LitCovid-sentences  

PMC:7696151 / 8583-18610 JSONTXT 3 Projects

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Id Subject Object Predicate Lexical cue
T72 0-6 Sentence denotes 2.2.1.
T73 7-12 Sentence denotes HIV-1
T74 13-128 Sentence denotes HIV is part of the genus Lentivirus, of the Retroviridae family, and it is divided into two lines: HIV-1 and HIV-2.
T75 129-228 Sentence denotes The most virulent and infectious is HIV-1, since it causes most of the HIV infections in the world.
T76 229-368 Sentence denotes The target cells of HIV are those rich in CD4 receptors, such as some lymphocytes called CD4+, which play a crucial role in human immunity.
T77 369-499 Sentence denotes Indeed, these lymphocytes activate different immune system cells depending on the type of unwanted host they come in contact with.
T78 500-611 Sentence denotes It seems that acute HIV infection is highly linked to a rapid depletion of CD4+ T cells in gut lymphoid tissue.
T79 612-784 Sentence denotes This event is related to an alteration of the intestinal mucosa integrity, resulting in bloodstream translocation of microbial products like lipopolysaccharides (LPS) [42].
T80 785-962 Sentence denotes It has been hypothesized that LPS, through the binding and activation of Toll-like receptor 4 (TLR-4), is responsible for the immune system activation observed in HIV infection.
T81 963-1177 Sentence denotes Although the real HCQ mechanism of action has not been well assessed, it seems that the anti-HIV effects are highly linked to the post-translational modification of glycoprotein 120 (gp120) in monocyte and T cells.
T82 1178-1300 Sentence denotes Consequently, there was a modification of gp120 immunogenic properties and a reduction of new virions infectivity [15,16].
T83 1301-1430 Sentence denotes The first randomized, double-blind, placebo-controlled clinical trial about the anti-HIV-1 activity of HCQ was published in 1995.
T84 1431-1542 Sentence denotes In this study, 40 asymptomatic HIV-infected patients received either 800 mg/day HCQ or placebo for eight weeks.
T85 1543-1732 Sentence denotes All patients treated with antiretroviral therapy (HAART = zidovudine (ZDV), 2′,3′-dideoxyinosine, or 2′,3′-dideoxycytidine) and stopped taking it four weeks before the clinical trial start.
T86 1733-1853 Sentence denotes Unlike placebo, at the eighth week, HCQ displayed a reduction in HIV-1 RNA total plasma levels in 12 out of 19 patients.
T87 1854-2066 Sentence denotes Furthermore, the percentage of CD4+ T cells decreased significantly in the placebo group and remained stable during the treatment with HCQ, indicating a probable stabilization of immune function in the HCQ group.
T88 2067-2167 Sentence denotes HCQ administration also induced a decrease in serum interleukin 6 (IL-6) and immunoglobulin G (IgG).
T89 2168-2242 Sentence denotes However, no significant changes were found in the IgA and IgM levels [17].
T90 2243-2458 Sentence denotes The anti-HIV-1 effect of HCQ was also compared with that of ZDV, a nucleoside reverse transcriptase inhibitor, in a randomized, placebo-controlled clinical trial conducted on 72 HIV-l-infected asymptomatic patients.
T91 2459-2554 Sentence denotes All subjects were treated for 16 weeks with 800 mg/day HCQ (n = 35) or 500 mg/day ZDV (n = 37).
T92 2555-2677 Sentence denotes As in the previous study, patients who had received HAART stopped taking it four weeks before the clinical trial’s outset.
T93 2678-2878 Sentence denotes After 16 weeks, total plasma HIV-1 RNA levels were reduced in both the ZDV group and HCQ group, although the extent of anti-HIV-l activity in HCQ patients was lower than that observed in ZDV subjects.
T94 2879-3043 Sentence denotes However, eight subjects in the Azithromycin (AZM) group showed an increase in HIV-1 RNA levels in the 16th week, indicating the rapid emergence of viral resistance.
