Table 1.
Characteristics and outcomes of included studies.
|
A) Studies investigating one dose of PPSV23† | ||||||||
|---|---|---|---|---|---|---|---|---|
| Study (year)* | Definition of seroconversion | Vaccination schedule | Subgroup | CD4 count (mean/median) cells/ mm3 | cART‡% |
Seroconversion rate n/N(%) |
||
| 6B | 14 | Overall | ||||||
| Almeida (2009)[23] | ≥ 2-fold IgG increase; Overall: to ≥ 4 serotypes (70%) | PPSV23 | 503 | 45% | 24/44(55) | 25/44 (57) | 11/44 (25) | |
| Amendola (2002)[22] | ≥ 2-fold IgG increase | PPSV23 | 433 | 40% | 4/10 (40) | NR| | NR | |
| CD4 <200 | ||||||||
| CD4 200–500 | 52% | 9/23 (39) | NR | NR | ||||
| CD4 >500 | 33% | 5/24 (21) | NR | NR | ||||
| HIV-§ | NR | 0% | 7/20 (35) | NR | NR | |||
| Chang (2000) [26] | NR | PPSV23 | HIV+ | 149 | 50% | NR | NR | NR |
| HIV- | NR | NA | NR | NR | NR | |||
| Falco (2006)[27] | ≥ 2-fold IgG increase Overall: to ≥ 3 serotypes (60%) | PPSV23 | HIV+ | 504 | 79% | 15/112 (13.4) | 71/111 (64) | 28/112 (25) |
| HIV- | NR | 11/30 (37) | 19/30 (63) | 14/30 (47) | ||||
| Hart (2007) [29] | ≥ 4-fold IgG increase | PPSV23 | HIV+ | 409 | 100% | NR | NR | NR |
| HIV- | 788 | NR | NR | NR | ||||
| Horster (2010) [30] | ≥ 2-fold IgG increase | PPSV23 | 446 | 85% | NR | NR | 67/98 (68) | |
| Huang (2018) [31] | Opsonic titer ≥ 8 | PPSV23 | HIV+ | 350–970 (range) | > 50% (NR) | 60/63 (95) | NR | NR |
| HIV- | NR | NA | 56/56 (100) | NR | NR | |||
| Hung (2010) [32]5-year follow-up data | ≥ 2-fold IgG increase (to any serotype, 25%) 5y | PPSV23 | CD4 <100 | 45 | 97% | NR | 2/22 (9.1) | 5y 47/141 (33) |
| CD4 100–199 | 146 | 100% | NR | 12/34 (35) | ||||
| CD4 200–349 | 263 | 100% | NR | 9/30 (30) | ||||
| CD4 ≥350 | 457 | 98% | NR | 17/56 (30) | ||||
| Kang (2016) [33] | NR | PPSV23 | NR | 95% | NR | NR | NR | |
| Leggat (2015) [34] | NR | PPSV23 | CD4>200 cART- | 553 | 0% | NR | NR | NR |
| CD4<200 cART- | 126 | 0% | NR | NR | NR | |||
| CD4<200 cART+ | 206 | 100% | NR | NR | NR | |||
| HIV- | NR | 0% | NR | NR | NR | |||
| MacLennan (2016) [38] | NR | PPSV23 | HIV+ | 500 | 83% | NR | NR | NR |
| HIV- | NR | NR | NR | |||||
| Payeras (2002) [40] | NR | PPSV23 | HIV+ recurrent bacterial infection | 242 | 76% | NR | NR | NR |
| HIV+ controls | 247 | 97% | NR | NR | NR | |||
| HIV- | NR | NA | NR | NR | NR | |||
| Rash (2015)[41] | ≥ 2-fold IgG increase AND ≥1.30 mcg/ml to 70% of serotypes | PPSV23 | NR | 100% | NR | NR | 16/23 (70) | |
| Rodriguez-Barradas (2003) [42] | ≥ 2-fold IgG increase OR ≥1.0 mcg/ml for ≥ 2 serotypes (33%) | PPSV23 | (cART+) first time | 352 | 100% | NR | NR | 25/46 (54) |
| (cART+) second time | 366 | 100% | NR | NR | 22/41(54) | |||
