Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1
Abstract
:1. Introduction
2. Experimental Section
2.1. Design and Study Population
2.2. Sample Collection and Processing
2.3. Mitochondrial DNA Parameters Assays
2.3.1. Mitochondrial DNA Copy Number Per Cell
2.3.2. Mitochondrial DNA Deletion
2.4. Statistical Analysis
2.5. Ethics Considerations
3. Results
3.1. Study Population Characteristics of the PrEP Group
3.2. mtDNA Content and Proportion of Deleted mtDNA at D7
3.3. mtDNA Content and Proportion of Deleted mtDNA after One Year of PrEP
3.4. Sub-Analysis of MCN and MDD Variations among CHEU from South Africa
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Appendix A. Methodology Details for Mitochondrial DNA Parameters Assay
Appendix A.1. Mitochondrial DNA Copy Number Per Cell
Appendix A.2. Mitochondrial DNA Deletion
Appendix B. Methodology Details for the Validation of qPCR
References
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Characteristic | LPV/r (n = 64) | 3TC (n = 75) | Total (n = 139) | p Value a |
---|---|---|---|---|
Gender; n (%) | 0.96 | |||
Male | 33 (51.6) | 39 (52.0) | 72 (51.8) | |
Weight (kg); mean ± SD | 3.1 ± 0.5 | 3.3 ± 0.4 | 3.2 ± 0.5 | 0.19 |
Height (cm); mean ± SD | 49.2 ± 2.1 | 49.8 ± 2.0 | 49.5 ± 2.0 | 0.11 |
Gestational age (week); mean ± SD | 38.3 ± 1.7 | 38.5 ± 1.9 | 38.4 ± 1.8 | 0.30 |
Preterm birth (week); n (%) | 0.82 | |||
No prematurity ≥ 37 | 53 (82.8) | 61 (81.3) | 114 (82.0) | |
Prematurity < 37 | 11 (17.2) | 14 (18.7) | 25 (18.0) | |
Hæmoglobin (g/dL); median [IQR] | 16.1 [15.0;17.3] | 16.1 [14.6;17.3] † | 16.1 [14.9;17.3] † | 0.91 |
ALT (U/L); n (%) | 0.88 | |||
Normal ≤ 40 | 59 (92.2) | 70 (93.3) | 129 (92.8) | |
Abnormal > 40 | 5 (7.8) | 5 (6.7) | 10 (7.2) | |
Mild [40;100] | 3 (4.7) | 4 (5.3) | 7 (5.0) | |
Moderate [100;200] | 2 (3.1) | 1 (1.3) | 3 (2.2) | |
Haemoglobin (g/dL); n (%) | 0.10 | |||
Normal > 13 | 62 (96.9) | 67 (90.5) † | 129 (93.5) † | |
Anemia ≤ 13 | 2 (3.1) | 7 (9.5) † | 9 (6.5) † | |
Mild [12;13] | 1 (1.6) | 6 (8.1) † | 7 (5.1) † | |
Moderate [10;12] | - | 1 (1.4) † | 1 (0.72) † | |
Very severe [0;9] | 1 (1.6) | - | 1 (0.72) † | |
Platelet count (103/mm3); n (%) | 0.43 | |||
Normal ≥125 | 59 (92.2) | 69 (97.2) ‡ | 128 (94.8) ‡ | |
Thrombocytopenia <125 | 5 (7.8) | 2 (2.8) ‡ | 7 (5.2) ‡ | |
Mild [100;125] | 3 (4.7) | 2 (2.8) ‡ | 5 (3.7) ‡ | |
Moderate [50;100] | 1 (1.6) | - | 1 (0.7) ‡ | |
Very severe [0;25] | 1 (1.6) | - | 1 (0.7) ‡ | |
White cell count (103/mm3); n (%) | NA | |||
Normal > 2.5 | 64 (100.0) | 73 (100.0) § | 137 (100.0) § | |
Neutrophil count (103/mm3); n (%) | 0.22 | |||
Normal > 1.5 | 62 (96.9) | 73 (100.0) § | 135 (98.5) § | |
Neutropenia ≤ 1.5 | 2 (3.1) | - | 2 (1.5) § | |
Mild [1.25;1.5] | 1 (1.6) | - | 1 (0.7) § | |
Moderate [1.0;1.25] | 1 (1.6) | - | 1 (0.7) § |
Characteristic | LPV/r (n = 64) | 3TC (n = 75) | Total (n = 139) | p Value a |
