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PMC:7696151 / 8583-18610 JSONTXT

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LitCovid-PubTator

Id Subject Object Predicate Lexical cue tao:has_database_id
227 271-274 Gene denotes CD4 Gene:920
228 318-321 Gene denotes CD4 Gene:920
229 575-578 Gene denotes CD4 Gene:920
230 858-878 Gene denotes Toll-like receptor 4 Gene:7099
231 880-885 Gene denotes TLR-4 Gene:7099
232 1146-1151 Gene denotes gp120 Gene:3700
233 1220-1225 Gene denotes gp120 Gene:3700
234 112-117 Species denotes HIV-1 Tax:11676
235 122-127 Species denotes HIV-2 Tax:11709
236 165-170 Species denotes HIV-1 Tax:11676
237 353-358 Species denotes human Tax:9606
238 13-16 Species denotes HIV Tax:12721
239 249-252 Species denotes HIV Tax:12721
240 1056-1059 Species denotes HIV Tax:12721
241 753-772 Chemical denotes lipopolysaccharides MESH:D008070
242 981-984 Chemical denotes HCQ MESH:D006886
243 200-214 Disease denotes HIV infections MESH:D015658
244 520-533 Disease denotes HIV infection MESH:D015658
245 948-961 Disease denotes HIV infection MESH:D015658
293 1885-1888 Gene denotes CD4 Gene:920
294 2119-2132 Gene denotes interleukin 6 Gene:3569
295 2134-2138 Gene denotes IL-6 Gene:3569
296 3394-3397 Gene denotes p24 Gene:140767
297 3508-3512 Gene denotes IL-6 Gene:3569
298 3675-3678 Gene denotes CD4 Gene:920
299 1475-1483 Species denotes patients Tax:9606
300 1547-1555 Species denotes patients Tax:9606
301 1798-1803 Species denotes HIV-1 Tax:11676
302 1844-1852 Species denotes patients Tax:9606
303 2449-2457 Species denotes patients Tax:9606
304 2581-2589 Species denotes patients Tax:9606
305 2707-2712 Species denotes HIV-1 Tax:11676
306 2824-2832 Species denotes patients Tax:9606
307 2957-2962 Species denotes HIV-1 Tax:11676
308 3195-3200 Species denotes HIV-1 Tax:11676
309 1386-1391 Species denotes HIV-1 Tax:11676
310 2252-2257 Species denotes HIV-1 Tax:11676
311 2802-2805 Species denotes HIV Tax:12721
312 1404-1407 Chemical denotes HCQ MESH:D006886
313 1511-1514 Chemical denotes HCQ MESH:D006886
314 1601-1611 Chemical denotes zidovudine MESH:D015215
315 1613-1616 Chemical denotes ZDV MESH:D015215
316 1619-1639 Chemical denotes 2′,3′-dideoxyinosine MESH:D016049
317 1644-1665 Chemical denotes 2′,3′-dideoxycytidine MESH:D016047
318 1769-1772 Chemical denotes HCQ MESH:D006886
319 1989-1992 Chemical denotes HCQ MESH:D006886
320 2056-2059 Chemical denotes HCQ MESH:D006886
321 2067-2070 Chemical denotes HCQ MESH:D006886
322 2268-2271 Chemical denotes HCQ MESH:D006886
323 2303-2306 Chemical denotes ZDV MESH:D015215
324 2514-2517 Chemical denotes HCQ MESH:D006886
325 2541-2544 Chemical denotes ZDV MESH:D015215
326 2763-2766 Chemical denotes HCQ MESH:D006886
327 2820-2823 Chemical denotes HCQ MESH:D006886
328 2910-2922 Chemical denotes Azithromycin MESH:D017963
329 2924-2927 Chemical denotes AZM MESH:D017963
330 3063-3066 Chemical denotes HCQ MESH:D006886
331 3308-3311 Chemical denotes HCQ MESH:D006886
332 3421-3424 Chemical denotes ZDV MESH:D015215
333 3429-3432 Chemical denotes HCQ MESH:D006886
334 3478-3481 Chemical denotes HCQ MESH:D006886
335 3591-3594 Chemical denotes HCQ MESH:D006886
336 1462-1474 Disease denotes HIV-infected MESH:D015658
337 2421-2435 Disease denotes HIV-l-infected MESH:D015658
338 3699-3718 Disease denotes autoimmune diseases MESH:D001327
339 3731-3744 Disease denotes HIV infection MESH:D015658
351 3855-3858 Gene denotes CD4 Gene:920
352 3970-3978 Species denotes patients Tax:9606
353 4242-4249 Species denotes rabbits Tax:9986
354 3808-3811 Species denotes HIV Tax:12721
355 4338-4341 Species denotes HIV Tax:12721
356 3883-3886 Chemical denotes HCQ MESH:D006886
357 4011-4014 Chemical denotes HCQ MESH:D006886
358 4094-4097 Chemical denotes HCQ MESH:D006886
