Differences in drug resistance of HIV-1 genotypes in CSF and plasma and analysis of related factors

Figures & data

Table 1. Characteristics of patients.

Characteristic	Total (n = 62)	ARV-non-treated patients (n = 51)	ARV-treated patients (n = 11)
Age, years, median (IQR)	51 (38–64)	56 (40–67)	45 (34–47)
Female, n (%)	12 (19.4)	10 (19.6)	2 (18.2)
Male, n (%)	50 (80.6)	41 (80.4)	9 (81.8)
Proteins of CSF mg/L, median (IQR)	474.67 (369.60–742.39)	479.82 (362.97–741.05)	469.52 (377.62–880.91)
Cerebrospinal fluid glucose mmol/L, median (IQR)	3.065 (2.40–3.59)	3.08 (2.33–3.63)	3.05 (2.75–3.54)
White blood cell count of CSF 10^6/L, median (IQR)	6.5 (1–26.75)	6 (1–26.5)	8 (3–26.5)
CSF HIV-1 RNA, log10 copies/mL, median (IQR)	4.88 (4.23–5.65)	4.99 (4.47–5.72)	4.47 (4.07–4.92)
Plasma HIV-1 RNA, log10 copies/mL, median (IQR)	5.78 (5.30–6.25)	5.80 (5.48–6.32)	5.30 (3.72–5.73)
Plasma zenith HIV-1 RNA, log10 copies/mL, median (IQR)	5.83 (5.50–6.37)	5.84 (5.52–6.40)	5.78 (4.74–6.10)
Nadir CD4 count, cells/mm^3, median (IQR)	52 (25–91)	55 (30–91)	21 (19–90.5)
CD4 count, cells/mm^3, median (IQR)	63 (29.75–121.50)	61 (35–106)	76 (23–136)
CD8 count, cells/mm^3, median (IQR)	364.5 (237–814.75)	365 (260–828.5)	283 (224.5–495)
CRF07-BC, n (%)	40 (64.5)^a	35 (68.6)^a	5 (45.5)
Current treatment, n (%)
NRTIs+INSTIs+FIs	1 (1.61)	/	1 (9.09)
NRTIs+NNRTIs	3 (4.84)	/	3 (27.27)
NRTIs+INSTIs	3 (4.84)	/	3 (27.27)
NRTIs+PIs	2 (3.23)	/	2 (18.18)
FIs+INSTIs	1 (1.61)	/	1 (9.09)
NRTIs	1 (1.61)	/	1 (9.09)

Note: IQR, interquartile range; CSF, Cerebrospinal Fluid; NRTIs, nucleotide reverse transcriptase inhibitors, NNRTIs, nonnucleoside reverse transcriptase inhibitors; INSTIs, integrase strand transfer inhibitors; PIs, protease inhibitors; FIs, fusion inhibitors.

^aTwo patients of the ARV-non-treated group, as designated at the time of HIV genotyping, had received ARV treatment in the past.

Table 2. Characteristics of HIV patients with drug resistance mutations.

