Background: Antiretroviral therapy (ART) can suppress the HIV-1 replication but is not able to eradicate the virus due to the existence of viral reservoirs. Optimal virological suppression remains often an ideal goal since some patients may show persistent plasma residual viremia (RV). To date, it is unclear if RV may be regarded as an indication of the potency and tolerability of the regimen, adherence, drug resistance, and pharmacokinetics. Recent studies have shown that other factors, closely related to host, could improve optimal viral suppression. It has been demonstrated that cellular miRNAs like miR-150, miR-33a-5p, miR-223, miR-382 could affect HIV-1 latency in resting CD4+ T cells and miR-324-5p interfere with HIV-1 replication. Moreover, other investigators have suggested the role of miR-34a and miR-132 as enhancer of viral replication. The aim of the study was to investigate if different miRNAs profile could be associated to residual replication in treated HIV-1 positive patients with different levels of viral suppression. Methods: To evaluate cellular expression of miR-33a-5p, miR-34a, miR-132, miR-150, miR-223 miR-324 -5p and miR-382 RT-Taqman assay was performed. Levels of miRNA were measured in peripheral blood mononuclear cells (PBMC) from 56 antiretroviral therapy (ART) treated patients grouped according viremia in group I (28 patients with a sustained undetectable viremia for at least 3 years) and group II (28 patients with at least 3 values of low level viremia (LLV) between 37 -200 copies /ml). Twenty-three cellular samples from healthy donor (HD) were used as a control group. Results: PBMCs levels of miR-33a-5p, miR-34a, miR-150, and miR-324-5p were significantly higher in HIV infected patients compared to HD (tab1). When we stratified levels of miRNA according to group I and II, miR-33a-5p, miR-34a, miR-150 were confirmed significantly higher in either groups compared to HD. On the contrary, the expression levels of miR-324-5p were similar to HD (tab1). A positive correlation between miR-150 and time of HIV diagnosis was found (r=0.47 p=0.012). There was not significant correlation between CD4+ T cell count and miRNA levels. Conclusions: The expression pattern of some miRNA is altered in HIV infected population but no differences between patients with maximal viral suppression and patients with LLV was detected.
TREATED HIV-1 PATIENTS WITH DIFFERENT LEVELS OF VIRAL SUPPRESSION: CHANGES IN MICRORNA EXPRESSION PROFILES / Falasca, Francesca; DI CARLO, Daniele; Calabretto, Marianna; Mazzuti, Laura; Celani, Luigi; D'Ettorre, Gabriella; Mezzaroma, Ivano; Antonelli, Guido; Turriziani, Ombretta. - (2018). (Intervento presentato al convegno 2nd national ISV Congress tenutosi a Roma, Italia).
TREATED HIV-1 PATIENTS WITH DIFFERENT LEVELS OF VIRAL SUPPRESSION: CHANGES IN MICRORNA EXPRESSION PROFILES
Francesca Falasca;Daniele Di Carlo;Marianna Calabretto;Laura Mazzuti;Luigi Celani;Gabriella D’Ettorre;Ivano Mezzaroma;Guido Antonelli;Ombretta Turriziani
2018
Abstract
Background: Antiretroviral therapy (ART) can suppress the HIV-1 replication but is not able to eradicate the virus due to the existence of viral reservoirs. Optimal virological suppression remains often an ideal goal since some patients may show persistent plasma residual viremia (RV). To date, it is unclear if RV may be regarded as an indication of the potency and tolerability of the regimen, adherence, drug resistance, and pharmacokinetics. Recent studies have shown that other factors, closely related to host, could improve optimal viral suppression. It has been demonstrated that cellular miRNAs like miR-150, miR-33a-5p, miR-223, miR-382 could affect HIV-1 latency in resting CD4+ T cells and miR-324-5p interfere with HIV-1 replication. Moreover, other investigators have suggested the role of miR-34a and miR-132 as enhancer of viral replication. The aim of the study was to investigate if different miRNAs profile could be associated to residual replication in treated HIV-1 positive patients with different levels of viral suppression. Methods: To evaluate cellular expression of miR-33a-5p, miR-34a, miR-132, miR-150, miR-223 miR-324 -5p and miR-382 RT-Taqman assay was performed. Levels of miRNA were measured in peripheral blood mononuclear cells (PBMC) from 56 antiretroviral therapy (ART) treated patients grouped according viremia in group I (28 patients with a sustained undetectable viremia for at least 3 years) and group II (28 patients with at least 3 values of low level viremia (LLV) between 37 -200 copies /ml). Twenty-three cellular samples from healthy donor (HD) were used as a control group. Results: PBMCs levels of miR-33a-5p, miR-34a, miR-150, and miR-324-5p were significantly higher in HIV infected patients compared to HD (tab1). When we stratified levels of miRNA according to group I and II, miR-33a-5p, miR-34a, miR-150 were confirmed significantly higher in either groups compared to HD. On the contrary, the expression levels of miR-324-5p were similar to HD (tab1). A positive correlation between miR-150 and time of HIV diagnosis was found (r=0.47 p=0.012). There was not significant correlation between CD4+ T cell count and miRNA levels. Conclusions: The expression pattern of some miRNA is altered in HIV infected population but no differences between patients with maximal viral suppression and patients with LLV was detected.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
