Risk Factors of Drug Resistance and the Potential Risk of HIV-1 Transmission of Patients with ART Virological Failure: A Population-Based Study in Sichuan, China

Figures & data

Figure 1 The distribution of people living with HIV/AIDS recruited in this study.

Figure 2 Resistance-drug transmission sketch map.

Figure 3 Continued.

Figure 3 HIV-1 transmission clusters. (A) Region-associated transmission clusters. Different colors represent different cities. (B) Genetic subtype-associated transmission networks. Different colors represent different subtypes: Orange: B subtype; blue: CRF_01AE; red: CRF_07BC; green: CRF_08BC; pink: CRF_85BC. (C) Infection route and region-associated transmission clusters. Different colors represent different infection routes: red: heterosexual transmission (Hetero); Orange: sexual transmission and injection drug users (IDUs); green: IDUs; blue: men who have sex with men (MSM); pink: mother to child transmission. (D) Drug resistance associated genetic transmission networks. Blue: CRF_01AE; red: CRF_07BC (E) Size of HIV-1 transmission clusters among the PLWH, size represents the number of individuals in a cluster. (F) Distribution of HIV-1 transmission degree. The node represents individuals in the network; degree represents the number of edges that link one node to other nodes.

Table 1 Urban Distribution of the Individuals Clustering of DR

City	Number of Infections	Clusters	Clustering Rate %	Clusters of DR	Clustering Rate of DR (%)
Chengdu	524	170	32.44%	37	7.06%
Deyang	240	166	69.17%	55	22.92%
Leshan	170	76	44.71%	26	15.29%
Suining	70	28	40.00%	7	10.00%
Ziyang	151	32	21.19%	14	9.27%
Mianyang	250	86	34.40%	39	15.60%
Yaan	125	41	32.80%	16	12.80%
Meishan	139	48	34.53%	18	12.95%
Yibin	595	330	55.46%	113	18.99%
Zigong	90	27	30.00%	8	8.89%
Neijiang	392	243	61.99%	97	24.74%
Luzhou	471	223	47.35%	94	19.96%
Bazhong	54	17	31.48%	8	14.81%
Nanchong	153	69	45.10%	38	24.84%
Dazhou	239	78	32.64%	17	7.11%
Guangyuan	53	23	43.40%	4	7.55%
Guangan	183	75	40.98%	23	12.57%
Panzhihua	144	60	41.67%	15	10.42%
Liangshan	1724	360	20.88%	130	7.54%
Aba	12	4	33.33%	1	8.33%
Ganzi	11	3	27.27%	1	9.09%
Total	5790	2159	37.29%	761	13.14%

Table 2 Risk Factors of Drug Resistant Nodes with Drug Resistance-Associated Transmission Links ≥2

