Hepatitis B virus vaccination in HIV-infected people: A review

Figures & data

Table 1. Vaccination against HBV in patients who had never been vaccinated.

Study (year)	Design	Schedule	% HAART Mean CD4 cell count (/µL)	Age (years) / %male	long-term response	Response rate	Predictors
Rey et al, 2000	Prospective	20µG M0–1–2	85%	30.5	Not assessed	55%	CD4 > 500
	N = 20	Boosters M3–4–5	470	70%
Fonseca et al, 2005	RCT	20µ vs 40µ	86%	37	NA	41% overall	CD4 > 350
		M 0–1–6	50% > 350 CD4	45 vs 50%		34% 20µ	HIV RNA < 10000 cp/mL
	N = 192					47% 40µ p = 0.07
Cornejo-Suarez et al, 2006	RCT	10 vs 40µg	65%	35.6 vs 34.1	NA	60.7% overall	CD4 > 200
	N = 79	M 0–1–6	245 vs 225	69.2 vs 72.5%		60% 10µg
						61.5% 40µ NS
Pasrischa et al, 2006	Prospective	20 vs 40µg	0	> 200: 30 YO, 63%	NA	> 200: 100%	Baseline CD4 > 200
	N = 40	M 0–1–6	< 200 / > 200	< 200: 32 YO, 46%		< 200: 47%
Veiga et al, 2006	Prospective	40µg M 0–1–6	100%	Responders:32 YO and 46%	NA	64%	Baseline CD4 and HIV VL
	N = 47		<200 or > 200	NR: 37 YO and 70%			CD4 memory T-lymphocytes
Cruciani et al, 2009	Prospective	40µ M0–1–2	80%	41	32.7% at 2 years	Overall = 89%	High CD4 cell count
		+/− 1–3 more	533	66%		M3 = 60%	Male, VL > 1000 cp/mL
	N = 92
Potsch et al, 2009	Prospective	40µg M0–1–2–6	79%	36	NA	89%	None
	N = 47		402	36%		79% > 100 UI/mL
Psevdos et al 2010	RCT	40 vs 20 µg after classic schedule	95 vs 86.9%	43 vs 45	NA	85 vs 59%	CD4 > 200
	N = 101		421 vs 413.	75 vs 63.9%			HAART
Launay et al, 2011	RCT	20µg M0–1–6	100%	43 / 72%	NA	65%	Female, Young, No smoking, high CD4,
	N = 437	40µg M0–1–2–6		42 / 66%		82% p<0.01
		4µg ID M0–1–2–6		43 / 64%		77% p = 0.02	HIV VL undetectable
De Vries et al, 2011	Non-inferiority RCT	10µg W0–1–3 vs	72.2 vs 70%	40 / 64.9%	NA	38.70%	NA
	N = 761	20µg M0–1–6	430 vs 440	40 / 69.7%		50%
						Non-inferiority for CD4 > 500
Postch et al, 2012	Prospective	40µg M0–1–2–6	80%	37	NA	91%	Undetectable HIV-1 VL
	N = 163		385	40%		80% > 100UI/mL
Mena et al, 2012	Retrospective	First schedule: 40µg	62.50%	36.9	NA	Global: 71%	HIV VL
	N = 474	W 0–4–24/48	488	71.30%		1^st schedule: 60.3%	CD4 count > 350
		W 0–4–8				58.10%	Rapid schedule or < 3doses
		D 0–7–21				69.20%
		+/− M 0–1–6				50.00%
						2^nd schedule: 58.6%
Ni et al, 2013	Meta-analysis of 5 RCT					Pooled OR for increased dose = 1.96 (95%CI 1.47–2.61)
	N = 833
Chaiklang et al, 2013	RCT	20µg M0–1–6	100%	41 / 18.9%	NA	88.60%	Delay diagnosis – treatment < 3M
	N = 132	20µg M0–1–2–6		42.2 / 20.4%		93.2% NS
		40µg M0–1–2–6		41 / 43.2%		95.4% NS
Fuster et al, 2016	Prospective	20µg M0–1–6	95%	42 / 68%	NA	62%	CD4 > 200
	N = 245						CD4 / CD8 > 0.4

HAART: highly active antiretroviral therapy

RCT: Randomized Controlled Trial

M: Month

W: week

D: Day

YO: Years Old

NR: Non Responders

VL: Virus Load

OR: Odd Ratio

NA: Not Assessed

NS: Not Significative

ID: IntraDermal

RCT: Randomized Controlled Trial

NR: Non Responders

VL: Viral Load]

M: Month

Table 2. Vaccination in people living with HIV with isolated anti-HBc serological profile.

