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Background: Human immunodeficiency virus-1 (HIV-1) that binds to the coreceptor CCR5 (R5 viruses) can evolve into viruses that bind to the coreceptor CXCR4 (X4 viruses), with high viral replication rates governing this coreceptor switch. Korean Red Ginseng (KRG) treatment of HIV-1 infected patients has been found to slow the depletion of CD4+ T cells. This study assessed whether the KRG-associated slow depletion of CD4+ T cells was associated with coreceptor switching., Methods: This study included 146 HIV-1-infected patients naïve to antiretroviral therapy (ART) and seven patients receiving ART. A total of 540 blood samples were obtained from these patients over 122 ± 129 months. Their env genes were amplified by nested PCR or RT-PCR and subjected to direct sequencing. Tropism was determined with a 10% false positive rate (FPR) cutoff., Results: Of the 146 patients naïve to ART, 102 were KRG-naïve, and 44 had been treated with KRG. Evaluation of initial samples showed that coreceptor switch had occurred in 19 patients, later occurring in 38 additional patients. There was a significant correlation between the amount of KRG and FPR. Based on initial samples, the R5 maintenance period was extended 2.35-fold, with the coreceptor switch being delayed 2.42-fold in KRG-treated compared with KRG-naïve patients. The coreceptor switch occurred in 85% of a homogeneous cohort. The proportion of patients who maintained R5 for ≥10 years was significantly higher in long-term slow progressors than in typical progressors., Conclusion: KRG therapy extends R5 maintenance period by increasing FPR, thereby slowing the coreceptor switch., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Background: The number of primary human immunodeficiency virus (HIV)-1 non-B subtype infections (non-B) and that of reports regarding the differences in the pathogenesis of subtype B and non-B infections are increasing. However, to the best of our knowledge, there have been no reports on gross deletion in the nef gene (gΔ nef ) in non-B infections., Methods: To determine whether there is a difference in the change in CD4 + T cells after treatment with Korean Red Ginseng (KRG) between patients with subtype B and non-B infections, we retrospectively analyzed and compared the annual decrease in CD4 + T cells (AD) and the proportion of gΔ nef in 77 patients who were followed for more than 10 years in the absence of combination antiretroviral therapy., Results: Overall, AD was significantly faster in patients with non-B infections than in those with subtype B infections. Survival analysis showed that the survival probability was significantly higher in subtype B than in non B-infected patients. These differences mainly resulted from significant differences in the amount of KRG and age. In the patients treated with KRG, there was a significant correlation between the amount of KRG and the AD in both subtypes. Interestingly, there was a significant correlation between the amount of KRG and the proportion of gΔ nef in patients infected with subtype B, but not in those infected with non-B. The same phenomenon was observed when the KRG dose was adjusted., Conclusion: Our results suggest that non-B may be biologically more stable than subtype B., Competing Interests: The authors declare no conflicts of interest., (© 2022 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Background: Korean Red Ginseng (KRG) extract has been shown to have beneficial effects in patients with atherosclerosis, suggesting that KRG extract may be effective in preventing subsequent ischemic stroke in patients with severe atherosclerosis., Methods: This double-blind, placebo-controlled trial randomized patients with severe atherosclerosis in major intracranial arteries or extracranial carotid artery, to ginseng group and placebo group. They were given two 500-mg KRG tablets or identical placebo tablets twice daily for 12 months according to randomization. The primary endpoint was the composite of cerebral ischemic stroke and transient ischemic attack during 12 months after randomization. The secondary endpoints were change in volumetric blood flow of the intracranial vessels and the incidence of newly developed asymptomatic ischemic lesions. Any adverse events were monitored., Results: Fifty-eight patients were randomized from June 2016 to June 2017, 29 to ginseng and 29 to placebo, and 52 (28 and 24, respectively) completed the study. One patient in the placebo group, but none in the ginseng group, experienced ischemic symptoms ( p  = 0.46). Changes in volumetric blood flow and the presence of ischemic brain lesions did not differ significantly in the two groups, and none of these patients experienced adverse drug reactions., Conclusion: Ginseng was well tolerated by patients with severe atherosclerosis, with these patients showing good compliance with ginseng dosing. Ginseng did not show significant effects compared with placebo, although none of the ginseng-treated patients experienced ischemic events. Long-term studies in larger patient populations are required to test the effect of ginseng., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Background: We have reported that internal deletions in the nef , gag , and pol genes in HIV-1-infected patients are induced in those treated with Korean Red Ginseng (KRG). KRG delays the development of resistance mutations to antiretroviral drugs., Methods: The  vif - vpr  genes over 26 years in 20 hemophiliacs infected with HIV-1 from a single source were sequenced to investigate whether  vif - vpr  genes were affected by KRG and KRG plus highly active antiretroviral therapy (ART) (hereafter called GCT) and compared the results with our previous data., Results: A significantly higher number of in-frame small deletions were found in the vif - vpr genes of KRG-treated patients than at the baseline, in control patients, and in ART-alone patients ( p  < 0.001). These were significantly reduced in GCT patients ( p  < 0.05). In contrast, sequences harboring a premature stop codon (SC) were more significant in GCT patients (10.1%) than in KRG-alone patients, control ( p  < 0.01), and ART-alone patients ( p  = 0.078 for peripheral blood mononuclear cells). The proportion of SC in Vpr was similar to that in Vif, whereas the proportion of sequences revealing SC in the env-nef genes was significantly lower than that in the pol-vif-vpr genes ( p  < 0.01). The genetic distance was 1.8 times higher in the sequences harboring SC than in the sequences without SC ( p  < 0.001). Q135P in the vif gene is significantly associated with rapid progression to AIDS ( p  < 0.01)., Conclusion: Our data show that KRG might induce sΔ in the v if - vpr genes and that v if - vpr genes are similarly affected by lethal mutations., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Korean Society of Ginseng. Publishing services by Elsevier B.V.)

