Trend of HIV Transmitted Drug Resistance After the Introduction of Single-Tablet Regimens in Southern Taiwan

Figures & data

Table 1 Demographic Data Among Treatment-Naïve of HIV-1 Infected Patients (n=369)

Parameters		Patient Numbers (%)
Gender	Male	365 (98.9)
	Female	4 (1.1)
Age	Median (IQR)	27 (23–33)
Risk factor	Heterosexual	11 (3)
	MSM	357 (96.7)
	IVDU	1 (0.3)
pol resistance	Y	36 (9.8)
	N	333 (90.2)
pol mutation	Y	59 (16)
	N	310 (84)
HIV subtype	CRF01_AE	24 (6.5)
	B	341 (92.4)
	CRF07_BC	4 (1.1)
CD4 (cell/ul)	Minimum	0
	Maximum	1098
	Median (IQR)	311 (201–431)
CD4 cut point (cell/ul) (n=366)	< 200	89 (24.3)
	≥ 200	277 (75.7)
Viral load (Log)	Minimum	2.47
	Maximum	7.00
	Median (IQR)	4.71 (4.34–5.11)
Viral load cut point (Log) (n=367)	< 4	41 (11.2)
	≥ 4	326 (88.8)
Syphilis	Negative	253 (68.6)
	Positive	116 (31.4)
IHA-AMEBIASIS (n=341)	≦ 128	326 (95.6)
	≧ 256	15 (4.4)
TOXOPLASMA-IgG (n=365)	Negative	339 (92.9)
	Positive	26 (7.1)
CMV-IgG (n=307)	Negative	6 (2)
	Positive	301 (98)
CRYPTOCOCCUS Ag (n=308)	Negative	305 (99)
	Positive	3 (1)
HAV Ab (n=366)	Negative	316 (86.3)
	Positive	50 (13.7)
HBs Ab (n=367)	Negative	188 (51.2)
	Positive	179 (48.8)
HBs Ag (n=367)	Negative	341 (92.9)
	Positive	26 (7.1)
HBc Ab (n=367)	Negative	277 (75.5)
	Positive	90 (24.5)
HCV Ab (n=367)	Negative	358 (97.5)
	Positive	9 (2.5)

Abbreviations: HIV, human immunodeficiency virus; IHA, indirect hemagglutination; CMV, cytomegalovirus; HAV, hepatitis A virus; HBs Ab, hepatitis B surface antibody; HBs Ag, hepatitis B surface antigen; HBc Ab, hepatitis B core antibody; HCV, hepatitis C virus; IQR, interquartile range; MSM, men who have sex with men; IVDU, intravenous drug abuser; Y, yes; N, no.

Table 2 Comparison the Differences of Demographic Information Among 208 Patients Enrolled Between 2013 to 2016 and 161 Patients Between 2017 to 2021