Variables	Total	%	≥Link2	%	OR	AOR
Gender
Male	1771	72.79	278	15.70	1
Female	662	27.21	95	14.35	0.90 (0.70~1.16)
Age (years)
≤14	90	3.70	3	3.33	1	1
15–49	1464	60.17	156	10.66	3.46 (1.08~11.06)*	2.07 (0.32~13.45)
≥50	879	36.13	214	24.35	9.33 (2.92~29.81)***	4.27 (0.64~28.34)
Occupation
Farmers	1559	64.08	261	16.74	1	1
Workers	63	2.59	13	20.63	1.29 (0.69~2.41)	1.68 (0.87~3.23)
Employed	656	26.96	75	11.43	0.64 (0.49~0.85)**	0.70 (0.51~0.97)*
Students/Children	108	4.44	7	6.48	0.35 (0.16~0.75)**	2.37 (0.66~8.51)
Retired	47	1.93	17	36.17	2.82 (1.53~5.19)**	1.79 (0.93~3.44)
Marital status
Married or living With spouse	1298	53.35	193	14.87	1	1
Single	562	23.10	64	11.39	0.74 (0.54~1.00)*	1.09 (0.75~1.58)
Divorced/widowed	573	23.55	116	20.24	1.45 (1.13~1.88)**	1.18 (0.93~1.55)
Ethnicity
Han	1773	72.87	307	17.32	1	1
Yi	639	26.26	63	9.86	0.52 (0.39~0.70)***	0.70 (0.42~1.16)
Others	21	0.86	3	14.29	0.80 (0.23~2.72)	0.93 (0.26~3.37)
Education level
Illiteracy	566	23.26	74	13.07	1	1
Primary school	939	38.59	184	19.60	1.62 (1.21~2.17)**	1.06 (0.75~1.49)
Middle school	619	25.44	77	12.44	0.95 (0.67~1.33)	0.76 (0.50~1.15)
High school or technical secondary school	219	9.00	26	11.87	0.90 (0.56~1.44)	0.83 (0.46~1.49)
Junior college or above	90	3.70	12	13.33	1.02 (0.53~2.00)	1.09 (0.49~2.42)
Route of transmission
Hetero	1752	72.01	296	16.89	1	1
MSM	195	8.01	27	13.85	0.79 (0.52~1.21)	1.38 (0.82~2.31)
IDUs	323	13.28	44	13.62	0.78 (0.55~1.09)	1.70 (1.05~2.76)*
Sexual and IDUs	56	2.30	2	3.57	0.18 (0.44~0.75)*	0.39 (0.09~1.70)
MCT	107	4.40	4	3.74	0.19 (0.07~0.52)**	0.28 (0.43~1.80)
Latest CD4+ T cell counts (cells/μL)
≤200	885	36.37	143	16.16	1	1
200~500	1402	57.62	216	15.41	0.95 (0.75~1.19)	1.07 (0.83~1.39)
>500	146	6.00	14	9.59	0.55 (0.31~0.98)*	0.71 (0.38~1.34)
Stage of disease
HIV	811	33.33	148	18.25	1	1
AIDS	1622	66.67	225	13.87	0.72 (0.58~0.91)**	0.69 (0.53~0.89)**
History of sexually transmitted diseases except for HIV
Never	2237	91.94	331	14.80	1	1
Ever	196	8.06	42	21.43	1.57 (1.10~2.25)*	1.69 (1.15~2.48)**
ART related information Time of ART, years
≤12	378	15.54	73	19.31	1	1
12~36	956	39.29	173	18.10	0.92 (0.68~1.25)	0.88 (0.64~1.22)
>36	1099	45.17	127	11.56	0.55 (0.40~0.75)***	0.66 (0.47~0.92)*
Initial treatment regimen
First-line treatment	2390	98.23	370	15.48	1	1
Second-line treatment	43	1.77	3	6.98	0.41 (0.13~1.33)	0.72 (0.21~2.42)
Subtype
CRF07_BC	1320	54.25	172	13.03	1	1
CRF01_AE	688	28.28	102	14.83	1.16 (0.89~1.51)	1.01 (0.75~1.37)
CRF08_BC	256	10.52	53	20.70	1.74 (1.24~2.45)**	1.29 (0.88~1.87)
CRF85_BC	107	4.40	46	42.99	5.03 (3.32~7.62)***	2.86 (1.81~4.51)***
B	62	2.55	0	0.00

Notes:*P < 0.05, **P < 0.01, ***P < 0.001.

Abbreviations: CI, confidence interval; Hetero, heterosexual transmission; MSM, men who have sex with men; IDUs, injection drug users; MCT, mother to child transmission.

Figure 4 The geographic dimension of HIV-1 Drug-resistance transmission. (A) HIV-1 transmission in Sichuan. (B) HIV-1 Drug Resistance transmission with virological failure of ART in Sichuan. Circles with different size represents the number of individuals with drug resistance-associated transmission links within the region; the lines with different colors represent the number of individuals with drug resistance-associated transmission links between regions.

