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  1. Article ; Online: Endovascular repair first for ruptured abdominal aortic aneurysms.

    Galovich, Justin / Donayre, Carlos / Lin, John / Walot, Irwin / White, Rodney A

    Texas Heart Institute journal

    2013  Volume 40, Issue 5, Page(s) 553–555

    MeSH term(s) Aged, 80 and over ; Aortic Aneurysm, Abdominal/diagnostic imaging ; Aortic Aneurysm, Abdominal/surgery ; Aortic Rupture/diagnostic imaging ; Aortic Rupture/surgery ; Blood Vessel Prosthesis Implantation/methods ; Endovascular Procedures/methods ; Female ; Follow-Up Studies ; Humans ; Male ; Prosthesis Design ; Tomography, X-Ray Computed
    Language English
    Publishing date 2013-10-25
    Publishing country United States
    Document type Case Reports ; Journal Article
    ZDB-ID 604761-0
    ISSN 1526-6702 ; 0730-2347
    ISSN (online) 1526-6702
    ISSN 0730-2347
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  2. Article: Phenotypic drug resistance patterns in subtype A HIV-1 clones with nonnucleoside reverse transcriptase resistance mutations.

    Eshleman, Susan H / Jones, Dana / Galovich, Justin / Paxinos, Ellen E / Petropoulos, Christos J / Jackson, J Brooks / Parkin, Neil

    AIDS research and human retroviruses

    2006  Volume 22, Issue 3, Page(s) 289–293

    Abstract: We analyzed the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) susceptibility of 29 subtype A HIV-1 clones isolated from 10 Ugandan women after single-dose nevirapine (NVP) administration. Six clones had no NNRTI resistance-associated ... ...

    Abstract We analyzed the nonnucleoside reverse transcriptase (RT) inhibitor (NNRTI) susceptibility of 29 subtype A HIV-1 clones isolated from 10 Ugandan women after single-dose nevirapine (NVP) administration. Six clones had no NNRTI resistance-associated mutations ("wild type"), eight had K103N, nine had Y181C, five had G190A, and one had Y181S. Three clones displayed unexpected phenotypic drug susceptibility/resistance based on their RT genotypes. One wild-type clone had reduced susceptibility to NVP, delavirdine (DLV), and efavirenz (EFV), one clone with K103N was susceptible to all three NNRTIs, and one clone with G190A had extreme hypersusceptibility to DLV. Three unusual HIV-1 RT amino acid substitutions may have contributed to the unexpected phenotypes of the clones: I31T, N136S, and N265D. These polymorphisms were rarely detected among 47,900 HIV-1 genotypes from clinical samples of predominantly United States origin. Further studies are needed to define the genetic correlates of antiretroviral drug resistance in nonsubtype B HIV-1.
    MeSH term(s) Amino Acid Substitution ; Anti-HIV Agents/pharmacology ; Benzoxazines ; Clone Cells ; Delavirdine/pharmacology ; Drug Resistance, Viral ; Female ; HIV Reverse Transcriptase/genetics ; HIV-1/classification ; HIV-1/drug effects ; Humans ; Mutation ; Nevirapine/pharmacology ; Oxazines/pharmacology ; Polymorphism, Genetic ; Reverse Transcriptase Inhibitors/pharmacology
    Chemical Substances Anti-HIV Agents ; Benzoxazines ; Oxazines ; Reverse Transcriptase Inhibitors ; Nevirapine (99DK7FVK1H) ; Delavirdine (DOL5F9JD3E) ; HIV Reverse Transcriptase (EC 2.7.7.49) ; efavirenz (JE6H2O27P8)
    Language English
    Publishing date 2006-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 639130-8
    ISSN 1931-8405 ; 0889-2229
    ISSN (online) 1931-8405
    ISSN 0889-2229
    DOI 10.1089/aid.2006.22.289
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  3. Article: Adjunctive passive immunotherapy in human immunodeficiency virus type 1-infected individuals treated with antiviral therapy during acute and early infection.