Study (year)	Design	Schedule	% HAART Median CD4 cell count (/µL)	HCV Co-infection	Age / %male	Anamnestic response	Response rate	Predictors
Piroth et al, 2016	Prospective	20µg W0 then 40µg W5–9–24	100%	30%	46 / 59%	46%	89%	NA
	N = 54		538
Kaech et al, 2012	Prospective	20µg M0 +/−	89%	51%	42 / 49%	22%	60%	Injected drug use
	N = 37	20µg M0–1–6	443
Chakvetadze et al, 2010	Prospective	20µg +/− 2–5 20µg W4–8–12–16–20	87.5%	12.5%	40 / 55%	32.5%	40.7% W10	None
	N = 40		463				64% W21
Gandhi et al, 2005	Prospective	20µg W 0–4–24	72%	33%	43 / 62%	16%	62%	Male sex HCV co-infection
	N = 69		518
Jongjirawisan et al, 2006	Prospective	20µg once	80%	12%	38.1 / 59.3%	7%	NA	Intravenous drug use and HCV co-infection
	N = 140		300

HCV: Hepatitis C Virus

M: Month

W: Week

NA: Not Assessed

Table 3. Anti-HBV vaccination studies using adjuvants.

Study (year)	Design	Schedule	% HAART Median CD4 cell count (/µL)	Tolerance	Age / %male	Response rate
Cooper et al, 2005,	RCT	Engerix B 40µg	100%	Injection site pain	43 vs 41 YO	100% B40 + GMT vs 89% B40 alone
		+/−1 mg CPG 7909	543 (B40µ alone) vs 647 (B40 + CPG7909)
		M0–1–2			18 vs 14%
		N = 19 each arm				Higher GMT in B40 + CPG7909
Cooper et al, 2008	RCT II	Follow-up previous study at 5 years	idem	ok	Idem	90 vs50% M60 p<0.04
						HR M54 43 vs 12% p < 0.05
Sasaki et al, 2003	RCT	M0: 40µg HBsAg + 20µg GM-CSF or Placebo	90%	25% mild-moderate local SE.	25.9 vs 28.1	62 vs 30% J60 p<0.0074
		M1–6: 40µg HBsAg.	487 vs 462
		N = 40 each arm			52 vs 50%	NSD at D210
Overton et al, 2010	RCT	40µg HBsAg +/− 250µg GM-CSF M0–1–3	77 vs 79%	Mild-moderate local SE, higher in GM-CSF p = 0.01	40 vs 41	52 vs 65%
		N = 24 each arm	445 vs 461		79 vs 75%	GMT 27vs 92 UI/mL
						NSD
Overton et al, 2011	RCT	Failed 3*20µg	70% each arm	Higher GM-CSF group (p < 0.001)	37.3 vs 38.5	35 vs 50%, NS
		B 40µg +/− 250µg GM-CSF
		N = 60			40 vs 43.3%

RCT: Randomized Controlled Trial

HAART: Highly Active Anti RetroViral Therapy

YO: Years Old

SE: Secondary Effect

NSD: Non Significant Difference

M: Month D: Day GMT: Geometric Mean Titer

Table 4. Vaccination against HBV in children living with HIV.

Study (year)	Design	Schedule	% HAART Median CD4 cell count (/µL)	Mean Age (years old)	Response rate	Predictors
Diamant et al, 1994	Prospective	M0–1–6	88%	47 months	25%	% normal CD4 count (25 vs 52%, p = 0.014)
	N = 24	Recombivax 2.5µ / Engerix B10 < 11YO	460/mm3			Age (25 vs 55months, p = 0.016)
		Recombivax 5µ / Engerix 20 > 11YO.
Rutstein et al, 1994	Retrospective	W 0–4/8–6/9	None	3.1 months	35%	NA
	N = 355	Recombivax 2.5µg if mother HBsAg neg	1393 / µL	Weight = 2.71kg
	HIV = 17	Recombivax 5µ if mother HBsAg +
Scolfaro et al, 1996	Prospective	10µg M0–1–6	None	38 months	45%	NA
	N = 20	+/− 20µg	NA		Total: 85%
Zuin et al, 1992	Prospective	20µg M0–1–6	None?	659 days	78%	NA
	N = 18	+/− 20µg
Choudhury et al, 1995	Prospective	Booster doses		21–30 months	14%
	N = 14	< 11YO: Engerix B-20
		> 11YO: Engerix B 40
Bunupuradah et al, 2011	RCT	M0–2–6:	91.30%	12.1 YO	90,2% ID	Weight < 35kg
	N = 80	2µg ID/ 10 µg IM		50% ♂	92.3% IM
Flynn et al, 2011	RCT	M0–1–6	44%	20.44 months	60%	CD4 cell count OR1.32, p = 0.03
	N = 336	Engerix B 20µg
		Engerix B 40µg		39% ♂	73.2% p = 0.04
		Twinrix			75.45% p = 0.02
Lao-araya et al, 2010	Prospective	M0–2–6	100%	10.1YO	At 3 years: 71%	CD4 cell count > 500/µL
	N = 63	Engerix B 10µg		32% ♂
		Booster for non-responders			83% after booster
Bose et al, 2015	Prospective	Engerix B20µg M0–1–2–6	82%	8 YO	94% High responders 90%	NA
	N = 33			76% ♂
Abzug et al, 2009	Prospective	Fail classic schedule	100%	9.1 YO	46% W8	NA
	N = 204	Booster 5µ Recombivax + Pc + MMR		66% > 7 YO	38% W96
					Booster: 37%
				46% ♂

RCT: Randomized Controlled Trial

M: Month

ID: Intra Dermal

IM: Intra Muscular

OR: Odds Ratio

Pc: Pneumococcus

MMR: Measles Mumps Rubella

HAART: Highly Active Anti Retroviral Therapy