Among the patients, 227/3,127 HIV seropositive women were found: 221/227 HIV-1, 4/227 HIV-2, and 2/227 mixed HIV infections. The RT-PCR test allowed the detection of 3/213 (1.4%) HIV infected children: 0/109 (0%) from mothers under ARV therapy and 3/104 (2.8%) from mothers treated with Nevirapine. All children had recombinant HIV-1 strain (CRF06_CPX) with: minor PR mutations (M36I, K20I) and RT mutations (R211K). Among them, two twins had Non-Nucleoside Reverse Transcriptase Inhibitor mutation (Y18CY). Both mothers acquired a major PR mutation (V8IV), investigated 6 months after a single-dose of Nevirapine. Prevention by single-dose of Nevirapine reduced significantly mother-to-child transmission of HIV, but caused many mutations and resistance to antiretroviral drugs. Based on present study the antiretroviral therapy protocol, together with the artificial-feeding, might represent the ideal strategy to avoid transmission of HIV from mother-to-child. J. Med. Virol. 79:873,879, 2007. © 2007 Wiley-Liss, Inc. [source] Cloning and characterization of SDF-1,, a novel SDF-1 chemokine transcript with developmentally regulated expression in the nervous systemEUROPEAN JOURNAL OF NEUROSCIENCE, Issue 6 2000Marc Gleichmann Abstract The cytokines SDF-1, and -1, are two alternatively spliced variants of the CXC (,) chemokines that are highly conserved among species. SDF-1, was shown to function as a B-cell maturation factor, a ligand for the CXCR4 (LESTR/fusin) chemokine receptor, thereby inhibiting replication of T cell-tropic HIV-1 strains and inducing cell death in human neuronal cell lines. In this report the cloning of the rat SDF-1, cDNA and a new SDF-1 isoform, SDF-1,, are presented. Using Northern blot analysis, the expression pattern of both isoforms was studied in different tissues and it is shown that during postnatal development of the central and peripheral nervous system SDF-1,- and SDF-1,-mRNA expression is inversely regulated. Whilst SDF-1,-mRNA is the predominant isoform in embryonic and early postnatal nerve tissue, SDF-1,-mRNA is expressed at higher levels in adulthood. After peripheral nerve lesion a transient increase in SDF-1,-mRNA expression is observed. As revealed by in situ hybridization, neurons and Schwann cells are the main cellular sources of both SDF-1, and SDF-1, mRNAs in the nervous system. Computer-assisted analysis revealed that both transcripts encode secreted peptides with putative proteolytic cleavage sites which might generate novel neuropeptides. [source] Structure,function relationship of novel X4 HIV-1 entry inhibitors , L- and D-arginine peptide-aminoglycoside conjugatesFEBS JOURNAL, Issue 24 2007Ravi Hegde We present the design, synthesis, anti-HIV-1 and mode of action of neomycin and neamine conjugated at specific sites to arginine 6- and 9-mers d - and l -arginine peptides (APACs). The d -APACs inhibit the infectivity of X4 HIV-1 strains by one or two orders of magnitude more potently than their respective l -APACs. d -arginine conjugates exhibit significantly higher affinity towards CXC chemokine receptor type 4 (CXCR4) than their l -arginine analogs, as determined by their inhibition of monoclonal anti-CXCR4 mAb 12G5 binding to cells and of stromal cell-derived factor 1, (SDF-1,)/CXCL12 induced cell migration. These results indicate that APACs inhibit X4 HIV-1 cell entry by interacting with CXCR4 residues common to glycoprotein 120 and monoclonal anti-CXCR4 mAb 12G5 binding. d -APACs readily concentrate in the nucleus, whereas the l -APACs do not. 9-mer- d -arginine analogues are more efficient inhibitors than the 6-mer- d -arginine conjugates and the neomycin- d -polymers are better inhibitors than their respective neamine conjugates. This and further structure,function studies of APACs may provide new target(s) and lead compound(s) of more potent HIV-1 cell entry inhibitors. [source] Isolated human astrocytes are not susceptible to infection by M- and T-tropic HIV-1 strains despite functional expression of the chemokine receptors CCR5 and CXCR4 ,GLIA, Issue 3 2001Agnès Boutet Abstract Within the brain, HIV-1 targets the microglia and astrocytes. Previous studies have reported that viral entry into astrocytes is independent of CD4, in contrast to microglia. We aimed to determine whether chemokine receptors play a role in mediating CD4-independent HIV-1 entry into astrocytes. We found that embryonic astrocytes and microglial cells express CCR5, CCR3, and CXCR4 transcripts. Intracellular calcium levels in astrocytes were found to increase following application of RANTES, MIP-1, (CCR5-agonist), SDF-1, (CXCR4-agonist), but not eotaxin (CCR3-agonist). In microglial cells, eotaxin was also able to modulate internal calcium homeostasis. CD4 was not present at the cell surface of purified astrocytes but CD4 mRNA could be detected by RT-PCR. Neither HIV-19533 (R5 isolate) nor HIV-1LAI (X4 isolate) penetrated into purified astrocytes. In