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Maternal antiretroviral therapy for the prevention of mother-to-child transmission of HIV in Malawi: maternal and infant outcomes two years after delivery.

Giuliano M, Andreotti M, Liotta G, Jere H, Sagno JB, Maulidi M, Mancinelli S, Buonomo E, Scarcella P, Pirillo MF, Amici R, Ceffa S, Vella S, Palombi L, Marazzi MC - PLoS ONE (2013)

Bottom Line: Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm(3) was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage.Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.

View Article: PubMed Central - PubMed

Affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy. marina.giuliano@iss.it

ABSTRACT

Background: Optimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART) administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease.

Methodology/principal findings: A total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period) if their CD4+ count was > 350/mm(3) at baseline (n = 147), or indefinitely if they met the criteria for treatment (n. 164). Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI) 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm(3). HIV-free survival of children was 85.8% (95% CI 81.4-90.1). Children born to mothers with baseline CD4+ count < 350/mm(3) were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1). Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm(3) was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.

Conclusions: HIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.

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Related in: MedlinePlus

Longitudinal assessment of CD4+ count (median cells/mm3), viral load (median log10 copies/ml) and hemoglobin levels (median g/dl) in women in continuous therapy (Cont.) and in those who had discontinued treatment 6 months postpartum (Disc.).Analysis conducted on the 288 women who had an alive child and breastfed. Number of determinations available are reported for each timepoint. Data of women in the discontinuing group who resumed ART were included until treatment re-initiation.
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pone-0068950-g003: Longitudinal assessment of CD4+ count (median cells/mm3), viral load (median log10 copies/ml) and hemoglobin levels (median g/dl) in women in continuous therapy (Cont.) and in those who had discontinued treatment 6 months postpartum (Disc.).Analysis conducted on the 288 women who had an alive child and breastfed. Number of determinations available are reported for each timepoint. Data of women in the discontinuing group who resumed ART were included until treatment re-initiation.

Mentions: Figure 3 reports the longitudinal assessment of maternal viro-immunological parameters and hemoglobin levels according to the maternal CD4+ group at baseline. Among the women on continuous therapy (baseline CD4+ count < 350/mm3) there was a progressive increase of the CD4+ count until Month 24, while, for women discontinuing drugs 6 months after partum, a progressive although slow decrease was observed between Month 6 and Month 24 (from a median of 711 cells/mm3 to a median of 623 cells/mm3). In both groups > 85% of women had HIV-RNA < 400 copies/ml at Month 6 (86.7% in the group with baseline CD4+ count > 350/mm3 and 91.7% in the group with < 350/mm3, P = 0.22). At Month 24 HIV replication was still suppressed in a high proportion of women in the group on continuous therapy (84.6% had HIV-RNA < 400 copies/ml compared to 20.8% in the group who had discontinued drugs at 6 months). Women on continuous therapy had a higher hemoglobin level at Month 24 compared to the women who had discontinued drugs (P = 0.001).


Maternal antiretroviral therapy for the prevention of mother-to-child transmission of HIV in Malawi: maternal and infant outcomes two years after delivery.

Giuliano M, Andreotti M, Liotta G, Jere H, Sagno JB, Maulidi M, Mancinelli S, Buonomo E, Scarcella P, Pirillo MF, Amici R, Ceffa S, Vella S, Palombi L, Marazzi MC - PLoS ONE (2013)

Longitudinal assessment of CD4+ count (median cells/mm3), viral load (median log10 copies/ml) and hemoglobin levels (median g/dl) in women in continuous therapy (Cont.) and in those who had discontinued treatment 6 months postpartum (Disc.).Analysis conducted on the 288 women who had an alive child and breastfed. Number of determinations available are reported for each timepoint. Data of women in the discontinuing group who resumed ART were included until treatment re-initiation.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3716887&req=5

pone-0068950-g003: Longitudinal assessment of CD4+ count (median cells/mm3), viral load (median log10 copies/ml) and hemoglobin levels (median g/dl) in women in continuous therapy (Cont.) and in those who had discontinued treatment 6 months postpartum (Disc.).Analysis conducted on the 288 women who had an alive child and breastfed. Number of determinations available are reported for each timepoint. Data of women in the discontinuing group who resumed ART were included until treatment re-initiation.
Mentions: Figure 3 reports the longitudinal assessment of maternal viro-immunological parameters and hemoglobin levels according to the maternal CD4+ group at baseline. Among the women on continuous therapy (baseline CD4+ count < 350/mm3) there was a progressive increase of the CD4+ count until Month 24, while, for women discontinuing drugs 6 months after partum, a progressive although slow decrease was observed between Month 6 and Month 24 (from a median of 711 cells/mm3 to a median of 623 cells/mm3). In both groups > 85% of women had HIV-RNA < 400 copies/ml at Month 6 (86.7% in the group with baseline CD4+ count > 350/mm3 and 91.7% in the group with < 350/mm3, P = 0.22). At Month 24 HIV replication was still suppressed in a high proportion of women in the group on continuous therapy (84.6% had HIV-RNA < 400 copies/ml compared to 20.8% in the group who had discontinued drugs at 6 months). Women on continuous therapy had a higher hemoglobin level at Month 24 compared to the women who had discontinued drugs (P = 0.001).

Bottom Line: Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm(3) was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage.Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.

View Article: PubMed Central - PubMed

Affiliation: Department of Therapeutic Research and Medicines Evaluation, Istituto Superiore di Sanità, Rome, Italy. marina.giuliano@iss.it

ABSTRACT

Background: Optimized preventive strategies are needed to reach the objective of eliminating pediatric AIDS. This study aimed to define the determinants of residual HIV transmission in the context of maternal antiretroviral therapy (ART) administration to pregnant women, to assess infant safety of this strategy, and to evaluate its impact on maternal disease.

Methodology/principal findings: A total of 311 HIV-infected pregnant women were enrolled in Malawi in an observational study and received a nevirapine-based regimen from week 25 of gestation until 6 months after delivery (end of breastfeeding period) if their CD4+ count was > 350/mm(3) at baseline (n = 147), or indefinitely if they met the criteria for treatment (n. 164). Mother/child pairs were followed until 2 years after delivery. The Kaplan-Meier method was used to estimate HIV transmission, maternal disease progression, and survival at 24 months. The rate of HIV infant infection was 3.2% [95% confidence intervals (CI) 1.0-5.4]. Six of the 8 transmissions occurred among mothers with baseline CD4+ count > 350/mm(3). HIV-free survival of children was 85.8% (95% CI 81.4-90.1). Children born to mothers with baseline CD4+ count < 350/mm(3) were at increased risk of death (hazard ratio 2.6, 95% CI 1.1-6.1). Among women who had stopped treatment the risk of progression to CD4+ count < 350/mm(3) was 20.6% (95% CI 9.2-31.9) by 18 months of drug discontinuation.

Conclusions: HIV transmission in this cohort was rare however, it occurred in a significative proportion among women with high CD4+ counts. Strategies to improve treatment adherence should be implemented to further reduce HIV transmission. Mortality in the uninfected exposed children was the major determinant of HIV-free survival and was associated to maternal disease stage. Given the considerable proportion of women reaching the criteria for treatment within 18 months of drug discontinuation, life-long ART administration to HIV-infected women should be considered.

Show MeSH
Related in: MedlinePlus