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      Salud Pública y erradicación de la infección por el Virus de la Inmunodeficiencia Humana Translated title: Public health and eradication of infection by the Human Immunodeficiency Virus

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          Abstract

          RESUMEN El Virus de la Inmunodeficiencia Humana (VIH) se integra en el genoma celular y permanece activo o latente de manera indefinida. La terapia antirretroviral suprime la replicación viral a niveles indetectables, pero no erradica el virus. Nuevas estrategias terapéuticas se están desarrollando, tales como la terapia génica, el llamado shock and kill, los anticuerpos monoclonales neutralizantes o las vacunas terapéuticas, que sumadas a intervenciones biomédicas (especialmente la profilaxis pre-exposición) están generando un elevado optimismo entre la comunidad científica como armas para la erradicación viral. Sin embargo, no prestamos suficientemente atención al comportamiento humano como elemento imprescindible para obtener la eliminación definitiva. Necesitamos potenciar la Salud Pública con las herramientas humanas y económicas pertinentes para poder alcanzar dicha erradicación. El desarrollo aislado de estrategias terapéuticas eficaces no evitará que el virus de la inmunodeficiencia humana continúe entre nosotros si no impulsamos y desarrollamos la Salud Pública.

          Translated abstract

          ABSTRACT The Human Immunodeficiency Virus (HIV) is integrated into the cellular genome remaining active or latent indefinitely. Antiretroviral therapy suppresses viral replication to undetectable levels but does not eradicate the virus. New therapeutic strategies are being developed, such as gene therapy, shock and kill, neutralizing monoclonal antibodies or therapeutic vaccines, which together with biomedical interventions, especially pre-exposure prophylaxis, are generating high optimism among the scientific community as weapons for a viral eradication. However, we do not pay enough attention to human behavior as an essential element to obtain eradication. We need to promote Public Health with the necessary human and economic tools to achieve eradication. The sole development of effective therapeutic strategies will not prevent the human immunodeficiency virus from continuing among us if we do not promote and develop Public Health.

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          Most cited references29

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          Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy

          Despite antiretroviral therapy, proviral latency of human immunodeficiency virus type 1 (HIV-1) remains a principal obstacle to curing the infection [1]. Inducing the expression of latent genomes within resting CD4+ T cells is the primary strategy to clear this reservoir [2]. While histone deacetylase (HDAC) inhibitors such as suberoylanilide hydroxamic acid (SAHA or vorinostat, VOR) can disrupt HIV-1 latency in vitro [3–5], the utility of this approach has never been directly proven in a translational clinical study of HIV-infected patients. Therefore we isolated the circulating resting CD4+ T cells of patients in whom viremia was fully suppressed by antiretroviral therapy (ART), and directly studied the effect of VOR in this latent reservoir. In each of eight patients studied, a single dose of VOR increased both biomarkers of cellular acetylation, and simultaneously induced an increase in HIV RNA expression in resting CD4+ cells (mean increase 4.8-fold). This is the first demonstration that a molecular mechanism known to enforce HIV latency can be therapeutically targeted in man, provides proof-of-concept for HDAC inhibitors as a new therapeutic class, and defines a precise approach to test novel strategies to directly attack and eradicate latent HIV infection.
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            Evidence for the cure of HIV infection by CCR5Δ32/Δ32 stem cell transplantation.

            HIV entry into CD4(+) cells requires interaction with a cellular receptor, generally either CCR5 or CXCR4. We have previously reported the case of an HIV-infected patient in whom viral replication remained absent despite discontinuation of antiretroviral therapy after transplantation with CCR5Δ32/Δ32 stem cells. However, it was expected that the long-lived viral reservoir would lead to HIV rebound and disease progression during the process of immune reconstitution. In the present study, we demonstrate successful reconstitution of CD4(+) T cells at the systemic level as well as in the gut mucosal immune system after CCR5Δ32/Δ32 stem cell transplantation, while the patient remains without any sign of HIV infection. This was observed although recovered CD4(+) T cells contain a high proportion of activated memory CD4(+) T cells, ie, the preferential targets of HIV, and are susceptible to productive infection with CXCR4-tropic HIV. Furthermore, during the process of immune reconstitution, we found evidence for the replacement of long-lived host tissue cells with donor-derived cells, indicating that the size of the viral reservoir has been reduced over time. In conclusion, our results strongly suggest that cure of HIV has been achieved in this patient.
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              Treatment with indinavir, zidovudine, and lamivudine in adults with human immunodeficiency virus infection and prior antiretroviral therapy.

              The new protease inhibitors are potent inhibitors of the human immunodeficiency virus (HIV), and in combination with other antiretroviral drugs they may be able to cause profound and sustained suppression of HIV replication. In this double-blind study, 97 HIV-infected patients who had received zidovudine treatment for at least 6 months and had 50 to 400 CD4 cells per cubic millimeter and at least 20,000 copies of HIV RNA per milliliter were randomly assigned to one of three treatments for up to 52 weeks: 800 mg of indinavir every eight hours; 200 mg of zidovudine every eight hours combined with 150 mg of lamivudine twice daily; or all three drugs. The patients were followed to monitor the occurrence of adverse events and changes in viral load and CD4 cell counts. The decrease in HIV RNA over the first 24 weeks was greater in the three-drug group than in the other groups (P<0.001 for each comparison). RNA levels decreased to less than 500 copies per milliliter at week 24 in 28 of 31 patients in the three-drug group (90 percent), 12 of 28 patients in the indinavir group (43 percent), and none of 30 patients in the zidovudine-lamivudine group. The increase in CD4 cell counts over the first 24 weeks was greater in the two groups receiving indinavir than in the zidovudine-lamivudine group (P< or =0.01 for each comparison). The changes in the viral load and the CD4 cell count persisted for up to 52 weeks. All the regimens were generally well tolerated. In most HIV-infected patients with prior antiretroviral therapy, the combination of indinavir, zidovudine, and lamivudine reduces levels of HIV RNA to less than 500 copies per milliliter for as long as one year.
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                Author and article information

                Journal
                resp
                Revista Española de Salud Pública
                Rev. Esp. Salud Publica
                Ministerio de Sanidad, Consumo y Bienestar social (Madrid, Madrid, Spain )
                1135-5727
                2173-9110
                2019
                : 93
                : e201912073
                Affiliations
                [1] Madrid orgnameComunidad de Madrid orgdiv1Consejería de Sanidad orgdiv2Servicio de Epidemiología. Dirección General de Salud Pública España
                Article
                S1135-57272019000100312 S1135-5727(19)09300000312
                8e5d4549-289f-4353-8a18-adef076d8259

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 International License.

                History
                : 07 June 2019
                : 24 May 2019
                Page count
                Figures: 0, Tables: 0, Equations: 0, References: 59, Pages: 0
                Product

                SciELO Public Health

                Categories
                Colaboraciones Especiales

                Human immunodeficiency virus,Acquired immunodeficiency syndrome,HIV-disease eradication,Pre-exposure prophylaxis,Virus de la inmunodeficiencia humana,Síndrome de inmunodeficiencia adquirida,Erradicación de la enfermedad VIH,Profilaxis pre-exposición

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