	2013–2016 (n=208)	2017–2021 (n=161)	p value	aHR	95% C.I
Gender
Male	208 (100)	157 (97.5)	0.035*
Female	0 (0)	4 (2.5)
Age (median, IQR)	26 (23–31)	28 (24–35)	0.005*
Risk factor, n (%)
MSM	202 (97.1)	155 (96.3)	0.770	0.767	0.243–2.425
Non-MSM	6 (2.9)	6 (3.7)
Viral load (log) (median, IQR)	4.8 (4.4–5.1)	4.6 (4.3–5.1)	0.011*
CD4 (median, IQR)	310 (201–432)	312 (198–429)	0.840
Cut point of viral load (log)
< 4	17 (8.2)	24 (15)	0.046*	0.507	0.262–0.980
≧ 4	190 (91.8)	136 (85)
Cut point of CD4
< 200	49 (23.7)	40 (25.2)	0.806	0.923	0.571–1.492
≧ 200	158 (76.3)	119 (74.8)
HIV subtype, n (%)
B	199 (95.7)	142 (88.2)	0.009*	0.338	0.149–0.769
Non-B	9 (4.3)	19 (11.8)
pol resistance, n (%)
Y	18 (8.7)	18 (11.2)	0.480	1.329	0. 667–2.645
N	190 (91.3)	143 (88.8)
pol mutation, n (%)
Y	28 (13.5)	31 (19.3)	0.153	1.533	0.877–2.680
N	180 (86.5)	130 (80.7)
NRTIs resistance, n=363
Y	8 (4)	4 (2.5)	0.560	0.618	0.183–2.090
N	194 (96)	157 (97.5)
NNRTIs resistance, n=363
Y	13 (6.4)	12 (7.5)	0.835	1.171	0.519–2.641
N	189 (93.6)	149 (92.5)
PIs resistance, n=363
Y	0 (0)	0 (0)
N	202 (100)	161 (100)
INSTIs resistance, n=339
Y	2 (1.1)	4 (2.6)	0.414	2.500	0.452–13.837
N	185 (98.9)	148 (97.4)
INSTIs mutation, n=339
Y	2 (1.1)	6 (3.9)	0.146	3.801	0.756–19.112
N	185 (98.9)	146 (96.1)
Syphilis
Y	70 (33.7)	46 (28.6)	0.311	0.789	0.504–1.233
N	138 (66.3)	115 (71.4)
HAV Ab, n=366
Y	22 (10.6)	28 (17.6)	0.065	1.797	0.985–3.280
N	185 (89.4)	131 (82.4)
HBsAg, n=367
Y	21 (10.1)	5 (3.1)	0.013*	0.286	0.105–0.775
N	186 (89.9)	155 (96.9)
HCV Ab, n=367
Y	5 (2.4)	4 (2.5)	1.000	1.036	0.274–3.922
N	202 (97.6)	156 (97.5)
Amebiasis-IHA, n=341
Y	5 (2.7)	10 (6.3)	0.122	2.376	0.794–7.105
N	177 (97.3)	149 (93.7)
Toxoplasma gondii IgG, n=365
Y	15 (7.2)	11 (7)	1.000	0.958	0.427–2.147
N	192 (92.8)	147 (93)
CMV IgG, n=307
Y	148 (99.3)	153 (96.8)	0.215	0.207	0.024–1.791
N	1 (0.7)	5 (3.2)
Cryptococcus Ag, n=308
Y	0 (0)	3 (1.9)	0.248
N	149 (100)	156 (98.1)

Note: *p<0.05.

Abbreviations: MSM, men who have sex with men; IQR, interquartile range; CI, confidence interval; aHR, adjusted hazard ratio; NTRI, nucleoside reverse transcriptase inhibitor; NNRTI, nonnucleoside reverse transcriptase inhibitor; PI, protease inhibitor; INSTI, integrase strand transfer inhibitor; IHA, indirect hemagglutination; CMV, cytomegalovirus; HAV Ab, hepatitis A virus antibody; HBs Ag, hepatitis B surface antigen; HCV Ab, hepatitis C virus antibody; Y, yes; N, no.

Table 3 Risk Factors Associated with pol resistance Among 369 HIV-1 Infected Treatment Naïve Patients Enrolled Between 2013 to 2021

	pol Resistance (n=36)	Non-pol Resistance (n=333)	p value	aHR	95% C.I
Gender
Male	36 (100)	329 (98.8)	1.000
Female	0 (0)	4 (1.2)
Age (median, IQR)	28 (24–33)	27 (23–33)	0.638
Risk factor, n (%)
MSM	34 (94.4)	323 (97)	0.330	0.526	0.111–2.502
Non-MSM	2 (5.6)	10 (3)
Year of sampling
2013–2016	18 (50)	190 (57.1)	0.480	1.329	0.667–2.645
2017–2021	18 (50)	143 (42.9)
Viral load (log) (median, IQR)	4.7 (4.1–5.1)	4.7 (4.3–5.1)	0.657
CD4 (median, IQR)	335 (236–487)	304 (198–430)	0.346
Cut point of viral load (log)
< 4	6 (16.7)	35 (10.6)	0.267	0.591	0.230–1.519
≧ 4	30 (83.3)	296 (89.4)
Cut point of CD4
< 200	6 (16.7)	83 (25.2)	0.311	1.680	0.676–4.179
≧ 200	30 (83.3)	247 (74.8)
HIV subtype, n (%)
B	36 (100)	305 (91.6)	0.093
Non-B	0 (0)	28 (8.4)
Syphilis
Y	7 (19.4)	109 (32.7)	0.130	0.496	0.211–1.168
N	29 (80.6)	224 (67.3)
Amebiasis-IHA, n=341
Y	2 (6.1)	13 (4.2)	0.646	1.464	0.316–6.788
N	31 (93.9)	295 (95.8)
Toxoplasma gondii IgG, n=365
Y	3 (8.3)	23 (7)	0.732	1.209	0.345–4.245
N	33 (91.7)	306 (93)
CMV IgG, n=307
Y	30 (100)	271 (97.8)	1.000
N	0 (0)	6 (2.2)
Cryptococcus Ag, n=308
Y	0 (0)	3 (1.1)	1.000
N	30 (100)	275 (98.9)
HAV Ab, n=366
Y	2 (5.6)	48 (14.5)	0.199	0.346	0.080–1.486
N	34 (94.4)	282 (85.5)
HBsAg, n=367
Y	3 (8.3)	23 (6.9)	0.731	1.217	0.347–4.273
N	33 (91.7)	308 (93.1)
HCV Ab, n=367
Y	3 (8.3)	6 (1.8)	0.048*	4.924	1.177–20.606
N	33 (91.7)	325 (98.2)