Table 3 Links of HIV DRMs with Subtype in Transmission Network

DRMs	B (n=15)		07BC (n=1975)		01AE (n=1450)		08BC (n=505)		85BC (n=896)		χ^2	P
Total	4	26.67%	306	15.49%	137	9.45%	92	18.22%	108	12.05%	40.83	<0.001
PI	0	0.00%	11	0.56%	1	0.07%	1	0.20%	0	0.00%	10.84	0.028
M46I/L	0	0.00%	0	0.00%	1	0.07%	1	0.20%	0	0.00%	4.46	0.347
I54V	0	0.00%	0	0.00%	1	0.07%	0	0.00%	0	0.00%	2.34	0.674
V82A	0	0.00%	0	0.00%	1	0.07%	0	0.00%	0	0.00%	2.34	0.674
K43T	0	0.00%	2	0.10%	0	0.00%	0	0.00%	0	0.00%	1.38	0.847
L10F/I	0	0.00%	0	0.00%	1	0.07%	0	0.00%	0	0.00%	2.34	0.674
L24I	0	0.00%	0	0.00%	1	0.07%	0	0.00%	0	0.00%	2.34	0.674
T74P	0	0.00%	0	0.00%	1	0.07%	0	0.00%	0	0.00%	2.34	0.674
Q58E	0	0.00%	10	0.51%	0	0.00%	0	0.00%	0	0.00%	14.54	0.006
NRTI	3	20.00%	169	8.56%	56	3.86%	63	12.48%	9	1.00%	113.24	<0.001
A62V	0	0.00%	1	0.05%	2	0.14%	0	0.00%	0	0.00%	2.28	0.686
D67N	0	0.00%	22	1.11%	15	1.03%	36	7.13%	1	0.11%	122.01	<0.001
E44D/A	0	0.00%	0	0.00%	1	0.07%	0	0.00%	0	0.00%	2.34	0.674
K65R/E	1	6.67%	12	0.61%	20	1.38%	11	2.18%	2	0.22%	23.63	<0.001
K70R/E/T/S/Q/H/G	1	6.67%	17	0.86%	20	1.38%	51	10.10%	2	0.22%	213.25	<0.001
K219E/Q/R	1	6.67%	20	1.01%	18	1.24%	45	8.91%	0	0.00%	178.59	<0.001
L74I/V/F	1	6.67%	4	0.20%	4	0.28%	1	0.20%	0	0.00%	32.56	<0.001
L210W	0	0.00%	10	0.51%	3	0.21%	0	0.00%	0	0.00%	8.19	0.085
M41L	0	0.00%	13	0.66%	3	0.21%	0	0.00%	1	0.11%	9.49	0.05
M184V/I	2	13.33%	81	4.10%	35	2.41%	52	10.30%	6	0.67%	97.89	<0.001
T215F/Y/S	0	0.00%	6	0.30%	7	0.48%	45	8.91%	1	0.11%	277.76	<0.001
V75I/M	0	0.00%	5	0.25%	3	0.21%	0	0.00%	0	0.00%	3.42	0.49
Y115F/Y	0	0.00%	3	0.15%	3	0.21%	0	0.00%	1	0.11%	1.22	0.875
NNRTI	4	26.67%	273	13.82%	134	9.24%	89	17.62%	103	11.50%	33.03	<0.001
A98G/A	0	0.00%	3	0.15%	4	0.28%	0	0.00%	1	0.11%	2.11	0.715
E138A/Q/G/K	0	0.00%	7	0.35%	2	0.14%	1	0.20%	0	0.00%	4.31	0.365
F227L/C	0	0.00%	5	0.25%	3	0.21%	0	0.00%	2	0.22%	1.30	0.862
G190A/S/C/Q	1	6.67%	14	0.71%	20	1.38%	10	1.98%	2	0.22%	19.55	0.001
H221Y	0	0.00%	8	0.41%	2	0.14%	7	1.39%	3	0.33%	14.49	0.006
K101E/Q/H/P/A	1	6.67%	13	0.66%	10	0.69%	2	0.40%	1	0.11%	14.36	0.006
K103N/S/E/Q	1	6.67%	164	8.30%	46	3.17%	34	6.73%	50	5.58%	39.26	<0.001
K238T/N	0	0.00%	0	0.00%	1	0.07%	0	0.00%	0	0.00%	2.34	0.674
L100I/S/V/F	0	0.00%	1	0.05%	1	0.07%	0	0.00%	0	0.00%	0.90	0.925
M230L/I	0	0.00%	2	0.10%	0	0.00%	1	0.20%	0	0.00%	3.47	0.483
P225H	1	6.67%	0	0.00%	2	0.14%	2	0.40%	1	0.11%	57.38	<0.001
V106M/V/A	2	13.33%	24	1.22%	18	1.24%	2	0.40%	10	1.12%	22.17	<0.001
V108I	0	0.00%	6	0.30%	14	0.97%	56	11.09%	0	0.00%	334.58	<0.001
V179D/E	0	0.00%	44	2.23%	22	1.25%	9	1.78%	31	3.46%	10.55	0.032
Y181C	1	6.67%	45	2.28%	11	0.76%	52	10.30%	5	0.56%	168.44	<0.001
Y188L/C	0	0.00%	4	0.20%	6	0.41%	0	0.00%	1	0.11%	3.99	0.407

Notes: PI: PI resistance in both connected sequences; NRTI: NRTI resistance in both connected sequences; NNRTI: NNRTI resistance in both connected sequences; each drug resistance site stands for the drug resistance site in both connected sequences; n: the total number of sides after the subtype sequence constructs the molecular network.

Abbreviations: NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor; PI, protease inhibitor.