Patient	Sex	Age (years)	Time since HIV diagnosis (weeks)	Total time under ARV treatment (weeks)	Time under current ARV treatment (weeks)	ARV	Subtype		HIV viral load (log10 copies/mL)		PI resistance mutations		NRTI resistance mutations		NNRTI resistance mutations		INSTI resistance mutations
							CSF	Plasma	CSF	Plasma	CSF	Plasma	CSF	Plasma	CSF	Plasma	CSF	Plasma
1	F	36	0	0	0	naive	CRF07_BC	CRF07_BC	6.09	5.99	Q58E	Q58E	None	None	None	None	None	None
2	M	85	0	0	0	naive	CRF08_BC	CRF08_BC	5.62	5.48	None	None	None	None	E138A	E138A	None	None
3	M	69	26	0	0	naive	CRF08_BC	CRF08_BC	6.01	7.00	None	None	None	None	E138A	E138A	None	None
4	M	63	223	0	0	naive	CRF07_BC	CRF07_BC	4.53	6.03	Q58E	Q58E	None	None	None	None	None	None
5	M	27	120	52	0	no	CRF55_01B	CRF55_01B	4.76	5.53	None	None	None	None	E138G, V179E	E138G, V179E	None	None
6	F	44	26	8	8	3TC+TDF+EFV	CRF07_BC	CRF07_BC	4.16	5.69	None	None	None	None	V106M, V179D	V106M, V179D	None	None
7	M	26	120	120	120	3TC+TDF+EFV	CRF01_AE	CRF01_AE	5.04	5.60	None	None	K65R, Y115F, M184V	K65R, Y115F, M184V	K101E, Y181C, G190A	K101E, Y181C, G190A,	None	None
8	M	33	21	16	9	3TC+TDF+EFV	CRF07_BC	CRF07_BC	4.78	5.30	None	None	M41L, K65R, M184V	M41L, K65R, M184V	K101E, V106M, Y181C, G190A	K101E, V106M, Y181C, G190A	None	None
9	M	35	369	365	365	3TC+TDF+LPV/r	CRF01_AE	CRF01_AE	4.47	3.33	M46I, I54V, V82A	M46I, I54V, V82A	D67N, K70E, M184V	D67N, K70E, M184V	K103N, V106I, F227L	K103N, V106I, F227L	None	None
10	M	47	257	257	28	3TC+ABC+LPV/r	A	A	3.78	2.45	None	None	M184I, K219N	M184I, K219N	None	None	None	None
11	M	46	9	9	4	EVG/c/FTC/TAF+ABT	CRF01_AE	CRF01_AE	6.55	6.55	None	None	M184I	M184I	None	None	None	None
12	M	45	411	411	9	3TC+TDF	CRF01_AE	CRF01_AE	4.20	5.00	None	None	K70Q, Y115F, M184V	K70Q, Y115F, M184V	V106I	V106I	None	None
13	M	49	9	5	5	ABT+DTG	CRF07_BC	CRF07_BC	3.25	3.87	Q58E	Q58E	None	None	None	None	None	None

Note: 3TC, lamivudine; TDF, tenofovir disoproxil fumarate; EFV, efavirenz; LPV/r, lopinavir/ritonavir; ABC, abacavir; DTG, dolutegravir; ABT, albuvirtide; EVG/c/FTC/TAF, elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide; F, female; M, male.

Table 3. Factors associated with HIV drug resistance in CSF.

Variables	Total (N)	n/N (%) with resistance	Univariate P value^a	Multivariate P value^a
Age (years)			0.263
25–45	21	6/21 (28.57%)
45–65	27	5/27 (18.52%)
≥65	14	2/14 (14.29%)
Sex			0.689
male	50	11/50 (22.00%)
female	12	2/12 (16.67%)
Time since HIV diagnosis (months)			0.394
0–6	42	5/42 (11.90%)
6–24	3	2/3 (66.67%)
24–60	6	3/6 (50.00%)
≥60	11	3/11 (27.27%)
Whether they are receiving ARV treatment			0.000***	0.000***
Yes	11	8/11 (72.73%)
No	51	5/51 (9.80%)
CD4 count (cells/mm3)			0.054*	0.370
<50	24	5/24 (20.83%)
50–100	20	2/20 (10.00%)
100–200	13	3/13 (23.08%)
≥200	5	3/5 (60.00%)
CSF HIV-1 RNA (log10 copies/mL)			0.480
3–4	12	2/12 (16.67%)
4–5	22	6/22 (27.27%)
5–6	19	2/19 (10.53%)
≥6	9	3/9 (33.33%)
subtype			0.271
A	1	1/1 (100.00%)
C	2	0/2 (0.00%)
CRF01-AE	11	4/11 (36.36%)
CRF07-BC	40	5/40 (12.50%)
CRF08-BC	7	2/7 (28.57%)
CRF55-01B	1	1/1 (100.00%)
Proteins of CSF (mg/L)			0.989
150–500	34	7/34 (20.59%)
500–1000	18	3/18 (16.67%)
1000–2000	6	2/6 (33.33%)
≥2000	4	1/4 (25.00%)
Cerebrospinal fluid glucose (mmol/L)			0.807
1–2	7	0/7 (00.00%)
2–3	22	6/22 (27.27%)
3–4	29	7/29 (24.14%)
≥4	4	0/4 (00.00%)
White blood cell count of CSF (10^6/L)			0.552
0–25	45	9/45 (20.00%)
25–50	5	2/5 (40.00%)
≥50	12	2/12 (16.67%)

Note: *** and * represent the significance level of 1% and 10% respectively.

ARV, antiretroviral; CSF, Cerebrospinal fluid.

a One-way ANOVA was used to analyse the effect of different levels of a single variable on drug resistance, and multivariate ANOVA was used to analyse the two variables with significant differences. P-values with significant differences are shown in bold.