Table 2.
ARV concentrations in the mother, milk and infant
| Drug (dose)/number of dosages in the mother and breastmilk | Median (IQR) time from drug intake, h | Median (IQR) plasma drug concentration in mother, ng/mL. [reference concentration]a | Median (IQR) drug concentrations in milk, ng/mL | Milk/plasma concentration ratiob | Median (IQR) estimated infant daily dose from breastmilk, mg/kgc | Relative infant dose, %c | Infant drug concentration, ng/mL (time interval from mother drug intake, h) |
|---|---|---|---|---|---|---|---|
| Efavirenz (600 mg once daily) n = 3 |
18.5 (18.0–18.8) | 2947 (2856–3038) [≈2400]10 |
2701 (2139–3228) | 0.86 (0.70–1.11) | 0.41 (0.32–0.48) | 1.35 (1.07–1.61) | 267 (17) |
| Nevirapine (400 mg once daily) n = 5 |
14.5 (13.6–18.1) | 3893 (2927–4108) [≈4000]11 |
2721 (1905–2806) | 0.70 (0.68–0.75) | 0.41 (0.29–0.42) | 3.40 (2.38–3.51) | 960 (12); 227 (21) |
| Rilpivirine (25 mg once daily) n = 2 |
15.5 (15.3–15.8) | 113 (120–126) [≈100]12 |
123 (107–140) | 1.08 (1.1–1.1) | 0.02 (0.02–0.02) | 4 (16) | |
| Bictegravir (50 mg once daily) n = 3 |
8.5 (5.5–11.5) | 5177 (3576–6010) [≈5000]5 |
57 (44–67) | 0.01 (0.01–0.01) | 0.01 (0.01–0.01) | 103 (19) | |
| Dolutegravir (50 mg once daily) n = 6 |
15 (13.0–19.7) | 2627 (2360–3244) [≈2000]12 |
107 (83–142) | 0.04 (0.03–0.05) | 0.02 (0.01–0.02) | 1.00 (0.78–1.33) | 279 (15); 100 (13) |
| Raltegravir (400 mg twice daily) n = 3 |
3.6 (3.1–5.7) | 4250 (2520–5111) [≈4000]13 |
1635 (973–2142) | 0.39 (0.39–0.42) | 0.25 (0.15–0.32) | 4.09 (2.43–5.35) | 21 (2) |
| Raltegravir (1200 mg once daily) n = 14 |
13.7 (10.4–15.9) | 160 (82–274) [≈200]14 |
111 (69–566) | 0.96 (0.44–2.68) | 0.02 (0.01–0.08) | 0.28 (0.17–1.42) | 0 (11); 0 (16); 0 (15); 14 (19); 0 (18); 0 (15) |
| Darunavir/r (800/100 mg once daily) n = 4 |
15.4 (11.6–16.5) | 2419 (2135–3503) [≈2600]15 |
316 (284–325) | 0.12 (0.10–0.14) | 0.05 (0.04–0.05) | 0.12 (0.11–0.12) | 0 (16) |
| Abacavir (600 mg once daily) n = 11 |
12.8 (10.3–13.6) | 50 (44–126) [≈50]16 |
91 (45–123) | 1.03 (0.78–1.66) | 0.01 (0.01–0.02) | 0.34 (0.17–0.46) | 1 (11); 1 (18); 9 (13); 49 (12) |
| Emtricitabine (200 mg once daily) n = 29 |
15.5 (13.1–17.5) | 201 (126–249) [≈200]17 |
803 (475–1118) | 3.92 (2.34–5.55) | 0.12 (0.07–0.17) | 4.02 (2.38–5.59) | 44 (2); 21 (15); 5 (21); 14 (16); 18 (15); 27 (19); 0 (19); 26 (20); 0 (15); 49 (16); 24 (16) |
| Lamivudine (300 mg once daily) n = 11 |
12.8 (10.3–13.6) | 371 (194–543) [≈200]16 |
1313 (787–1628) | 3.74 (2.77–4.73) | 0.20 (0.12–0.24) | 4.92 (2.95–6.10) | 15 (11); 4 (18); 20 (13); 91 (12) |
| TAFd (25 mg once daily) n = 5 |
8.5 (5.0–15.0) | 13 (11–14) [≈10]18 |
45 (37–54) | 4.09 (3.38–4.92) | 0.007 (0.006–0.008) | 0 (19) | |
| TDFd (300 mg once daily) n = 24 |
16 (14.3–17.9) | 61 (53.3–97.0) [≈10]19 |
5 (4–10) | 0.08 (0.06–0.10) | 0.001 (0.001–0.002) | 0.01 (0.01–0.02) | 0 (2); 0 (15); 0 (21); 0 (16); 0 (15); 0 (19); 0 (20); 0 (15); 0 (16); 0 (16) |
TAF, tenofovir alafenamide; TDF, tenofovir disoproxil fumarate.
Expected ARV concentration considering the time interval from drug intake based on reference studies evaluating full pharmacokinetic profiles or population pharmacokinetic analyses of the corresponding ARV in non-pregnant individuals.
Detailed milk/plasma ratios at Months 1, 3 and 6 are presented in the Supplementary material.
The median estimated infant daily dose and the relative infant dose were calculated as detailed in the Supplementary data. These values were calculated considering the situation of a fully breastfed infant; however, it should be noted that a significant proportion of infants in the study were partially breastfed and also received formula milk.
Prodrugs of tenofovir, measured levels refer to tenofovir.