Background
Methods
Literature search strategy
Study selection
Data extraction and data analysis
Results
Study characteristics
First author, year | Study population/Study setting | Study design/Sample size | Sample | Intervention | Comparison | Study qualitya |
---|---|---|---|---|---|---|
Rathunde, 2014 [37] | Adult HIV patients at specialized ambulatory facilities in academic tertiary care hospital in Curitiba, Brazil | Cross-sectional (N = 107) | Venous | Alere Pima™ CD4 (Pima) | FACSCalibur | 9 |
Galiwango, 2014 [49] | HIV infected patients (pre and experienced ART persons) at field clinics in Rakai, Uganda | Cross-sectional (N = 903) | Venous | Pima | FACSCalibur | 10 |
van Rooyen, 2013 [15] | Known HIV-positive individuals older than 18 years in KwaZulu-Natal, South Africa (SA) | Prospective cohort (N = 671) | Capillary (Pima); venous (FACSCalibur) | Pima | FACSCalibur | Moderate |
Myer, 2013 [45] | HIV infected pregnant women at a single large antenatal clinic in Cape Town, SA | Cross-sectional (N = 546) | Venous | Pima | Beckman-Coulter PLG technology | 8 |
Mnyani, 2012 [51] | HIV infected pregnant women at first ANC visit to Chiawelo clinic in Johannesburg, SA | Cross-sectional (N = 305) | Capillary (Pima); venous (Ref. tests) | Pima | Beckman Coulter Flow Cytometer | 10 |
Mwau, 2013 [53] | Patients attending 9 health facilities (for HIV treatment and care) offering CD4 count in Kenya | Cross-sectional (N = 1539) | Venous (Pima & reference methods); capillary (Pima) | Pima | FACSCount, Partec Cy-flow, GUAVA and FACSCalibur | 8 |
Glencross, 2012 [22] | Adult HIV patients attending (1) Hospital based antenatal HCT clinic in Johannesburg-phase II (2) Two Primary health care HCT clinic in Limpopo province-phase IIIA; and (3) Inner-city primary health care clinic in Johannesburg, South Africa-phase IIIB | Cross-sectional (N = 91; N = 96; N = 139) | Venous and capillary | Pima | Simplified single platform (SP) PLG CD4 | 12 |
Thakar, 2012 [36] | HIV positive patients aged 18–60 attending 21 ART centers in different parts of India | Cross-sectional (N = 1790) | Venous and capillary | Pima | FACSCalibur; FACSCount; Partec CyFlow | 12 |
Manabe, 2012 [46] | HIV infected patients at Adult Infectious Diseases Institute Clinic in Mulago Hospital, Kampala, Uganda | Cross-sectional (N = 206) | Venous and capillary | Pima | FACSCalibur | 11 |
Jani, 2011 [39] | HIV infected individuals attending 2 primary health care ART clinics in Maputo, Mozambique | Cross-sectional (N = 697) | Capillary (Pima); venous (Ref. tests) | Pima | FACSCalibur | 7 |
Diaw, 2011 [44] | Patients (adults & children; HIV +/−) presenting for HIV follow-up at three out-patient clinic & one lab in Dakar, Senegal | Cross-sectional (N = 300) | Venous (200 patients); capillary (finger/heel-prick) 100 patients | Pima | FACSCount | 11 |
Mtapuri-Zinyowera, 2010 [50] | Newly diagnosed HIV positive patients at a VCT center in Harare, Zimbabwe | Cross-sectional (N = 165) | Capillary (Pima); venous (Ref. tests) | Pima | FACSCalibur | 11 |
Wade, 2014 [40] | HIV infected patients presenting for routine CD4 testing at infectious disease clinic in Dar es Salam, Tanzania | Cross-sectional (N = 200) | Capillary (Pima); venous (Ref. tests) | Pima | FACSCalibur | 11 |
