Serologic response to primary vaccination with 7-valent pneumococcal conjugate vaccine is better than with 23-valent pneumococcal polysaccharide vaccine in HIV-infected patients in the era of combination antiretroviral therapy

Figures & data

Figure 1. Study flow of vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) and 7-valent pneumococcal conjugate vaccine (PCV) in HIV-infected patients

Table 1. Baseline characteristics of patients receiving 23-valent pneumococcal polysaccharide vaccine (PPV) or 7-valent pneumococcal conjugate vaccine (PCV)

	PPV group	PCV group	p value
Patient number, n	104	104
Male sex, n (%)	100 (96.2)	99 (95.2)	0.73
Age at first vaccination, mean (SD), y	39.4 (10.9)	38.6 (10.4)	0.59
HBsAg-positive, n (%)	15 (14.4)	18 (18.0)	0.49
Anti-HCV-positive, n (%)	11 (10.9)	6 (5.9)	0.21
Receipt of cART, n (%)	104 (100)	75 (72.1)	< 0.001
Nadir CD4 count, mean (SD), cells/µl	183.1 (211.6)	268.0 (218.7)	0.01
CD4 at vaccination, mean (SD), cells/µl	408.4 (248.0)	403.0 (189.7)	0.86
< 200, n (%)	21 (20.2)	14 (13.5)	0.19
200–349	24 (23.1)	25 (24.0)	0.87
350–499	29 (27.9)	32 (30.8)	0.65
> 500	30 (28.8)	33 (31.7)	0.65
PVL at vaccination, mean (SD), log10, copies/ml	2.7 (0.7)	2.8 (1.3)	0.44
< 2.6 log10, n (%)	88 (84.6)	61 (58.7)	< 0.001
Pre-immunization antibody level
Serotype 14, median level (IQR, ng/ml)	2345.3 (1248.2–4156.2)	1826.2 (836.8–3835.2)	0.47
Serotype 19F, median level (IQR, ng/ml)	1616.6 (983.3–2457.8)	1802.8 (1239.6–2545.3)	0.68
Serotype 23F median level (IQR, ng/ml)	781.6 (641.2–1528.8)	737.5 (495.5–1160.9)	0.69

Abbreviations: cART, combination antiretroviral therapy; HBsAg, hepatitis B virus surface antigen; HCV, hepatitis C virus; IQR, interquartile range; PVL, plasma HIV RNA load; SD, standard deviation.

Table 2. Median antibody titers (interquartile range, ng/ml) of the four serotypes studied for subjects receiving 23-valent pneumococcal polysaccharide vaccine and those receiving 7-valent pneumococcal conjugate vaccine

Serotype		6B	14	19F	23F
23-valent PPV	Baseline	NA	2345.3 (1248.2–4156.2)	1616.6 (983.3–2457.8)	781.6 (641.2–1528.8)
	24 weeks	NA	3183.6 (1749.8–9435.9)	1996.6 (1157.4–3438.8)	976.0 (667.0–2315.7)
	48 weeks	NA	3144.8 (1539.3–10619.6)	1995.8 (1061.4–3571.5)	858.0 (653.3–1751.2)
7-valent PCV	Baseline	756.0 (525.0–1274.2)	1826.2 (836.8–3835.2)	1802.8 (1239.6–2545.3)	737.5 (495.5–1160.9)
	24 weeks	1316.4 (920.0–2270.2)	6791.6 (2806.5–23667.2)	2899.9 (1876.1–5116.5)	1968.9 (927.5–5620.5)
	48 weeks	1061.8 (666.9–1767.0)	5004.4 (2139.2–14322.1)	2240.9 (1378.9–4269.8)	1329.4 (595.0–3012.3)

Abbreviation: NA, not available because of undetectable antibody responses.

Figure 2. Serologic response rate to at least one and two serotypes in patients who received vaccination with PPV and PCV 24 and 48 weeks after vaccination.

Table 3. Factors associated with a significant antibody response in multivariate analysis

	To at least one serotype		To at least two serotypes
	AOR	95% CI	AOR	95% CI
PCV vaccination	2.42	1.23–4.78	3.58	1.76–7.28
CD4 count < 200 cells/µl at vaccination	0.55	0.25–1.22	0.96	0.40–2.28
Suppressed plasma HIV RNA load at vaccination	1.47	0.60–3.64	3.62	1.11–11.81

Abbreviations: AOR, adjusted odds ratio; CI: confidence interval; PCV, pneumococcal conjugate vaccine

Table 4. Summary of studies of vaccination with pneumococcal conjugate vaccine in immunocompromised adult patients

Reference	Population	No.	First dose	Second dose	Dosing Interval	Follow up period	Definition of serologic response	Positive predictors for response	Negative predictors for response
Dransfield et al.^12	COPD patients	57	PCV	nil	NA	1 mo	> 2 folds	PCV vaccination	older age
		63	PPV	nil	NA				previously vaccination with PPV
Dransfield et al.^17	COPD patients	90	PCV	nil	NA	2 y	OPK	PCV vaccination
		91	PPV	nil	NA
Kumar et al.^18	Renal transplant recipients	30	PCV	nil	NA	8 weeks	> 2 folds + > 1 ng/ml
		30	PPV	nil	NA
Kumar et al.^19	Renal transplant recipients	23	PCV	nil	NA	3 y	> 2 folds + > 0.35 ng/ml	initial response to multi-serotype
		24	PPV	nil	NA
Kumar et al.^20	Liver transplant recipients	56	PCV	PPV	8 weeks	16 weeks	> 2 folds + > 0.35 ng/ml		corticosteroid use
		57	Placebo	PPV	NA
Lu et al.^25	HIV-infected patients	115	PCV	nil	NA	48 weeks	> 2 folds + > 1 ng/ml
		115	PCV	PCV	4 weeks
Lesprit et al.^15	HIV-infected patients	105	PCV	PPV	4 weeks	24 weeks	> 2 folds + > 1 ng/ml	priming with PCV	hepatitis C carrier
		103	nil	PPV	NA				ever smoker
Feikin et al.^14	HIV-infected patients	15	PCV	PCV	8 weeks	16 weeks	> 2 folds	priming with PCV
		18	PCV	PPV
		16	PCV	PPV
		18	Placebo	Placebo
Penaranda et al.^22	HIV-infected patients	110	PCV	PPV	4 weeks	8 weeks	> 2 folds + > 1 ng/ml	nadir CD4 count > 200 cells/μl
		110	nil	PPV	NA			no previous pneumonia
[Present study]	HIV-infected patients	104	PCV	nil	NA	48 weeks	> 2 folds	PCV vaccination CD4 count > 350 cells/µl at vaccination
		104	PPV	nil	NA			Lower plasma HIV RNA load

Abbreviations: COPD, chronic obstructive pulmonary diseases; NA: not applicable; OPK, opsonophagocytic assay; PPV, 23-valent pneumococcal polysaccharide vaccine; PCV, 7-valent pneumococcal conjugate vaccine

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