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Maternal Lopinavir/Ritonavir Is Associated with Fewer Adverse Events in Infants than Nelfinavir or Atazanavir.

Smith C, Weinberg A, Forster JE, Levin MJ, Davies J, Pappas J, Kinzie K, Barr E, Paul S, McFarland EJ - Infect Dis Obstet Gynecol (2016)

Bottom Line: Combination antiretroviral therapy (cART) is successfully used for prevention of perinatal HIV transmission.In conclusion, hematologic and hepatic AE were frequent, but rarely serious.In this predominantly protease inhibitor-treated population, lopinavir/ritonavir was associated with the lowest rate of infant AE.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, USA.

ABSTRACT
Combination antiretroviral therapy (cART) is successfully used for prevention of perinatal HIV transmission. To investigate safety, we compared adverse events (AE) among infants exposed to different maternal cART regimens. We reviewed 158 HIV-uninfected infants born between 1997 and 2009, using logistic regression to model grade ≥1 AE and grade ≥3 AE as a function of maternal cART and confounding variables (preterm, C-section, illicit drug use, race, ethnicity, infant antiretrovirals, and maternal viremia). Frequently used cART regimens included zidovudine (63%), lamivudine (80%), ritonavir-boosted lopinavir (37%), nelfinavir (26%), and atazanavir (10%). At birth, anemia occurred in 13/140 infants (9%), neutropenia in 27/107 (25%), thrombocytopenia in 5/133 (4%), and liver enzyme elevation in 21/130 (16%). Corresponding rates of AE at 4 weeks were 59/141 (42%), 54/130 (42%), 3/137 (2%), and 3/104 (3%), respectively. Serious AE (grade ≥ 3) exceeded 2% only for neutropenia (13% at birth; 9% at 4 weeks). Compared with infants exposed to maternal lopinavir/ritonavir, infants exposed to nelfinavir and atazanavir had a 5-fold and 4-fold higher incidence of AE at birth, respectively. In conclusion, hematologic and hepatic AE were frequent, but rarely serious. In this predominantly protease inhibitor-treated population, lopinavir/ritonavir was associated with the lowest rate of infant AE.

No MeSH data available.


Related in: MedlinePlus

Frequency of infant adverse events at birth by maternal protease inhibitor. Bars represent the percentage of infants with a laboratory adverse event of any grade (a) or the percentage of infants whose most severe adverse event was represented by that particular grade (b). Number of infants per group: atazanavir ± ritonavir (16), lopinavir/ritonavir (54), and nelfinavir (35). Hgb, hemoglobin; ANC, absolute neutrophil count; plts, platelet count; AST, aspartate aminotransferase; ALT, alanine aminotransferase. AOR = 7.4 (95% CI 1.4–39.0), p = 0.02; BOR = 18.3 (95% CI 1.2–267.8), p = 0.03; COR = 10.6 (95% CI 1.7–66.4), p = 0.01; DOR = 4.2 (95% CI 1.0–17.5), p = 0.046; EOR = 5.3 (95% CI 1.9–14.9), p = 0.002.
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fig2: Frequency of infant adverse events at birth by maternal protease inhibitor. Bars represent the percentage of infants with a laboratory adverse event of any grade (a) or the percentage of infants whose most severe adverse event was represented by that particular grade (b). Number of infants per group: atazanavir ± ritonavir (16), lopinavir/ritonavir (54), and nelfinavir (35). Hgb, hemoglobin; ANC, absolute neutrophil count; plts, platelet count; AST, aspartate aminotransferase; ALT, alanine aminotransferase. AOR = 7.4 (95% CI 1.4–39.0), p = 0.02; BOR = 18.3 (95% CI 1.2–267.8), p = 0.03; COR = 10.6 (95% CI 1.7–66.4), p = 0.01; DOR = 4.2 (95% CI 1.0–17.5), p = 0.046; EOR = 5.3 (95% CI 1.9–14.9), p = 0.002.

Mentions: Rates of infant laboratory AE relative to antenatal exposure to maternal ARV were compared in a multivariate analysis. At birth, infants exposed to maternal NFV compared to LPV/r had a higher rate of anemia (OR 7.4 (95% CI 1.4–39.0), p = 0.02), neutropenia (OR 10.6 (95% CI 1.7–66.4), p = 0.01), and any AE (OR 5.3 (95% CI 1.9–14.9), p = 0.002) (Figure 2). This association was maintained when limited to infants exposed to the same maternal NRTI backbone (ZDV and lamivudine) (Table 3). The difference was primarily the result of grade 1 AE; rates of grade ≥3 AE remained relatively low in both groups (9% versus 14% of LPV/r-exposed versus NFV-exposed infants, resp.; Figure 2). Exposure to maternal ATV was also associated with a higher rate of any laboratory AE compared to LPV/r (OR 4.2 (95% CI 1.0–17.5), p = 0.046) with the difference primarily due to higher rates of neutropenia (OR 18.3 (95% CI 1.2–267.8), p = 0.03) (Figure 2). At 4 weeks, there were no longer significant differences in AE between infants exposed to different PI (Table 4).


Maternal Lopinavir/Ritonavir Is Associated with Fewer Adverse Events in Infants than Nelfinavir or Atazanavir.