Background: We have reported that defective nef and gag genes are induced in HIV-1-infected patients treated with Korean Red Ginseng (KRG)., Methods: To investigate whether KRG treatment and highly active antiretroviral therapy (HAART) affect genetic defects in the pol gene, we amplified and sequenced a partial pol gene (p- pol ) containing the integrase portion (1.2 kb) by nested PCR with sequential peripheral blood mononuclear cells over 20 years and compared it with those patients at baseline, in control patients, those taking ginseng-based combination therapy (GCT; KRG plus combinational antiretroviral therapy) and HAART alone. We also compared our findings to look for the full-length pol gene ( pol ) (3.0-kb)., Results: Twenty-patients infected with subtype B were treated with KRG for 116 ± 58 months in the absence of HAART. Internal deletion in the pol gene (Δ pol ) was significantly higher in the KRG group (11.9%) than in the control group and at baseline; its detection was significantly inhibited during GCT as much as during HAART. In addition, the Δ pol in p-pol significantly depended on the duration of KRG treatment. In pol , the proportion of Δpol was significantly higher in the KRG group (38.7%) than in the control group, and it was significantly inhibited during GCT and HAART. In contrast, the proportion of stop codon appeared not to be affected by KRG treatment. The PCR success rate was significantly decreased with longer GCT., Conclusion: The proportion of Δ pol depends on template size as well as KRG treatment. HAART decreases the detection of Δ pol., (© 2019 The Korean Society of Ginseng, Published by Elsevier Korea LLC.)

Background: To date, no study has described disease progression in Asian patients infected with HIV-1 subtype D., Methods: To determine whether the disease progression differs in patients infected with subtypes D and B prior to starting combination antiretroviral therapy, the annual decline (AD) in CD4 + T cell counts over 96 ± 59 months was retrospectively analyzed in 163 patients and compared in subtypes D and B based on the nef gene., Results: CD4 + T cell AD was significantly higher in the six subtype D-infected patients than in the 157 subtype B-infected patients irrespective of Korean Red Ginseng (KRG) treatment ( p  < 0.001). Of these, two subtype D-infected patients and 116 subtype B-infected patients had taken KRG. AD was significantly lower in patient in the KRG-treated group than in those in the KRG-naïve group irrespective of subtype ( p  < 0.05). To control for the effect of KRG, patients not treated with KRG were analyzed, with AD found to be significantly greater in subtype D-infected patients than in subtype B-infected patients ( p  < 0.01). KRG treatment had a greater effect on AD in subtype D-infected patients than in subtype B-infected patients (4.5-fold vs. 1.6-fold). Mortality rates were significantly higher in both the 45 KRG-naïve ( p  < 0.001) and all 163 ( p  < 0.01) patients infected with subtype D than subtype B., Conclusion: Subtype D infection is associated with a >2-fold higher risk of death and a 2.9-fold greater rate of progression than subtype B, regardless of KRG treatment.

