Using Nevirapine to Prevent Mother-to-Child HIV Transmission During Breastfeeding

NCT00074412 | Completed Phase 3 Results

• 2 other identifiers: HPTN 04610142
• Study Type: interventional
• Target: 2,026
• Locations: 4 countries
• Sites: 5

Brief Summary

The many benefits of breastfeeding are well documented. However, because of the risk of mother-to-child transmission (MTCT) of HIV from an HIV infected mother to her infant, there is considerable concern over the practice, especially in developing countries. The purpose of this study is to determine the safety and effectiveness of the anti-HIV drug nevirapine (NVP) in preventing MTCT of HIV in breastfeeding infants born to HIV infected women in South Africa, Tanzania, Uganda, and Zimbabwe.

Conditions

HIV Infections

Keywords

HIV Seronegativity; Treatment Experienced; Treatment Naive

Outcome Measures

Primary Outcomes (2)

• HIV Infection in Infants Determined to be HIV Uninfected at 6 Weeks Enrolled in Each Arm of the Study

  At Month 6

• Frequency and Severity of Adverse Reactions Among Participating Infants

  For those infants who were randomized at 6 weeks and who initiated study drug we looked at the frequency and severity of adverse reactions through 18 months of study. The severity of all AEs was graded according to the DAIDS Table for Grading the Severity of Adult and Pediatric Adverse Events. The term severity is described as the intensity grade or level for specific event (i.e. mild, moderate, severe, or life-threatening). Severity is not the same as seriousness.

  6 weeks through 18 months

Secondary Outcomes (3)

• Proportion of Infants Who Are Alive and HIV-uninfected in the Two Arms

  At Months 6 and 18

• Relative Rates of HIV Infection in the Two Arms

  At Month 18

• Infant Survival Rates (Mortality Regardless of HIV Infection) in the Two Arms

  At Month 18

Study Arms (2)

2A

EXPERIMENTAL

For infants: extended treatment with NVP

Drug: Nevirapine

2B

PLACEBO COMPARATOR

For infants: extended treatment with NVP placebo

Drug: Nevirapine placebo

Interventions

Nevirapine DRUG

10 mg/ml oral suspension taken once daily up to 6 months of age. Dosage will increase throughout study.

Also known as: NVP

2A

Nevirapine placebo DRUG

Oral suspension taken once daily up to 6 months of age

Also known as: NVP placebo

2B

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age or older
• HIV infected
• In third trimester of pregnancy, or at most 3 days post-delivery
• If baby is not yet born, planning to deliver at a facility where the study is being conducted
• Plan to breastfeed

You may not qualify if:

• Complications with this pregnancy
• Serious medical condition that would interfere with the study (e.g., that would prevent breastfeeding or adherence to the follow-up schedule), as judged by the on-site clinician
• Born to an HIV infected mother who is eligible for the study
• Weighed at least 2000 grams (4.4 lbs) at birth
• Blood sample obtained from the infant for HIV-1 DNA PCR, CBC with differential, and ALT
• Infants in a multiple birth are eligible only if both/all infants are eligible for the study and assigned to the same study group
• Able to breastfeed (e.g., mother and infant alive with no condition apparent that would prevent breastfeeding)
• HIV DNA PCR positive at birth
• ALT of Grade 2 or higher at birth
• Hemoglobin, absolute neutrophil count, or platelet count of Grade 3 or higher at birth
• Skin rash of Grade 2B (urticaria), Grade 3, or above
• Confirmed or suspected clinical hepatitis
• Serious illness or condition that would interfere with compliance with study procedures

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institute on Drug Abuse (NIDA): collaborator
• National Institute of Mental Health (NIMH): collaborator

Study Sites (5)

CAPRISA Umlazi CRS

Umlazi, KwaZulu-Natal, South Africa

Location

Muhimbili University of Health and Allied Sciences (MUHAS) CRS

Dar es Salaam, Tanzania

Location

Makerere University- JHU Research Collaboration {MUJHU CARE LTD} CRS

Kampala, Mpigi, Uganda

Location

Seke North CRS

Chitungwiza, Zimbabwe

Location

St Mary's CRS

Chitungwiza, Zimbabwe

Location

Related Publications (10)

• Jackson JB, Musoke P, Fleming T, Guay LA, Bagenda D, Allen M, Nakabiito C, Sherman J, Bakaki P, Owor M, Ducar C, Deseyve M, Mwatha A, Emel L, Duefield C, Mirochnick M, Fowler MG, Mofenson L, Miotti P, Gigliotti M, Bray D, Mmiro F. Intrapartum and neonatal single-dose nevirapine compared with zidovudine for prevention of mother-to-child transmission of HIV-1 in Kampala, Uganda: 18-month follow-up of the HIVNET 012 randomised trial. Lancet. 2003 Sep 13;362(9387):859-68. doi: 10.1016/S0140-6736(03)14341-3.

  PMID: 13678973 BACKGROUND

• Mitchla Z, Sharland M. Current treatment options to prevent perinatal transmission of HIV. Expert Opin Pharmacother. 2000 Jan;1(2):239-48. doi: 10.1517/14656566.1.2.239.

  PMID: 11249545 BACKGROUND

• Mofenson LM. Advances in the prevention of vertical transmission of human immunodeficiency virus. Semin Pediatr Infect Dis. 2003 Oct;14(4):295-308. doi: 10.1053/j.spid.2003.09.003.

