Frequent gross deletions in pol gene in 10 HIV-1 infected patients treated with Korean red ginseng for 3 years: dosage dependency

Background

To my knowledge, there is only one report on gross deletions in the pol gene (gΔpol) [1] although there are many reports on gross deletions in the nef gene (gΔnef). It is known that Korean red ginseng (KRG) slows depletion of CD4 T cells in human immunodeficiency virus type 1-infected patients [2]. We reported an association between KRG intake and gΔnef [3] in 10 HIV-1 infected patients treated with KRG. Here, we investigated whether KRG intake also induces gΔpol.

Materials and methods

This study consisted of 10 patients (men;women: 8;2) infected with HIV-1 subtype B. All patients had consistently taken pure KRG powder for 42 ± 4 months (mean total KRG over this time, 4,197 ± 1,278 g) for up to 3 years, with at least five blood samples available. The average monthly dose was 99 ± 25 g (range, 51 to 146 g). The daily dose was 5.4 g for men and 2.7 g for women. They were not treated with antiretroviral therapy. We amplified the pol gene (1,232 bp encompassing terminal portion of reverse transcriptase and integrase region) using 68 PBMC samples from these 10 patients. The pol gene was amplified using two primer sets, outer primers OBP1/ OBP2 (nt. 3733 to 3752/ 5297 to 5278) and inner primers OBP3/OBP4 (nt. 3837 to 3860/ 5049 to 5068). Nucleotide positions were based on NL4-3.

Results

We obtained 277 amplicons of the pol gene in the 10 patients. Among the 277 amplicons, 25 were grossly deleted. There was no amplicon with a stop codon. Size of deletion was 660 ± 277 bp (49 to 1008). Seven patients exhibited gΔpol, ranging from 4.8% to 19.2%, with significant increases after KRG intake relative to baseline (12.3% vs. 1.7%) (p<0.05). Interestingly, 3 of 4 patients who took KRG <100 grams per month did not reveal any gΔpol, whereas all 6 patients who took KRG > 100 grams per month revealed gΔpol (>10% of amplicons). The proportion of gΔpol increased about 2-fold over the first 6 months on KRG and was statistically significantly higher after 6 months. Median time to the first detection of gΔpol was 22 months.

Conclusion

These findings show that occurrence of gΔpol is associated with KRG intake.