Prevention of Perinatal Transmission of HIV-1 Without Nucleoside Reverse Transcriptase Inhibitors

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

91 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-07-06

Study Completion Date

2020-07-16

Brief Summary

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The overall goal is to study the feasibility of darunavir/ritonavir (DRV/r) monotherapy as treatment simplification (switch) in pretreated pregnant women, associated with neonatal prophylaxis with nevirapine, constituting a PMTCT strategy without any Nucleoside Reverse Transcriptase Inhibitor (NRTIs) .

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Detailed Description

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90 participants will be enrolled and switch to darunavir monotherapy early in pregnancy (before 16 weeks of amenorrhea) in order to reduce exposure to the antiretroviral nucleos(t)ide analogues. The study treatment during the pregnancy is: darunavir 600 mg + ritonavir 100 mg 2 times 24 (DRV/r) monotherapy This regimen will be started after checking the tolerance of DRV/r 600 mg/100 mg twice daily (recommended dosage for pregnancy in French national recommendations) to replace whatever prior antiretrovirals (ARVs) were used, while maintaining the NRTI backbone for 2 weeks. Woman already receiving a triple drug combination with DRV/r will proceed directly to treatment simplification. If clinical tolerance of DRV/r is satisfactory after 2 weeks, nucleos(t)ides will be stopped. In case of intolerance, the treatment will be determined by the investigator but follow-up of the patient will continue.

No zidovudine will be administered at delivery in case of virological control, according to French Guidelines (Morlat Report 2015).

After delivery, the choice of maternal antiretrovial therapy (ART) is left to the discretion of the clinician and patient.

The mothers are followed up monthly until delivery and the last visit is planes at W4-W6 postpartum. Virological efficacy and safety will be assessed monthly.

In neonates, the prophylactic treatment, nevirapine oral solution, will be administrated as soon as possible in the first 12 hours of life and then for 14 days, once a day at a daily dose of 15 mg for a birthweight ≥ 2.5 kg ; 10 mg for a birthweight ≥ 2 kg and \< 2.5 kg and 2 mg / kg for a birthweight \< 2 kg (WHO Guidelines 2013 - French Guidelines, "Morlat Report" 2015).

Clinical and virological monitoring will be performed at Day 3, Day 15 in case of hospitalization, M1, M3 and M6.

Statistical Methods The analysis of the primary endpoint is the proportion of virological success (VL \< 50 copies/mL at delivery among women remaining on DRV/r). All changes in antiretroviral therapy because of VL ≥ 50 copies/ml will be considered as failures. Women who change antiretroviral therapy for other reasons and/or when pregnancy outcome is before 22 weeks of amenorrhea and \< 500g (non-viable pregnancy according to WHO) will be removed from the denominator.

Analysis of treatment changes, tolerance for the mother and child and factors associated with virological failure will be done by estimating percentages (categorical variables), average and median (continuous variables) with their intervals 95% confidence, overall and compared between the groups with virological success or failure per protocol (primary endpoint) or by intention to treat (secondary endpoint). The evolution of the parameters measured in children at birth, at 1, 3, and 6, months will be explored using non-parametric curves and compared between groups by repeated data taking into account the nonlinearity developments.

No interim analysis is planned.

Conditions

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Maternal-fetal Infection Transmission

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Single Group

Intervention: Darunavir monotherapy darunavir/ritonavir 600 mg/100mg twice day in monotherapy.

Group Type EXPERIMENTAL

darunavir monotherapy

Intervention Type DRUG

darunavir 600 mg + ritonavir 100 mg 2 times 24 (DRV/r) monotherapy started after checking the tolerance of DRV/r600 mg/100 mg twice daily to replace whatever prior ARVs were used, while maintaining the NRTI backbone for 2 weeks.

Interventions

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darunavir monotherapy

darunavir 600 mg + ritonavir 100 mg 2 times 24 (DRV/r) monotherapy started after checking the tolerance of DRV/r600 mg/100 mg twice daily to replace whatever prior ARVs were used, while maintaining the NRTI backbone for 2 weeks.

Intervention Type DRUG

Other Intervention Names

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ritonavir

Eligibility Criteria

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Inclusion Criteria

* Pregnant woman, under 15 weeks gestational age at screening
* Documented Human Immunodeficiency Virus (HIV) HIV-1 infection (serology and/or plasma HIV RNA viral load)
* Current treatment with at least two ARVs
* Virological suppression for at least 12 months, defined by a PVL \< 50 copies / mL. A blip (transiently ≥ 50 but \< 400 copies/mL) will not be considered as an exclusion criterion, if it is followed by 2 successive controls with CV \< 50 at least one month before enrollment
* Plasma viral load \< 50 copies/mL at pre-inclusion
* CD4 ≥ 250 cells/mm3 at pre-inclusion
* Informed written consent
* Health care coverage

* Mother enrolled in the trial
* Informed written consent by parents or legal guardians

Exclusion Criteria

* Infection by HIV-2
* History of treatment failure and/or resistance with any Protease Inhibitor (PI). Treatment failure is defined by a viral replication (≥ 50 copies/mL) during antiretroviral treatment. An increasing CV due to treatment interruption will not be considered as a failure, providing that the absence of resistance mutations to at least one PI can be confirmed by genotyping.
* Documented CD4 lymphocyte less than 200/mm3
* Known intolerance to darunavir or ritonavir
* Hepatitis B Virus (HBV) co-infection (HBs Ag-positive and/or detectable HBV DNA) on therapy with analogs (tenofovir, emtricitabine, lamivudine)
* Known resistance of maternal viral strain to darunavir or nevirapine
* Intended absence (travel abroad, moving ...)
* Expected delivery in a maternity hospital not participating in the trial
* Participation in the trial during previous pregnancy
* Persons under guardianship or deprived of liberty by a judicial or administrative decision

* Refusal by parent (s) or legal guardian (s)

Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No