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Disease Transmission, VerticalPhase 3NCT00099359

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

A Phase 3 study testing Zidovudine, Nevirapine (NVP) and Epivir (3TC) in people with Disease Transmission, Vertical and Vertical Human Immunodeficiency Virus Transmission, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 17 sites in 5 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

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. Read more about this study

Who is it for?
Ages Up to 2 daysHealthy volunteers can take part
What is being tested?
Zidovudine, Nevirapine (NVP) and Epivir (3TC)
Could I receive a placebo?
No, everyone receives an active treatment
How many people
1,735 participants
Where
17 sitesin 5 countries
Study dates
Feb 2004to Feb 2011
Phase
Phase 3
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 2 days
  • All sexes
  • Healthy volunteers accepted
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.

Trial locations and contacts

17 sites in 5 countries.

17 sites in 5 countries

Brazil8 sites

  • Federal University of Minas Gerais (UFMG)

    Belo Horizonte, Minas Gerais, 30130-100

  • Hospital Fêmina S.A. Unidade Perinatal de Transmissão Vertical

    Porto Alegre, Rio Grande do Sul, 90430001

  • Hospital Santa Casa (HSC)

    Porto Alegre, Rio Grande do Sul, 90850 530

  • Hospital Nossa Senhora da Conceicao (GHC)

    Porto Alegre, Rio Grande do Sul, 91350-200

  • Hospital dos Servidores do Estado (HSE)

    Rio de Janeiro, 20221-903

  • Hospital Geral de Novo Iguacu

    Rio de Janeiro, 26030-380

  • Universidade de Sao Paulo (USP) , MD

    São Paulo, Ribeirão Preto, 14024-250

  • 5088 - Universidade Federal de Sao Paulo (UFSP)

    São Paulo, 04939-002

Other trials in Brazil

United States5 sites

  • University of FL

    Gainesville, Florida, 32610-0296

  • Texas Childrens Hospital

    Houston, Texas, 77030

  • University of FL-HSC

    Jacksonville, Florida, 32209

  • Miller Children's Hospital

    Long Beach, California, 90806

  • University Medical and Dental School of NJ-Newark Campus

    Newark, New Jersey, 07103

Other trials in United States

South Africa2 sites

  • Tygerberg Hospital

    Cape Town

  • Chris Hani Baragwanath Hospital

    Johannesburg

Other trials in South Africa

Argentina1 site

  • Hospital I. G. A. Dr. Diego Paroissien

    Buenos Aires

Other trials in Argentina

Puerto Rico1 site

  • San Juan Hospital

    San Juan, 00936-8344

Other trials in Puerto Rico

About this study

Official title: 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.

Read the 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.

Being tested
Zidovudine, Nevirapine (NVP), Epivir (3TC), Nelfinavir (NFV)
Keywords
HIV, Perinatal, Prevention, Transmission, Nevirapine, Epivir, Zidovudine, Nelfinavir, ZDV, NVP, 3TC, NFV, Viracept, Viramune, HIV Seronegativity, Treatment Naive
Medical subject headings
HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ZidovudineDrug

    Also called Retrovir

    Given for 6 weeks. 12mg PO BID if birthweight (BW) > 2000 grams 8 mg PO BID if BW < 2000 grams

  • Nevirapine (NVP)Drug

    Also called Viramune

    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

  • Epivir (3TC)Drug

    Also called Lamivudine

    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

  • Nelfinavir (NFV)Drug

    Also called Viracept

    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 </= 2000 grams for 2 weeks

Study groups in NCT00099359
Study groupRoleWhat they receive
AExperimentalStandard of care ( Zidovudine only)
Receives: Drug: Zidovudine
BExperimentalStandard of care (Zidovudine) plus Nevirapine
Receives: Drug: Nevirapine (NVP)
CExperimentalStandard of Care (Zidovudine) plus 2 weeks of Epivir and Nelfinavir
Receives: Drug: Epivir (3TC); Drug: Nelfinavir (NFV)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Infant HIV Infection Status

    Intrapartum HIV infection at 3 Months

    Measured: 3 months

  2. Participants With Serious Adverse Events

    Serious Adverse Events by System Organ Class=Blood and lymphatic system disorders

    Measured: through age 6 months.

Secondary outcomes (6)

  1. Infant HIV-1 Infection Status

    In utero HIV-1 infection rate

    Measured: birth

  2. Participant Deaths

    Measured: through age 6 months

  3. Clinical Covariates of HIV-1 Infection

    Compare HIV-1 RNA levels; CD4+ lymphocyte counts; and rates of genotypic and phenotypic resistance among the three treatment regimens.

    Measured: through age 3 months

  4. 3TC and NFV Pharmacokinetics

    Descriptive study of 3TC and NFV pharmacokinetics during first two weeks of life using weight band dosing regimen in a subset of enrolled infants.

    Measured: through age 14 days

  5. Risk Factors for Perinatal HIV-1 Transmission

    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.

    Measured: through age 3 months

  6. NVP Pharmacokinetics

    Descriptive study of NVP pharmacokinetics during first two weeks of life using weight band dosing in a subset of enrolled infants.

    Measured: 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Dec 2004 (estimated)
  2. Study startFeb 2004
  3. Primary completionFeb 2011
  4. Study completionFeb 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
1,735 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00099359
Sponsor's protocol ID
NICHD/HPTN 040 (P1043)
Status last verified
Feb 2011
First submitted
10 Dec 2004
Last updated
4 Dec 2012
Data monitoring committee
Yes

Publications

  • Mirochnick M, Nielsen-Saines K, Pilotto JH, Pinto J, Veloso VG, Rossi S, Moye J, Bryson Y, Mofenson L, Camarca M, Watts DH; NICHD HPTN 040/PACTG 1043 PROTOCOL Team. Nelfinavir and Lamivudine pharmacokinetics during the first two weeks of life. Pediatr Infect Dis J. 2011 Sep;30(9):769-72. doi: 10.1097/INF.0b013e3182242950.