---|---|---|---|---|
At randomisation (D7) | ||||
Social demographic characteristics | ||||
Age (year); median [IQR] | 27.1 [24.1;30.7]] | 28.2 [24.2;32.6] | 27.4 [24.1;32.2] | 0.25 |
Parity; median [IQR] | 3.0 [2.0;3.5] | 2.0 [1.0;4.0] | 3.0 [2.0;4.0] | 0.56 |
Clinical and biological characteristics | ||||
BMI; median [IQR] | 24.0 [21.4;27.5] | 23.4 [21.4;27.7] | 23.8 [21.4;27.7] | 0.88 |
CD4 cells count (cells/mm3); median [IQR] | 556.0 [407.0;784.0] † | 584 [433.0;760] ‡ | 558.0 [420.0;766.0] § | 0.91 |
HIV viral load (Log copies/mL); median [IQR] | 2.2 [2.2;3.3] | 2.2 [2.2;3.3] ¶ | 2.2 [2.2;3.3] ¶ | 0.79 |
HIV viral load control; n (%) | 0.33 | |||
Controlled <1000 copies/mL | 40 (62.5) | 52 (70.3) ¶ | 92 (66.7) ¶ | |
Uncontrolled ≥1000 copies/mL | 24 (37.5) | 22 (29.7) ¶ | 46 (33.3) ¶ | |
WHO HIV staging; n (%) | 1.00 | |||
Stage 1 | 60 (93.8) | 71 (94.7) | 131 (94.2) | |
Stage 2 | 4 (6.2) | 4 (5.3) | 8 (5.8) | |
Antiretroviral prophylaxis | ||||
ARV prophylaxis during pregnancy; n (%) | 0.47 | |||
ZDV | 45 (70.3) | 51 (68.0) | 96 (69.1) | |
ZDV + 3TC | 11 (17.2) | 18 (24.0) | 29 (20.9) | |
No ARV prophylaxis | 8 (12.5) | 6 (8.0) | 14 (10.1) | |
Duration of ARV prophylaxis taken during pregnancy (week); median [IQR] | 8.0 [5.5;12.5] ⱡ | 8.0 [4.0;14.0] ¤ | 8.0 [5.0;13.0] £ | 0.63 |
During the trial | ||||
HIV viral load at W38 (Log copies/mL); median [IQR] | 3.7 [2.2;4.8] | 3.4 [2.2;4.5] | 3.5 [2.2;4.7] | 0.23 |
HIV viral load control at W38; n (%) | 0.18 | |||
Controlled < 1000 copies/mL | 21 (32.8) | 33 (44.0) | 54 (38.9) | |
Uncontrolled ≥ 1000 copies/mL | 43 (67.2) | 42 (56.0) | 85 (61.2) | |
Duration of breastfeeding (week); median [IQR] | 45.6 [38.8;48.8] | 46.0 [35.7;48.6] | 45.9 [37.6;48.1] | 0.95 |
Site | PrEP | n | MCN Median [IQR] | n | Children with MDD, n (%) |
---|---|---|---|---|---|
Burkina Faso | All | 46 | 922 [700;1112] | 44 | 43 (97.7) |
LPV/r | 23 | 947 [757;1253] | 23 | 22 (95.7) | |
3TC | 23 | 833 [671;1112] | 21 | 21 (100.0) | |
South Africa | All | 48 | 473 [329;799] | 48 | 48 (100.0) |
LPV/r | 20 | 624 [447;1191] | 20 | 20 (100.0) | |
3TC | 28 | 422 [273;715] | 28 | 28 (100.0) | |
Uganda | All | 45 | 976 [814;1099] | 45 | 45 (100.0) |
LPV/r | 21 | 975 [814;1083] | 21 | 21 (100.0) | |
3TC | 24 | 1002 [819;1100] | 24 | 24 (100.0) | |
All | All | 139 | 846 [555;1082] | 137 | 136 (99.3) |
LPV/r | 64 | 897 [614;1135] | 64 | 63 (98.4) | |
3TC | 75 | 803 [484;1056] | 73 | 73 (100.0) |
Site | PrEP | n | Decrease of MCN Median [IQR] | p Value a | Children with Depletion, n (%) | p Value b |
---|---|---|---|---|---|---|
Burkina Faso | All | 46 | 30.2% [2.5;54.4] | 13 (28.3) | ||
LPV/r | 23 | 39.3% [12.1;65.9] | 0.12 | 8 (34.8) | 0.33 | |
3TC | 23 | 17.3% [−7.7;49.8] | 5 (21.7) | |||
South Africa | All | 48 | 63.3% [37.8;75.0] | 30 (62.5) | ||
