Manifestations and Related Risk Factors of Thrombocyte Abnormalities in HIV-Positive Patients Before and After the Initiation of ART

Figures & data

Table 1 Demographic Data and Clinical Characteristics of the Study Subjects at the Beginning of Antiretroviral Therapy (n=6637)

Variables	Thrombocytopenia (n=176)	Thrombocytosis (n=388)	Normal (n=6073)
Age (years)	34(29, 46)	30(25, 38)	30(26, 37)
Sex
Male	166 (94.3)	364(93.8)	5820(95.8)
Female	10 (5.7)	24(6.2)	253(4.2)
Transmission route
Homosexual	115 (65.3)	294(75.8)	4893(80.6)
Heterosexual	38 (21.6)	58(14.9)	733(12.1)
Other/unknown	23 (13.1)	36(9.3)	447(7.3)
WHO clinical stage
I–II	152(86.4)	347(91.1)	5513(92.2)
III–IV	24 (13.6)	34(8.9)	469(7.8)
BMI (kg/m^2)
18.5–24.0	88 (66.2)	186(61.4)	3136(65.6)
< 18.5	19 (14.3)	40(13.2)	472(9.9)
>24.0	26 (19.5)	77(25.4)	1171(24.5)
HBsAg
Negative	148(85.5)	363(95.3)	5649(94.7)
Positive	25(14.5)	18(4.7)	314(5.3)
Anti-HCV
Negative	166(96.0)	378(99.5)	5833(98.0)
Positive	7(4.0)	2(0.5)	119(2.0)
Syphilis
Negative	105(64.4)	205(59.8)	3688(64.9)
Positive	58(35.6)	138(40.2)	1992(35.1)
Baseline VL (copies/mL)
<100,000	88(51.5)	237(62.7)	4143(70.4)
≥100,000	83(48.5)	141(37.3)	1740(29.6)
Baseline CD4 count (cells/μL)
<350	144(82.8)	219(56.9)	3595(60.0)
≥350	30(17.2)	166(43.1)	2397(40.0)
Baseline CD4/CD8 ratio
<0.4	151(87.3)	272(71.0)	4238(71.9)
≥0.4	22(12.7)	111(29.0)	1658(28.1)
WBC (×10^9 /L)
≥4.0	106(60.2)	353(91.0)	5288(87.1)
<4.0	70(39.8)	35(9.0)	785(12.9)
HGB (g/L)
≥110(Female) or ≥120(Male)	119(67.6)	308(79.4)	5651(93.1)
<110(Female) or >120(Male)	57(32.4)	80(20.6)	422(6.9)
NLR
<2.0	79(46.5)	168(45.8)	3589(61.2)
2.0–4.0	60(35.3)	130(35.4)	1791(30.5)
>4.0	31(18.2)	69(18.8)	488(8.3)

Notes: Data are presented as n (%), or median (interquartile range). Variable had missing values: WHO clinical stage = 98; BMI = 1422; HBV = 120; HCV =132; Syphilis = 451; VL = 205; CD4 count = 86; CD4/CD8 ratio = 185; NLR = 232.

Abbreviations: WHO, world health organization; BMI, body mass index; HBsAg, hepatitis B surface antigen; Anti-HCV, antibody to hepatitis C virus; VL, viral load; WBC, white blood cell; HGB, haemoglobin; NLR, neutrophil-lymphocyte ratio.

Table 2 Logistic Regression Analysis to Identify Factors Associated with Thrombocytopenia or Thrombocytosis in ART-Naïve Patients