| (cART-) | 274 | 0% | NR | NR | 23/39 (61) | |||
| Rodriguez-Barradas (2015)[49] | ≥ 2-fold IgG increase AND ≥1.0 mcg/ml; Overall: for 3 serotypes (60%) | PPSV23/Placebo (mo 0, mo 9–12) | 303 | 0% | NR | NR | 5/36 (14) | |
| Placebo/PPSV23 (mo 0, mo 9–12) | 470 | 100% | NR | NR | 3/36 (8.3) | |||
| Tasker (2002)[57] | ≥ 2-fold IgG increase; Overall: for ≥ 2 serotypes (50%) | PPSV23 | first time (cART-) | 579 | 0% | 9/14 (64) | 11/14 (79) | 13/14 (93) |
| second time (cART+) | 274 | 52% | 9/56 (16) | 25/56 (45) | 25/56 (45) | |||
| Placebo | second time (cART+) | 269 | 45% | 0/29 (0) | 1/29 (3) | 0/29 (0) | ||
|
Tsachouridou (2015)[45] |
≥ 2-fold IgG increase | PPSV23 | cART+ | 709 | 100% | NR | NR | 24/35 (69) |
| cART- | 638 | 0% | 26/31 (84) | |||||
|
B) Studies investigating PCV¶/Multiple PCV doses | ||||||||
|---|---|---|---|---|---|---|---|---|
| Study (year)* | Definition of seroconversion | Vaccination schedule | Subgroup | CD4 count (mean/median) cells/ mm3 | cART‡% |
Seroconversion rate n/N(%) |
||
| 6B | 14 | Overall | ||||||
| Bhorat (2015) [25] | NR | 3x PCV13 (mo 0,1,2) + PPSV23 (mo 3) | 537 | 96.7% | NR | NR | NR | |
| Glesby (2015) [28] | NR | PCV13+PCV13+PCV13 (0,6,12 mo) | 605 | 95% | NR | NR | NR | |
| Lu (2012)[36] | ≥ 2-fold IgG increase AND ≥1.0 mcg/ml Overall: for ≥ 2 (50%) | PCV7 (wk 0) | 439 | 72% | NR | NR | 63/107 (59) | |
| PCV7+PCV7 (wk 0,wk 4) | 450 | 71% | NR | NR | 97/113 (86) | |||
| Cheng (2016) [46] 5-years follow-up Lu (2012) | ≥ 2-fold IgG increase Overall: to ≥ 2 serotypes (50%) | PCV7 (wk0) | 407 | 77% | 57/102 (56) | 73/102 (72) | 63/102 (62) | |
| PCV7+PCV7 (wk0,4) | 446 | 81% | 56/103(54) | 79/103 (77) | 78/103 (76) | |||
| Rossheim (2016) [43] | NR | PCV13 | (PPSV23 1–3 years earlier) | 657 | 100% | NR | NR | NR |
| (PPSV23 >3 years earlier) | 602 | 100% | NR | NR | NR | |||
| Song (2019) [44] | ≥4-fold increase of OPA titer | PCV13 | CD4 >349 | 579 | 100% | 25/34 (74) | NR | |
| PCV13 | CD4 <350 | 200 | 100% | 20/33 (61) | NR | |||
| C) Studies investigating PCV + PPSV23 combined | ||||||||
| Study (year)* | Definition of seroconversion | Vaccination schedule | Subgroup | CD4 count (mean/median) cells/ mm3 | cART‡% |
Seroconversion rate n/N(%) |
||
|---|---|---|---|---|---|---|---|---|
| 6B | 14 | Overall | ||||||
| Deloria-Knoll (2006)[50] | NR | PCV 7 + PPSV23 (mo 0, mo 6) | 402 | 11% | 23/63 (37) | 40/63 (64) | 29/62 (47) | |
| Farmaki (2018)[5] | ≥ 2-fold IgG increase | PCV13+PPSV23 (0,12 mo) | 530 | 100% | NR | 40/40 (100) | NR | |