Wade, 2013 [42] | (Anonymous) HIV infected patients attending normal CD4 test monitoring and HIV-negative donors from blood bank of Regional Hospital and two Healthcare Centers in Ziguinchor, Senegal | Cross-sectional (N = 128) | Venous | Pima | FACSCount | 11 |
Gous, 2013 [52] | HIV infected patients > 18 years old visiting comprehensive care management and treatment clinic for ART initiation or monitoring at Tshwane District Hospital in Pretoria, SA | Cross-sectional (N = 300) | Capillary (Pima); venous (Ref. tests) | Pima | PLG CD4 FC 500 | 10 |
Malagun, 2014 [38] | HIV infected adults >18 year old attending one urban (Heduru HIV clinic at Port Moresby General Hospital, Port Moresby) and 2 rural (Asaro District Health Centre and Kainantu Rural Hospital) clinics in Papua New Guinea | Cross-sectional (N = 237) | Venous | Pima | FACSCount | 11 |
Picken, 2014 [43] | HIV positive mother of children with CD4 count < 500 cells/μl and not on ART at Tygerberg hospital, Cape Town, SA | Cross-sectional (N = 52) | Capillary (Pima); venous (Ref. tests) | Pima | Beckman Coulter FC 500 MPL® | 11 |
Mwau, 2014 [48] | HIV infected patients ≥ 18 years old at Comprehensive clinics of 2 health care facilities in Busia county of Western province, Kenya | Cross-sectional (N = 276) | Capillary (Pima); venous (Ref. tests) | MyT4 POC CD4 | FACSCalibur and FACSCount | 11 |
Gumbo, 2013 [41] | HIV infected adult patients attending Harare Central hospital opportunistic infection clinic, Zimbabwe | Cross-sectional (N = 104) | Venous | PointCare NOW | BD FACSCalibur | 9 |
Bergeron, 2012 [47] | HIV infected adult patients; unknown HIV status; and HIV infected children aged 12–59 months attending: (1) the Instituto Nacional de Saude (INS) Maputo, Mozambique; (2) the Institute of Tropical Medicine of Antwerp (Belgium) in Tete, Mozambique; (3) Wits University, Johannesburg, SA | Cross-sectional (N = 472) | Venous | PointCare NOW | FACSCalibur and the EPICS- XL | 8 |
Zeh, 2014 [35] | HIV infected patients in Western Kenya | Cross-sectional (N = 147) | Venous and capillary | Pima | FACSCalibur | - |
Arnet N, 2013 [33] | HIV infected patients from 5 PMTCT and HIV treatment sites in Dar-es-Salaam, Tanzania | Cross-sectional (N = 1060) | Venous and capillary | Pima | FACSCalibur | - |
Performance of POC CD4 tests in field settings
Failure rates
Author, year | Performance of Pima on capillary blood | Author, year | Performance of Pima on venous blood | ||||||
---|---|---|---|---|---|---|---|---|---|
Bias/LoA; Sample size (N) | Sensitivity Specificity | Total Misclassification | Failure rate | Bias/LoA Sample size (N) | Sensitivity | Total Misclassification | Failure rate | ||
Specificity | |||||||||
Reference test = FACSCalibur | |||||||||
(van Rooyen, Barnabas et al. 2013) [14] | Mean bias: 16 cells/μl (LoA: −1 to 32; N = 193) |
Not reported (NR)
|
NR
|
NR
| (Rathunde, Kussen et al. 2014) [32] | Bias/LoA NR; N = 107 | At CD4 threshold of 350 cells/μl: Sensitivity 94 % Specificity 93 % |
NR
|
NR
|
(Jani, Sitoe et al. 2011) [34] | Accurate absolute counts |
NR
| At CD4 thresholds of 200 cells/μl: 5.2 % |
NR
| (Galiwango, Lubyayi et al. 2014) [45] | Pima significantly underestimate CD4 count particularly at higher CD4 count. | At CD4 threshold of 350 cells/μl: Sensitivity 88.6 % specificity 87.5 % | 12.2 % |
NR
|
Bias: −52.8 cell/μl (LoA: −250.9 to 145.2; N = 135). | |||||||||