    Mehandru, Saurabh / Vcelar, Brigitta / Wrin, Terri / Stiegler, Gabriela / Joos, Beda / Mohri, Hiroshi / Boden, Daniel / Galovich, Justin / Tenner-Racz, Klara / Racz, Paul / Carrington, Mary / Petropoulos, Christos / Katinger, Hermann / Markowitz, Martin

    Journal of virology

    2007  Volume 81, Issue 20, Page(s) 11016–11031

    Abstract: Three neutralizing monoclonal antibodies (MAbs), 2G12, 2F5, and 4E10, with activity in vitro and in vivo were administered in an open-label, nonrandomized, proof-of-concept study to attempt to prevent viral rebound after interruption of antiretroviral ... ...

    Abstract Three neutralizing monoclonal antibodies (MAbs), 2G12, 2F5, and 4E10, with activity in vitro and in vivo were administered in an open-label, nonrandomized, proof-of-concept study to attempt to prevent viral rebound after interruption of antiretroviral therapy (ART). Ten human immunodeficiency virus type 1-infected individuals identified and treated with ART during acute and early infection were enrolled. The first six patients were administered 1.0 g of each of the three MAbs per infusion. The remaining four patients received 2G12 at 1.0 g/infusion and 2.0 g/infusion of 2F5 and 4E10. The MAbs were well tolerated. Grade I post-partial thromboplastin time prolongations were noted. Viral rebound was observed in 8/10 subjects (28 to 73 days post-ART interruption), and 2/10 subjects remained aviremic over the course of the study. In seven of eight subjects with viral rebound, clear resistance to 2G12 emerged, whereas reductions in the susceptibilities of plasma-derived recombinant viruses to 2F5 and 4E10 were neither sustained nor consistently measured. Viral rebound was associated with a preferential depletion of CD4(+) T cells within the gastrointestinal tract. Though safe, the use of MAbs generally delayed, but did not prevent, virologic rebound. Consideration should be given to further pilot studies with alternative combinations of MAbs and perhaps additional novel treatment modalities.
    MeSH term(s) Anti-Retroviral Agents/therapeutic use ; Antibodies, Monoclonal/administration & dosage ; Antibodies, Viral/administration & dosage ; Blood Coagulation Tests ; CD4-Positive T-Lymphocytes/drug effects ; CD4-Positive T-Lymphocytes/virology ; Drug Resistance, Viral ; Gastrointestinal Tract ; HIV Infections/therapy ; HIV-1 ; Humans ; Immunization, Passive/methods ; Male ; Secondary Prevention ; Treatment Outcome
    Chemical Substances Anti-Retroviral Agents ; Antibodies, Monoclonal ; Antibodies, Viral
    Language English
    Publishing date 2007-10
    Publishing country United States
    Document type Clinical Trial ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.01340-07
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  4. Article: Neutralizing antibody responses against autologous and heterologous viruses in acute versus chronic human immunodeficiency virus (HIV) infection: evidence for a constraint on the ability of HIV to completely evade neutralizing antibody responses.

    Deeks, Steven G / Schweighardt, Becky / Wrin, Terri / Galovich, Justin / Hoh, Rebecca / Sinclair, Elizabeth / Hunt, Peter / McCune, Joseph M / Martin, Jeffrey N / Petropoulos, Christos J / Hecht, Frederick M

    Journal of virology

    2006  Volume 80, Issue 12, Page(s) 6155–6164

    Abstract: Acute human immunodeficiency virus (HIV) infection is associated with the rapid development of neutralization escape mutations. The degree to which viral evolution persists in chronic infection has not been well characterized, nor is it clear if all ... ...

