Table 1. Summary of paired human maternal-fetal transfer data at time of delivery.
The range of average cord (or neonatal) ARV levels and average cord (or neonatal) to maternal ARV plasma ratios are included for each ARV. The “averages” reported from each article are typically medians but also include means. All ARVs were assumed to have reached steady-state prior to measurement unless otherwise noted.
| ARV | Number of Studies* | Total Number Paired Samples** | Range of Average§ Cord Levels (mg/L) | Range of Average§ C:M | Comments |
|---|---|---|---|---|---|
| NRTIs | |||||
| Abacavir [6, 7] | 2 | 14 | 0.26 - 0.83 | 1.03-1.06 | |
| Didanosine [7] | 1 | 10 | < 0.05 | 0.38 | 14 additional excluded from C:M as maternal plasma levels were < LOQ |
| Emtricitabine [13-15] | 3 | 22 | 0.25 – 0.26 | 1.2 – 1.7 | |
| Lamivudine [7-11] | 5 | 258 | 0.22 – 0.4 | 0.93 – 1.22 | |
| Stavudine [7, 12] | 2 | 22 | 0.04 – 0.14 | 1.0 – 1.3 | Median of 0.04 for n=32, but 20 of these were excluded from study's C:M (1.3) as maternal levels were < LOQ [7] |
| Tenofovir | |||||
| Steady-state [10, 14, 15] | 3 | 18 | 0.03, 0.05 [10, 15] | 0.82 (n=14) [14] 1.1 (n = 1) [15] 6.0 (n=3) [10] |
|
| Labor only [16] | 1 | 99 | 0.08 (600mg) 0.12 (900mg) |
0.60 | n=63 on 600mg, n=36 on 900mg |
| Vaginal [17] | 1 | 16 | 0.002 (IQR 0.001 – 0.003) | 0.5 (IQR 0.5-0.6) | Single dose of 1% vaginal gel (40mg tenofovir) 2 hours prior to scheduled Cesarean |
| Zidovudine [7, 8, 10, 18-24] | 10 | 153 | 0.12 – 0.70 (9 studies) | 0.81 – 1.6 (8 studies) | All studies assumed steady-state prior to labor but increased and/or switched to IV at start of labor |
|
| |||||
| NNRTIs | |||||
| Efavirenz | |||||
| Cord data [28] | 1 | 23 | 1.1 (0.47-4.5) | 0.49 (0.37-0.74) | |
| Neonate plasma [29] | 1 | 56 | 1.7 (0.05-7.9) | 0.1 | C:M median estimated from figure (average not reported) |
| Etravirine | 3 case reports | Singleton cases [30, 15]: | 0.11, 0.22 | 0.33, 0.51 | |
| Twin case [31]: | 0.41 (twin 1), 0.35 (twin 2) | - | No maternal plasma levels at delivery; dizygotic | ||
| Nevirapine | |||||
| Steady-state [10, 32-37] | 7 | 70 | 1.5-3.4 (for studies with n > 2, minimum = 2.4) | 0.59-1.0 | C:M values evenly dispersed across wide range |
| Labor only [38-41] | 4 | 74 | 0.76 – 1.4 | 0.71-0.92 (3 studies) | In all 3 studies, average 4-5 hours from dose to delivery. Average of 0.92 as weighted mean from 3 subgroups reported in 1 study [38]. |
| Rilpivirine [42] | 1 | 1 | 0.016 | 0.74 | |
|
| |||||
| Protease Inhibitors | |||||
| Atazanavir [35, 43-48] | 7 | 158 | 300mg: 0.13-0.22 400mg: 0.18-0.200 |
13 – 0.24 | 3 studies with 300mg daily [43-45], 1 with 400mg [47], 1 with both [46], 2 unspecified [35, 48]; all with 100mg RTV |
| Darunavir | All doses with 100mg RTV | ||||
| Study, 600mg BID [70] | 1 | 9 | 0.38 | 0.15 | |
| Case Reports, 600mg BID [15, 31, 67, 69] | 4 | 5 | Single: 0.21-1.4 Twins: 0.58, 1.0 |
0.15 – 0.32 (excludes twins) | Includes 3 case reports (4 patients) of single gestation [15, 67, 69] and 1 case report of dizygotic twins (for which no paired maternal concentration provided) [31] |
| Case Report, 800mg once daily [68] | 1 | 1 | 0.43 | 0.11 | |
| Fosamprenavir [71] | 1 | 7 | 0.11 | 0.27 | For amprenavir active metabolite. |
| Indinavir | 3 | n = 21 [56] n = 4 [57] n = 19 [63] |
All cords < LOQ 0.00 0.12 |
0.00 0.01 0.12 |
GMR of 0.12 excluded 7/26 cords with ARV < LOQ [63] |
| Lopinavir | |||||
| 400mg (+ 100 RTV) BID [10, 33, 49-53] | 7 | 63 | 0.45 – 0.70 (4 studies) | 0.16 – 0.22 (6 studies) | One study did not provide cord levels. Two studies had outlying levels: 1) 1.3 mg/L (n=1) with C:M in range [50], 2) 0.08 mg/L and C:M 0.57 (n=6) [10] |
| 533mg (+ 133 RTV) BID [54] | 1 | 23 | 0.89 mg/L | 0.23 | |
| 600mg (+150 RTV) BID [29, 53, 55] | 3 | 83 | 0.88 - 1.0 | 0.16 – 0.20 | One study [29] with neonate plasma instead of cord |
| Dose not specified [32, 35, 36] | 3 | 54 | 0.00 - 0.96 | 0.00 - 0.24 | Detectable in study with 42 patients [36]; not detectable in any cord samples in study with 11 patients [35] and case report [32] |
| Nelfinavir [10, 32, 33, 35, 36, 56-62] | 12 | 217 | 0.00 – 0.27 (10 studies) | 0 – 0.49 | Many cord samples < LOQ; studies reporting higher values for cord and C:M typically excluded the LOQ samples. Median values for studies fairly evenly distributed throughout the ranges specified. |
| Saquinavir [32, 33, 56, 57, 64-66] | 7 | 37 | < LOQ in 5/6 reporting cord levels | 0.00 – 0.04 (6 studies) | 1 study with median 0.128 mg/L in cord (n = 7) but no ratio reported [66] |
| Tipranavir [72] | 1 | 1 | 15.6 | 0.41 | |
|
| |||||
| Ritonavir (booster only, 100-150mg) [10, 29, 33, 51, 53, 57, 70] | 7 | 132 | 0 – 35.8 | 0.00 – 0.55 | 1 study (n=6) with ratio 0.55 [10], otherwise highest ratio was 0.24 [53] |
|
| |||||
| Other ARVs | |||||
| Enfuvirtide [31, 72-74] | 4 | 11 | Undetectable in | all cord samples. | 3 of these records are case reports (n ≤ 2) |
| Maraviroc [15] | 1 | 1 | 0.069 | 0.37 | |
| Raltegravir [50, 75, 76] | 3 | 5 | 0.19 (cord) 0.21-3.8 (neonate) |
C:M 1.00 N:M 1.63-15.5 |
All case reports. N:M concentrations evenly distributed throughout range reported. |
*
Number of studies, ranging from case reports to large trials.
**
Sum of patients included in each study for the paired C:M reading; occasionally more patients were included in each study's report of average cord ARV level (unpaired).
§
Reported as median by most articles but reported by some as means.
Abbreviations in order of appearance: ARV = antiretroviral drug; C:M = cord to maternal plasma ARV ratio; N:M = neonatal to maternal plasma ARV ratio (prior to neonatal ARV dosing); NRTI = nucleoside reverse transcriptase inhibitor; NNRTI = non-nucleoside reverse transcriptase inhibitor; GM(R) = geometric mean (ratio); LOQ, limit of quantification of assay; IQR = interquartile range; RTV, ritonavir