Trial of Three Neonatal Antiretroviral Regimens for Prevention of Intrapartum HIV Transmission

October 26, 2012 updated by: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Phase III Randomized Trial of the Safety and Efficacy of Three Neonatal Antiretroviral Regimens for Prevention of Intrapartum HIV-1 Transmission

Giving anti-HIV medications to babies born of HIV positive mothers right after birth can lower the babies' risk of contracting HIV. This study will assess the safety and efficacy of two different combinations of anti-HIV medications compared to a one drug standard regimen in preventing mother to baby transmission. The one drug standard treatment and two combinations to be studied are: 1) zidovudine, 2) zidovudine/nevirapine and 3) zidovudine/lamivudine/nelfinavir.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Despite the notable reductions in perinatal transmission of HIV-1 with antiretroviral therapy and other interventions, perinatal transmission continues to occur at rates of 20-30% among pregnant women who are not identified as HIV-1-infected and/or are not provided with antiretroviral therapy. The optimum treatment strategy for prevention of transmission of HIV-1 to infants born to these women is unknown. No trials have evaluated the efficacy of neonatal antiretroviral therapy alone but observational data suggest benefit from zidovudine (ZDV) therapy given to the infant beginning within 48 hours of birth and continued for six weeks. This protocol will compare the safety and efficacy of three antiretroviral regimens administered in the neonatal period: Arm A- ZDV, Arm B- ZDV plus nevirapine (NVP), and Arm C- ZDV plus nelfinavir (NFV) and lamivudine (3TC). Two regimens were selected based on expected antiretroviral activity, pharmacokinetic data, and toxicity profiles. Standard of care (6 weeks of ZDV) alone will be compared to the 6 weeks of ZDV plus either 3 doses of NVP or 2 weeks of 3TC and NFV. Arm B (ZDV + NVP) is the regimen expected to provide the best profile when factors of efficacy, safety, cost, acceptability and convenience are considered. The comparison of Arms B and C is also of considerable interest since the 2-drug Arm B is easier to implement and less expensive than the triple drug Arm C. Although triple drug therapies have been recommended for post-exposure prophylaxis for needle-stick injuries in high-risk circumstances, it is unknown whether the triple drug arm will provide better efficacy than the 2-drug arm for post-exposure prophylaxis of the infant.

This open-label study is expected to accrue 1731 infants of women identified in labor as being HIV positive or who are HIV positive but have not received antiretroviral medication during the pregnancy. If eligible the infant will be randomized at birth to one of three aforementioned treatment arms. Medical history, social, demographic, physical exam, RNA and T- lymphocyte data are collected on the mother during the delivery visit. The infant will have a birth visit and then return for 1-week, 2-week, 4-week, 3-month and a final 6-month visit. Infant evaluations will include: a medical history and physical exam, DNA testing, CBC and liver function tests, cells for long-term storage and RNA/CD4/CD8 testing if HIV positive. The initial study drug doses will be given to the infant while in the hospital. Mothers will administer the infants' remaining treatment doses at home depending on ability.

Study Type

Interventional

Enrollment (Actual)

1735

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Hospital I. G. A. Dr. Diego Paroissien
  • Brazil
      • Rio de Janeiro, Brazil, 20221-903
        • Hospital dos Servidores do Estado (HSE)
      • Rio de Janeiro, Brazil, 26030-380
        • Hospital Geral de Novo Iguacu
      • São Paulo, Brazil, 04939-002
        • 5088 - Universidade Federal de Sao Paulo (UFSP)
    • MG
      • Belo Horizonte, MG, Brazil, 30130-100
        • Federal University of Minas Gerais (UFMG)
    • Ribeirão Preto
      • São Paulo, Ribeirão Preto, Brazil, 14024-250
        • Universidade de Sao Paulo (USP) , MD
    • Rio Grande do Sul
      • Porto Alegre, Rio Grande do Sul, Brazil, 90430001
        • Hospital Fêmina S.A. Unidade Perinatal de Transmissão Vertical
      • Porto Alegre, Rio Grande do Sul, Brazil, 90850 530
        • Hospital Santa Casa (HSC)
      • Porto Alegre, Rio Grande do Sul, Brazil, 91350-200
        • Hospital Nossa Senhora da Conceicao (GHC)
  • Puerto Rico
      • San Juan, Puerto Rico, 00936-8344
        • San Juan Hospital
  • South Africa
      • Cape Town, South Africa
        • Tygerberg Hospital
      • Johannesburg, South Africa
        • Chris Hani Baragwanath Hospital
  • United States
    • California
      • Long Beach, California, United States, 90806
        • Miller Children's Hospital
    • Florida
      • Gainesville, Florida, United States, 32610-0296
        • University of FL
      • Jacksonville, Florida, United States, 32209
        • University of FL-HSC
    • New Jersey
      • Newark, New Jersey, United States, 07103
        • University Medical and Dental School of NJ-Newark Campus
    • Texas
      • Houston, Texas, United States, 77030
        • Texas Childrens Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