| Sögaard (2010)[47] | ≥ 2-fold IgG increase AND ≥1.0 mcg/ml; Overall: for ≥ 5 PCV7 serotypes (70%) | PCV7/PCV7/PPSV23 (mo 0, 3,9) | No adjuvans | 605 | 79% | 32/47 (68) | 34/47 (72) | 24/47 (51) |
| CPG7909 adjuvans | 673 | 79% | 35/42 (83) | 36/42 (85) | 36/41 (88) | |||
| D) Studies comparing PCV (or multiple PCV doses) to PPSV23 | ||||||||
| Study (year)* | Definition of seroconversion | Vaccination schedule | Subgroup | CD4 count (mean/median) cells/ mm3 | cART‡% |
Seroconversion rate n/N(%) |
||
|---|---|---|---|---|---|---|---|---|
| 6B | 14 | Overall | ||||||
| Crum-Cianflone (2010)[48] | ≥ 2-fold IgG increase AND ≥1.0 mcg/ml; Overall: to ≥ 2 serotypes (50%) | PPSV23 | HIV+ | 513 | 77% | NR | 28/ 64 (44) | 23/63 (36) |
| PCV7 | HIV+ | 533 | 85% | NR | 61/120 (51) | 68 /120 (57) | ||
| HIV- | NR | 0% | NR | 18/25 (72) | 22/25 (88) | |||
| Feikin (2001)[51] | ≥ 2-fold IgG increase | PCV7+PCV7 (0,8wk) | 378 | 67% | 6/15 (40) from graph | 4/15 (27) from graph | NR | |
| PCV7+PPSV23 (0,8wk) | 434 | 28% | 8/18 (44) from graph | 7/18 (39) from graph | NR | |||
| Placebo+PPSV23 (0,8wk) | 508 | 31% | 3/16 (19) from graph | 7/16 (44) from graph | NR | |||
| 2 doses of placebo (0,8wk) | 403 | 44% | NR | NR | NR | |||
| Ho (2013) [52] | ≥ 4-fold IgG increase | PPSV23+Placebo (mo 0, mo 2) | 548 | 73% | 7/89 (7.9) | 35/89 (39) | NR | |
| PCV7/Placebo (mo 0, mo 2) | 545 | 76% | 27/91 (30) | 50/91 (56) | NR | |||
| PCV7/PPSV23 (mo 0, mo 2) | 492 | 81% | 27/91 (30) | 42/91 (46) | NR | |||
| Lombardi (2016)[13] | ≥ 2-fold IgG increase; Overall for ≥ 9 PCV serotypes (70%) | PCV13+PCV13 (wk 0, 8) | 591 | 98% | 27/46 (59) | 28/46 (61) | 10/46 (22) | |
| PPSV23 (wk0) | 639 | 100% | 20/49 (41) | 33/49 (67) | 14/49 (29) | |||
| Belmonti (2019) [24] 5-years follow-up Lombardi (2016) | ≥ 2-fold IgG increase; Overall: to ≥ ≥9 serotypes (70%) | PCV13+PCV13 (wk 0, 8) | 591 | 98% | 17/42(40) | 13/42 (31) | 2/42 (4.8) | |
| PPSV23 (wk0) | 639 | 100% | 9/49(18) | 14/49 (29) | 3/49 (6.1) | |||
| Lu (2014) [35] | ≥ 2-fold IgG increase AND ≥1.0 mcg/ml; Overall: for ≥ 2 serotypes (50%) | PPSV23 (wk 0) | 519 | 100% | NR | NR | 11/97 (11) | |
| PCV7 (wk 0) | 565 | 90% | NR | NR | 16/36 (44) | |||
| PCV7+PCV7 (wk 0,wk 4) | 479 | 91% | NR | NR | 28/39 (72) | |||
| Lu (2013) [37] | ≥ 2-fold IgG increase AND ≥1.0 mcg/ml; Overall: for ≥ 2 serotypes (50%) | PPSV23 | 408 | 100% | NR | NR | 21/104 (20) | |
| PCV7 | 403 | 72% | NR | NR | 39/104 (38) | |||
| Slayter (2013)[14] | ≥ 2-fold IgG increase; Overall: for 4 serotypes (57%) | PCV7 | (immediate | delayed) | (82|77) | 97% | 7/19(37) 7/10 (70) | 10/19 (53) 7/10 (70) | 7/19 (37) | 7/10 (70) |
| PPSV23 | (immediate | delayed) | (64|90) | 100% | 10/18 (56) 6/17 (35) | 8/18 (44) 11/17 (65) | 11/18 (61) | 11/17 (65) | ||
