RESUMO
Dual therapy with lopinavir/ritonavir (LPV/r) plus lamivudine (3TC) has been demonstrated to be non-inferior to the triple drug regimen including LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) in 48-week studies. However, little is known about the long-term efficacy and drug resistance of this simplified strategy. A randomized, controlled, open-label, non-inferiority trial (ALTERLL) was conducted to assess the efficacy, drug resistance, and safety of dual therapy with LPV/r plus 3TC (DT group), compared with the first-line triple-therapy regimen containing tenofovir (TDF), 3TC plus efavirenz (EFV) (TT group) in antiretroviral therapy (ART)-naïve HIV-1-infected adults in Guangdong, China. The primary endpoint was the proportion of patients with plasma HIV-1 RNA < 50 copies/ml at week 144. Between March 1 and December 31, 2015, a total of 196 patients (from 274 patients screened) were included and randomly assigned to either the DT group (n = 99) or the TT group (n = 97). In the primary intention-to-treat (ITT) analysis at week 144, 95 patients (96%) in the DT group and 93 patients (95.9%) in the TT group achieved virological inhibition with plasma HIV-1 RNA <50 copies/ml (difference: 0.1%; 95% CI, -4.6-4.7%), meeting the criteria for non-inferiority. The DT group did not show significant differences in the mean increase in CD4+ cell count (247.0 vs. 204.5 cells/mm3; p = 0.074) or the CD4/CD8 ratio (0.47 vs. 0.49; p = 0.947) from baseline, or the inflammatory biomarker levels through week 144 compared with the TT group. For the subgroup analysis, baseline high viremia (HIV-1 RNA > 100,000 copies/ml) and genotype BC did not affect the primary endpoint or the mean increase in CD4+ cell count or CD4/CD8 ratio from baseline at week 144. However, in patients with genotype AE, the DT group showed a higher mean increase in CD4+ cell count from baseline through 144 weeks than the TT group (308.7 vs. 209.4 cells/mm3; p = 0.038). No secondary HIV resistance was observed in either group. Moreover, no severe adverse event (SAE) or death was observed in any group. Nonetheless, more patients in the TT group (6.1%) discontinued the assigned regimen than those in the DT group (1%) due to adverse events. Dual therapy with LPV/r plus 3TC manifests long-term non-inferior therapeutic efficacy, low drug resistance, good safety, and tolerability compared with the first-line triple-therapy regimen in Guangdong, China, indicating dual therapy is a viable alternative in resource-limited areas. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR1900024611].
RESUMO
BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play immunosuppressive roles in cancers and some infectious diseases; however, their role in dengue fever (DF) remains unknown. This study evaluated the clinical significance of MDSCs in DF patients. METHODS: This study comprised 178 non-severe DF patients, 20 non-dengue fever (NDF) controls, and 30 healthy donors. The DF patients were divided into the following five groups based on the fever duration from its onset to the day of sample collection: fever duration of 1-2, 3-4, 5-6, 7-8, and > 9 days. Among these DF patients, 14 were monitored for eight days, and their peripheral blood samples were collected every two days. The mononuclear cells were isolated and analyzed using flow cytometry. The correlation between the MDSCs and clinical and immunological indicators of the DF patients was evaluated using Spearman analysis. RESULTS: The count of the peripheral blood MDSCs, especially monocytic MDSCs, of the 178 DF patients were dramatically higher than those of the NDF and healthy controls, and remarkably decreased with the fever duration. Moreover, the MDSC count correlated with some indicators, including the dengue viral load (rho = 0.367, p < .001), body temperature (rho = 0.263, p = .005), prothrombin time (rho = 0.475, p < .001), CD4+ T cell number (rho = - 0.317, p < .001), CD8+ T cell number (rho = - 0.361, p < .001), "programmed cell death protein 1" (PD-1) (rho = - 0.347, p < .001), "T cell immunoglobulin domain and mucin domain-3" (Tim3) (rho = - 0.258, p = .001), interferon-α (IFN-α) (rho = 0.43, p < .001), and "regulated upon activation normal T-cell expressed and secreted" (RANTES) (rho = 0.278, p = .019). Furthermore, the level of arginase-1, but not nitric oxide, was higher in the DF patients than in the healthy controls and was closely related to the number of MDSCs (rho = 0.265, p = .024). CONCLUSIONS: Our study reveals a significant correlation between MDSCs and DF clinical indicators, posing MDSCs as potential target cells for DF treatment.
