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

Evaluation of the Use of Antiretroviral Regimens Containing Raltegravir for Prophylaxis of Mother-to-child-transmission of HIV Infection in Pregnant Women Presenting With Detectable Viral Load After 32 Weeks of Gestation: a Pilot Study

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.

Study Overview

• Status: Terminated
• Conditions: Pregnancy; HIV
• Intervention / Treatment: Drug: Raltegravir; Drug: Lopinavir/Ritonavir

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.

• Study Type: Interventional
• Enrollment (Actual): 33
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Bahia
    • Salvador, Bahia, Brazil, 40110-010
      • Fundação Bahiana de Infectologia/SEI

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Raltegravir; Use of Raltegravir plus backbone treatment for pregnant women	Drug: 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).; Other Names: Isentress
Active Comparator: Lopinavir/Ritonavir; Use of standard PI treatment (Lopinavir/r) plus backbone treatment for pregnant women	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; Other Names: Kaletra

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HIV Viral Load at Delivery	Number of participants presenting with PVL<50 copies/mL at delivery	2, 4, 6 weeks and at delivery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Adverse Events up to Delivery	Frequency of clinical and laboratory abnormalities by arm	2, 4, 6 weeks and at delivery
Number of Children Infected With HIV	Detectable plasma HIV-1 RNA viral load at 4 weeks after delivery	4 weeks after delivery

Collaborators and Investigators

• Sponsor: Fundação Bahiana de Infectologia
• Investigators: Principal Investigator: Carlos Brites, MD, PhD, Fundação Bahiana de Infectologia

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Actual): August 2, 2017
• Study Completion (Actual): August 2, 2017

Study Registration Dates

• First Submitted: April 22, 2013
• First Submitted That Met QC Criteria: May 13, 2013
• First Posted (Estimated): May 16, 2013

Study Record Updates

• Last Update Posted (Actual): October 15, 2024
• Last Update Submitted That Met QC Criteria: September 23, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Keywords: Treatment; HIV; Pregnancy
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Urogenital Diseases; Genital Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; HIV Integrase Inhibitors; Integrase Inhibitors; HIV Protease Inhibitors; Viral Protease Inhibitors; Raltegravir Potassium; Ritonavir; Lopinavir
• Other Study ID Numbers: PregnantHIV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All data regarding the protocol will be made freely available at the website of Fundação Bahiana de Infectologia.
• IPD Sharing Time Frame: September/1st/2017
• IPD Sharing Access Criteria: open access
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF; CSR