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1.
Braz. j. infect. dis ; 24(2): 150-159, Mar.-Apr. 2020. tab, graf
Article Dans Anglais | LILACS, ColecionaSUS | ID: biblio-1132431

Résumé

ABSTRACT Background: Latent HIV-1 is a major hurdle in obtaining HIV-1 sustained virological remission (SVR). Here we explored histone deacetylation inhibition property of nicotinamide (NAM; n = 17) for the first time in comparison to a combination of methyltransferase inhibitors (MTIs; Chaetocin and BIX01294; n = 25) to reactivate latent HIV ex vivo in CD8-depleted PBMCs from antiretroviral treated aviremic individuals. Results: NAM reactivated HIV-1 from 13/17 (76.4%) samples compared to 20/25 (80.0%) using MTIs with mean viral load (VLs) of 4.32 and 3.22 log10 RNA copies/mL, respectively (p = 0.004). Mean purging time after NAM and MTIs stimulation was 5.1 and 6.75 days, respectively (p = 0.73). Viral purging in autologous cultures exhibited blunted HIV recovery with fluctuating VLs followed by a complete viral extinction when expanded in allogenic system. Electron microscopy from five supernatants revealed anomalous viral particles, with lack of complete viral genomes when characterized by ultradeep sequencing through metagenomics approach (n = 4). Conclusion: NAM alone was more potent HIV-1 activator than combination of MTIs, with potential of clinical use.


Sujets)
Adulte , Femelle , Humains , Mâle , Adulte d'âge moyen , Jeune adulte , Quinazolines/pharmacologie , Azépines/pharmacologie , Activation virale/effets des médicaments et des substances chimiques , Infections à VIH/virologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1)/effets des médicaments et des substances chimiques , Nicotinamide/pharmacologie , Methyltransferases/antagonistes et inhibiteurs , Pipérazines/pharmacologie , Agranulocytes/virologie , Lymphocytes T CD4+ , Régulation de l'expression des gènes viraux , Latence virale , Charge virale/effets des médicaments et des substances chimiques , Tropisme viral/effets des médicaments et des substances chimiques
2.
Mem. Inst. Oswaldo Cruz ; 107(1): 96-101, Feb. 2012. graf
Article Dans Anglais | LILACS | ID: lil-612812

Résumé

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm³ [standard deviation (SD) = 99] and a mean viral load of 5.09 log10 copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno[clinical20 percent] algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3 percent) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naÏve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.


Sujets)
Adulte , Femelle , Humains , Mâle , Thérapie antirétrovirale hautement active , Agents antiVIH/usage thérapeutique , Infections à VIH/traitement médicamenteux , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Tropisme viral/effets des médicaments et des substances chimiques , Benzoxazines/usage thérapeutique , Études de cohortes , Méthode en double aveugle , Infections à VIH/immunologie , Infections à VIH/virologie , VIH-1 (Virus de l'Immunodéficience Humaine de type 1) , Lopinavir/usage thérapeutique , Études prospectives , Résultat thérapeutique , Charge virale
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