Antiretroviral Drug Concentrations in African Women During Pregnancy
Quick Facts
Funder: Falk Trust
Countries: Uganda
Key Partner in Uganda:
Infectious Diseases Institute, College of Health Sciences, Makerere University
Northwestern University and its partner, Makerere University in Uganda, received the generous support of the Falk Trust to investigate the changes in antiretorviral drug levels that may occur as a result of pregnancy in African women. Nevirapine (NVP)-based antiretroviral therapy (ART) is recommended for prevention of mother-to-child transmission of HIV-1 in developing countries. There are conflicting data on the effect of pregnancy on steady-state NVP plasma concentrations, while NVP concentrations during pregnancy have never been characterized in East African pregnant women.
Methods
This was a prospective, non-blinded study of antiretroviral pharmacokinetics (PK) in Ugandan women receiving NVP-based ART during pregnancy. Subjects underwent intensive 12-hour PK sampling between weeks 20-24 (T2; n=4) and weeks 32-36 (T3; n=15) of gestation; followed by six weeks postpartum (PP; n=15). Patients were excluded if they did not complete the PP visit. All patients received NVP 200mg twice daily for at least two weeks before PK sampling. HIV-1 RNA was performed within two weeks of each study visit. Estimation of NVP concentration was performed by reverse-phase high-performance liquid chromatography with a quantification limit of 0.5 mcg/mL. NVP concentration 12-hours post-dose (C12) <3 mcg/mL was considered sub-therapeutic based on the DHHS suggested target trough concentration for therapeutic drug monitoring. Area under the concentration time curve (AUC0-12) was calculated by non-compartmental analysis. Intrapartum and postpartum pharmacokinetic parameters were compared using geometric mean ratios and the Wilcoxon signed rank test.
Results
The table provides intrapartum and postpartum NVP PK parameters and comparisons between T2, T3, and PP (geometric means and ratios, 90% confidence ntervals). HIV-1 RNA was <1000 copies/mL at T3 and <400 copies/mL at PP in all patients.
Nevirapine
|
2nd Trimester
|
3rd Trimester
|
Postpartum
|
2nd Trimester
|
P
|
3rd Trimester
|
P
|
| C12 (mcg/mL) |
3.03 (2.80-3.35) |
3.12 (2.68-4.14) |
3.93 (3.48-4.86) |
0.87 (0.74-1.02) |
0.27 | 0.79 (0.70-0.90) |
0.01 |
| C12 <3 mcg/mL; n(%) |
3 (75%) | 10 (66.7%) | 4 (26.7%)* | ||||
| AUC0-12 (mcg.h/mL) |
42.99 (41.27-45.05) |
47.33 (41.57-58.89) |
59.40 (53.60-69.58) |
0.76 (0.70-0.83) |
0.07 | 0.80 (0.72-0.88) |
<0.01 |
*Three out of the 10 subjects with a NVP C12 below the threshold at T3 remained below this level at the PP visit.
Conclusion
NVP exposure was reduced approximately 20% in Ugandan women during their 3rd trimester compared to the same women postpartum. Through adequate virologic suppression was observed despite sub-therapeutic concentrations in pregnancy, the long term implications of these sub-optimal concentrations has not been assessed.
Publications
Lamorde M, Byakika-Kibwika P, Okaba-Kayom V, Flaherty JP, Boffito M, Namakula R, Ryan M, Nakabiito C, Back DJ, Khoo S, Merry C, Scarsi KK. Suboptimal Nevirapine Steady-State Pharmacokinetics During Intrapartum Compared With Postpartum in HIV-1-Seropositive Ugandan Women. J Acquir Immune Defic Syndr. 2010 Jul 8. [Epub ahead of print]
This page last updated Aug 31, 2011