LPV/r | 20 | 73.2% [50.9;85.6] | 0.02 | 15 (75.0) | 0.13 | |
3TC | 28 | 52.8% [34.8;70.4] | 15 (53.5) | |||
Uganda | All | 45 | 35.4% [4.8;52.9] | 15 (33.3) | ||
LPV/r | 21 | 17.8% [0.4;43.1] | 0.08 | 4 (19.0) | 0.06 | |
3TC | 24 | 49.2% [21.1;59.3] | 11 (45.8) | |||
All | All | 139 | 41.7% [12.1;64.4] | 58 (41.7) | ||
LPV/r | 64 | 40.1% [14.6;72.7] | 0.35 | 27 (42.2) | 0.97 | |
3TC | 75 | 42.2% [6.9;60.2] | 31 (41.3) |
Group | PrEP | n | W6 MCN Median [IQR] | p Value a | W26 MCN Median [IQR] | p Value a |
---|---|---|---|---|---|---|
Control | No | 38 | 347 [258;407] | 194 [167;248] | ||
PrEP | Yes | 47 | 458 [310;796] | <0.01 | 138 [122;148] | <0.01 |
LPV/r | 19 | 682 [364;1220] | <0.01 | 132 [123;143] | <0.01 | |
3TC | 28 | 422 [273;691] | 0.07 | 141 [122;148] | <0.01 |
Group | PrEP | n | Decrease of MCN Median [IQR] | p Value a | Children with mtDNA Depletion, n (%) |
---|---|---|---|---|---|
Control | No | 38 | 47.7% [10.4;55.9] | 16 (42.0) | |
PrEP | Yes | 47 | 71.3% [59.0;88.1] | <0.01 | 39 (83.0) |
LPV/r | 19 | 79.4% [61.8;88.2] | <0.01 | 17 (89.5) | |
3TC | 28 | 70.5% [55.3;78.9] | <0.01 | 22 (78.6) |
Independent Variable | Crude Estimates | Adjusted Estimates | ||||
---|---|---|---|---|---|---|
PR | 95% CI (LB-UB) | p Value | PR | 95% CI (LB-UB) | p Value | |
Gender | ||||||
Girl | 1.0 | 1.00 | ||||
Boy | 1.42 | 1.03–1.97 | 0.03 | 1.39 | 1.05–1.84 | 0.02 |
PrEP * | ||||||
No | 1.0 | 1.00 | ||||
Yes | 1.97 | 1.33–2.92 | <0.01 | 1.63 | 1.08–2.45 | 0.02 |
Mother age (per 5 years) | 1.05 | 0.92–1.19 | 0.47 | |||
Parity | 0.95 | 0.81–1.12 | 0.56 | |||
Duration of breastfeeding (weeks) | ||||||
<39 | 1.00 | |||||
≥39 | 0.85 | 0.63–1.15 | 0.30 | |||
Gestational age (weeks) | 1.05 | 0.98–1.13 | 0.17 | 1.08 | 0.98–1.19 | 0.11 |
Weight of the infant at W6 (per 500 g) | 0.98 | 0.91–1.07 | 0.69 |
© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
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Monnin, A.; Nagot, N.; Periès, M.; Vallo, R.; Meda, N.; Singata-Madliki, M.; Tumwine, J.K.; Kankasa, C.; Ngandu, N.; Goga, A.; et al. Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1. J. Clin. Med. 2020, 9, 2972. https://doi.org/10.3390/jcm9092972
Monnin A, Nagot N, Periès M, Vallo R, Meda N, Singata-Madliki M, Tumwine JK, Kankasa C, Ngandu N, Goga A, et al. Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1. Journal of Clinical Medicine. 2020; 9(9):2972. https://doi.org/10.3390/jcm9092972
Chicago/Turabian StyleMonnin, Audrey, Nicolas Nagot, Marianne Periès, Roselyne Vallo, Nicolas Meda, Mandisa Singata-Madliki, James K. Tumwine, Chipepo Kankasa, Nobubelo Ngandu, Ameena Goga, and et al. 2020. "Mitochondrial DNA Parameters in Blood of Infants Receiving Lopinavir/Ritonavir or Lamivudine Prophylaxis to Prevent Breastfeeding Transmission of HIV-1" Journal of Clinical Medicine 9, no. 9: 2972. https://doi.org/10.3390/jcm9092972