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

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.

Adverse effects in children exposed to maternal HIV and antiretroviral therapy during pregnancy in Brazil: a cohort study

“…Hepatic changes at birth was a frequent adverse effect in our cohort (36%) associated mostly with NVP exposure. Consistent with our results, one recent American study showed that children exposed to lopinavir/ritonavir presented lower incidence of hematological and hepatic changes [ 40 ]. However, in other studies no association was found between hepatic change and specific drug regimens, including a Brazilian study [ 41 ].…”

Adverse perinatal outcomes associated with protease inhibitor-based antiretroviral therapy in pregnant women living with HIV: A systematic review and meta-analysis

“…Characteristics of included studies are summarised in Table 1 . 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 11 prospective (32%) and 23 retrospective (68%) cohort studies analysed data from 57,546 WLHIV in 22 countries ( Table 1 ). 24 studies (71%) took place in high income countries (HICs), and 10 studies (29%) took place in LMICs ( Table 1 ).…”

“…40 France High Retrospective 2005 to 2015 1597 Women enrolled from French Perinatal Cohort Regression analysis, risk factor analysis LNMP confirmed by ultrasound Average Smith et al. 59 USA High Retrospective 1997 to 2009 158 Twins excluded, data from Children's Hospital Immunodeficiency Program (CHIP), 12% IDU None No description Poor Snijdewind et al. 41 Netherlands High Retrospective 1/1997 to 2/2015 1392 Twins excluded, women recruited from 26 nationwide sites, 10.8% smoking, 11.7% alcohol use, 0.6% IDU Risk factor analysis Early ultrasound or LNMP Average Szyld et al.…”

“…40 96.0% PI-ART, 4.0% non-PI-ART (INSTI-ART) 46.3% LPV/r 34.8% ATV/r 18.7% DRV/r Preconception Yes Yes No VSGA Smith et al. 59 100% PI-ART 50.9% LPV/r, 13.8% ATV/r, 35.3% NFV Mixed No Yes Yes PTB, VSGA Snijdewind et al. 41 66.7% PI-ART, 33.3% non-PI-ART (NNRTI-ART) Unspecified Mixed Yes No No PTB, VPTB, LBW, VLBW, SGA Szyld et al.…”

A hierarchical modeling approach for assessing the safety of exposure to complex antiretroviral drug regimens during pregnancy

“…39 While their common mechanism of action supports an assumption that drugs within a class would behave similarly, and some studies have documented similar rates of outcomes, 40 there are also specific individual drugs which may confer increased or decreased risk as compared to others within the same class. 1,41,42 For example, the drug efavirenz (EFV) has been more commonly associated with psychiatric adverse effects than other drugs within the NNRTI class. 42 Given a plausible biological justification, the hierarchical modeling approach thus seems appealing.…”