No older than 2 days (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

Infants who meet all of the following criteria are eligible for the study:

  • Mother known to be HIV-1-infected prior to labor or identified at the time of labor or <48 hours postpartum. HIV-1 infection for the purposes of enrollment into this study is defined as: (a) Single positive HIV-1 rapid test in mother or her infant; or (b) Historical documentation of a positive HIV-1 diagnostic test confirmed by repeat diagnostic testing for HIV-1 according to country guidelines in mother (written documentation of test results must be present in the medical record).
  • Maternal written informed consent for study participation.
  • Mother has not received any antiretroviral therapy during the current pregnancy prior to the onset of labor and delivery; women may have received intravenous or oral ZDV during labor. Women may have received any antiretroviral therapy in previous pregnancies for prevention of vertical HIV-1 transmission.
  • Infant is <48 hours old. Infant may have received up to 48 hours of ZDV as standard care before study enrollment.

Exclusion Criteria:

Infants who meet any of the following criteria will be excluded from the study:

  • Extreme prematurity (< 32 weeks of gestation).
  • Birth weight <1500 grams.
  • Presence of life-threatening conditions.
  • Inability to take oral medication throughout the first 48 hours of life (must be able to receive oral medication by age 48 hours).
  • Maternal inability to provide informed consent because of a lack of a conscious state, psychiatric conditions, or language barriers.
  • Mother received any antiretroviral therapy during labor and delivery other than intravenous or oral ZDV.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: A
Standard of care ( Zidovudine only)
Drug: Zidovudine
Given for 6 weeks. 12mg PO BID if birthweight (BW) > 2000 grams 8 mg PO BID if BW < 2000 grams
Other Names:
  • Retrovir
Experimental: B
Standard of care (Zidovudine) plus Nevirapine
Drug: Nevirapine (NVP)

Standard of Care (Zidovudine) plus

NVP, first dose initiated within 48 hrs of birth, second dose 48 hrs (+ 4 hours) after the first dose, and third dose 96 hours (+ 4 hours) after the second dose :

12 mg PO per dose if BW > 2000 grams, 8 mg PO per dose if BW < 2000 grams

Other Names:
  • Viramune
Experimental: C
Standard of Care (Zidovudine) plus 2 weeks of Epivir and Nelfinavir
Drug: Epivir (3TC)

Stand of care (Zidovudine) plus

3TC, given for 2 weeks: 6 mg po bid if BW > 2000 grams 4 mg po bid if BW < 2000 grams AND

NFV, given for 2 weeks:

200 mg po bid if BW > 3000 grams 150 mg po bid if BW > 2,000 - 3000 grams 100 mg PO BID if BW < 2000 grams

Other Names:
  • Lamivudine
Drug: Nelfinavir (NFV)
200 mg BID if birth weight (BW) > 3000 grams for 2 weeks;150 mg BID if BW > 2000-3000 grams for 2 weeks; 100 mg BID BW
Other Names:
  • Viracept

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infant HIV Infection Status
Time Frame: 3 months
Intrapartum HIV infection at 3 Months
3 months
Participants With Serious Adverse Events
Time Frame: through age 6 months.
Serious Adverse Events by System Organ Class=Blood and lymphatic system disorders
through age 6 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Infant HIV-1 Infection Status
Time Frame: birth
In utero HIV-1 infection rate
birth
Participant Deaths
Time Frame: through age 6 months
through age 6 months
Clinical Covariates of HIV-1 Infection
Time Frame: through age 3 months
Compare HIV-1 RNA levels; CD4+ lymphocyte counts; and rates of genotypic and phenotypic resistance among the three treatment regimens.
through age 3 months
3TC and NFV Pharmacokinetics
Time Frame: through age 14 days
Descriptive study of 3TC and NFV pharmacokinetics during first two weeks of life using weight band dosing regimen in a subset of enrolled infants.
through age 14 days
Risk Factors for Perinatal HIV-1 Transmission
Time Frame: through age 3 months
Risk factors to be assessed include maternal HIV-1 RNA levels at delivery, maternal syphilis and other infections, obstetrical factors such as duration of membrane rupture, and adherence to neonatal medication.
through age 3 months
NVP Pharmacokinetics
Time Frame: 14 days
Descriptive study of NVP pharmacokinetics during first two weeks of life using weight band dosing in a subset of enrolled infants.
14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

  • Study Chair: Karin Nielsen, MD, University of California, Los Angeles

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2004

Primary Completion (Actual)

February 1, 2011

Study Completion (Actual)

February 1, 2011

Study Registration Dates

First Submitted

December 10, 2004

First Submitted That Met QC Criteria

December 10, 2004

First Posted (Estimate)

December 13, 2004

Study Record Updates

Last Update Posted (Estimate)

December 4, 2012

Last Update Submitted That Met QC Criteria

October 26, 2012

Last Verified

February 1, 2011

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NICHD/HPTN 040 (P1043)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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