contrast, mixed CNS cell cultures were infected by HIV-19533 and this was inhibited by anti-CD4 mAb in 4/4 tested cultures and by anti-CCR5 mAb in 2/4. Thus, the HIV-1 R5 strain requires CD4 to penetrate into brain cells, suggesting that CCR5 cannot be used as the primary receptor for M-tropic HIV-1 strains in astrocytes. Moreover, inconstant inhibition of HIV-1 entry by anti-CCR5 mAb supports the existence of alternative coreceptors for penetration of M-tropic isolates into brain cells. GLIA 34:165,177, 2001. © 2001 Wiley-Liss, Inc. [source] Early emergence of raltegravir resistance mutations in patients receiving HAART salvage regimensJOURNAL OF MEDICAL VIROLOGY, Issue 1 2010Fausto Baldanti Abstract The emergence of drug-resistance mutations in HIV-1 integrase of patients receiving HAART salvage regimens including raltegravir was investigated in 11 heavily pretreated patients (median number of treatment failures 12, range 5,22) within an expanded access program in Pavia, Italy. HIV-1 RNA levels in plasma, CD4+ T-cell counts and sequencing of HIV-1 reverse transcriptase (RT), protease (PR), gp41, and integrase genes were performed at baseline and after 1, 2, 3, 6, and 12 months. The treatment baseline median HIV-1 RNA levels in plasma decreased from 7,510 (range 118,407,107) to <50,copies/ml (range <50,7,562), while median CD4+ T-cell counts remained unchanged (from 212,cells/µl, range 10,764 to 262,cells/µl, range 13,760). Mutations at positions involved in raltegravir resistance (E92G, G140S, Q148H, and N155H) were detected in 4 of 11 (36.3%) patients as early as 1 month after initiating salvage HAART. Of note, the E,,,G change at codon 92 was not reported previously. In two patients with raltegravir resistance, the simultaneous appearance of additional mutations (Y143R and E170A) with an unclear impact on susceptibility to raltegravir or on integrase activity was observed. It is concluded that raltegravir resistant HIV-1 strains may emerge as early as 1 month after initiating HAART salvage regimens. A new mutation associated with the emergence of raltegravir resistance is described, and the simultaneous appearance of primary and secondary mutations was observed. The effect of single and multiple mutations on integrase activity, raltegravir susceptibility, and on the capacity of viral replication remains to be elucidated. J. Med. Virol. 82:116,122, 2010. © 2009 Wiley-Liss, Inc. [source] Genetic characterization of complex inter-recombinant HIV-1 strains circulating in Spain and reliability of distinct rapid subtyping tools,JOURNAL OF MEDICAL VIROLOGY, Issue 3 2008Africa Holguín Abstract Genetic recombination and high rate of mutation increase HIV-1 diversity, allowing viruses to escape more easily from the host immune response or antiretroviral drugs. The recombinant nature of full-length HIV-1 genomic sequences derived from viruses infecting five epidemiologically unlinked individuals carrying HIV-1 non-B variants was investigated. Overlapping PCR amplifications followed by direct sequencing of viral products derived from plasma and phylogenetic analyses were carried out. Four viral sequences clustered with CRF06_cpx and one with CRF02_AG. However, subtyping of separate genes within the same genome revealed that four were recombinant forms involving different subtypes and/or CRFs with distinct breakpoints. Two specimens included CRF02_AG and CRF06_cpx sequences with several fragments from other HIV-1 clades along their genomes. Three rapid subtyping tools (Stanford, NCBI, and REGA) showed discrepant results when interpreting these viral sequences. This is the first description of CRF02_AG/CRF06_ cpx recombinants in Spain. The results highlight the tremendous heterogeneity of HIV-1 recombinant strains currently in circulation. J. Med. Virol. 80:383,391, 2008. © 2008 Wiley-Liss, Inc. [source] Serotyping and genotyping of HIV-1 infection in residents of Khayelitsha, Cape Town, South AfricaJOURNAL OF MEDICAL VIROLOGY, Issue 12 2006G.B. Jacobs Abstract It is estimated that between 5.5 and 6.1 million people are infected with HIV/acquired immunodeficiency syndrome (AIDS) in South Africa, with subtype C responsible for the majority of these infections. The Khayelitsha suburb of Cape Town has one of the highest HIV prevalence rates in South Africa. Overcrowding combined with unemployment and crime in parts of the area perpetuates high-risk sexual behavior, which increases exposure to infection by HIV. Against this background, the objective of this study was to characterize HIV-1 in residents confirmed to be seropositive. Serotyping was performed through a competitive enzyme-linked immunosorbent assay (cPEIA). Genotyping methods included RNA isolation followed by RT-PCR and sequencing of the gag p24, env gp41 immunodominant region (IDR), and env gp120 V3 genome regions of HIV-1. With the exception of a possible C/D recombinant strain, all HIV-1 strains were characterized as HIV-1 group M subtype C. One individual was shown to harbor multiple strains of HIV-1 subtype C. In Southern Africa, the focus has been to develop a subtype C candidate vaccine, as this is the major subtype found in this geographical area. Therefore, the spread of HIV-1 and its recombinant strains needs to be monitored closely. J. Med. Virol. 