Trial record 1 of 17 for:    " December 27, 2006":" January 26, 2007"[FIRST-RECEIVED-DATE]AND HIV[CONDITION]
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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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Kaletra (lopinavir/ritonavir)
Drug: Kaletra (lopinavir/ritonavir) + Combivir (zidovudine/lamivudine)
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: 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

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Proportion of mother with plasma HIV1 below 200 copies per ml after 8 weeks of treatment [ Time Frame: W8 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 105
Study Start Date: March 2007
Study Completion Date: November 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Kaletra (lopinavir/ritonavir)
Drug: Kaletra (lopinavir/ritonavir)
(200/50 mg x2)x 2/d= 2 pills twice daily
Active Comparator: 2
Kaletra (lopinavir/ritonavir) + Combivir (zidovudine/lamivudine)
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

Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

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,)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00424814

Locations
France
Hopital Pitie salpetriere
Paris, France, 75013
Sponsors and Collaborators
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Abbott
Investigators
Principal Investigator: Roland Tubiana, MD AP-HP Hopital Pitie salpetriere
Study Chair: Josiane Warszawski, MD INSERM - INED Unité U822 France
  More Information

No publications provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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     History of Changes
Other Study ID Numbers: 2006-006200-11, ANRS 135 PRIMEVA
Study First Received: January 19, 2007
Last Updated: July 17, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HIV mother to child prevention
HIV Infections
Kaletra
Combivir
HIV Seronegativity

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Lamivudine
Reverse Transcriptase Inhibitors
Lamivudine, zidovudine drug combination
Ritonavir
Lopinavir
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
HIV Protease Inhibitors
Protease Inhibitors

ClinicalTrials.gov processed this record on July 09, 2014