Background: Long-term ginseng intake can increase longevity in healthy individuals. Here, we examined if long-term treatment with Panax ginseng Meyer (Korean Red Ginseng, KRG) can also enhance survival duration (SD) in patients with human immunodeficiency virus type 1 (HIV-1) infection., Methods: We retrospectively analyzed 252 HIV-1 patients diagnosed from 1986 to 2013 prior to the initiation of antiretroviral therapy. Overall, 162 patients were treated with KRG (3,947 ± 4,943 g) for 86 ± 63 mo. The effects of KRG on SD were analyzed according to the KRG intake level and the length of the follow-up period., Results: There were significant correlations between the total amount of KRG and SD in the KRG intake group ( r  = 0.64, p  < 0.0001) as well as between total amount of KRG and mean annual decrease in CD4 + T-cell count in all 252 patients ( r  = -0.17, p  < 0.01). The annual decrease in CD4 + T-cell count (change in cells/μL) was significantly slower in KRG-treated patients than in patients receiving no KRG (48 ± 40 vs. 106 ± 162; p  < 0.001). The SD (in months) was also significantly longer in the KRG group than in the no-KRG group (101 ± 64 vs. 59 ± 40, p  < 0.01)., Conclusion: KRG prolongs survival in HIV-1 patients, possibly by slowing the decrease in CD4 + T-cell count.

Background: The presence of gross deletions in the human immunodeficiency virus nef gene (gΔ nef ) is associated with long-term nonprogression of infected patients. Here, we investigated how quickly genetic defects in the nef gene are associated with Korean Red Ginseng (KRG) intake in 10 long-term slow progressors., Methods: This study was divided into three phases over a 20-yr period; baseline, KRG intake alone, and KRG plus highly active antiretroviral therapy (ART). nef gene amplicons were obtained using reverse transcription polymerase chain reaction (PCR) and nested PCR from 10 long-term slow progressors ( n  = 1,396), and nested PCR from 36 control patients ( n  = 198), and 28 ART patients ( n  = 157), and these were then sequenced. The proportion of gΔ nef , premature stop codons, and not in-frame insertion or deletion of a nucleotide was compared between three phases, control, and ART patients., Results: The proportion of defective nef genes was significantly higher in on-KRG patients (15.6%) than in baseline (5.7%), control (5.6%), on-KRG plus ART phase (7.8%), and on-ART patients (6.6%; p  < 0.01). Small in-frame deletions or insertions were significantly more frequent among patients treated with KRG alone compared with controls ( p  < 0.01). Significantly fewer instances of genetic defects were detected in samples taken during the KRG plus ART phase (7.8%; p  < 0.01). The earliest defects detected were gΔ nef and small in-frame deletions after 7 mo and 67 mo of KRG intake, respectively., Conclusion: KRG treatment might induce genetic defects in the nef gene. This report provides new insight into the importance of genetic defects in the pathogenesis of AIDS.

We investigated whether Korean red ginseng (KRG) and highly active antiretroviral therapy (HAART) affect the frequency of gross deletion in 5'LTR/gag in 20 hemophiliacs. This study is a prospective study in 20 hemophiliacs who were infected with Korean subclade B of HIV-1 from two cash-paid plasma donors in 1990. Over a 13-year period, we obtained 436 amplicons of 5'LTR/gag genes by nested polymerase chain reaction using 147 peripheral blood mononuclear cells. Of the 436 amplicons, 92 (21.1%) showed gross deletion in 5'LTR/gag. Despite of a 2.3-fold higher monthly dose of KRG intake, the frequency of gross deletion in 5'LTR/gag (16.4%) was significantly decreased during HAART compared with 28.1% prior to HAART (p<0.01). Gross deletion in 5'LTR/gag was 10% more detected on KRG-therapy than prior to KRG-therapy (p<0.05). In addition, we also obtained 28 amplicons containing premature stop codon or isoleucine at initiation codon of 254 amplicons sequenced on KRG intake (7.5%) or HAART (13.6%) compared with 0% before KRG intake. These findings indicate that high frequency of gross deletion in 5'LTR/gag and genetic defects prior to HAART are significantly associated with KRG intake and the detection of gross deletion in 5'LTR/gag is decreased by HAART.