Lopinavir/Ritonavir Monotherapy as a Nucleoside Analogue—Sparing Strategy to Prevent HIV-1 Mother-to-Child Transmission: The ANRS 135 PRIMEVA Phase 2/3 Randomized Trial

• Published in: Clinical infectious diseases Vol. 57; no. 6; pp. 891 - 902
• Main Authors: Tubiana, Roland, Mandelbrot, Laurent, Le Chenadec, Jérome, Delmas, Sandrine, Rouzioux, Christine, Hirt, Deborah, Treluyer, Jean-Marc, Ekoukou, Dieudonné, Bui, Eda, Chaix, Marie-Laure, Blanche, Stéphane, Warszawski, Josiane
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 15.09.2013
• Subjects: Adolescent; Adult; AIDS; Anti-HIV Agents - therapeutic use; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiretroviral drugs; Antiretrovirals; Antiviral agents; Biological and medical sciences; Children; Clinical outcomes; Disease transmission; Female; HIV; HIV 1; HIV Infections - drug therapy; HIV Infections - prevention & control; HIV Infections - transmission; HIV/AIDS; Human immunodeficiency virus; Human viral diseases; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunology; Immunopathology; Infant, Newborn; Infants; Infectious Disease Transmission, Vertical - prevention & control; Infectious diseases; Lopinavir - therapeutic use; Male; Maternal & child health; Medical sciences; Pharmacology. Drug treatments; Pregnancy; Pregnancy Complications, Infectious - drug therapy; Pregnancy Complications, Infectious - prevention & control; Pregnancy Complications, Infectious - virology; Ritonavir - therapeutic use; Statistical median; Test ranges; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids; Virology; Immunopathology; Antiretroviral agent; HIV-1 virus; Enzyme; Ritonavir; Lopinavir; Enzyme inhibitor; Retroviridae; AIDS; Maternal diseases; Immune deficiency; Lentivirus; Infection; Virus; Prevention; Peptidases; Viral disease; Hydrolases; Nucleoside analog; Antiviral; Vertical transmission; Human immunodeficiency virus; Protease inhibitor; lopinavir/ritonavir; PMTCT; zidovudine; HIV; monotherapy
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1093/cid/cit390

Background. Prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV) is usually based on zidovudine-containing regimens, despite potential toxicities. This multicenter trial evaluated whether lopinavir/ritonavir (LPV/r) monotherapy in HIV type 1—infected women not requiring antiretrovirals for themselves could control maternal viral load (VL). Methods. Overall, 105 pregnant women with baseline VL <30 000 copies/mL and CD4 ≥350 cells/μL were randomized to start open-label LPV/r 400/100 mg twice daily alone (monotherapy group, n = 69) or combined with zidovudine/lamivudine 300/150 mg twice daily (triple therapy group, n = 36) from 26 gestational weeks to delivery. According to a Fleming 2-stage phase 2 design, monotherapy was considered to be efficacious if at least 59 patients achieved VL <200 copies/mL at 8 weeks of treatment (primary endpoint). Secondary endpoints were VL at delivery and tolerance. Results. Monotherapy was efficacious as defined: 62 women in the monotherapy group achieved VL <200 copies/mL at 34 weeks' gestation (ie, 8 weeks of treatment; 89.9%; 95% confidence interval [CI], 80.2%–95.8%). At delivery, proportions with VL <200 copies/mL were similar in the monotherapy and triple therapy groups (92.8% vs 97.2%; P = .66); however, fewer had VL <50 copies/mL in the monotherapy group (78.3% vs 97.2%; P = .01). Changes for intolerance were less frequent in the monotherapy than in the triple therapy group (1.4% vs 11.1%, respectively; P = .046). Cesarean delivery and preterm delivery rates did not differ. All children were liveborn; 1 case of HIV-1 transmission occurred in the triple therapy group, none in the monotherapy group (95% CI upper limit = 5.2%). Conclusions. LPV/r monotherapy achieved satisfactory virologic efficacy in women treated solely for PMTCT, providing proof of concept for future nucleoside-sparing strategies. Clinical Trials Registration. NCT00424814; Afssaps AIDS Clinical Trial Group A61176-34.