Bias was smaller at lower CD4 count (<500: −24.4) than at higher CD4 count (>500: −107.9). | At CD4 thresholds of 350 cells/μl: 17 % | Bias: −34.6 cells/μl (LoA: −219.8 to +150.6; N = 903) | At CD4 threshold of 500 cells/μl: Sensitivity 96.1 % specificity 83.0 % | 9.5 % | |||||
At 350 cut-off: +5.1 cells/μl (LoA: −126.6 to +136.8) vs −51.0 cells/μl (LoA: −245.4 to +143.4) | |||||||||
At 500 cut-off:-10.9 cells/μl (LoA: −147.3 to +125.5) vs −66.3 cells/μl (LoA: −286.6 to +154.0) | |||||||||
(Mtapuri-Zinyowera, Chideme et al. 2010) [46] | Mean bias: 7.6 cells/μl (LoA: −173.8 to +189.0). | At CD4 threshold of 200 cells/μl: Sensitivity: 95.1 % Specificity: 91.6 % | 6.7 % |
NR
| (Mwau, Adungo et al. 2013) [49] | Bias: −64.8 cells/μl (LoA: −332.5 to +203.0; N = 396) | At CD4 threshold of 350 cells/μl (in those ≥ 5 years old N = 389): Sensitivity: 89.7 % Specificity: 87 % | 11.9 % (47/396) |
NR
|
Bias was small at both low (<400 cells/μl) and high (>400 cells/μl) | With sub-samples of FACSCalibur results of (100 to 300 cells/μl) | 12.8 % | At CD4 threshold of 200 cells/μl (in those ≥ 5 years old N = 389): Sensitivity: 86.7 % Specificity: 94.1 % |
NR
| |||||
At CD4 threshold of 350 cells/μl: Sensitivity: 94.7 % Specificity: 87.5 % | 6.7 % | ||||||||
With sub-samples of FACSCalibur results of (200 to 500 cells/μl) | 14.1 % | ||||||||
(Thakar, Mahajan et al. 2012) [31] | Relative bias: −9.1 %; LoA: −46 % to 27 %; N = 175 |
NR
|
NR
|
NR
| (Thakar, Mahajan et al. 2012) [31] | Among patients with CD4 < 350 cells/μl: relative bias: +4 % (N = 121) | At CD4 threshold of 350 cells/μl: Sensitivity: 96 %; Specificity: 91 % |
NR
|
NR
|
(Manabe, Wang et al. 2012) [41] | Bias: −66.3 cells/μl (LoA: −83.4 to +49.2; p < 0.001; N = 176) |
NR
|
NR
| 17.7 % | (Manabe, Wang et al. 2012) [41] | Bias: −68.5 cells/μl (LoA: −79.6 to −57.4; p < 0.001; N = 206) |
NR
|
NR
| 8.1 % |
Bias was smaller at lower CD4 counts (−10.8 cells/μl; LoA: −27.3 to +5.6; p = 0.19 for CD4 range 0–250 cells/μl) and much greater at higher CD4 count (−120.6 cells/μl; LoA: −162.8 to −78.4; p < 0.001 for CD4 > 500 cells/μl) | Bias was smaller at lower CD4 counts: +13.6 cells/μl (LoA: 2.52 to 24.7; p = 0.02 for CD4 range 0–250 cells/μl) and much greater at higher CD4 counts: −121.7 cells/μl (LoA: −147.9 to −95.4; p < 0.001 for CD4 > 500 cells/μl) | ||||||||
(Wade, Daneau et al. 2014) [35] | Relative bias: −0.9 %; (LoA: −57.3 to +55.6); N = 200 | At CD4 threshold of 200 cells/μl: Sensitivity: 100 % Specificity: 94 % | 4 % (16/410) | 4.5 % (9/200) | (Wade, Daneau et al. 2014) [35] | Relative mean bias: −9.4 % (LoA: −54.4 to +35.6) | At CD4 threshold of 200 cells/μl: Sensitivity: 98 % Specificity: 95 % | 3 % (14/440) | 6.5 % (13/200) |
Sub-samples of CD4 ≤ 200: 5 % (−78 to +89); CD4 200–500: 0 % (−49 to +49); CD4 ≥ 500: −8 % (−49 to +34) | At CD4 threshold of 350 cells/μl: Sensitivity: 87 % Specificity: 90 % | 13.4 % (55/410) | Sub-samples of CD4 ≤ 200: 1 % (LoA: −75 to 77); CD4 200–500: −11 % (LoA: −46 to +25); CD4 ≥ 500: −15 % (LoA: −34 to +4) | At CD4 threshold of 350 cells/μl: Sensitivity: 97 % Specificity: 80 % | 9 % (40/440) | ||||
At CD4 threshold of 500 cells/μl: Sensitivity: 97 % Specificity: 82 % |
NR
| At CD4 threshold of 500 cells/μl: Sensitivity: 99 % Specificity: 78 % | NR | ||||||
