Hepatitis A virus infection and hepatitis A vaccination in human immunodeficiency virus-positive patients: A review

Table 7 Primary response rates and predictors of seroconversion after hepatitis A virus vaccination in human immunodeficiency virus-positive patients

Ref.	Dates	Design/Country	No. of patient1	HAV/dosing schedules (mo)	CD4, cells/mm3	PVL, log10, copies/mL	ART	Timing of response2, mo/cut-off3, mIU/mL/assay	Response rate (%): ITT/PP	Predictors and comments4
Tseng et al[115]	2009-2010	Prospective, Taiwan	Standard 2-dose	HAVRIX 1440 U/	Mean, 538	Mean, 2.5	67.1%	12, 18/20, a. CIA (ARCHITECT HAVAb-IgG) b. ELISA (ETIAB- HAVK PLUS)	12 m (CIA): 75.7/81.7	MSM only study; Higher baseline CD4 and suppressed PVL; 3 doses over 2 doses
			All 126;	2 doses (0, 6)					12 m (ELISA): NA/88.6
			CD4 matched, 114						18 m (ELISA): NA/86.6
			3-dose	HAVRIX 1440/	Mean, 452	Mean, 3	58.2%		12 m (CIA): 77.8/81.8
			All, 213;	3 doses (0, 1, 6)					12 m (ELISA): NA/89.2
			CD4 matched, 114						18 m (ELISA): NA/86.9
			Standard 2-dose	HAVRIX 1440/	NA	NA	NA		12 m (CIA): 88.5/97.9
			HIV-negative, 193	2 doses (0, 6)					12 m (ELISA): NA/100
									18 m (ELISA): NA/100
Mena et al[116]	1997-2009	Retrospective, Spain	Standard 2-dose, 241	HAVRIX 1440/	Median, 531	55.3%5	61.4%	10-16/20, CIA (Advia Centaur)	NA/80.7	Higher CD4/CD8 ratio; 2 or more doses compared to 1 dose only; female; no HCV infection
				(0, 6-12)
			Accelerated, 41	TWINRIX 720/	Median, 543	73.2%	80.5%	5/20, CIA (Advia Centaur)	NA/70.7
				(0, 7, 21 d, 6-12)
Jimenez et al[117]	2002-2008	Retrospective, United States	Standard 2-dose, 125	HAVRIX 1440/ (0, 6-12)	Median, 410	Median, 3.1	70.0%	Variable/< 0.8 signal relative to cut-off, CIA (Vitros ECi)	NA/54	Higher baseline CD4 count and suppressed PVL
			101	TWINRIX 720/					NA/53
				(0, 1, 6-12)
Kourkounti et al[118]		Retrospective, Greece	cART-experienced, 63	HAVRIX 1440 or Vaqta 50/ (0, 6-12)	628	< 1.7	100.0%	7-13/20, ELFA (VIDAS)	NA/78	Higher baseline CD4 count
			cART-naïve, 50		472	3.9	0.0%		NA/76
Weinberg et al[119]	1994-2010	Prospective observational, United States	Hormone oral contraceptive, 13	2 doses (0, 6) or 3 doses (0, 2, 6)	478	47%5	78.0%	NA/20, ELISA (Mediagnost)	NA/62	Women only study; Higher baseline CD4 count and suppressed PVL
			No contraceptive, 149						NA/51
Launay et al[120]	2003-2005	Randomized controlled trial, France	Standard 2-dose, 49	HAVRIX 1440/ (0, 6)	Median, 355	Median, < 1.7	78.0%	6-18/20, ELISA (ETIAB- HAVK PLUS)	6 m: 44.9/46.8	Absence of tobacco smoking
									7 m: 69.4/72.3
									18 m: 61.2/69.8
			3-dose, 46	HAVRIX 1440/ (0, 1, 6)	Median, 351	Median, < 1.7	83.0%		6 m: 69.6/74.4
									7 m: 82.6/88.4
									18 m: 78.3/85.7
Overton et al[121]	1997-2004	Retrospective, United States	1 or 2-dose, 268	HAVRIX 1440/	Mean, 447	Mean, 2.9	67.5%	NA/NA	NA/49.6	Male; PVL < 1000 copies/mL
				NA (1 or 2 doses)				ELISA (Not specified)
Weissman et al[122]	2001-2003	Retrospective, United States	Standard 2-dose, 138	HAVRIX 1440/	Mean, 424	NA	81.9%	6-13/18, EIA (Abbot IMx HAV Ab)	48.6 (67/138)	Female; CD4 count at vaccination > 200 cells/mm3
				(0, 6-12)
Wallace et al[123]	1997-1998	Randomized controlled trial, United States	Standard 2-dose, HIV-positive, 55	Vaqta 50/ (0, 6)	Mean, 457.5	4.52	76.0%	1, 6, 7, 12/10, Quantitative modified HAVAb assay (NA)	1 m: NA/61,	100% of subjects with CD4 counts ≥ 300 cells/mm3 seroconverted
									CD4 < 300/ 300+, 48/74
									7 m: NA/94,
									CD4 < 300/ 300+, 87/100
									12 m: NA/90,
									CD4 < 300/ 300+, 80/100
			Standard 2-dose, HIV-negative, 72	Vaqta 50/ (0, 6)	NA	NA	NA		1 m: NA/90
									7 m: NA/100
									13 m: NA/90