    Abstract Acute human immunodeficiency virus (HIV) infection is associated with the rapid development of neutralization escape mutations. The degree to which viral evolution persists in chronic infection has not been well characterized, nor is it clear if all patients develop high-level neutralization antibody escape. We therefore measured neutralizing antibody responses against autologous and heterologous viruses in a cohort of acutely and chronically infected subjects (n = 65). Neutralizing antibody responses against both autologous virus and heterologous viruses were lower among individuals with acute infection than among those with chronic infection. Among chronically infected individuals, there was a negative correlation between the level of neutralizing antibodies against autologous virus and the level of viremia. In contrast, there was a positive correlation between the level of neutralizing antibodies against a panel of heterologous viruses and the level of viremia. Viral evolution, as defined by the presence of higher neutralizing titers directed against earlier viruses than against contemporaneous viruses, was evident for subjects with recent infection but absent for those with chronic infection. In summary, neutralizing antibody responses against contemporaneous autologous viruses are absent in early HIV infection but can be detected at low levels in chronic infection, particularly among those controlling HIV in the absence of therapy. HIV replication either directly or indirectly drives the production of increasing levels of antibodies that cross-neutralize heterologous primary isolates. Collectively, these observations indicate that although HIV continuously drives the production of neutralizing antibodies, there may be limits to the capacity of the virus to evolve continuously in response to these antibodies. These observations also suggest that the neutralizing antibody response may contribute to the long-term control of HIV in some patients while protecting against HIV superinfection in most patients.
    MeSH term(s) Acute Disease ; Antibodies, Heterophile ; Antibody Formation ; Chronic Disease ; HIV/immunology ; HIV Antibodies/biosynthesis ; HIV Infections/immunology ; Humans ; Virus Replication/immunology
    Chemical Substances Antibodies, Heterophile ; HIV Antibodies
    Language English
    Publishing date 2006-06
    Publishing country United States
    Document type Comparative Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.00093-06
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  5. Article: Neutralizing antibody responses drive the evolution of human immunodeficiency virus type 1 envelope during recent HIV infection.

    Frost, Simon D W / Wrin, Terri / Smith, Davey M / Kosakovsky Pond, Sergei L / Liu, Yang / Paxinos, Ellen / Chappey, Colombe / Galovich, Justin / Beauchaine, Jeff / Petropoulos, Christos J / Little, Susan J / Richman, Douglas D

    Proceedings of the National Academy of Sciences of the United States of America

    2005  Volume 102, Issue 51, Page(s) 18514–18519

    Abstract: HIV type 1 (HIV-1) can rapidly escape from neutralizing antibody responses. The genetic basis of this escape in vivo is poorly understood. We compared the pattern of evolution of the HIV-1 env gene between individuals with recent HIV infection whose ... ...

    Abstract HIV type 1 (HIV-1) can rapidly escape from neutralizing antibody responses. The genetic basis of this escape in vivo is poorly understood. We compared the pattern of evolution of the HIV-1 env gene between individuals with recent HIV infection whose virus exhibited either a low or a high rate of escape from neutralizing antibody responses. We demonstrate that the rate of viral escape at a phenotypic level is highly variable among individuals, and is strongly correlated with the rate of amino acid substitutions. We show that dramatic escape from neutralizing antibodies can occur in the relative absence of changes in glycosylation or insertions and deletions ("indels") in the envelope; conversely, changes in glycosylation and indels occur even in the absence of neutralizing antibody responses. Comparison of our data with the predictions of a mathematical model support a mechanism in which escape from neutralizing antibodies occurs via many amino acid substitutions, with low cross-neutralization between closely related viral strains. Our results suggest that autologous neutralizing antibody responses may play a pivotal role in the diversification of HIV-1 envelope during the early stages of infection.
    MeSH term(s) Adult ; Evolution, Molecular ; Gene Products, env/chemistry ; Gene Products, env/genetics ; Gene Products, env/immunology ; HIV Antibodies/immunology ; HIV Infections/immunology ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/immunology ; Humans ; Male ; Middle Aged ; Molecular Sequence Data ; Neutralization Tests ; Phenotype ; Time Factors
    Chemical Substances Gene Products, env ; HIV Antibodies
    Language English
    Publishing date 2005-12-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.0504658102
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  6. Article: Neutralization profiles of newly transmitted human immunodeficiency virus type 1 by monoclonal antibodies 2G12, 2F5, and 4E10.