(Zeh, Inzaule et al. 2014) [30] | Bias: −44 cells/μl; N = 147 | At CD4 threshold of 350 cells/μl: Sensitivity: 86 % Specificity: 99 % |
NR
|
NR
| (Zeh, Inzaule et al. 2014) [30] | Bias: −86 cells/μl; N = 147 | At CD4 threshold of 350 cells/μl: Sensitivity: 94 % Specificity: 95 % |
NR
|
NR
|
(Arnett N 2013) [28] | Bias: 0 (PIMA –Microtube) and −20 cell/μl (PIMA –direct); N = 1060 |
NR
|
NR
| 8.6 % (Micro-tube) and 10.1 % (direct) | (Arnett N 2013) [28] | Bias: −10 cells/μl |
NR
|
NR
| 7.7 % |
Reference test = FACSCount | |||||||||
(Mwau, Adungo et al. 2013) [49] | Mean bias: +8.6 cells/μl (LoA: −235.4 to 252.7; N = 521) | At CD4 threshold of 350 cells/μl: Sensitivity: 79.4 % Specificity: 86.9 % | 16.5 % (86/521) |
NR
| (Mwau, Adungo et al. 2013) [49] | Mean bias: +7.8 cells/μl (LoA: −168.9 to 184.4; N = 822) | At CD4 threshold of 350 cells/μl (in those ≥ 5 years old N = 813): Sensitivity: 79.4 % Specificity: 83.4 % |
NR
|
NR
|
At CD4 of 200 cells/μl (in those ≥ 5 years old N = 813): Sensitivity: 83 % Specificity: 98.2 % |
NR
| ||||||||
(Thakar, Mahajan et al. 2012) [31] | Among patients with CD4 < 350 cells/μl: Mean relative bias: −5 % (N = 206) | At CD4 threshold of 350 cells/μl: Sensitivity: 92 %; Specificity: 91 % |
NR
| ||||||
(Diaw, Daneau et al. 2011) [39] | Of 95 HIV (+) patients, Absolute bias: −39 cells/μl (LoA: −258 to +179) | At CD4 threshold of 200 cells/μl: Sensitivity: 91 % | 5.3 % (5/95); of finger-prick samples | 14 % total; 23 % in one study site | (Diaw, Daneau et al. 2011) [39] | For 100 HIV(+) patients, Absolute bias: −32 cells/μl (LoA: −146 to +84) | At CD4 threshold of 200 cells/μl: Sensitivity: 90 % | 4 % | 4.8 % |
Specificity: 97 % | Specificity: 98 % | ||||||||
Sub-samples of CD4 < 200: bias: +15 cells/μl (LoA: −89 to 118); Sub-samples of CD4 > 500: bias: −112 cells/μl (LoA: −429 to 204) | At CD4 threshold of 350 cells/μl: Sensitivity: 91 %; Specificity: 80 % |
NR
| Sub-samples of CD4 < 200: bias: +9.4 cells/μl (LoA: −76 to 94); Sub-samples of CD4 > 500: bias: −77 cells/μl (LoA: −217 to 63) | At CD4 threshold of 350 cells/μl: |
NR
| ||||
Sensitivity: 98 % | |||||||||
Specificity: 79 % | |||||||||
For 99 HIV(−) controls Absolute bias: −125 cells/μl (LoA: −434 to +184 cells/μl for all ranges of CD4 | |||||||||
(Wade, Diaw et al. 2013) [37] | Bias: −30 cells/μl (LoA: −160 to 101; N = 128: 111 HIV+ & 17 HIV-) | At CD4 threshold of 200 cells/μl: |
NR
|
NR
| |||||
Sensitivity 95 % | |||||||||
Specificity 96 % | |||||||||
Sub-samples of CD4 < 200: Bias: +6.0 cells/μl (LoA: −39 to +51) | At CD4 threshold of 350 cells/μl: | ||||||||
Sensitivity 97 % | |||||||||
Specificity 90 % | |||||||||
Sub-samples of CD4 > 500: Bias: −65 cells/μl (LoA: −224 to +93) | At CD4 threshold of 500 cells/μl:: Sensitivity 99 % Specificity 72 % | ||||||||
(Malagun, Nano et al. 2014) [33] | Urban clinic: Bias: −46.4 cells/μl (LoA:-199.8 to 107.0); N = 139 | At CD4 threshold of 350 cells/μl: Sensitivity: 99.2 %; specificity: 77.1 % | 10.7 % | Error rate: 5.1 % | |||||
Rural clinic: Bias: −55.8 cells/μl (LoA: −182.9 to 71.2); N = 98 | |||||||||
Reference test = Beckman-Coulter flow cytometry using Pan-leucogating (PLG) method | |||||||||
(Mnyani, McIntyre et al. 2012) [47] | Bias: −20.5 cells/μl (LoA: −175.0 to +133.9; p < 0.001; N = 296) | At CD4 threshold of 350 cells/μl: | 10.8 %; mostly in favor of patient treatment. |