Kemper et al[124]	1995-1997	Double-blind, placebo-controlled trial, United States	Standard 2-dose, HIV-positive, 48	HAVRIX 1440/ (0, 6)	376	3.29	91.0%	1, 6, 7, 9/33, ELISA (Enzymun; Boehringer Mannheim)	1 m: NA/11	Subjects with higher baseline CD4 counts were more likely to seroconvert and to have higher antibody titers
									CD4 < 200/ 200+, 0/16
									6 m: NA/9
									CD4 < 200/ 200+, 0/13
									7 m: NA/49,
									CD4 < 200/ 200+, 11/62
									9 m: NA/52,
									CD4 < 200/ 200+, 9/67
Neilsen et al[125]	Pre-1996	Randomized controlled trial, Australia	Accelerated 2-dose, HIV-positive, 48	HAVRIX 1440/ (0, 1)	Mean 569	NA	NA	1, 3/20, ELISA (Enzymun; Boehringer Mannheim)	1 m: NA/80.0	MSM only study; subjects with higher baseline CD4 counts were more likely to seroconvert and to have higher antibody titers; Vaccine schedule did not affect response; HIV-negative subjects had higher seroconversion rates and GMTs
									7 m: NA/93.2
									CD4 ≤ 200, 64
			Standard 2-dose, HIV-positive, 42	HAVRIX 1440/ (0, 6)	Mean 454	NA	NA	1, 7/20, ELISA (Enzymun; Boehringer Mannheim)	1 m: NA/75.6
									7 m: NA/81.3
									CD4 ≤ 200, 64
			Standard 2-dose, HIV-negative, 46	HAVRIX 1440/ (0, 6)	NA	NA	NA	1, 7/20, ELISA (Enzymun; Boehringer Mannheim)	1 m: NA/90.2
									7 m: NA/100
Wilde et al[126]	Pre-1995	Prospective, United Kingdom	Three mini-dose, HIV-positive hemophiliacs, 31	HAVRIX 720/ (0, 1, 6)	Median 450 (IgG positive after 2 doses)	NA	0	1, 2, 7/20, EIA (SORIN Biomedica INCstar, Italy)	2 m: NA/29	Hemophiliacs only (all anti-HCV positive); no patients with CD4 counts < 170 cells/mm3 seroconverted
					Median 335 (IgG positive after 3 doses)				7 m: NA/55
Tilzey et al[127]	Pre-1995	Prospective, United Kingdom	Three mini-dose, HIV-positive hemophiliacs, 25	HAVRIX 720/ (0, 1, 6)	NA	NA	NA	1, 2, 6, 7/20, ELISA (Boehringer-Mannheim)	1 m: NA/26	Men only study; After 3 doses, all HIV-positive hemophiliacs with anti-HAV titers of < 50 mIU/mL had CD4 counts < 100 cells/mm3. HAVRIX 1440 was given as a 4th booster dose to the 4 HIV vaccinees with anti-HAV < 50 mIU/mL after 3 doses; only 1 subsequently developed anti-HAV > 50 mIU/mL
									2 m: NA/50
									6 m: NA/47
									7 m: NA/76
			Three mini-dose, HIV-negative hemophiliacs, 8	HAVRIX 720/ (0, 1, 6)	NA	NA	NA		1 m: NA/57
									2 m: NA/86
									6 m: NA/100
									7 m: NA/100
			Three mini-dose, HIV-negative healthy controls, 25	HAVRIX 720/ (0, 1, 6)	NA	NA	NA		1 m: NA/100
									2 m: NA/100
									6 m: NA/100
									7 m: NA/100
Hess et al[128]	Pre-1994	Prospective, controlled, Germany	Three mini-dose, HIV-positive MSM, 26	HAVRIX 720/ (0, 1, 6)	495	NA	NA	1, 2, 6, 7/20, ELISA (SB Biologicals)	2 m: NA/78.6	MSM only study; Seroconversion rates were independent of CD4 counts
									7 m: NA/76.9
			Three mini-dose, HIV-negative MSM, 20	HAVRIX 720/ (0, 1, 6)	NA	NA	NA		2 m: NA/100
									7 m: NA/100
Santagostino et al[129]	Pre-1994	NA, Italy	Three mini-dose, HIV-positive hemophiliacs, 47	HAVRIX 720 (0, 1, 6)	NA	NA	NA	1, 2, 7, 12/20	12 m: NA/76.6	Hemophiliacs; Seroconversion rates were dependent on stage of HIV disease
			Three mini-dose, HIV-negative hemophiliacs, 66	HAVRIX 720 (0, 1, 6)	NA	NA	NA	NA	12 m: NA/100

¹Number of HIV-positive individuals with baseline negative anti-HAV and data available;

²Duration specified after the first dose when primary serological response was assayed;

³Cut-off value of specific anti-HAV IgG used to define serological response;

⁴Factors identified by multivariate analysis in HIV-positive individuals unless specified;

⁵Percentage of patients with undetectable plasma HIV RNA load. cART: Combination of antiretroviral therapy; CIA: Chemiluminescence immunoassay; EIA: Enzyme immunoassay; ELISA: Enzyme linked immunosorbent assay; HAV: Hepatitis A virus; HCV: Hepatitis C virus; ITT: Intention-to-treat; NA: Not available; PVL: Plasma HIV RNA load; PP: Per-protocol.