78:1529,1536, 2006. © 2006 Wiley-Liss, Inc. [source] Characterization of drug-resistance mutations in HIV-1 isolates from non-HAART and HAART treated patients in Burkina FasoJOURNAL OF MEDICAL VIROLOGY, Issue 11 2006W.M. Nadembega Abstract Non-B HIV subtypes have been estimated to account for 88% of HIV infections in the world. These subtypes are particularly relevant in view of the availability of antiretroviral (ARV) drugs, since subtype-specific mutations are associated with drug-resistance in developing countries. Therefore, the pol gene sequences in HIV-1 isolates were examined from the three distinct groups of 39 infected patients from Ouagadougou in Burkina Faso: 17 patients who had not received any antiretroviral therapy (ART); 16 patients received ART, and 6 HIV-infected children, from infected mothers, received a single Nevirapine dose prophylaxis during birth. HIV-1 pol sequencing was successful for 29 samples. As expected, all patients presented the common (non-B subtype) M36I polymorphism and 26/29 (90%) the K20I mutation. Phylogenetic studies showed high predominance of recombinant HIV-1 strains: CRF06_cpx 16/29 (55.17%), CRF02_AG 9/29 (31.03%), A1 2/29 (6.89%), G 1/29 (3.44%), and CRF09_cpx 1/29 (3.44%). Two twins showed, 6 months after birth, a NNRTI-mutation (Y181C/Y). During the same period, the twin mother presented a different NNRTI-mutation (V106I), thus suggesting that the different blood drug concentration may determine a different drug-resistance pathway. Among 17 non-highly active antiretroviral therapy (HAART) patients, 3/17 (17.64%) presented virus with reverse transcriptase (RT) mutations [V118I: 1/17 patients (5.88%), V179E: 2/17 patients (11.76%)]. 10/17 (58.82%) presented virus with minor protease (PR) mutations [L63P: 5/17 patients (29.41%), V77I: 3/17 patients (17.64%), L10I: 2/17 patients (11.76%)]. 4/17 patients did not show any PR and RT mutations (23.52%). Among six HAART-treated patients, 6/6 and 3/6 had M36I and L63LP protease minor subtypes, respectively; and only two (33.33%) presented virus with K103N mutation. The low prevalence of drug-resistant associated mutations in Burkina Faso is encouraging. However, further studies with a larger cohort with a high non-B subtype prevalence are necessary to optimize ART in developing countries. J. Med. Virol. 78:1385,1391, 2006. © 2006 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] Safety and Efficacy of Raltegravir in HIV-Infected Transplant Patients Cotreated with Immunosuppressive DrugsAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009L. Tricot Solid organ transplantations (SOT) are performed successfully in selected HIV-infected patients. However, multiple and reciprocal drug,drug interactions are observed between antiretroviral (ARV) drugs and calcineurin inhibitors (CNIs) through CYP450 metabolization. Raltegravir (RAL), a novel HIV-1 integrase inhibitor, is not a substrate of CYP450 enzymes. We retrospectively reviewed the outcomes of 13 HIV-infected transplant patients treated by an RAL + two nucleosidic reverse transcriptase inhibitor (NRTI) regimen, in terms of tolerability, ARV efficacy (plasma viral load, CD4 cell count), drug interactions, RAL pharmacokinetics and transplant outcome. Thirteen patients with liver (n = 8) or kidney (n = 5) transplantation were included. RAL was initiated (400 mg BID) either at time of transplantation (n = 6), or after transplantation (n = 7). Median RAL trough concentration was 507 ng/mL (176,890), which is above the in vitro IC95 for wild type HIV-1 strains (15 ng/mL). Target trough levels of CNIs were promptly obtained with standard dosages of tacrolimus or cyclosporine. RAL tolerability was excellent. There was no episode of acute rejection. HIV infection remained controlled. After a median follow-up of 9 months (range: 6,14), all patients were alive with satisfactory graft function. The use of an RAL + two NRTI-based regimen is a good alternative in HIV-infected patients undergoing SOT. [source] Bis-Tetrahydrofuran: a Privileged Ligand for Darunavir and a New Generation of HIV Protease Inhibitors That Combat Drug ResistanceCHEMMEDCHEM, Issue 9 2006Two inhibitors that incorporate bis-THF as an effective high-affinity P2 ligand for the HIV-1 protease substrate binding site maintain impressive potency against mutant strains resistant to currently approved protease inhibitors. Crystallographic structures of protein,ligand complexes help to explain the superior antiviral property of these inhibitors and their potency against a wide spectrum of HIV-1 strains. [source] | |||||||||||||