Mother to Infant Transmission of ART in Utero
Mother to Infant Transmission of ART in Utero
We report analyses of plasma and hair samples for antiretroviral concentrations from 51 mother–infant pairs where the mother received LPV/r and 56 pairs where the woman received EFV in the Ugandan PROMOTE trial at 0, 8, and 12 weeks postpartum. Women in this sample initiated antiretrovirals at a median of 22.6 weeks of gestation. By 12 weeks postpartum, 99.1% of women in the overall sample reported any breastfeeding, 90.4% of women reported exclusively breastfeeding, and 93.9% reported predominantly breastfeeding. There were no statistically significant differences between rates of breastfeeding (any, exclusively, or predominantly) among women on LPV/r and women on EFV in this sample. Due to changes in the Ugandan Ministry of Health guidelines for infant prophylaxis during the study period, 77 of infants in the overall study received 1 week of zidovudine and 297 of infants received 6 weeks of postpartum nevirapine. There were no statistically significant differences between rates of zidovudine versus nevirapine receipt among infants born of mothers on LPV/r and mothers on EFV in this sample. All the infants in this sample remained HIV uninfected at 12, 24, and 58 weeks postpartum.
Table 1 shows mean plasma antiretroviral concentrations of each drug for mothers and infants and the percent of each group with detectable plasma levels at each of the 3 time points. Figure 1A shows the ratios of infant/maternal concentrations in plasma at 12 weeks by drug. At 0, 8, and 12 weeks postpartum, most mothers on LPV/r-based regimens had detectable plasma LPV levels (82%, 94%, and 91%, respectively). In contrast, although 41% of infants had detectable LPV plasma concentrations at delivery, only 1 infant had detectable LPV levels at 8 weeks, and none had detectable LPV plasma levels by 12 weeks. For RTV, most women, but few infants, had detectable plasma levels at all time points. For EFV, 100% of both mothers and infants had detectable plasma levels at 0, 8, and 12 weeks postpartum. Correlation coefficients for LPV and RTV plasma levels between mothers and their breastfeeding infants were low at all time points, whereas correlation coefficients for EFV levels between women and infants at 0, 8, and 12 weeks postpartum were high and statistically significant ( Table 2 ).
(Enlarge Image)
Figure 1.
A, Ratios of infant/maternal plasma concentrations at 12 weeks by drug (n = 56 for EFV and n = 51 for LPV/RTV). B, Ratios of infant/maternal hair concentrations at 12 weeks by drug.
At 12 weeks postpartum, almost all mothers and infants had detectable LPV, RTV, and EFV concentrations in hair samples (Table 1). The mean concentration of LPV in hair for mothers was 5.8 ng/mg and the mean LPV hair levels in their infants was 5.1 ng/mg. The mean concentrations of EFV in maternal and infant hair samples were 6.3 and 1.9 ng/mg, respectively. Correlation coefficients for LPV and EFV hair levels between mothers and their breastfeeding infants were high and statistically significant at 12 weeks postpartum; the correlation coefficient for RTV between mothers and infants was lower and not significant (Table 2). Individual ratios of infant to maternal hair concentrations at 12 weeks postpartum were calculated (Fig. 1B) and the mean of those ratios was 0.87 for LPV, 0.47 for RTV, and 0.40 for EFV (Table 3).
No infants in this sample acquired HIV infection by 58 weeks. The cumulative frequency of any infant adverse event (grade 1 or above) was 4.2%, 19.3%, and 20.7% at 0, 8, and 12 weeks postpartum, respectively. Only 2.1%, 7.0%, and 8.6% of infants in the sample had grade 3 or higher anemia at 0, 8, and 12 weeks postpartum, respectively, as defined by the DAIDS grading scale. None of the infants were neutropenic at delivery, although approximately 9% of infants by 12 weeks of life had neutropenia of any grade. There was no significant correlation between infant plasma and hair levels of LPV, RTV, or EFV at any time point with individual adverse events. Furthermore, there was no correlation between antiretroviral levels in infant plasma or hair with any grade 1–2 events, any grade 3–4 events, any grade 3–4 anemia events, or any grade 3–4 neutropenia events.