Variables	Thrombocytopenia				Thrombocytosis
	OR (95% CI)	P value	AOR (95% CI)	P value	OR (95% CI)	P value	AOR (95% CI)	P value
Age (years)	1.041(1.029, 1.052)	<0.001	1.029(1.015, 1.042)	<0.001	0.995(0.984, 1.005)	0.316
Sex
Male	Ref	–			Ref	–
Female	1.386(0.723, 2.656)	0.326			1.517(0.985, 2.336)	0.059
Transmission route
Homosexual	Ref	–			Ref	–
Heterosexual	2.206(1.516, 3.209)	<0.001			1.317(0.983, 1.764)	0.065
Other/unknown	2.189(1.385, 3.461)	0.001			1.340(0.936, 1.920)	0.110
WHO clinical stage
I–II	Ref	–			Ref	–
III–IV	1.868(1.202, 2.904)	0.005			1.152(0.800, 1.658)	0.448
BMI (kg/m^2)
18.5–24.0	Ref	–			Ref	–
< 18.5	1.455(0.878, 2.412)	0.145			1.429(1.002, 2.038)	0.049
> 24.0	0.799(0.513, 1.244)	0.321			1.109(0.843, 1.458)	0.461
HBsAg
Negative	Ref	–	Ref	–	Ref	–
Positive	3.309(1.960, 4.713)	<0.001	2.825(1.782, 4.480)	<0.001	0.892(0.548, 1.451)	0.646
Anti-HCV
Negative	Ref	–			Ref	–
Positive	2.067(0.950, 4.499)	0.067			0.259(0.064, 1.053)	0.059
Syphilis
Negative	Ref	–			Ref	–
Positive	1.023(0.739, 1.416)	0.892			1.246(0.998, 1.557)	0.053
Baseline VL (copies/mL)
<100,000	Ref	–			Ref	–
≥100,000	2.246(1.655, 3.047)	<0.001			1.417(1.142, 1.758)	0.002
Baseline CD4 count (cells/μL)
<350	Ref	–	Ref	–	Ref	–	Ref	–
≥350	0.312(0.210, 0.465)	<0.001	0.527(0.338, 0.821)	0.005	1.144(0.930, 1.409)	0.203	1.616(1.231, 2.122)	0.001
Baseline CD4/CD8 ratio
<0.4	Ref	–			Ref	–
≥0.4	0.378(0.243, 0.588)	<0.001			1.071(0.855, 1.341)	0.553
WBC (×10^9 /L)
≥4.0	Ref	–	Ref	–	Ref	–	Ref	–
<4.0	4.455(3.264, 6.080)	<0.001	2.464(1.717, 3.536)	<0.001	0.669(0.469, 0.954)	0.027	0.467(0.291, 0.750)	0.002
HGB (g/L)
≥110(Female) or ≥120(Male)	Ref	–	Ref	–	Ref	–	Ref	–
<110(Female) or <120(Male)	6.265(4.494, 8.734)	<0.001	2.962(2.005, 4.377)	<0.001	3.496(2.682, 4.558)	<0.001	4.012(2.750, 5.854)	<0.001
NLR
<2.0	Ref	–			Ref	–	Ref	–
2.0–4.0	1.521(1.082, 2.137)	0.016			1.551(1.225, 1.963)	<0.001	1.542(1.172, 2.029)	0.002
>4.0	2.885(1.884, 4.418)	<0.001			3.021(2.247, 4.060)	<0.001	2.008(1.334, 3.021)	0.001

Note: Data are presented as n (%), or median (interquartile range).

Abbreviations: OR, odds ratio; AOR, adjusted odds ratio; CI, confidence interval; WHO, world health organization; BMI, body mass index; HBsAg, hepatitis B surface antigen; Anti-HCV, antibody to hepatitis C virus; VL, viral load; WBC, white blood cell; HGB, haemoglobin; NLR, neutrophil-lymphocyte ratio.

Figure 1 Recovery rate of thrombocyte abnormalities at different treatment duration. Recovery rate of thrombocytopenia and thrombocytosis after 12, 24, 36, and 48 months of antiretroviral therapy (blue: thrombocytopenia; red: thrombocytosis).

Figure 2 Incidence of new-onset thrombocyte abnormalities at different treatment duration. (A) Rate of new-onset thrombocytopenia after 12, 24, 36, 48, 60, 72, and 84 months of antiretroviral therapy. (B) Rate of new-onset thrombocytosis after 12, 24, 36, 48, 60, 72, and 84 months of antiretroviral therapy.

Figure 3 The proportion of different antiretroviral treatment regimens among HIV-infected patients. (A) The proportion of different antiretroviral treatment regimens among total subjects (n=5195). (B) The proportion of different antiretroviral treatment regimens in subjects with thrombocytosis (n=375).

Abbreviations: AZT, zidovudine; TDF, tenofovir; LPV/r, lopinavir/ritonavir; INSTIs, integrase inhibitors.

Table 3 The Ratio of Thrombocytosis in Each Regimen After 12 Months of Therapy

ART Regimen	Total Number
	Normal	Thrombocytosis
TDF based	4596(92.83%)	355(7.17%)
AZT based	123(92.48%)	10(7.52%)
LPV/r based	75(88.24%)	10(11.76%)
INSTIs	26(100%)	0(0%)

Abbreviations: ART, antiretroviral therapy; TDF, tenofovir disoproxil fumarate; AZT, zidovudine; LPV/r, lopinavir/ritonavir; INSTIs, integrase inhibitors.