Smith C, Weinberg A, Forster JE, Levin MJ, Davies J, Pappas J, Kinzie K, Barr E, Paul S, McFarland EJ - Infect Dis Obstet Gynecol (2016)

Frequency of infant adverse events at birth by maternal protease inhibitor. Bars represent the percentage of infants with a laboratory adverse event of any grade (a) or the percentage of infants whose most severe adverse event was represented by that particular grade (b). Number of infants per group: atazanavir ± ritonavir (16), lopinavir/ritonavir (54), and nelfinavir (35). Hgb, hemoglobin; ANC, absolute neutrophil count; plts, platelet count; AST, aspartate aminotransferase; ALT, alanine aminotransferase. AOR = 7.4 (95% CI 1.4–39.0), p = 0.02; BOR = 18.3 (95% CI 1.2–267.8), p = 0.03; COR = 10.6 (95% CI 1.7–66.4), p = 0.01; DOR = 4.2 (95% CI 1.0–17.5), p = 0.046; EOR = 5.3 (95% CI 1.9–14.9), p = 0.002.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4834394&req=5

fig2: Frequency of infant adverse events at birth by maternal protease inhibitor. Bars represent the percentage of infants with a laboratory adverse event of any grade (a) or the percentage of infants whose most severe adverse event was represented by that particular grade (b). Number of infants per group: atazanavir ± ritonavir (16), lopinavir/ritonavir (54), and nelfinavir (35). Hgb, hemoglobin; ANC, absolute neutrophil count; plts, platelet count; AST, aspartate aminotransferase; ALT, alanine aminotransferase. AOR = 7.4 (95% CI 1.4–39.0), p = 0.02; BOR = 18.3 (95% CI 1.2–267.8), p = 0.03; COR = 10.6 (95% CI 1.7–66.4), p = 0.01; DOR = 4.2 (95% CI 1.0–17.5), p = 0.046; EOR = 5.3 (95% CI 1.9–14.9), p = 0.002.
Mentions: Rates of infant laboratory AE relative to antenatal exposure to maternal ARV were compared in a multivariate analysis. At birth, infants exposed to maternal NFV compared to LPV/r had a higher rate of anemia (OR 7.4 (95% CI 1.4–39.0), p = 0.02), neutropenia (OR 10.6 (95% CI 1.7–66.4), p = 0.01), and any AE (OR 5.3 (95% CI 1.9–14.9), p = 0.002) (Figure 2). This association was maintained when limited to infants exposed to the same maternal NRTI backbone (ZDV and lamivudine) (Table 3). The difference was primarily the result of grade 1 AE; rates of grade ≥3 AE remained relatively low in both groups (9% versus 14% of LPV/r-exposed versus NFV-exposed infants, resp.; Figure 2). Exposure to maternal ATV was also associated with a higher rate of any laboratory AE compared to LPV/r (OR 4.2 (95% CI 1.0–17.5), p = 0.046) with the difference primarily due to higher rates of neutropenia (OR 18.3 (95% CI 1.2–267.8), p = 0.03) (Figure 2). At 4 weeks, there were no longer significant differences in AE between infants exposed to different PI (Table 4).

Bottom Line: Combination antiretroviral therapy (cART) is successfully used for prevention of perinatal HIV transmission.In conclusion, hematologic and hepatic AE were frequent, but rarely serious.In this predominantly protease inhibitor-treated population, lopinavir/ritonavir was associated with the lowest rate of infant AE.

View Article: PubMed Central - PubMed

Affiliation: Division of Infectious Diseases, Department of Pediatrics, University of Colorado School of Medicine and Children's Hospital Colorado, Aurora, CO 80045, USA.

ABSTRACT
Combination antiretroviral therapy (cART) is successfully used for prevention of perinatal HIV transmission. To investigate safety, we compared adverse events (AE) among infants exposed to different maternal cART regimens. We reviewed 158 HIV-uninfected infants born between 1997 and 2009, using logistic regression to model grade ≥1 AE and grade ≥3 AE as a function of maternal cART and confounding variables (preterm, C-section, illicit drug use, race, ethnicity, infant antiretrovirals, and maternal viremia). Frequently used cART regimens included zidovudine (63%), lamivudine (80%), ritonavir-boosted lopinavir (37%), nelfinavir (26%), and atazanavir (10%). At birth, anemia occurred in 13/140 infants (9%), neutropenia in 27/107 (25%), thrombocytopenia in 5/133 (4%), and liver enzyme elevation in 21/130 (16%). Corresponding rates of AE at 4 weeks were 59/141 (42%), 54/130 (42%), 3/137 (2%), and 3/104 (3%), respectively. Serious AE (grade ≥ 3) exceeded 2% only for neutropenia (13% at birth; 9% at 4 weeks). Compared with infants exposed to maternal lopinavir/ritonavir, infants exposed to nelfinavir and atazanavir had a 5-fold and 4-fold higher incidence of AE at birth, respectively. In conclusion, hematologic and hepatic AE were frequent, but rarely serious. In this predominantly protease inhibitor-treated population, lopinavir/ritonavir was associated with the lowest rate of infant AE.

No MeSH data available.


Related in: MedlinePlus