359 4298-4301 Chemical denotes HCQ MESH:D006886
360 3957-3969 Disease denotes HIV-infected MESH:D015658
361 4434-4456 Disease denotes HIV immunopathogenesis MESH:D015658
402 5067-5070 Gene denotes CD4 Gene:920
403 6089-6092 Gene denotes CD4 Gene:920
404 6275-6278 Gene denotes CD4 Gene:920
405 7064-7071 Gene denotes HLA-B27 Gene:3106
406 6158-6161 Gene denotes CD8 Gene:925
407 4816-4824 Species denotes patients Tax:9606
408 4878-4886 Species denotes patients Tax:9606
409 5297-5305 Species denotes patients Tax:9606
410 5424-5432 Species denotes patients Tax:9606
411 5598-5606 Species denotes patients Tax:9606
412 5671-5679 Species denotes patients Tax:9606
413 5764-5772 Species denotes patients Tax:9606
414 6595-6603 Species denotes patients Tax:9606
415 7051-7058 Species denotes patient Tax:9606
416 4523-4526 Species denotes HIV Tax:12721
417 4605-4608 Species denotes HIV Tax:12721
418 6591-6594 Species denotes HIV Tax:12721
419 6921-6924 Species denotes HIV Tax:12721
420 4528-4531 Chemical denotes HCQ MESH:D006886
421 4640-4643 Chemical denotes HCQ MESH:D006886
422 4686-4697 Chemical denotes hydroxyurea MESH:D006918
423 4717-4727 Chemical denotes didanosine MESH:D016049
424 5204-5207 Chemical denotes HCQ MESH:D006886
425 5209-5220 Chemical denotes hydroxyurea MESH:D006918
426 5226-5236 Chemical denotes didanosine MESH:D016049
427 5350-5353 Chemical denotes HCQ MESH:D006886
428 5362-5373 Chemical denotes hydroxyurea MESH:D006918
429 5390-5400 Chemical denotes didanosine MESH:D016049
430 5939-5949 Chemical denotes didanosine MESH:D016049
431 5995-5998 Chemical denotes HCQ MESH:D006886
432 6212-6215 Chemical denotes HCQ MESH:D006886
433 6488-6491 Chemical denotes HCQ MESH:D006886
434 6493-6504 Chemical denotes hydroxyurea MESH:D006918
435 6510-6520 Chemical denotes didanosine MESH:D016049
436 6812-6815 Chemical denotes HCQ MESH:D006886
437 6937-6940 Chemical denotes HCQ MESH:D006886
438 4801-4815 Disease denotes HIV-1 infected MESH:D015658
439 5278-5290 Disease denotes HIV-infected MESH:D015658
440 6350-6362 Disease denotes HIV-infected MESH:D015658
441 7083-7120 Disease denotes spondyloarthropathy and HIV infection MESH:D015658
459 7954-7957 Gene denotes CD4 Gene:920
460 7651-7654 Gene denotes CD4 Gene:920
461 7258-7266 Species denotes patients Tax:9606
462 7352-7360 Species denotes patients Tax:9606
463 7614-7622 Species denotes patients Tax:9606
464 7818-7826 Species denotes patients Tax:9606
465 8383-8391 Species denotes patients Tax:9606
466 7907-7910 Species denotes HIV Tax:12721
467 7283-7286 Chemical denotes HCQ MESH:D006886
468 7462-7465 Chemical denotes HCQ MESH:D006886
469 7582-7585 Chemical denotes HCQ MESH:D006886
470 7776-7779 Chemical denotes HCQ MESH:D006886
471 8115-8118 Chemical denotes HCQ MESH:D006886
472 8188-8191 Chemical denotes HCQ MESH:D006886
473 8534-8537 Chemical denotes HCQ MESH:D006886
474 8751-8754 Chemical denotes HCQ MESH:D006886
475 7832-7853 Disease denotes chronic HIV infection MESH:D015658
488 9437-9442 Gene denotes gp120 Gene:3700
489 8833-8838 Species denotes women Tax:9606
490 9093-9098 Species denotes women Tax:9606
491 9079-9082 Species denotes HIV Tax:12721
492 8957-8960 Chemical denotes HCQ MESH:D006886
493 9344-9347 Chemical denotes HCQ MESH:D006886
494 9402-9405 Chemical denotes HCQ MESH:D006886
495 9511-9514 Chemical denotes HCQ MESH:D006886
496 9876-9879 Chemical denotes HCQ MESH:D006886
497 8852-8865 Disease denotes HIV infection MESH:D015658
498 9009-9022 Disease denotes HIV infection MESH:D015658
499 10013-10026 Disease denotes HIV infection MESH:D015658

LitCovid-PD-HP

Id Subject Object Predicate Lexical cue hp_id
T10 3699-3718 Phenotype denotes autoimmune diseases http://purl.obolibrary.org/obo/HP_0002960

LitCovid-sentences

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.