    Mehandru, Saurabh / Wrin, Terri / Galovich, Justin / Stiegler, Gabriela / Vcelar, Brigitta / Hurley, Arlene / Hogan, Christine / Vasan, Sandhya / Katinger, Hermann / Petropoulos, Christos J / Markowitz, Martin

    Journal of virology

    2004  Volume 78, Issue 24, Page(s) 14039–14042

    Abstract: As the AIDS epidemic continues unabated, the development of a human immunodeficiency virus (HIV) vaccine is critical. Ideally, an effective vaccine should elicit cell-mediated and neutralizing humoral immune responses. We have determined the in vitro ... ...

    Abstract As the AIDS epidemic continues unabated, the development of a human immunodeficiency virus (HIV) vaccine is critical. Ideally, an effective vaccine should elicit cell-mediated and neutralizing humoral immune responses. We have determined the in vitro susceptibility profile of sexually transmitted viruses from 91 patients with acute and early HIV-1 infection to three monoclonal antibodies, 2G12, 2F5, and 4E10. Using a recombinant virus assay to measure neutralization, we found all transmitted viruses were neutralized by 4E10, 80% were neutralized by 2F5, and only 37% were neutralized by 2G12. We propose that the induction of 4E10-like antibodies should be a priority in designing immunogens to prevent HIV-1 infection.
    MeSH term(s) Antibodies, Monoclonal/administration & dosage ; Antibodies, Monoclonal/immunology ; Female ; HIV Antibodies/administration & dosage ; HIV Antibodies/immunology ; HIV Infections/prevention & control ; HIV Infections/transmission ; HIV Infections/virology ; HIV-1/genetics ; HIV-1/immunology ; Humans ; Male ; Neutralization Tests ; Recombination, Genetic ; Sexual Behavior
    Chemical Substances Antibodies, Monoclonal ; HIV Antibodies
    Language English
    Publishing date 2004-12
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/JVI.78.24.14039-14042.2004
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  7. Article: Characterization of a subtype D human immunodeficiency virus type 1 isolate that was obtained from an untreated individual and that is highly resistant to nonnucleoside reverse transcriptase inhibitors.

    Gao, Yong / Paxinos, Ellen / Galovich, Justin / Troyer, Ryan / Baird, Heather / Abreha, Measho / Kityo, Cissy / Mugyenyi, Peter / Petropoulos, Christos / Arts, Eric J

    Journal of virology

    2004  Volume 78, Issue 10, Page(s) 5390–5401

    Abstract: Human immunodeficiency virus type 1 (HIV-1) isolates derived from HIV-infected, treatment-naive Ugandan infants were propagated and tested for sensitivity to antiretroviral (ARV) drugs. Although most subtype A and D isolates displayed inhibition profiles ...

    Abstract Human immunodeficiency virus type 1 (HIV-1) isolates derived from HIV-infected, treatment-naive Ugandan infants were propagated and tested for sensitivity to antiretroviral (ARV) drugs. Although most subtype A and D isolates displayed inhibition profiles similar to those of subtype B strains, a subtype D isolate identified as D14-UG displayed high-level resistance to nevirapine in peripheral blood mononuclear cell cultures (>2,000-fold) and in MT4 cell cultures ( approximately 800-fold) but weaker resistance to delavirdine ( approximately 13-fold) and efavirenz ( approximately 8-fold) in MT4 cell cultures. To investigate the possible mechanism for this resistance to nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs), the RT coding region in pol was sequenced and compared to the consensus RT sequence of NNRTI-resistant and NNRTI-sensitive subtype A, B, and D HIV-1 isolates. D14-UG did not contain the classic amino acid substitutions conferring NNRTI resistance (e.g., Y181C, K103N, and G190A) but did have some putative sites associated with drug resistance, I135L, T139V, and V245T. Wild-type and mutated protease-RT genes from D14-UG and an NNRTI-sensitive subtype D isolate from Uganda (D13-UG) were cloned into pNL4-3 to produce recombinant viruses and to determine the effects of the mutations on susceptibility to ARV drugs, specifically, NNRTIs. The results showed that I135L and/or V245T mutations can confer high-level resistance to nevirapine and delavirdine as well as low level cross-resistance to efavirenz. Finally, ex vivo fitness analyses suggested that NNRTI-resistant sites 135L and 245T in wild-type isolate D14-UG may reduce RT fitness but do not have an impact on the fitness of the primary HIV-1 isolate.
    MeSH term(s) Drug Resistance, Viral ; HIV Reverse Transcriptase/genetics ; HIV-1/classification ; HIV-1/drug effects ; Humans ; Mutation ; Polymorphism, Genetic ; Reverse Transcriptase Inhibitors/pharmacology
    Chemical Substances Reverse Transcriptase Inhibitors ; HIV Reverse Transcriptase (EC 2.7.7.49)
    Language English
    Publishing date 2004-04-20
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 80174-4
    ISSN 1098-5514 ; 0022-538X
    ISSN (online) 1098-5514
    ISSN 0022-538X
    DOI 10.1128/jvi.78.10.5390-5401.2004
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  8. Article: High prevalence of antiretroviral resistance in treated Ugandans infected with non-subtype B human immunodeficiency virus type 1.