Table 4 Cox Proportional Hazard Regression Analysis to Identify Risk Factors Related to Thrombocytosis After 12 Months of Treatment

Factors	Thrombocytosis (n=375)		Normal (n=4820)		Univariate Analysis		Multivariate Analysis
	N	%	N	%	HR (95% CI)	P value	HR (95% CI)	P value
Age (years)
<30	195	52	2433	50.5	Ref	–
≥30	180	48	2387	49.5	0.897(0.733, 1.099)	0.295
Sex
Male	333	88.8	4654	96.6	Ref	–	Ref	–
Female	42	11.2	166	3.4	2.746(1.992, 3.786)	<0.001	3.422(2.418, 4.843)	<0.001
Transmission route
Homosexual	282	75.2	3908	81.1	Ref	–
Heterosexual	66	17.6	551	11.4	1.640(1.254, 2.143)	<0.001
Other/unknown	27	7.2	361	7.5	1.043(0.702, 1.547)	0.836
WHO clinical stage
I–II	344	91.7	4352	90.3	Ref	–
III–IV	23	6.1	388	8.0	0.674(0.442, 1.029)	0.067
BMI (kg/m^2)
18.5–24.0	173	46.1	2503	51.9	Ref	–	Ref	–
< 18.5	23	6.1	354	7.3	0.995(0.618, 1.475)	0.835	0.984(0.636, 1.524)	0.943
>24.0	96	25.6	887	18.4	1.437(1.119, 1.844)	0.004	1.472(1.145, 1.894)	0.003
HBsAg
Negative	352	93.9	4494	93.2	Ref	–
Positive	17	4.5	258	5.4	0.785(0.482, 1.277)	0.329
Anti-HCV
Negative	367	97.9	4639	96.2	Ref	–
Positive	4	1.1	100	2.1	0.462(0.173, 1.238)	0.125
Syphilis
Negative	241	64.3	3008	62.4	Ref	–
Positive	113	30.1	1617	33.5	0.847(0.678, 1.059)	0.146
Baseline VL (copies/mL)
<100,000	248	66.1	3312	68.7	Ref	–
≥100,000	119	31.7	1361	28.2	1.097(0.882, 1.366)	0.405
Baseline CD4 count (×10^9 /L)
<350	205	54.7	2862	59.4	Ref	–
≥350	164	43.7	1900	39.4	1.214(0.989, 1.491)	0.064
Baseline CD4/CD8 ratio
<0.4	267	71.2	3329	69.1	Ref	–
≥0.4	95	25.3	1351	28.0	0.943(0.746, 1.192)	0.626
CD4 count at 1 year of ART (×10^9 /L)
<350	73	19.5	1014	21.0	Ref	–
≥350	226	60.3	2781	57.7	1.150(0.884, 1.496)	0.297
WBC (×10^9 /L)
≥4.0	342	91.2	4196	87.1	Ref	–	Ref	–
<4.0	33	8.8	624	12.9	0.634(0.443, 0.906)	0.012	0.537(0.349, 0.824)	0.004
HGB (g/L)
≥110(Female) or ≥120(Male)	348	92.8	4506	93.5	Ref	–
<110(Female) or >120(Male)	27	7.2	314	6.5	1.032(0.697, 1.526)	0.876
NLR
<2.0	237	63.2	2867	59.5	Ref	–
2.0–4.0	101	26.9	1460	30.3	0.863(0.682, 1.090)	0.216
>4.0	31	8.3	369	7.7	1.060(0.733, 1.534)	0.755

Notes: Data are presented as n (%), or median (interquartile range). Variable had missing values: WHO clinical stage = 88; BMI = 1159; HBV = 74; HCV =85; Syphilis = 216; VL = 155; CD4 count = 64; CD4/CD8 ratio = 153; CD4 count at 1 year of ART = 1101; NLR = 130.

Abbreviations: HR, hazard ratio; CI, confidence interval; WHO, world health organization; BMI, body mass index; HBsAg, hepatitis B surface antigen; Anti-HCV, antibody to hepatitis C virus; VL, viral load; WBC, white blood cell; HGB, haemoglobin; NLR, neutrophil-lymphocyte ratio.