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

NCT ID: NCT01854762

Last Updated: 2024-10-15

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-06-01
• Study Completion Date: 2017-08-02

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.

Detailed Description

A total of 44 late-presenters (gestational age >28 weeks), HIV-infected pregnant women will be randomly assigned to receive an antiretroviral regimen based on Zidovudine (AZT)+Lamivudine (3TC)+Raltegravir or AZT+3TC+Lopinavir/r (LPV/r). They will be followed up to the delivery, and plasma viral load will be measured. The rate of HIV mother-to-child-transmission will be compared between groups. The newborns will be followed up to 6 months, to register any adverse event during this period of time.

Conditions

HIV; Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Raltegravir

Use of Raltegravir plus backbone treatment for pregnant women

Group Type: EXPERIMENTAL

Raltegravir

Intervention Type: 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).

Lopinavir/Ritonavir

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

Group Type: ACTIVE_COMPARATOR

Lopinavir/Ritonavir

Intervention Type: 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

Interventions

Raltegravir

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).

Intervention Type: DRUG

Lopinavir/Ritonavir

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

Intervention Type: DRUG

Other Intervention Names

Isentress; Kaletra

Eligibility Criteria

Inclusion Criteria

• 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

Exclusion Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 50 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Fundação Bahiana de Infectologia

OTHER

Sponsor Role: lead

Responsible Party

Carlos Brites

Senior Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carlos Brites, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Fundação Bahiana de Infectologia

Locations

Fundação Bahiana de Infectologia/SEI

Salvador, Estado de Bahia, Brazil

Countries

Brazil

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

PregnantHIV

Identifier Type: -

Identifier Source: org_study_id