    Richard, Nathalie / Juntilla, Marisa / Abraha, Awet / Demers, Korey / Paxinos, Ellen / Galovich, Justin / Petropoulos, Christo / Whalen, Christopher C / Kyeyune, Fred / Atwine, Diana / Kityo, Cissy / Mugyenyi, Peter / Arts, Eric J

    AIDS research and human retroviruses

    2004  Volume 20, Issue 4, Page(s) 355–364

    Abstract: This study examined the emergence and prevalence of drug-resistant mutations in reverse transcriptase and protease coding regions in human immunodeficiency virus type 1 (HIV-1)-infected Ugandans treated with antiretroviral drugs (ARV). Genotypic ... ...

    Abstract This study examined the emergence and prevalence of drug-resistant mutations in reverse transcriptase and protease coding regions in human immunodeficiency virus type 1 (HIV-1)-infected Ugandans treated with antiretroviral drugs (ARV). Genotypic resistance testing was performed on 50 and 16 participants who were enrolled in a cross-sectional and longitudinal observational cohort, respectively. The majority of the 113 HIV-1 PR-RT sequences were classified as subtypes A and D. Drug resistance mutations were prevalent in 52% of ARV-experienced individuals, and 17 of 27 ARV-resistant isolates had three mutations or more in reverse transcriptase. Resistance mutations in protease were less prevalent but only 17 of the 50 patients were receiving a protease inhibitor upon sample collection. Mutations conferring drug resistance were also selected in 3 of 16 participants in the longitudinal cohort, i.e., less than 8 months after the initiation of ARV treatment. Rapid emergence of ARV resistance was associated with poor adherence to treatment regimens, which was related to treatment costs. ARV resistance did, however, appear at a slightly higher prevalence in HIV-1 subtype D (21 of 33) than subtype A (7 of 25) infected individuals. Overall, this observational study suggests that ARV-resistant HIV-1 isolates are emerging rapidly in ARV-treated individual in Uganda and possibly other developing countries.
    MeSH term(s) Adult ; Anti-HIV Agents/pharmacology ; Anti-HIV Agents/therapeutic use ; Cross-Sectional Studies ; DNA, Viral/chemistry ; DNA, Viral/isolation & purification ; Drug Resistance, Viral/genetics ; Female ; Genotype ; HIV Infections/drug therapy ; HIV Infections/virology ; HIV Protease/genetics ; HIV Reverse Transcriptase/genetics ; HIV-1/classification ; HIV-1/drug effects ; HIV-1/genetics ; HIV-1/isolation & purification ; Humans ; Longitudinal Studies ; Male ; Middle Aged ; Molecular Sequence Data ; Mutation, Missense ; Phylogeny ; Proviruses/genetics ; Proviruses/isolation & purification ; Risk Factors ; Treatment Refusal ; Uganda ; Viremia
    Chemical Substances Anti-HIV Agents ; DNA, Viral ; HIV Reverse Transcriptase (EC 2.7.7.49) ; HIV Protease (EC 3.4.23.-)
    Language English
    Publishing date 2004-04
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S.
    ZDB-ID 639130-8
    ISSN 1931-8405 ; 0889-2229
    ISSN (online) 1931-8405
    ISSN 0889-2229
    DOI 10.1089/088922204323048104
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