Results
We report analyses of plasma and hair samples for antiretroviral concentrations from 51 mother–infant pairs where the mother received LPV/r and 56 pairs where the woman received EFV in the Ugandan PROMOTE trial at 0, 8, and 12 weeks postpartum. Women in this sample initiated antiretrovirals at a median of 22.6 weeks of gestation. By 12 weeks postpartum, 99.1% of women in the overall sample reported any breastfeeding, 90.4% of women reported exclusively breastfeeding, and 93.9% reported predominantly breastfeeding. There were no statistically significant differences between rates of breastfeeding (any, exclusively, or predominantly) among women on LPV/r and women on EFV in this sample. Due to changes in the Ugandan Ministry of Health guidelines for infant prophylaxis during the study period, 77 of infants in the overall study received 1 week of zidovudine and 297 of infants received 6 weeks of postpartum nevirapine. There were no statistically significant differences between rates of zidovudine versus nevirapine receipt among infants born of mothers on LPV/r and mothers on EFV in this sample. All the infants in this sample remained HIV uninfected at 12, 24, and 58 weeks postpartum.
Infant/Maternal Plasma Concentrations
Table 1 shows mean plasma antiretroviral concentrations of each drug for mothers and infants and the percent of each group with detectable plasma levels at each of the 3 time points. Figure 1A shows the ratios of infant/maternal concentrations in plasma at 12 weeks by drug. At 0, 8, and 12 weeks postpartum, most mothers on LPV/r-based regimens had detectable plasma LPV levels (82%, 94%, and 91%, respectively). In contrast, although 41% of infants had detectable LPV plasma concentrations at delivery, only 1 infant had detectable LPV levels at 8 weeks, and none had detectable LPV plasma levels by 12 weeks. For RTV, most women, but few infants, had detectable plasma levels at all time points. For EFV, 100% of both mothers and infants had detectable plasma levels at 0, 8, and 12 weeks postpartum. Correlation coefficients for LPV and RTV plasma levels between mothers and their breastfeeding infants were low at all time points, whereas correlation coefficients for EFV levels between women and infants at 0, 8, and 12 weeks postpartum were high and statistically significant ( Table 2 ).
(Enlarge Image)
Figure 1.
A, Ratios of infant/maternal plasma concentrations at 12 weeks by drug (n = 56 for EFV and n = 51 for LPV/RTV). B, Ratios of infant/maternal hair concentrations at 12 weeks by drug.
Infant/Maternal Hair Concentrations
At 12 weeks postpartum, almost all mothers and infants had detectable LPV, RTV, and EFV concentrations in hair samples (Table 1). The mean concentration of LPV in hair for mothers was 5.8 ng/mg and the mean LPV hair levels in their infants was 5.1 ng/mg. The mean concentrations of EFV in maternal and infant hair samples were 6.3 and 1.9 ng/mg, respectively. Correlation coefficients for LPV and EFV hair levels between mothers and their breastfeeding infants were high and statistically significant at 12 weeks postpartum; the correlation coefficient for RTV between mothers and infants was lower and not significant (Table 2). Individual ratios of infant to maternal hair concentrations at 12 weeks postpartum were calculated (Fig. 1B) and the mean of those ratios was 0.87 for LPV, 0.47 for RTV, and 0.40 for EFV (Table 3).
Correlation Between Infant Plasma and Hair Levels and Adverse Event
No infants in this sample acquired HIV infection by 58 weeks. The cumulative frequency of any infant adverse event (grade 1 or above) was 4.2%, 19.3%, and 20.7% at 0, 8, and 12 weeks postpartum, respectively. Only 2.1%, 7.0%, and 8.6% of infants in the sample had grade 3 or higher anemia at 0, 8, and 12 weeks postpartum, respectively, as defined by the DAIDS grading scale. None of the infants were neutropenic at delivery, although approximately 9% of infants by 12 weeks of life had neutropenia of any grade. There was no significant correlation between infant plasma and hair levels of LPV, RTV, or EFV at any time point with individual adverse events. Furthermore, there was no correlation between antiretroviral levels in infant plasma or hair with any grade 1–2 events, any grade 3–4 events, any grade 3–4 anemia events, or any grade 3–4 neutropenia events.
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