T95 3044-3249 Sentence denotes Contrarily, in the HCQ group, increased antiviral activity was revealed after 16 weeks rather than after 8 weeks, and no subject showed an increase in HIV-1 RNA levels at either 8 or 16 weeks of treatment.
T96 3250-3372 Sentence denotes This evidence suggests that no resistance developed under HCQ therapy or that it might develop more slowly than under ZDV.
T97 3373-3545 Sentence denotes A reduction in serum p24 antigen levels in both ZDV and HCQ groups was also described, while only in the HCQ group could a decrease in IL-6 and IgG levels be observed [18].
T98 3546-3745 Sentence denotes This reduction of IgG levels displayed after HCQ treatment in both studies may be significant since autoantibodies contribute to CD4+ cell depletion and autoimmune diseases observed in HIV infection.
T99 3746-4031 Sentence denotes Further, as lymphoid tissue is considered the primary site of HIV reservoirs and a critical site affected by CD4+ T cells depletion, the HCQ concentration was assessed in the plasma and adenoid tissue (At) of 8 HIV-infected patients administrating 400 or 800 mg of HCQ for eight weeks.
T100 4032-4163 Sentence denotes After taking these dosages, it was demonstrated that the mean HCQ concentration was significantly higher in At than in plasma [21].
T101 4164-4322 Sentence denotes This different drug distribution was also confirmed by an in vivo study using rabbits as an experimental model, receiving 15 mg/kg of HCQ subcutaneously [22].
T102 4323-4473 Sentence denotes Thus, the anti-HIV activity of HCQ could be linked to its accumulation in lymphoid tissue, a relevant site for HIV immunopathogenesis and replication.
T103 4474-4609 Sentence denotes Since monotherapy is not recommended in treating HIV, HCQ has also been tested in synergy with other drugs commonly used to manage HIV.
T104 4610-4859 Sentence denotes In this regard, 400 mg/day of HCQ in a combination regimen with 1000 mg/day hydroxyurea and 250–400 mg/day didanosine (dosed per body weight) was administered for 48 weeks to 22 asymptomatic HIV-1 infected patients naïve to antiretroviral treatment.
T105 4860-4902 Sentence denotes Only 16 out of 22 patients were evaluable.
T106 4903-5026 Sentence denotes These 16 subjects, at the 12th week, showed a significant reduction in viral load which was maintained until the 48th week.
T107 5027-5154 Sentence denotes Furthermore, at week 12, an increase in CD4+ percentage was also shown, and this improvement was kept until the 48th week [19].
T108 5155-5320 Sentence denotes To evaluate the long-term efficacy and safety of HCQ, hydroxyurea, and didanosine combination, they were also tested on 17 HIV-infected naïve patients for 144 weeks.
T109 5321-5413 Sentence denotes All subjects received 200 mg HCQ, 500 mg hydroxyurea, and 125–200 mg didanosine twice daily.
T110 5414-5500 Sentence denotes Of the 17 patients who started treatment, 14 remained until the end of the 144th week.
T111 5501-5758 Sentence denotes After 114 weeks, viral load was reduced by 1.6 Log10 copies/mL under baseline (p < 0.001), eight patients (47%) had an unnoticeable viral load (< 400 copies/mL), and two patients (12%) had a measurable viral load, but resistance mutations were not detected.
T112 5759-5999 Sentence denotes Four patients (24%) had both detectable viral load and resistance mutation: one with both 62V and 65R and three with both 74V and 184V mutations; the latter three were assessed as didanosine resistant, while no resistance was found for HCQ.
T113 6000-6084 Sentence denotes However, in all cases, the viral load remained below the baseline at the 144th week.
T114 6085-6206 Sentence denotes The CD4+ cell count had increased significantly, while the percentage of CD8 cells was reduced up to the 144th week [20].