| NCT02717494 (2020) [56] | ≥ 2-fold IgG increase for at least 1 serotype | PCV10 | 596 | 100% | NR | NR | 112/114 (98) | |
| PPSV23 | 585 | 100% | NR | NR | 106/110 (96) | |||
| Placebo | 564 | 100% | NR | NR | 7/113 (6.2) | |||
| E) PPSV23 versus PCV+PPSV23 combined | ||||||||
| Study (year)* | Definition of seroconversion | Vaccination schedule | Subgroup | CD4 count (mean/median) cells/ mm3 | cART‡% |
Seroconversion rate n/N(%) |
||
|---|---|---|---|---|---|---|---|---|
| 6B | 14 | Overall | ||||||
| Feikin (2001)[51] | ≥ 2-fold IgG increase | PCV7+PCV7 (0,8wk) | 378 | 67% | 6/15 (40) from graph | 4/15 (27) from graph | NR | |
| PCV7+PPSV23 (0,8wk) | 434 | 28% | 8/18 (44) from graph | 7/18 (39) from graph | NR | |||
| Placebo+PPSV23 (0,8wk) | 508 | 31% | 3/16 (19) from graph | 7/16 (44) from graph | NR | |||
| 2 doses of placebo (0,8wk) | 403 | 44% | NR | NR | NR | |||
| Ho (2013) [52] | ≥ 4-fold IgG increase | PPSV23+Placebo (mo 0, mo 2) | 548 | 73% | 7/89 (7.9) | 35/89 (39) | NR | |
| PCV7/Placebo (mo 0, mo 2) | 545 | 76% | 27/91 (30) | 50/91 (56) | NR | |||
| PCV7/PPSV23 (mo 0, mo 2) | 492 | 81% | 27/91 (30) | 42/91 (46) | NR | |||
| Lesprit (2007)[53] | ≥ 2-fold IgG increase AND ≥1.00 mcg/ml; Overall: for ≥ 5 PCV7 serotypes (70%) | PCV7+PPSV23 (wk 0, wk 4) | 351 | 88% | 57/105 (54) | 74/105 (70) | 62/105 (59) | |
| PPSV23 (wk4) | 350 | 86% | 53/103 (51) | 70/103 (68) | 41/103 (40) | |||
| Ohtola (2016)[39] | ≥ 2-fold increase AND ≥1.00 mcg/ml for 0, 1, 2 serotypes | PPSV23 | HIV+ | 652 | 100% | NR | NR | 12/22 (55) |
| PCV13+PPSV23 (wk 0, 8) | HIV+ | 717 | 100% | NR | NR | 11/15 (73) | ||
| HIV- | NR | NA | NR | NR | 12/14 (86) | |||
| Peñaranda (2010)[54] | ≥ 2-fold increase AND ≥1.00 mcg/ml to ≥ 4 serotypes (57%) | PCV7/PPSV23 (wk0, wk4) | 368 | 98% | 31/98 (32) | 49/98 (50) | NR | |
| PPSV23 (wk 0) | 351 | 91% | 30/100 (30) | 49/100(49) | NR | |||
| Sadlier (2016)[55] | ≥ 2-fold increase AND ≥1.0 mcg/ml; Overall: for ≥ 7 serotypes (58%) | PCV13+PPSV23 (wk 0, 4) | 447 | 52% | NR | NR | 16/26 (62) | |
| PPSV23 (wk 4) | 572 | 40% | NR | NR | 11/28 (39) | |||
⁎
Studies printed in bold were included in the meta-analysis. For additional information on study design, methodology, patient characteristics and outcomes of individual studies we refer to the supplementary material.
†
PPSV23 = 23-valent pneumococcal polysaccharide vaccine.
‡
cART= combination antiretroviral treatment, defined as a combination of at least antiretroviral drugs.
§
HIV= human Immunodeficiency virus.
|
NR = not reported.
¶
PCV= pneumococcal conjugate vaccine.