Antiretroviral Regimens Containing Raltegravir for Prophylaxis of Mother-to-child-transmission of HIV Infection

NCT01854762 | Terminated Phase 2 Results

• 1 other identifier: PregnantHIV
• Study Type: interventional
• Target: 33
• Locations: 1 country
• Sites: 1

Brief Summary

The current available antiretroviral (ARV) agents make possible a successful treatment of virtually all HIV-infected patients, even those heavily experienced subjects, with a history of previous failure to ARV drugs of different classes. However, some problems are still present, especially for specific populations, like pregnant women and infants. For these groups, most of currently available drugs are not used, because the lack of information on safety, efficacy, and pharmacokinetic/dynamic behavior of ARVs drugs. The mother to child transmission (MTCT) is still a problem in certain areas of the world, especially in resource-limited settings. In some settings, women often present to their first antenatal care visit late in the pregnancy, posing an additional problem: how to effectively treat these patients to assure they will have an undetectable viral load at the moment of delivering? Depending on the plasma viremia magnitude, and viral susceptibility it can take 6 or more weeks to reduce the viral load to less than the desired 1,000 copies of HIV-1 RNA / ml of plasma. To achieve this goal, it would be necessary the use of a potent, very efficacious ARV regimen that could provide such viral decay in a very short period. Raltegravir (RAL), the first HIV-1 integrase inhibitor, is a potent and safe ARV drug. The available evidence suggest it has no genotoxic potential, and promotes a rapid decline in HIV-1 plasma viremia. In addition, RAL is highly active against viral strains presenting different degree of resistance to other ARV drugs. Thus, RAL could be an ideal candidate to be used for prevention of MTCT for women with detectable viral load, presenting late in the course of pregnancy. Another attractive point is to consider that, due to the similarity between the integrase enzyme of HIV-1 and Human T-cell lymphotropic virus type-1 (HTLV-1); RAL could be active against HTLV-1, blocking its replication. If our hypothesis is correct, the use f RAL-containing ARV regimens would reduce the MTCT of both agents. This study has the objective of evaluating the efficacy of RAL containing ARV regimens in reducing the HIV-1 RNA plasma viral load below 50 copies/ml, at the end of pregnancy, for late-presenters pregnant women and to compare the frequency of adverse events for women using RAL-based ARV regimens and comparators, and for their babies.

Conditions

HIV; Pregnancy

Keywords

HIV; Treatment; Pregnancy

Outcome Measures

Primary Outcomes (1)

• HIV Viral Load at Delivery

  Number of participants presenting with PVL\<50 copies/mL at delivery

  2, 4, 6 weeks and at delivery

Secondary Outcomes (2)

• Overall Adverse Events up to Delivery

  2, 4, 6 weeks and at delivery

• Number of Children Infected With HIV

  4 weeks after delivery

Study Arms (2)

Raltegravir

EXPERIMENTAL

Use of Raltegravir plus backbone treatment for pregnant women

Drug: Raltegravir

Lopinavir/Ritonavir

ACTIVE COMPARATOR

Use of standard PI treatment (Lopinavir/r) plus backbone treatment for pregnant women

Drug: Lopinavir/Ritonavir

Interventions

Raltegravir DRUG

a raltegravir-based antiretroviral regimen (AZT+3TC+Raltegravir) will be administered for intervention arm patients (AZT+3TC will be administered in a fixed combination of AZT 300mg +3TC 150 mg, BID. Raltegravir will be administered in a dosis of 1 400 mg pill BID).

Also known as: Isentress

Raltegravir

Lopinavir/Ritonavir DRUG

The second arm (comparator)patients will use a regimen composed by AZT+3TC (same dosis/schedule of active arm)+ LPV 200mg combined with rtv 50 mg, 2 pills BID

Also known as: Kaletra

Lopinavir/Ritonavir

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Pregnant women with confirmed HIV-1 infection (positive Western blot or plasma HIV-1 RNA \>1,000 copies/ml)
• Gestational age higher than 28 weeks
• Age equal or higher than 15 years
• HIV-1 plasma viral load ≥ 1,000 copies of HIV-1 RNA/ml

You may not qualify if:

• Age lower than 15 years
• Undetectable plasma viral load at screening
• Previous use of RAL

Sponsors & Collaborators

• Fundação Bahiana de Infectologia: lead

Study Sites (1)

Fundação Bahiana de Infectologia/SEI

Salvador, Estado de Bahia, 40110-010, Brazil

Location

MeSH Terms

Interventions

Raltegravir Potassium; Lopinavir; lopinavir-ritonavir drug combination

Intervention Hierarchy (Ancestors)

Pyrrolidinones; Pyrrolidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidinones; Pyrimidines

Limitations and Caveats

Small sample size and current limited use of LPV/r as a first-choice drug

Results Point of Contact

• Title: Dr. Carlos Brites
• Organization: Fundação Bahiana de Infectologia / Universidade Federal da Bahia

crbrites@gmail.com

5571992329552

Study Officials

• Carlos Brites, MD, PhD

  Fundação Bahiana de Infectologia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Investigator

Model Details: Pilot randomized single-center open label clinical trial

Study Record Dates

• First Submitted: April 22, 2013
• First Posted: May 16, 2013
• Study Start: June 1, 2015
• Primary Completion: August 2, 2017
• Study Completion: August 2, 2017
• Last Updated: October 15, 2024
• Results First Posted: October 15, 2024

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, ICF, CSR
• Time Frame: September/1st/2017
• Access Criteria: open access

Locations

BR (1)