T115 6207-6439 Sentence denotes This HCQ noticeable impact on immune activation, thereby increasing CD4+ T cells, was also demonstrated in a prospective study conducted on 20 HIV-infected immunologic no responders treated with standard antiretroviral therapy [23].
T116 6440-6604 Sentence denotes These results suggested that the combination of HCQ, hydroxyurea, and didanosine could be a valid alternative to the highly active commercial HAART in HIV-patients.
T117 6605-6743 Sentence denotes Nonetheless, these latter studies have some limitations, such as the small number of subjects included and the absence of a control group.
T118 6744-6893 Sentence denotes Therefore, it is not possible to determine the contribution made by HCQ to the overall decrease in viral load obtained from the combination of drugs.
T119 6894-7126 Sentence denotes Anyway, the potential anti-HIV efficacy of HCQ, when added to existing treatment with an antiretroviral regimen, was also confirmed by a case report about a patient with HLA-B27-associated spondyloarthropathy and HIV infection [43].
T120 7127-7347 Sentence denotes In contrast to the results mentioned above has been published a randomized, double-blind, placebo-controlled trial performed on 83 patients to which 400 mg HCQ (n = 42) or placebo (n = 41) were administered for 48 weeks.
T121 7348-7549 Sentence denotes All patients were naïve to HAART or had stopped this therapy 22 months before the trial began; 17 subjects in the HCQ group and 8 in the placebo group interrupted study medication before the 48th week.
T122 7550-7744 Sentence denotes At the end of treatment, in the HCQ group, compared to placebo, patients showed a reduction in total CD4 cell count and a significant viral load increased from the 12th week above baseline [24].
T123 7745-7971 Sentence denotes Hence, based on these results, HCQ did not decrease immune activation in patients with chronic HIV infection who were naïve to HAART, as there was an increase in HIV viral replication and a negative effect on CD4+ cell counts.
T124 7972-8221 Sentence denotes In light of these results, there was the need to consider that the first two described clinical trials, which reported the antiviral effect of HCQ, were on short-term treatments (8 or 16 weeks) and that they used an HCQ dosage of 800 mg/day [17,18].
T125 8222-8337 Sentence denotes In contrast, the latter used only 400 mg/day [24], corresponding to the maximum recommended dose for long-time use.
T126 8338-8617 Sentence denotes Besides, the latter study also enrolled more patients than the other studies, and unlike the trial of Piconi et al. [23], which described significative effects in reducing immune activation after HCQ administration, was conducted in the absence of antiretroviral treatments [24].
T127 8618-8809 Sentence denotes Therefore, further clinical trials involving a larger number of subjects would be necessary to assess the real antiviral activity of HCQ in monotherapy and synergy with antiretrovirals drugs.
T128 8810-9023 Sentence denotes Finally, assuming that women resistant to HIV infection show a low activation of the immune system at the level of the female genital tract (FGT), HCQ has been investigated as a drug able to prevent HIV infection.
T129 9024-9150 Sentence denotes It has been shown that the “immune quiescent” state of HIV-resistant women keeps the immune response against pathogens intact.
T130 9151-9348 Sentence denotes For this reason, it was thought to induce pharmacologically, in a rabbit model, this immunological quiescence state through an intravaginal implant capable of providing a controlled release of HCQ.
T131 9349-9619 Sentence denotes Considering that a concentration above 6.48 μg/mL of HCQ was able to interfere with the gp120 glycosylation process, the vaginal implant was projected to release HCQ with the longest possible duration at a concentration greater than 4.34 μg/mL but lower than 21.7 μg/mL.
T132 9620-9868 Sentence denotes After six days, this implant improved mucosal epithelial integrity, reduced submucosal immune cell recruitment, decreased gene expression and protein of T cell activation markers, and minimized the activation of key pro-inflammatory mediators [25].
T133 9869-10027 Sentence denotes Hence, HCQ can be considered a promising drug able to maintain a low baseline level of immune activation and may also play a role in preventing HIV infection.