  PMID: 14724794 BACKGROUND

• Piwoz EG, Ross J, Humphrey J. Human immunodeficiency virus transmission during breastfeeding: knowledge, gaps, and challenges for the future. Adv Exp Med Biol. 2004;554:195-210.

  PMID: 15384577 BACKGROUND

• Bhattacharya D, Guo R, Tseng CH, Emel L, Sun R, Zhang TH, Chiu SH, Stranix-Chibanda L, Chipato T, Ship H, Mohtashemi NZ, Kintu K, Manji KP, Moodley D, Maldonado Y, Currier JS, Thio CL. Hepatitis B virus clinical and virologic characteristics in an HIV perinatal transmission study in sub-Saharan Africa. AIDS. 2024 Mar 1;38(3):329-337. doi: 10.1097/QAD.0000000000003752. Epub 2023 Oct 17.

  PMID: 37861675 DERIVED

• Bhattacharya D, Guo R, Tseng CH, Emel L, Sun R, Chiu SH, Stranix-Chibanda L, Chipato T, Mohtashemi NZ, Kintu K, Manji KP, Moodley D, Thio CL, Maldonado Y, Currier JS. Maternal HBV Viremia and Association With Adverse Infant Outcomes in Women Living With HIV and HBV. Pediatr Infect Dis J. 2021 Feb 1;40(2):e56-e61. doi: 10.1097/INF.0000000000002980.

  PMID: 33181788 DERIVED

• Nandlal V, Moodley D, Grobler A, Bagratee J, Maharaj NR, Richardson P. Anaemia in pregnancy is associated with advanced HIV disease. PLoS One. 2014 Sep 15;9(9):e106103. doi: 10.1371/journal.pone.0106103. eCollection 2014.

  PMID: 25222119 DERIVED

• Fowler MG, Coovadia H, Herron CM, Maldonado Y, Chipato T, Moodley D, Musoke P, Aizire J, Manji K, Stranix-Chibanda L, Fawzi W, Chetty V, Msweli L, Kisenge R, Brown E, Mwatha A, Eshleman SH, Richardson P, Allen M, George K, Andrew P, Zwerski S, Mofenson LM, Jackson JB; HPTN 046 Protocol Team. Efficacy and safety of an extended nevirapine regimen in infants of breastfeeding mothers with HIV-1 infection for prevention of HIV-1 transmission (HPTN 046): 18-month results of a randomized, double-blind, placebo-controlled trial. J Acquir Immune Defic Syndr. 2014 Mar 1;65(3):366-74. doi: 10.1097/QAI.0000000000000052.

  PMID: 24189151 DERIVED

• Coovadia HM, Brown ER, Fowler MG, Chipato T, Moodley D, Manji K, Musoke P, Stranix-Chibanda L, Chetty V, Fawzi W, Nakabiito C, Msweli L, Kisenge R, Guay L, Mwatha A, Lynn DJ, Eshleman SH, Richardson P, George K, Andrew P, Mofenson LM, Zwerski S, Maldonado Y; HPTN 046 protocol team. Efficacy and safety of an extended nevirapine regimen in infant children of breastfeeding mothers with HIV-1 infection for prevention of postnatal HIV-1 transmission (HPTN 046): a randomised, double-blind, placebo-controlled trial. Lancet. 2012 Jan 21;379(9812):221-8. doi: 10.1016/S0140-6736(11)61653-X. Epub 2011 Dec 22.

  PMID: 22196945 DERIVED

• Aizire J, Fowler MG, Wang J, Shetty AK, Stranix-Chibanda L, Kamateeka M, Brown ER, Bolton SG, Musoke PM, Coovadia H. Extended prophylaxis with nevirapine and cotrimoxazole among HIV-exposed uninfected infants is well tolerated. AIDS. 2012 Jan 28;26(3):325-33. doi: 10.1097/QAD.0b013e32834e892c.

  PMID: 22112598 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Nevirapine

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)

Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

The rate of maternal highly active antiretroviral therapy use was higher than expected in our study. Thus there were fewer infant infections which decreased the power to detect differences in HIV transmission risks between study groups.

Results Point of Contact

• Title: Statistical Research Associate
• Organization: Statistical Center for HIV/AIDS Research and Prevention

cherron@fhcrc.org

2066677524

Study Officials

• Hoosen M. Coovadia, MD, MBBS

  Centre for HIV Networking (HIVAN), Nelson Mandela School of Medicine, University of Natal

  STUDY CHAIR

• Laura Guay, MD

  Johns Hopkins University

  STUDY CHAIR

• Wafaie Fawzi, MD, PhD

  Department of Nutrition, Harvard School of Public Health

  STUDY CHAIR

• Yvonne Maldonado, MD

  Stanford University

  STUDY CHAIR

• Daya Moodley, MSc, PhD

  Department of Obstetrics and Gynaecology, Nelson R Mandela School of Medicine, University of Natal

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 11, 2003
• First Posted: December 15, 2003
• Study Start: January 1, 2007
• Primary Completion: September 1, 2011
• Study Completion: November 1, 2011
• Last Updated: February 16, 2023
• Results First Posted: September 16, 2013

Record last verified: 2023-01

Locations

TA (1); ZA (1); UG (1); ZI (2)