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      Diagnosis, antiretroviral therapy, and emergence of resistance to antiretroviral agents in HIV-2 infection: a review

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          Abstract

          Human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) are the causative agents of AIDS. HIV-2 is prevalent at moderate to high rates in West African countries, such as Senegal, Guinea, Gambia, and Cape Verde. Diagnosis of HIV-2 is made with a positive HIV-1/HIV-2 ELISA or simple/rapid assay, followed by one or two confirmatory tests specific for HIV-2. Following CD4+ T cell counts, HIV-2 viral burden and clinical signs and symptoms of immunodeficiency are beneficial in monitoring HIV-2 disease progression. Although non-nucleoside reverse transcriptase inhibitors are ineffective in treating HIV-2, nucleoside reverse transcriptase inhibitors and protease inhibitors can be effective in dual and triple antiretroviral regimens. Their use can decrease HIV-2 viral load, increase CD4+ T cell counts and improve AIDS-related symptoms. HIV-2 resistance to various nucleoside reverse transcriptase inhibitors and protease inhibitors, including zidovudine, lamivudine, ritonavir and indinavir, has been identified in some HIV-2 infected patients on antiretroviral therapy. The knowledge of HIV-2 peculiarities, when compared to HIV-1, is crucial to helping diagnose and guide the clinician in the choice of the initial antiretroviral regimen and for monitoring therapy success.

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          Most cited references72

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          Rapid changes in human immunodeficiency virus type 1 RNA load and appearance of drug-resistant virus populations in persons treated with lamivudine (3TC).

          The effect of the appearance of drug-resistant human immunodeficiency virus type 1 (HIV-1) on viral RNA load was studied in patients treated with the reverse transcriptase inhibitor lamivudine. During the first 12 weeks of treatment, HIV-1 RNA concentrations and amino acid changes in codon 184, causing high-level resistance to lamivudine, were determined in longitudinal serum samples from HIV-1 p24 antigen-positive and -negative patients. A marked decline in the amount of HIV-1 RNA (approximately 95% below baseline) and HIV-1 p24 antigen was observed within 2 weeks, followed by a rise that coincided with the appearance of lamivudine-resistant viruses in serum (isoleucine mutants initially, which were subsequently replaced by valine variants). After 12 weeks, a partial antiviral effect was observed despite the presence of a complete codon 184 mutant virus population in serum. This study shows that the rapid appearance of drug-resistant virus in serum is followed by an increase in viral RNA load.
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            L-735,524: an orally bioavailable human immunodeficiency virus type 1 protease inhibitor.

            To date, numerous inhibitors of the human immunodeficiency virus type 1 protease have been reported, but few have been studied extensively in humans, primarily as a consequence of poor oral bioavailability in animal models. L-735,524 represents a class of human immunodeficiency virus type 1 protease inhibitors, termed hydroxyaminopentane amides, that incorporate a basic amine into the hydroxyethylene inhibitor backbone. L-735,524 is a potent inhibitor of virus replication in cell culture and inhibits the protease-mediated cleavage of the viral precursor polyproteins that results in the production of noninfectious progeny viral particles. The compound is effective against viruses resistant to reverse transcriptase inhibitors and is synergistically active when used in combination with reverse transcriptase inhibitors. Most importantly, L-735,524 exhibits good oral bioavailability and plasma pharmacokinetic profiles in two species of laboratory animals by using clinically acceptable formulations. Accordingly, the compound was selected for evaluation of safety and pharmacokinetic studies in humans.
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              Possible protective effect of HIV-2 against incident HIV-1 infection: review of available epidemiological and in vitro data.

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                Author and article information

                Contributors
                Role: ND
                Role: ND
                Journal
                bjid
                Brazilian Journal of Infectious Diseases
                Braz J Infect Dis
                Brazilian Society of Infectious Diseases (Salvador )
                1678-4391
                February 2003
                : 7
                : 1
                : 07-15
                Affiliations
                [1 ] Universidade Federal de São Paulo Brazil
                Article
                S1413-86702003000100002
                10.1590/S1413-86702003000100002
                3cfbcae1-28d1-4793-a5d9-7b1a58066919

                http://creativecommons.org/licenses/by/4.0/

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                Product

                SciELO Brazil

                Self URI (journal page): http://www.scielo.br/scielo.php?script=sci_serial&pid=1413-8670&lng=en
                Categories
                INFECTIOUS DISEASES

                Infectious disease & Microbiology
                review,HIV-2,antiretroviral treatment
                Infectious disease & Microbiology
                review, HIV-2, antiretroviral treatment

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