NR
| (Myer, Daskilewicz et al. 2013) [40] | Bias: −22.7 cells/μl (LoA: −174.6 to 129.2); N = 546. | At CD4 threshold of 350 cells/μl: | 10 % | 61/546 samples required 83 additional test; 4 returned no result due to repeated machine errors |
No significant variability in the level of agreement related to age and gestational age | Sensitivity: 93 % (95 % CI 87–96), Specificity: 86 % (95 % CI 80–91) | Bias increased with increasing gestational age | Sensitivity: 92 % | ||||||
Specificity: 89 %; | |||||||||
Sensitivity & specificity did not vary significantly across gestational age | |||||||||
(Glencross, Coetzee et al. 2012) [42] | Phase II (Hospital ANC clinic: Bias: −37.9 cells/μl (LoA: −389.1 to 309.8; N = 77 |
NR
|
NR
|
NR
| (Glencross, Coetzee et al. 2012) [42] | Phase II (Hospital ANC clinic: Bias: −19.6 cells/μl (LoA: −149.1 to 110.0; N = 91) |
NR
|
NR
| 10.4 % (5/48) & 20.9 % (9/43) for 2 devices |
Phase IIIA Rural/poor resourced clinic: Not applicable (NA) |
NA
|
NA
|
NA
| Substantial, clinically significant difference to predicate: Bias +105.7 cells/μl (LoA −336.1 to 547.5; N = 96) | Among 32 patients with CD4 < 350: 10 patients (31.2 %) would have missed ART (upward misclassification) | 6.8 % (7/103) | |||
Larger bias and wider LoA for samples with CD4 < 350: +131.4 cells/μl (LoA: −275.8 to +538.6; N = 32) as compared to samples with CD4 < 500: +102.3 cells/μl (LoA: −289 to 493.6; N = 52) = > increasing error at CD4 range of less than 350 cells/μl | |||||||||
Phase IIIB well resourced clinic: NA |
NA
|
NA
|
NA
| Results showed considerably less bias and tighter LoA variance, as compared to phase IIIA, irrespective of lancet used: lancet 1 (Sarstedt) bias: +8.9 cells/μl (LoA: −211.1 to 229; N = 87); lancet 2 (Caralet Blue) bias: −11.2 cells/μl (LoA: −147 to 124; N = 52) | 9 % (14/153) | ||||
(Gous, Scott et al. 2013) [48] | Phase I: Multiple POC testing from multiple finger-sticks: mean bias was −32 cells/μl (N = 98) PIMA overestimate at low CD4 count (<350) and underestimate at high CD4 count (>500 cells/μl) | At CD4 threshold of 350 cells/μl: Sensitivity 86.4 %, Specificity 88.5 % | 12.4 % | 16.3 % |
NA
|
NA
|
NA
|
NA
| |
Phase II: Multiple POC testing from single finger-stick: Mean bias - 30 cells/μl (N = 73) | At CD4 threshold of 350 cells/μl: Sensitivity 97.5 %, Specificity 95 % | 4.1 %; | 19.2 % |
NA
|
NA
|
NA
|
NA
| ||
(Picken, Williams et al. 2014) [38] | Bias: 23.8 cells/μl (LoA: −166.1 to 213.8; N = 50 | At CD4 threshold of 350 cells/μl: Sensitivity: 88.9 %, specificity: 90.6 % | 10 % | 1.9 % | |||||
Reference test = Partec Cyflow | |||||||||
(Mwau, Adungo et al. 2013) [49] | Mean bias: −10.0 cells/μl (LoA: −261.4 to 241.4; N = 162) |
NR
|
NR
|
NR
| (Mwau, Adungo et al. 2013) [49] | Mean bias: −24.2 cells/μl (LoA: −277.6 to +229.3; N = 407) |
NR
|
NR
|
NR
|
(Thakar, Mahajan et al. 2012) [31] | Among patients with CD4 < 350 cells/μl: mean relative bias +8 % (N = 550) | At CD4 350 threshold: Sensitivity: 91 %; Specificity: 96 % |
NR
|
NR
| |||||
Reference test = GUAVA | |||||||||
(Mwau, Adungo et al. 2013) [49] | Mean bias: +23.9 cells/μl (LoA −329.6 to 281.9; N = 176) |
NR
|
NR
|
NR
| (Mwau, Adungo et al. 2013) [49] | Mean bias: −0.3 cells/μl (LoA: −315.0 to 315.6; N = 191) |
NR
|
NR
|
NR
|