Browsing by Author "Tierney, Camlin"

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    Maternal Human Immunodeficiency Virus (HIV) Drug Resistance Is Associated With Vertical Transmission and Is Prevalent in Infected Infants
    (Clinical Infectious Diseases, 2021) Boyce, Ceejay L.; Sils, Tatiana; Ko, Daisy; Wong-on-Wing, Annie; Beck, Ingrid A.; Styrchak, Sheila M.; DeMarrais, Patricia; Tierney, Camlin; Stranix-Chibanda, Lynda; Flynn, Patricia M.; Taha, Taha E.; Owor, Maxensia; Glenn Fowler, Mary; Frenkel, Lisa M.
    We aimed to assess if maternal human immunodeficiency virus (HIV) drug resistance is associated with an increased risk of HIV vertical transmission and to describe the dynamics of drug resistance in HIV-infected infants. Methods. This was a case-control study of PROMISE study participants. “Cases” were mother-infant pairs with HIV vertical transmission during pregnancy or breastfeeding and “controls” were mother-infant pairs without transmission matched 1:3 by delivery date and clinical site. Genotypic HIV drug resistance analyses were performed on mothers’ and their infants’ plasma at or near the time of infant HIV diagnosis. Longitudinal analysis of genotypic resistance was assessed in available specimens from infants, from diagnosis and beyond, including antiretroviral therapy (ART) initiation and last study visits. Results. Our analyses included 85 cases and 255 matched controls. Maternal HIV drug resistance, adjusted for plasma HIV RNA load at infant HIV diagnosis, enrollment CD4 count, and antepartum regimens, was not associated with in utero/peripartum HIV transmission. In contrast, both maternal plasma HIV RNA load and HIV drug resistance were independent risk factors associated with vertical transmission during breastfeeding. Furthermore, HIV drug resistance was selected across infected infants during infancy. Conclusions. Maternal HIV drug resistance and maternal viral load were independent risk factors for vertical transmission during breastfeeding, suggesting that nevirapine alone may be insufficient infant prophylaxis against drug-resistant variants in maternal breast milk. These findings support efforts to achieve suppression of HIV replication during pregnancy and suggest that breastfeeding infants may benefit from prophylaxis with a greater barrier to drug resistance than nevirapine alone.
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    Pharmacokinetics and Safety of Zidovudine, Lamivudine, and Lopinavir/Ritonavir in HIV-infected Children With Severe Acute Malnutrition in Sub-Saharan Africa: IMPAACT Protocol P1092
    (The Pediatric Infectious Disease Journal, 2021) Owor, Maxensia; Tierney, Camlin; Ziemba, Lauren; Browning, Renee; Moye, John; Graham, Bobbie; Reding, Christina; Costello, Diane; Norman, Jennifer; Wiesner, Lubbe; Hughes, Emma; Whalen, Meghan E.; Purdue, Lynette; Mmbaga, Blandina Theophil; Kamthunzi, Portia; Kawalazira, Rachel; Nathoo, Kusum; Bradford, Sarah; Coletti, Anne; Aweeka, Francesca; Musoke, Philippa
    Severe acute malnutrition (SAM) may alter the pharmacokinetics (PK), efficacy, and safety of antiretroviral therapy. The phase IV study, IMPAACT P1092, compared PK, safety, and tolerability of zidovudine (ZDV), lamivudine (3TC), and lopinavir/ritonavir (LPV/r) in children with and without SAM. Materials and methods: Children living with HIV 6 to <36 months of age with or without World Health Organization (WHO)-defined SAM received ZDV, 3TC, and LPV/r syrup for 48 weeks according to WHO weight band dosing. Intensive PK sampling was performed at weeks 1, 12, and 24. Plasma drug concentrations were measured using liquid chromatography tandem mass spectrometry. Steady-state mean area under the curve (AUC0–12h) and clearance (CL/F) for each drug were compared. Grade ≥3 adverse events were compared between cohorts. Results: Fifty-two children were enrolled across 5 sites in Africa with 44% (23/52) female, median age 19 months (Q1, Q3: 13, 25). Twenty-five children had SAM with entry median weight-for-height Z-score (WHZ) −3.4 (IQR −4.0, −3.0) and 27 non-SAM had median WHZ −1.0 (IQR −1.8, −0.1). No significant differences in mean AUC0–12h or CL/F were observed (P ≥ 0.09) except for lower 3TC AUC0–12h (GMR, 0.60; 95% CI, 0.4–1.0; P = 0.047) at week 12, higher ZDV AUC0–12h (GMR, 1.52; 1.2–2.0; P = 0.003) at week 24 in the SAM cohort compared with non-SAM cohort. Treatment-related grade ≥3 events did not differ significantly between cohorts (24.0% vs. 25.9%). Conclusion: PK and safety findings for ZDV, 3TC, and LPV/r support current WHO weight band dosing of syrup formulations in children with SAM.