Durability of serologic responses to inactivated hepatitis A virus vaccination among people living with HIV following acute hepatitis A outbreak: a 5-year follow-up study

Figures & data

Figure 1. Study flow. Abbreviations: HAV, hepatitis A virus; IgG, immunoglobulin G; PLWH, people living with HIV.

Table 1. Clinical characteristics of included PLWH with and those without seroreversion at month 60 of the second dose of HAV vaccination.

	Overall (n = 986)	With seroreversion (n = 92)	Without seroreversion (n = 894)	P
Age, median (IQR), years	34 (29-40)	36 (32-43)	34 (28-40)	0.001
Male sex, n (%)	973 (98.7)	91 (98.9)	882 (98.7)	0.838
Men who have sex with men, n (%)	942 (95.5)	84 (91.3)	858 (96.0)	0.039
Weight, median (IQR), kg	67 (60-75)	71 (63-77)	66 (60-74)	0.001
Body-mass index, median (IQR), kg/m^2	22.6 (20.7-24.7)	23.8 (21.4-26.1)	22.5 (20.7-24.6)	0.002
HBsAg positivity, n (%)	88 (8.9)	13 (14.1)	75 (8.4)	0.066
Anti-HCV positivity, n (%)	61 (6.2)	10 (10.9)	51 (5.7)	0.050
Receiving immunosuppressant^a, n (%)	3 (0.3)	1 (1.1)	2 (0.2)	0.152
Receiving ART at vaccination, n (%)	945 (95.8)	89 (96.7)	856 (95.7)	0.651
Lowest-ever CD4 count, median (IQR), cells/µL	266 (133-386)	172 (70-330)	273 (150-387)	0.003
CD4 count at vaccination, median (IQR), cells/µL	587 (452-764)	510 (407-679)	592 (458-766)	0.003
PVL at vaccination, median (range), log copies/mL	UD^b (UD-6.3)	UD (UD-5.4)	UD (UD-6.3)	0.011
PVL <200 copies/ml at vaccination, n (%)	909 (92.4)	80 (87.0)	829 (92.7)	0.040
CD4 count at the end of follow-up, median (IQR), cells/µL	667 (519-855)	557 (454-741)	676 (529-866)	0.001
PVL at the end of follow-up, median (range), log copies/mL	UD (UD-5.6)	UD (UD-4.4)	UD (UD-5.6)	0.452
PVL <200 copies/mL at the end of follow-up, n (%)	968 (98.2)	89 (96.7)	879 (98.3)	0.280
Combinations of HAV vaccine, n (%)				0.009
Havrix-Havrix	19 (1.9)	2 (2.2)	17 (1.9)
Havrix-Vaqta	351 (35.6)	46 (50.0)	305 (34.1)
Vaqta-Vaqta	616 (62.5)	44 (47.8)	572 (64.0)
Peak anti-HAV IgG titers, median (IQR), S/CO	10.1 (7.6-11.8)	4.7 (2.8-6.4)	10.4 (8.7-12.1)	<0.001
Syphilis during follow-up, n (%)	348 (35.3)	39 (42.4)	309 (34.6)	0.135

^a Including concurrent use of chemotherapy and immunomodulation agents.

^b UD, < 20 copies/mL.

Abbreviations: ART, antiretroviral therapy; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; IgG, immunoglobulin G; IQR, interquartile range; PLWH, people living with HIV; PVL, plasma HIV RNA load; UD, undetectable; S/CO, signal-to-cutoff.

Table 2. Factors associated with seroreversion at month 60 of the second dose of HAV vaccination

	Univariable		Multivariable
	OR (95% CI)	P value	AOR^a (95% CI)	P value
Age, per 1-year increase	1.04 (1.02–1.07)	0.002	1.00 (0.99–1.00)	0.975
Male sex	1.24 (0.16–9.63)	0.838
Body-mass index, per 1-kg/m^2 increase	1.10 (1.04–1.16)	0.002	1.10 (1.04–1.17)	0.002
HBsAg positivity	1.80 (0.95–3.38)	0.069	1.56 (0.78–3.13)	0.209
Anti-HCV positivity	2.02 (0.99–4.12)	0.055	1.74 (0.72–4.23)	0.217
Receiving immunosuppressant^b	4.90 (0.44–54.58)	0.196
Receiving ART at vaccination	1.32 (0.40–4.35)	0.652
Lowest-ever CD4 count, per 10-cells/µL increase	0.98 (0.97–0.99)	0.004	0.98 (0.97–1.00)	0.044
CD4 count at vaccination, per 10-cells/µL increase	0.99 (0.98–1.00)	0.010	1.00 (0.99–1.01)	0.850
PVL <200 copies/ml at vaccination	0.51 (0.26–0.98)	0.042	0.28 (0.14–0.59)	0.001
CD4 count at the end of follow-up, per 10-cells/µL increase	0.99 (0.98–0.99)	0.003	0.99 (0.98–1.00)	0.120
PVL <200 copies/ml at the end of follow-up	0.51 (0.14–1.78)	0.289
Combinations of HAV vaccine
Havrix-Havrix	Reference
Havrix-Vaqta	1.28 (0.29–5.73)	0.745
Vaqta-Vaqta	0.65 (0.15–2.92)	0.578
First dose of HAV vaccine, Vaqta vs. Havrix	0.52 (0.34–0.79)	0.003	0.44 (0.27–0.70)	0.001
Second dose of HAV vaccine, Vaqta vs. Havrix	0.87 (0.20–3.84)	0.857
Syphilis during follow-up	1.39 (0.90–2.15)	0.136

^a The ORs are the estimates of the effect of covariates on seroreversion at month 60 of vaccination, adjusted for age, body-mass index, HBsAg positivity, anti-HCV positivity, lowest-ever CD4 count, CD4 count and PVL at vaccination, CD4 count at the end of follow-up, and first dose of HAV vaccine using logistic regression model.

^b Including concurrent use of chemotherapy and immunomodulation agents.

Abbreviations: AOR, adjusted odds ratio; ART, combination antiretroviral therapy; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; OR, odds ratio; PVL, plasma HIV RNA load; S/CO, signal-to-cutoff.

Figure 2. Percentages of persistent responders in 60 months of the second dose of HAV vaccination in the per-protocol analysis. *n, number of individuals with available test results of anti-HAV IgG. Abbreviations: HAV, hepatitis A virus; IgG, immunoglobulin G.