Note: *p<0.05.

Abbreviations: MSM, men who have sex with men; IQR, interquartile range; CI, confidence interval; aHR, adjusted hazard ratio; IHA, indirect hemagglutination; CMV, cytomegalovirus; HAV Ab, hepatitis A virus antibody; HBs Ag, hepatitis B surface antigen; HCV Ab, hepatitis C virus antibody; Y, yes; N, no.

Table 4 Risk Factors Associated with HIV Transmitted Drug Resistance Among 369 Patients Enrolled in This Study from 2013 to 2021

Variable	Number (%)	Univariate Analysis		Multivariate Analysis
		HR (95% CI)	P value	aHR (95% CI)	P value
HIV subtype
B	341 (92.4)		0.093		0.998
Non-B	28 (7.6)
Syphilis
Y	7 (19.4)	0.496 (0.211–1.168)	0.130	0.516 (0.216–1.231)	0.136
N	29 (80.6)	1
HAV Ab
Y	2 (5.6)	0.346 (0.080–1.486)	0.199	0.364 (0.083–1.608)	0.183
N	34 (94.4)	1
HCV Ab
Y	3 (8.3)	4.924 (1.177–20.606)	0.048*	5.767 (1.232–26.991)	0.026*
N	33 (91.7)	1

Notes: Statistical Analysis: Variables with p<0.20 in univariate analysis were considered for inclusion in logistic regression models. A p<0.05 was considered statistically significant. *p<0.05.

Abbreviations: aHR, adjusted hazard ratio; CI, confidence interval; HR, hazard ratio; HAV Ab, hepatitis A virus antibody; HCV Ab, hepatitis C virus antibody; Y, yes; N, no.

Figure 1 Prevalence of drug resistance (pol) and drug resistance-associated mutations (A) among the 369 HIV-1-infected treatment-naïve patients enrolled from 2013 to 2021 (B).

Abbreviations: INSTI, integrase strand transfer inhibitor; PI, protease inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor.

Figure 2 Comparisons of the prevalence of drug resistance (A) and drug resistance-associated mutations (B) between the two study periods (2013–2016 and 2017–2021).

Abbreviations: INSTI, integrase strand transfer inhibitor; PI, protease inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor.

Figure 3 Differences in the prevalence of drug resistance to NRTIs, NNRTIs, PIs and INSTIs (A) between the two study periods (2013–2016 and 2017–2021) (B and C).

Abbreviations: STR, single-tablet regimen; INSTI, integrase strand transfer inhibitor; PI, protease inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor.

Figure 4 Differences in the prevalence of mutations associated with drug resistance to NRTIs, NNRTIs, PIs and INSTIs (A) between the two study periods (2013–2016 and 2017–2021) (B and C).

Abbreviations: STR, single-tablet regimen; INSTI, integrase strand transfer inhibitor; PI, protease inhibitor; NNRTI, non-nucleoside reverse transcriptase inhibitor; NRTI, nucleoside reverse transcriptase inhibitor.