Tripterygium wilfordii Hook F extract in cART-treated HIV patients with poor immune response: a pilot study to assess its immunomodulatory effects and safety

Figures & data

Figure 1. Patient flowchart.

Table 1. Population characteristics

	INR (n = 9)	InaR (n = 9)	P value
Age, mean ± SEM (years)	41 ± 3	44 ± 2	0.378
Sex, n (%)			0.471
Male	7 (77.8)	9 (100.0)
Female	1 (11.1)	0 (0.0)
Transgender	1 (11.1)	0 (0.0)
Route of transmission, n (%)			0.294
Sex	8 (88.9)	5 (55.6)
Blood	1 (11.1)	4 (44.4)
CD4+T cell count before TwHF use, mean ± SEM (cells/μl)	134 ± 9	241 ± 10	< 0.001
Nadir CD4+T cell count, median, interquartile range (cells/μl)	21 (17, 46)	99 (21, 157)	0.058
Duration of viral suppression#, mean ± SEM (years)	1.4 ± 0.1	2.6 ± 0.5	0.004
Duration of current cART use before TwHF extract administration, mean ± SEM (years)	2.0 ± 0.2	3.6 ± 0.7	0.038
Viral load before cART, mean ± SEM (log copies/ml)	5.05 ± 0.70	4.65 ± 0.57	0.248
NRTI, n (%)			>0.999
3TC+AZT	5 (55.6)	5 (55.6)
3TC+TDF	4 (44.4)	4 (44.4)
Third antiretroviral therapy, n (%)			0.576
NNRTI (NVP or EFV)	8 (88.9)	6 (66.7)
PI (LPV/r)	1 (11.1)	3 (33.3)
HBsAg positive, n (%)^※	0 (0.0)	0 (0.0)	N/A
HCV antibody positive, n (%)^※	2 (22.2)	2 (25.0)	>0.999

Note: INR, immune nonresponders; InaR, inadequate responders; SEM, standard error of mean; cART, combined antiretroviral therapy

* xscalculated by using Fisher's exact test

# in INR group, viral load of patient 16 before TwHF extract use was missing, but this patient received three years of cART before TwHF extract use

‡ patient 16 in INR group and patient 11, 14 in InaR group did not have baseline viral load since their viral load was measured at other hospitals and was not available

※ baseline HBV and HCV profiles in patient 11 (InaR group) were missing. P values were calculated by using Fisher's exact test.

Figure 2. Association between TwHF extract and CD4 cell recovery. (A–C) an increase in total and memory CD4 cell count was observed during TwHF use. In B and C, data from 14 patients were available for T-cell subgroup analysis (n = 7 in INR group and n = 7 in InaR group). In Fig. 2A–C, gray asterisks indicate a significant difference between T-cell subsets before TwHF use and at TwHF initiation; black asterisks indicate a significant difference between T-cell subsets after TwHF use and at TwHF initiation. Dashed lines indicate TwHF initiation. (D, E) increase in total and memory CD4 T cells calculated by generalized estimating equation (GEE). Rates of CD4 cell recovery and 95% confidential intervals (CI) before and after TwHF extract use are labeled in these figures. (F–H) increase rates of CD4 cell and subgroups before and after TwHF extract use. The rate of increase in each patient was derived from linear regression, and the comparison was made using paired t-test, with changes in mean (95% CI) rates of increase labeled in these figures. *, 0.01 < P < 0.05; * *, 0.001 < P ≤ 0.01; * * *, P ≤ 0.001.

Figure 3. CD4 cell recovery for each patient. Horizontal lines with arrows indicate TwHF extract use. cART was administered at the beginning of each graph.

Figure 4. Association between TwHF extract use and immune activation in patients with poor immune response. (A, B) CD8 and CD4 cell activation profiles during TwHF extract treatment (n = 13 in month 0 and 3, n = 10 in month 6, n = 11 in month 9, n = 5 in month 12). P values were derived by using Wilcoxon paired test. Median level of immune activation is also labeled in figures. (C–F) correlation between CD38(+)HLA-DR(+) double positive CD8 or CD4 T-cell percentage and total or memory CD4 cell count. *, 0.01 < P < 0.05; * *, 0.001 < P ≤ 0.01; * * *, P ≤ 0.001.