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HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

Papp E, Mohammadi H, Loutfy MR, Yudin MH, Murphy KE, Walmsley SL, Shah R, MacGillivray J, Silverman M, Serghides L - J. Infect. Dis. (2014)

Bottom Line: In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight.Progesterone supplementation resulted in a significant improvement in fetal weight.In HIV-infected women, progesterone levels correlated significantly with birth weight percentile.

View Article: PubMed Central - PubMed

Affiliation: Toronto General Research Institute, University Health Network.

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Related in: MedlinePlus

Progesterone supplementation partially reverses protease inhibitor (PI)–induced fetal weight defect. Mated mice were exposed to Combivir plus Kaletra (PI based combination antiretroviral therapy [PI-cART]) or water as a control (Ctr) by gavage once daily starting on gestational day 1 (GD1). Mice were then injected subcutaneously with either 0.5 mg progesterone (P4) suspended in corn oil or corn oil as a control on GD1, GD5, GD9, and GD13. All fetal and placenta parameters were assessed on GD15. A, Percentage of fetuses that were viable (light grey), nonviable (as assessed by pedal reflex; white), or resorbed (dark grey) for each treatment group is shown. χ2 analysis yielded the following findings: Ctr vs PI-cART, P < .001; PI-cART vs PI-cART + P4, P = not significant; and Ctr vs PI-cART + P4, P < .05. B, Average fetal weight per litter. C, Average placental weight per litter. Data were acquired from the same experiment, with 8 values for the Ctr, 10 for the PI-cART group, and 11 for the PI-cART + P4 group. Experiments were repeated once. *P < .05, **P < .01, and ***P < .001, by the Kruskal–Wallis test with the Dunn post hoc test.
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JIU393F3: Progesterone supplementation partially reverses protease inhibitor (PI)–induced fetal weight defect. Mated mice were exposed to Combivir plus Kaletra (PI based combination antiretroviral therapy [PI-cART]) or water as a control (Ctr) by gavage once daily starting on gestational day 1 (GD1). Mice were then injected subcutaneously with either 0.5 mg progesterone (P4) suspended in corn oil or corn oil as a control on GD1, GD5, GD9, and GD13. All fetal and placenta parameters were assessed on GD15. A, Percentage of fetuses that were viable (light grey), nonviable (as assessed by pedal reflex; white), or resorbed (dark grey) for each treatment group is shown. χ2 analysis yielded the following findings: Ctr vs PI-cART, P < .001; PI-cART vs PI-cART + P4, P = not significant; and Ctr vs PI-cART + P4, P < .05. B, Average fetal weight per litter. C, Average placental weight per litter. Data were acquired from the same experiment, with 8 values for the Ctr, 10 for the PI-cART group, and 11 for the PI-cART + P4 group. Experiments were repeated once. *P < .05, **P < .01, and ***P < .001, by the Kruskal–Wallis test with the Dunn post hoc test.

Mentions: To investigate whether decreases in progesterone levels directly contributed to reduced fetal weight, we supplemented PI-cART with 0.5 mg progesterone every 4 days, beginning on GD1. We observed a significant increase in fetal weight at GD15 in mice that received PI-cART supplemented with progesterone (Figure 3B), although fetal weight did not recover to the same levels as in the control. There was also a trend toward higher placental weight in the progesterone-supplemented group (Figure 3C). However, the number of resorptions was unaffected by the supplementation (Figure 3A), suggesting that cART must exert additional progesterone-independent effects during pregnancy that require further investigation. Progesterone administration did not significantly alter the birth outcomes of control mice (Supplementary Materials).Figure 3.


HIV protease inhibitor use during pregnancy is associated with decreased progesterone levels, suggesting a potential mechanism contributing to fetal growth restriction.

Papp E, Mohammadi H, Loutfy MR, Yudin MH, Murphy KE, Walmsley SL, Shah R, MacGillivray J, Silverman M, Serghides L - J. Infect. Dis. (2014)

Progesterone supplementation partially reverses protease inhibitor (PI)–induced fetal weight defect. Mated mice were exposed to Combivir plus Kaletra (PI based combination antiretroviral therapy [PI-cART]) or water as a control (Ctr) by gavage once daily starting on gestational day 1 (GD1). Mice were then injected subcutaneously with either 0.5 mg progesterone (P4) suspended in corn oil or corn oil as a control on GD1, GD5, GD9, and GD13. All fetal and placenta parameters were assessed on GD15. A, Percentage of fetuses that were viable (light grey), nonviable (as assessed by pedal reflex; white), or resorbed (dark grey) for each treatment group is shown. χ2 analysis yielded the following findings: Ctr vs PI-cART, P < .001; PI-cART vs PI-cART + P4, P = not significant; and Ctr vs PI-cART + P4, P < .05. B, Average fetal weight per litter. C, Average placental weight per litter. Data were acquired from the same experiment, with 8 values for the Ctr, 10 for the PI-cART group, and 11 for the PI-cART + P4 group. Experiments were repeated once. *P < .05, **P < .01, and ***P < .001, by the Kruskal–Wallis test with the Dunn post hoc test.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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JIU393F3: Progesterone supplementation partially reverses protease inhibitor (PI)–induced fetal weight defect. Mated mice were exposed to Combivir plus Kaletra (PI based combination antiretroviral therapy [PI-cART]) or water as a control (Ctr) by gavage once daily starting on gestational day 1 (GD1). Mice were then injected subcutaneously with either 0.5 mg progesterone (P4) suspended in corn oil or corn oil as a control on GD1, GD5, GD9, and GD13. All fetal and placenta parameters were assessed on GD15. A, Percentage of fetuses that were viable (light grey), nonviable (as assessed by pedal reflex; white), or resorbed (dark grey) for each treatment group is shown. χ2 analysis yielded the following findings: Ctr vs PI-cART, P < .001; PI-cART vs PI-cART + P4, P = not significant; and Ctr vs PI-cART + P4, P < .05. B, Average fetal weight per litter. C, Average placental weight per litter. Data were acquired from the same experiment, with 8 values for the Ctr, 10 for the PI-cART group, and 11 for the PI-cART + P4 group. Experiments were repeated once. *P < .05, **P < .01, and ***P < .001, by the Kruskal–Wallis test with the Dunn post hoc test.
Mentions: To investigate whether decreases in progesterone levels directly contributed to reduced fetal weight, we supplemented PI-cART with 0.5 mg progesterone every 4 days, beginning on GD1. We observed a significant increase in fetal weight at GD15 in mice that received PI-cART supplemented with progesterone (Figure 3B), although fetal weight did not recover to the same levels as in the control. There was also a trend toward higher placental weight in the progesterone-supplemented group (Figure 3C). However, the number of resorptions was unaffected by the supplementation (Figure 3A), suggesting that cART must exert additional progesterone-independent effects during pregnancy that require further investigation. Progesterone administration did not significantly alter the birth outcomes of control mice (Supplementary Materials).Figure 3.

Bottom Line: In pregnant mice, PI-based cART but not dual-NRTI therapy was associated with significantly lower progesterone levels that directly correlated with fetal weight.Progesterone supplementation resulted in a significant improvement in fetal weight.In HIV-infected women, progesterone levels correlated significantly with birth weight percentile.

View Article: PubMed Central - PubMed

Affiliation: Toronto General Research Institute, University Health Network.

Show MeSH
Related in: MedlinePlus