Nevirapine Study for the Prevention of Maternal-Infant HIV Transmission in Uganda - Full Text View

Purpose

The increase in pediatric HIV infection has a substantial impact on childhood mortality in the developing world. A number of recent studies suggest that as many as half or more of mother-to-child HIV transmissions in developing countries occur in late pregnancy or during labor and delivery. Interventions targeted during the perinatal period have shown to be effective and to have a significant impact in reducing transmission. The purpose of this study is to investigate the effectiveness of nevirapine (NVP) plus immunoprophylaxis or extended NVP dosing regimens in HIV-infected pregnant women and their infants during the perinatal period.

Condition	Intervention	Phase
HIV Infections	Drug: Nevirapine Drug: HIV immune globulin solution	Phase 3


Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver) Primary Purpose: Prevention
Official Title:	A Phase III Randomized Clinical Trial of the Standard Two Dose Nevirapine (NVP) Regimen With the Addition of HIV Immune Globulin(HIVIGLOB) or Extended Infant NVP Dosing Compared With the Standard NVP Regimen Alone for the Prevention of Maternal-Infant HIV Transmission in Uganda

Resource links provided by NLM:

MedlinePlus related topics: HIV/AIDS HIV/AIDS and Pregnancy

Drug Information available for: Nevirapine Nevirapine hemihydrate

U.S. FDA Resources

Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Primary Outcome Measures:

Rate of HIV infection in infants born to study participants in each arm of the study [ Time Frame: At Birth, Weeks 2, 6, and 14, and Months 6, 12, and 18 ] [ Designated as safety issue: Yes ]
Safety and tolerance of HIVIGLOB given to pregnant women at 36-37 weeks gestation and neonates at birth in combination with NVP and of NVP alone [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Rate of immunologic progression in HIV-infected infants in each arm [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Infant mortality [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Maternal plasma HIV RNA levels at delivery [ Time Frame: At Birth ] [ Designated as safety issue: Yes ]
Immunologic, virologic, and pharmacologic factors [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]


Enrollment:	722
Study Start Date:	July 2004
Study Completion Date:	July 2007
Primary Completion Date:	July 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Mother dosing regimen: Single dose of 200 mg NVP taken orally at onset of labor Infant dosing regimen: Single dose of 2 mg/kg NVP taken orally within the first week after delivery	Drug: Nevirapine 200 mg Nevirapine tablet Other Name: NVP Viramune
Experimental: 2 Mother dosing regimen: Single dose of 200 mg NVP taken orally at onset of labor Infant dosing regimen: 2 mg/kg NVP taken orally within the first week after delivery and 5 mg NVP taken orally daily from Day 8 through Week 6	Drug: Nevirapine 200 mg Nevirapine tablet Other Name: NVP Viramune
Experimental: 3 Mother dosing regimen: Single 12 gm intravenous dose of HIVIGLOB at 36 - 37 weeks gestation and 200 mg NVP taken orally at onset of labor Infant dosing regimen: Single 1.2 gm intravenous dose HIVIGLOB within 18 hours of birth and 2 mg/kg NVP taken orally within the first week after delivery	Drug: Nevirapine 200 mg Nevirapine tablet Other Name: NVP Viramune Drug: HIV immune globulin solution 5% intravenous HIV immune globulin solution Other Name: HIVIGLOB

Detailed Description:

There is an urgent need to find safe, effective means of preventing mother-to-child-transmission (MTCT) of HIV that can be used in developing countries. One of the greatest obstacles to prevention in these areas remains HIV transmission through breast milk. The primary purpose of this trial is to determine if nevirapine (NVP) plus immunoprophylaxis (by intravenous HIV immune globulin [HIVIGLOB]) or extended NVP dosing of the neonate during the perinatal period can safely and effectively reduce the risk of peripartum or early breastfeeding-related HIV MTCT.

This study will last 11-18 weeks for each mother and 18 months for each infant. HIV-infected pregnant women will be randomly assigned to one of three arms. Participants in Arm 1 will receive a single dose of 200 mg NVP orally at the onset of labor. Infants in Arm 1 will receive a single dose of 2 mg/kg NVP orally within the first week after delivery. Arm 2 participants will receive a single dose of 200 mg NVP orally at the onset of labor. Infants in Arm 2 will receive 2 mg/kg NVP orally within the first week after delivery and 5 mg NVP taken orally daily from Day 8 through Week 6. Arm 3 participants will receive a 12 gm intravenous dose of HIVIGLOB at 36-37 weeks gestation and 200 mg NVP orally at the onset of labor. Infants in Arm 3 will receive a single 1.2 gm intravenous dose HIVIGLOB within 18 hours of birth and 2 mg/kg NVP orally within the first week after delivery.

There will be five or six study visits for pregnant participants. A targeted medical history, physical examination, and blood collection will occur at all visits. After birth, there will be 11 study visits for infants in Arms 1 and 2 and 12 study visits for infants in Arm 3. Medical history and a targeted physical exam will occur at all visits. Blood collection will occur at some visits.

Eligibility


Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Pregnant between 32-36 weeks estimated gestation
HIV Infected
Intent to breastfeed infant
Certain laboratory criteria. More information on this criterion can be found in the protocol.

Exclusion Criteria:

Sensitivity to immune globulin preparations or any benzodiazepine
Clinically significant disease, as determined by the investigator, that would compromise the ability of the participant to complete the study requirements
Currently receiving antiretroviral therapy (other than the intrapartum NVP or other peripartum regimens)
Participation in any HIV vaccine trials
History of cytotoxic chemotherapy within one month of study entry
Uncontrolled hypertension
Chronic alcohol or illicit drug use
History of non-compliance with visits or medication
Women who become pregnant again during study follow-up will not be eligible for re-enrollment in the trial

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00639938

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators


Principal Investigator:	Brooks Jackson, MD	Johns Hopkins School of Medicine

More Information

Publications:

Colvin M, Chopra M, Doherty T, Jackson D, Levin J, Willumsen J, Goga A, Moodley P; Good Start Study Group. Operational effectiveness of single-dose nevirapine in preventing mother-to-child transmission of HIV. Bull World Health Organ. 2007 Jun;85(6):466-73.

Flys TS, Mwatha A, Guay LA, Nakabiito C, Donnell D, Musoke P, Mmiro F, Jackson JB, Eshleman SH. Detection of K103N in Ugandan women after repeated exposure to single dose nevirapine. AIDS. 2007 Oct 1;21(15):2077-82.

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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Onyango-Makumbi C, Omer SB, Mubiru M, Moulton LH, Nakabiito C, Musoke P, Mmiro F, Zwerski S, Wigzell H, Falksveden L, Wahren B, Antelman G, Fowler MG, Guay L, Jackson JB. Safety and efficacy of HIV hyperimmune globulin for prevention of mother-to-child HIV transmission in HIV-1-infected pregnant women and their infants in Kampala, Uganda (HIVIGLOB/NVP STUDY). J Acquir Immune Defic Syndr. 2011 Dec 1;58(4):399-407. doi: 10.1097/QAI.0b013e31822f8914.

Six Week Extended-Dose Nevirapine (SWEN) Study Team, Bedri A, Gudetta B, Isehak A, Kumbi S, Lulseged S, Mengistu Y, Bhore AV, Bhosale R, Varadhrajan V, Gupte N, Sastry J, Suryavanshi N, Tripathy S, Mmiro F, Mubiru M, Onyango C, Taylor A, Musoke P, Nakabiito C, Abashawl A, Adamu R, Antelman G, Bollinger RC, Bright P, Chaudhary MA, Coberly J, Guay L, Fowler MG, Gupta A, Hassen E, Jackson JB, Moulton LH, Nayak U, Omer SB, Propper L, Ram M, Rexroad V, Ruff AJ, Shankar A, Zwerski S. Extended-dose nevirapine to 6 weeks of age for infants to prevent HIV transmission via breastfeeding in Ethiopia, India, and Uganda: an analysis of three randomised controlled trials. Lancet. 2008 Jul 26;372(9635):300-13. doi: 10.1016/S0140-6736(08)61114-9.


Responsible Party:	Brooks Jackson, MD, Johns Hopkins School of Medicine
ClinicalTrials.gov Identifier:	NCT00639938 History of Changes
Other Study ID Numbers:	R01-AI-34235
Study First Received:	March 18, 2008
Last Updated:	April 1, 2008
Health Authority:	United States: Food and Drug Administration NIAID DSMB

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):


Pregnancy, High-Risk HIV Seronegativity

Additional relevant MeSH terms:


Acquired Immunodeficiency Syndrome HIV Infections Immune System Diseases Immunologic Deficiency Syndromes Lentivirus Infections RNA Virus Infections Retroviridae Infections Sexually Transmitted Diseases Sexually Transmitted Diseases, Viral Slow Virus Diseases Virus Diseases Antibodies Immunoglobulins	Nevirapine Anti-HIV Agents Anti-Infective Agents Anti-Retroviral Agents Antiviral Agents Enzyme Inhibitors Immunologic Factors Molecular Mechanisms of Pharmacological Action Nucleic Acid Synthesis Inhibitors Pharmacologic Actions Physiological Effects of Drugs Reverse Transcriptase Inhibitors Therapeutic Uses

ClinicalTrials.gov processed this record on February 25, 2015