    PubMed 21666540

  • Mirochnick M, Nielsen-Saines K, Pilotto JH, Pinto J, Jimenez E, Veloso VG, Parsons T, Watts DH, Moye J, Mofenson LM, Camarca M, Bryson Y; NICHD/HPTN 040/PACTG 1043 Protocol Team. Nevirapine concentrations in newborns receiving an extended prophylactic regimen. J Acquir Immune Defic Syndr. 2008 Mar 1;47(3):334-7.

    PubMed 18398973

  • Nielsen-Saines K, Watts DH, Veloso VG, Bryson YJ, Joao EC, Pilotto JH, Gray G, Theron G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Ceriotto M, Machado D, Bethel J, Morgado MG, Dickover R, Camarca M, Mirochnick M, Siberry G, Grinsztejn B, Moreira RI, Bastos FI, Xu J, Moye J, Mofenson LM; NICHD HPTN 040/PACTG 1043 Protocol Team. Three postpartum antiretroviral regimens to prevent intrapartum HIV infection. N Engl J Med. 2012 Jun 21;366(25):2368-79. doi: 10.1056/NEJMoa1108275.

    PubMed 22716975

  • Adachi K, Xu J, Ank B, Watts DH, Camarca M, Mofenson LM, Pilotto JH, Joao E, Gray G, Theron G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Machado DM, Ceriotto M, Morgado MG, Bryson YJ, Veloso VG, Grinsztejn B, Mirochnick M, Moye J, Nielsen-Saines K; MPH for the NICHD HPTN 040 Study Team. Congenital Cytomegalovirus and HIV Perinatal Transmission. Pediatr Infect Dis J. 2018 Oct;37(10):1016-1021. doi: 10.1097/INF.0000000000001975.

    PubMed 30216294

  • Yeganeh N, Watts DH, Xu J, Kerin T, Joao EC, Pilotto JH, Theron G, Gray G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Veloso V, Camarca M, Mofenson L, Moye J, Nielsen-Saines K. Infectious Morbidity, Mortality and Nutrition in HIV-exposed, Uninfected, Formula-fed Infants: Results From the HPTN 040/PACTG 1043 Trial. Pediatr Infect Dis J. 2018 Dec;37(12):1271-1278. doi: 10.1097/INF.0000000000002082.

    PubMed 29750766

  • Adachi K, Xu J, Yeganeh N, Camarca M, Morgado MG, Watts DH, Mofenson LM, Veloso VG, Pilotto JH, Joao E, Gray G, Theron G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Ceriotto M, Machado DM, Bryson YJ, Grinsztejn B, Moye J, Klausner JD, Bristow CC, Dickover R, Mirochnick M, Nielsen-Saines K; NICHD HPTN 040 Study Team. Combined evaluation of sexually transmitted infections in HIV-infected pregnant women and infant HIV transmission. PLoS One. 2018 Jan 5;13(1):e0189851. doi: 10.1371/journal.pone.0189851. eCollection 2018.

    PubMed 29304083

  • Adachi K, Xu J, Ank B, Watts DH, Mofenson LM, Pilotto JH, Joao E, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata MM, Gray G, Theron G, Morgado MG, Bryson YJ, Veloso VG, Klausner JD, Moye J, Nielsen-Saines K; NICHD HPTN 040 Study Team. Cytomegalovirus Urinary Shedding in HIV-infected Pregnant Women and Congenital Cytomegalovirus Infection. Clin Infect Dis. 2017 Aug 1;65(3):405-413. doi: 10.1093/cid/cix222.

    PubMed 28369278

  • Adachi K, Klausner JD, Bristow CC, Xu J, Ank B, Morgado MG, Watts DH, Weir F, Persing D, Mofenson LM, Veloso VG, Pilotto JH, Joao E, Nielsen-Saines K; NICHD HPTN 040 Study Team. Chlamydia and Gonorrhea in HIV-Infected Pregnant Women and Infant HIV Transmission. Sex Transm Dis. 2015 Oct;42(10):554-65. doi: 10.1097/OLQ.0000000000000340.

    PubMed 26372927

  • Yeganeh N, Watts HD, Camarca M, Soares G, Joao E, Pilotto JH, Gray G, Theron G, Santos B, Fonseca R, Kreitchmann R, Pinto J, Mussi-Pinhata M, Ceriotto M, Machado DM, Grinzstejn B, Veloso VG, Morgado MG, Bryson Y, Mofenson LM, Nielsen-Saines K; NICHD HPTN 040P1043 Study Team. Syphilis in HIV-infected mothers and infants: results from the NICHD/HPTN 040 study. Pediatr Infect Dis J. 2015 Mar;34(3):e52-7. doi: 10.1097/INF.0000000000000578.

    PubMed 25742089

Questions about this trial

What is this clinical trial studying?

A Phase 3 study testing Zidovudine, Nevirapine (NVP) and Epivir (3TC) in people with Disease Transmission, Vertical and Vertical Human Immunodeficiency Virus Transmission, run by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) at 17 sites in 5 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 4 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 17 sites in Brazil, United States, South Africa, Argentina, Puerto Rico. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 4 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Infant HIV Infection Status (time frame: 3 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00099359, which also lists 9 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Dec 2012.

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