title: A randomized controlled trial to assess safety, tolerability, and antepartum viral load with increased lopinavir/ritonavir dosage in pregnancy.
abstract: HIV mother-to-child transmission (MTCT) is significantly reduced if antepartum viral load (apVL) is<50 copies/mL. Pharmacokinetic studies suggest increasing the dosage of lopinavir/ritonavir (LPV/r) in pregnancy. It is important to assess tolerance, safety, and rate of patients presenting a apVL<50 copies/mL when treating with increased dose of LPV/r during pregnancy. Confirmed HIV-infected pregnant women with a fetus at a gestational age of 14-33 weeks were randomly assigned to receive LPV/r 400/100 or 600/150 mg b.i.d. plus two nucleoside analogues (NRTIs). Treatment was discontinued in the case of alanine transaminase (ALT) of grade III elevation or higher, glucose, or triglycerides. Thirty-two women were randomized to the LPV/r 400/100 mg dose, and 31 women were randomized to the 600/150 mg dose. Overall, 9.4% of the women receiving the conventional dose, and 17.2% receiving the increased dose, discontinued treatment because of adverse events (p=0.29). The rates of gastrointestinal (GI) symptoms, laboratory abnormalities, preterm delivery, and low birth weight were similar in both groups. There were no cases of HIV MTCT. Among the women with a baseline VL>50 copies/mL assigned to the conventional dose group, 45% (95% confidence interval [CI] 62.5-27.5%) had a apVL>50 copies/mL compared with 10.5% (95% CI 21.6-0.6%) of those assigned to the increased dose group (p=0.01). There was no significant difference found for the patients with a baseline VL<50 copies/mL. In pregnant women with a baseline VL>50 copies/mL, it may be warranted to initiate LPV/r dosing at 600/150 mg, whereas the conventional dose is sufficient for pregnant women with a baseline VL<50 copies/mL.
authors.affiliation: Reference Center for HIV-Infected Pregnant Women - NUPAIG, Division of Infectious Diseases, Universidade Federal de São Paulo , São Paulo, Brazil .
authors.forename: Simone Martins
authors.initials: SM
authors.lastname: Bonafe
authors.forename: Durval A Gomes
authors.initials: DA
authors.lastname: Costa
authors.forename: Maria J Rodrigues
authors.initials: MJ
authors.lastname: Vaz
authors.forename: Jorge Figueiredo
authors.initials: JF
authors.lastname: Senise
authors.forename: Henrique
authors.initials: H
authors.lastname: Pott-Junior
authors.forename: Rachel H Vieira
authors.initials: RH
authors.lastname: Machado
authors.forename: Adauto
authors.initials: A
authors.lastname: Castelo
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects; D018791:CD4 Lymphocyte Count; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D015658:HIV Infections / Q000175:diagnosis / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D061466:Lopinavir / Q000008:administration & dosage / Q000009:adverse effects*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011264:Pregnancy Trimesters; D011295:Prenatal Care; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D012367:RNA, Viral / Q000097:blood; D019438:Ritonavir / Q000008:administration & dosage / Q000009:adverse effects*; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; D011480:Protease Inhibitors; D012367:RNA, Viral; D061466:Lopinavir; D019438:Ritonavir