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

NCT00099359 | Completed Phase 3 Results DMC

• 1 other identifier: NICHD/HPTN 040 (P1043)
• Study Type: interventional
• Target: 1,735
• Locations: 5 countries
• Sites: 17

Brief 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. The one drug standard treatment and two combinations to be studied are: 1) zidovudine, 2) zidovudine/nevirapine and 3) zidovudine/lamivudine/nelfinavir.

Conditions

Disease Transmission, Vertical; Vertical Human Immunodeficiency Virus Transmission; HIV Infections

Keywords

HIV; Perinatal; Prevention; Transmission; Nevirapine; Epivir; Zidovudine; Nelfinavir; ZDV; NVP; 3TC; NFV; Viracept; Viramune; HIV Seronegativity; Treatment Naive

Outcome Measures

Primary Outcomes (2)

• Infant HIV Infection Status

  Intrapartum HIV infection at 3 Months

  3 months

• Participants With Serious Adverse Events

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

  through age 6 months.

Secondary Outcomes (6)

• Infant HIV-1 Infection Status

  birth

• Participant Deaths

  through age 6 months

• Clinical Covariates of HIV-1 Infection

  through age 3 months

• 3TC and NFV Pharmacokinetics

  through age 14 days

• Risk Factors for Perinatal HIV-1 Transmission

  through age 3 months

Study Arms (3)

A

EXPERIMENTAL

Standard of care ( Zidovudine only)

Drug: Zidovudine

B

EXPERIMENTAL

Standard of care (Zidovudine) plus Nevirapine

Drug: Nevirapine (NVP)

C

EXPERIMENTAL

Standard of Care (Zidovudine) plus 2 weeks of Epivir and Nelfinavir

Drug: Epivir (3TC); Drug: Nelfinavir (NFV)

Interventions

Zidovudine DRUG

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

Also known as: Retrovir

A

Nevirapine (NVP) DRUG

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

Also known as: Viramune

B

Epivir (3TC) DRUG

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

Also known as: Lamivudine

C

Nelfinavir (NFV) DRUG

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

Also known as: Viracept

C

Eligibility Criteria

• Age: Up to 2 Days
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): lead
• National Institute of Allergy and Infectious Diseases (NIAID): collaborator

Study Sites (17)

Miller Children's Hospital

Long Beach, California, 90806, United States

Location

University of FL

Gainesville, Florida, 32610-0296, United States

Location

University of FL-HSC

Jacksonville, Florida, 32209, United States

Location

University Medical and Dental School of NJ-Newark Campus

Newark, New Jersey, 07103, United States

Location

Texas Childrens Hospital

Houston, Texas, 77030, United States

Location

Hospital I. G. A. Dr. Diego Paroissien

Buenos Aires, Argentina

Location

Federal University of Minas Gerais (UFMG)

Belo Horizonte, Minas Gerais, 30130-100, Brazil

Location

Universidade de Sao Paulo (USP) , MD

São Paulo, Ribeirão Preto, 14024-250, Brazil

Location

Hospital Fêmina S.A. Unidade Perinatal de Transmissão Vertical

Porto Alegre, Rio Grande do Sul, 90430001, Brazil

Location

Hospital Santa Casa (HSC)

Porto Alegre, Rio Grande do Sul, 90850 530, Brazil

Location

Hospital Nossa Senhora da Conceicao (GHC)

Porto Alegre, Rio Grande do Sul, 91350-200, Brazil

Location

Hospital dos Servidores do Estado (HSE)

Rio de Janeiro, 20221-903, Brazil

Location

Hospital Geral de Novo Iguacu

Rio de Janeiro, 26030-380, Brazil

Location

5088 - Universidade Federal de Sao Paulo (UFSP)

São Paulo, 04939-002, Brazil

Location

San Juan Hospital

San Juan, 00936-8344, Puerto Rico

Location

Tygerberg Hospital

Cape Town, South Africa

Location

Chris Hani Baragwanath Hospital

Johannesburg, South Africa

Location

Related Publications (9)

• 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.

  PMID: 21666540 RESULT

• 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.

  PMID: 18398973 RESULT

• 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.

  PMID: 22716975 RESULT

• 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.

  PMID: 30216294 DERIVED

• 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.

  PMID: 29750766 DERIVED

• 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.

  PMID: 29304083 DERIVED

• 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.

  PMID: 28369278 DERIVED

• 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.

  PMID: 26372927 DERIVED

• 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.

  PMID: 25742089 DERIVED

Related Links

• home page of the National Institute of Child Health and Human Development

MeSH Terms

Conditions

HIV Infections

Interventions

Zidovudine; Nevirapine; Lamivudine; Nelfinavir

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Pyridines; Zalcitabine; Deoxycytidine; Cytidine; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Margaret Camarca, Project Director
• Organization: Westat

margaretcamarca@westat.com

301-517-4128

Study Officials

• Karin Nielsen, MD

  University of California, Los Angeles

  STUDY CHAIR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 10, 2004
• First Posted: December 13, 2004
• Study Start: February 1, 2004
• Primary Completion: February 1, 2011
• Study Completion: February 1, 2011
• Last Updated: December 4, 2012
• Results First Posted: December 4, 2012

Record last verified: 2011-02

Locations

US (5); PR (1); ZA (2); AR (1); BR (8)