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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00424814
• Other study ID #: 2006-006200-11
• Secondary ID: ANRS 135 PRIMEVA
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: January 19, 2007
• Last updated: July 17, 2013
• Start date: March 2007
• Est. completion date: November 2012

Study information

• Verified date: July 2013
• Source: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: November 2012
• Est. primary completion date: September 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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,)

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• Kaletra (lopinavir/ritonavir)
(200/50 mg x2)x 2/d= 2 pills twice daily
• 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

Locations

Country	Name	City	State
France	Hopital Pitie salpetriere	Paris

Sponsors (2)

Lead Sponsor	Collaborator
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)	Abbott

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of mother with plasma HIV1 below 200 copies per ml after 8 weeks of treatment		W8	Yes
Secondary	Proportion of women maintained with monotherapy until delivery,		delivery	No
Secondary	Proportion of women with a VL below 50 copies per ml at delivery		delivery	Yes
Secondary	Proportion of women harbouring resistant HIV strains four weeks after delivery		W4 post partum	No
Secondary	Concentrations of studied drug in plasma and in cord-blood		at delivery	No
Secondary	HIV-1 detection and concentrations of studied drug in vaginal secretion before and after treatment		W0, W8 of treatment	No
Secondary	concentrations of studied drugs in the new born gastric fluid, HIV diagnostic in infant (criteria for stopping the trial at second infection)		birth	No