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Prevention of HIV1 Mother to Child Transmission Without Nucleoside Analogue Reverse Transcriptase Inhibitors in the Pre-partum Phase. ANRS 135 Primeva

This study has been completed.
Sponsor:
Collaborator:
Abbott
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
ClinicalTrials.gov Identifier:
NCT00424814
First received: January 19, 2007
Last updated: July 17, 2013
Last verified: July 2013

January 19, 2007
July 17, 2013
March 2007
September 2011   (final data collection date for primary outcome measure)
Proportion of mother with plasma HIV1 below 200 copies per ml after 8 weeks of treatment [ Time Frame: W8 ] [ Designated as safety issue: Yes ]
Proportion of mother with plasma HIV1 below 200 copies per ml after 8 weeks of treatment
Complete list of historical versions of study NCT00424814 on ClinicalTrials.gov Archive Site
  • Proportion of women maintained with monotherapy until delivery, [ Time Frame: delivery ] [ Designated as safety issue: No ]
  • Proportion of women with a VL below 50 copies per ml at delivery [ Time Frame: delivery ] [ Designated as safety issue: Yes ]
  • Proportion of women harbouring resistant HIV strains four weeks after delivery [ Time Frame: W4 post partum ] [ Designated as safety issue: No ]
  • Concentrations of studied drug in plasma and in cord-blood [ Time Frame: at delivery ] [ Designated as safety issue: No ]
  • HIV-1 detection and concentrations of studied drug in vaginal secretion before and after treatment [ Time Frame: W0, W8 of treatment ] [ Designated as safety issue: No ]
  • concentrations of studied drugs in the new born gastric fluid, HIV diagnostic in infant (criteria for stopping the trial at second infection) [ Time Frame: birth ] [ Designated as safety issue: No ]
  • Proportion of women maintained with monotherapy until delivery,
  • Proportion of women with a VL below 50 copies per ml at delivery,
  • Proportion of women harbouring resistant HIV strains four weeks after delivery,
  • Concentrations of studied drug in plasma and in cord-blood,
  • HIV-1 detection in vaginal secretion before and after treatment and in the new born gastric fluid, HIV diagnostic in infant (criteria for stopping the trial at second infection)
Not Provided
Not Provided
 
Prevention of HIV1 Mother to Child Transmission Without Nucleoside Analogue Reverse Transcriptase Inhibitors in the Pre-partum Phase. ANRS 135 Primeva
Prevention of HIV1 Mother to Child Transmission Without Nucleoside Analogue Reverse Transcriptase Inhibitors in the Pre-partum Phase. A Multicenter Randomised Phase II/III Open Label Study With a Group of 100 Pregnant Women Receiving Lopinavir/Ritonavir and a Group of 50 Receiving Lopinavir/Ritonavir Plus Zidovudine and Lamivudine. ANRS 135 Primeva

In the pre-partum phase the use of antiretroviral therapy for the mother during the last trimester of pregnancy is mandatory. The use of HAART during pregnancy, usually two nucleosides analogues and a protease inhibitor exposes the mother and the child to cumulate toxicities related to both families. The aim of this study is to assess the use of a boosted protease inhibitor without nucleoside analogue during the pre-partum phase for women with no indication of antiretroviral therapy for their own.

Recent data from the French perinatal cohort and others indicate that HIV-RNA levels at delivery correlate with risk of transmission among women treated with antiretroviral agents. Most of these treatments include zidovudine alone or in combination. Mitochondrial toxicity related to nucleoside analogues exposure (zidovudine and lamivudine) has been reported in adults and in infants with in utero exposure to these drugs. In addition, biological markers of genotoxicity on nuclear DNA have recently been shown in exposed newborn. These issues raised the concern of the risk/benefit of multiple therapy in the context of mother to child transmission for women who do not meet the standard criteria for antiretroviral therapy. In women with CD4≥350 and VL<30 000 copies/ml a treatment with lopinavir/ritonavir should achieve a rapid control of HIV1 viremia below 1000 copies/ml without harm in term of resistance. In this study we would like to assess under strict control, the safety and efficacy of such regimen compared to the same boosted PI + zidovudine and lamivudine as standard regimen. The treatment will start at 26 weeks of gestation, and the follow up will include safety and efficacy parameters as well as pharmacokinetics in plasma and genital tract for the women, blood/cord ratio, testing for ARV resistance. Women will stop their treatment after delivery. Infants will be closely monitored up to 24 months with HIV DNA and HIV.RNA-PCR for HIV testing and biochemical and haematology usual safety evaluation. In addition frozen samples will be collected for specific evaluation of nucleoside analogue foetal mitochondrial and nuclear DNA interactions.

In term of transmission safety, the end point would be to reach a viral load below 200 copies after 8 weeks of treatment. In case of failure, this would allow a sufficient delay for a treatment modification: i.e. addition of NRTI and an elective caesarian could be programmed.

Interventional
Phase 2
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
HIV Infections
  • Drug: Kaletra (lopinavir/ritonavir)
    (200/50 mg x2)x 2/d= 2 pills twice daily
  • Drug: Kaletra (lopinavir/ritonavir) + Combivir (zidovudine/lamivudine)
    Kaletra (lopinavir/ritonavir): (200/50 mg x2)x 2/d= 2 pills twice daily Combivir (zidovudine/lamivudine): (300/150mg) x 2/d=1 pill twice daily
  • Experimental: 1
    Kaletra (lopinavir/ritonavir)
    Intervention: Drug: Kaletra (lopinavir/ritonavir)
  • Active Comparator: 2
    Kaletra (lopinavir/ritonavir) + Combivir (zidovudine/lamivudine)
    Intervention: Drug: Kaletra (lopinavir/ritonavir) + Combivir (zidovudine/lamivudine)
Tubiana R, Mandelbrot L, Le Chenadec J, Delmas S, Rouzioux C, Hirt D, Treluyer JM, Ekoukou D, Bui E, Chaix ML, Blanche S, Warszawski J; ANRS 135 PRIMEVA (Protease Inhibitor Monotherapy Evaluation) Study Group. 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. Clin Infect Dis. 2013 Sep;57(6):891-902. doi: 10.1093/cid/cit390. Epub 2013 Jun 12.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
105
November 2012
September 2011   (final data collection date for primary outcome measure)

Inclusion Criteria: Assessed between 20 and 24 months of pregnancy

  • Pregnancy known before 24 weeks of gestation
  • Documented HIV-1 infection without indication for ARV therapy
  • CD4 count above or equal to 350 per mm3
  • VL under 30 000 copies per ml
  • Naïve for PI (except treatment during previous pregnancy)
  • Informed consent signed

Exclusion Criteria:

  • HIV2 infection or HIV1 group O infection
  • Any pathology related to pregnancy
  • Contra-indication to study drugs
  • Unstable hypertension or diabetes
  • Known risk of premature delivery
  • In case of previous treatment with a protease inhibitor : presence of resistance mutations on the HIV-1 protease gene by genotyping analysis (1 mutation among V32I et I47A, I50V V82A/F/S/T, I84V, L90 M or more than 3 mutations among L10 F/I/R/V, K20/M/R, L24I, L33F, M46I/L, F53L, I54M/L/T/V, L63P, A71L/V/T,)
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
France
 
NCT00424814
2006-006200-11, ANRS 135 PRIMEVA
Yes
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Abbott
Principal Investigator: Roland Tubiana, MD AP-HP Hopital Pitie salpetriere
Study Chair: Josiane Warszawski, MD INSERM - INED Unité U822 France
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
July 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP