Daily Nevirapine to Prevent Mother to Infant Transmission of HIV - Full Text View

Sponsored by:	National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00061321

Purpose

Infants who are breast-fed by HIV infected mothers have an increased risk of becoming infected with HIV. Standard therapy for the prevention of HIV infections in infants included zidovudine (ZDV) prior to the onset of labor, a single dose of nevirapine (NVP) for women during labor, and a single dose of NVP for newborns given 72 hours after birth. This study will determine if giving low dose daily NVP to breastfed infants of HIV infected mothers, in addition to standard therapy, will be more effective than standard therapy alone at preventing HIV infections in these infants.

Condition	Intervention	Phase
HIV Infections	Drug: Nevirapine and mulitvitamins	Phase III

MedlinePlus related topics: AIDS Breast Feeding

Drug Information available for: Nevirapine

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Prevention, Randomized, Open Label, Active Control, Crossover Assignment, Safety/Efficacy Study
Official Title:	Prevention of Maternal to Infant HIV Transmission in India

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

Primary Outcome Measures:

HIV infection rate of infants [ Time Frame: 6 months of age ] [ Designated as safety issue: No ]
Safety of the regimens for HIV-infected mothers and their breast-fed infants [ Time Frame: Through 12 months post-partum ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Acceptability and compliance of intervention regimens [ Time Frame: Until 6 weeks of age ] [ Designated as safety issue: No ]
Time to HIV infection by treatment regimen [ Time Frame: over 12 months of age ] [ Designated as safety issue: No ]
Time to infection by infant feeding practice and time to weaning [ Time Frame: Until 12 months post-partum ] [ Designated as safety issue: No ]
Maternal ZDV and NVP resistance [ Time Frame: Baseline and post-partum ] [ Designated as safety issue: No ]
Infant morbidity and mortality by treatment arm [ Time Frame: Until 12 months post partum ] [ Designated as safety issue: Yes ]
Infant NVP resistance by treatment arm [ Time Frame: Up to 12 months post partum ] [ Designated as safety issue: Yes ]
Maternal NVP pharmacokinetics [ Time Frame: Up to 12 months post-partum ] [ Designated as safety issue: No ]
Infant NVP pharmacokinetics [ Time Frame: Up to 12 months post-partum ] [ Designated as safety issue: No ]

Enrollment:	770
Study Start Date:	August 2002
Study Completion Date:	September 2007
Primary Completion Date:	April 2007 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Active Comparator Mothers: One dose of intrapartum nevirapine by mouth (200mg) at onset of labor Infants: One dose of liquid nevirapine by mouth within 72 hours of birth (2mg/kg) Infants: Liquid multivitamins (1ml/day) week 1 through week 6 post-partum	Drug: Nevirapine and mulitvitamins Mothers: One dose of intrapartum nevirapine by mouth (200mg) at onset of labor Infants: One dose of liquid nevirapine by mouth within 72 hours of birth (2mg/kg) Infants: Liquid multivitamins (1ml/day) week 1 through week 6 post-partum Infants (Arm 2 Only): Liquid nevirapine (5 mg/day) by mouth, from week 1 through week 6 post-partum
2: Experimental Mothers: One dose of intrapartum nevirapine by mouth (200mg) at onset of labor Infants: One dose of liquid nevirapine by mouth within 72 hours of birth (2mg/kg) Infants: Liquid multivitamins (1ml/day)by mouth, from week 1 through week 6 post-partum Infants: Liquid nevirapine (5 mg/day) by mouth, from week 1 through week 6 post-partum	Drug: Nevirapine and mulitvitamins Mothers: One dose of intrapartum nevirapine by mouth (200mg) at onset of labor Infants: One dose of liquid nevirapine by mouth within 72 hours of birth (2mg/kg) Infants: Liquid multivitamins (1ml/day) week 1 through week 6 post-partum Infants (Arm 2 Only): Liquid nevirapine (5 mg/day) by mouth, from week 1 through week 6 post-partum

Detailed Description:

This study will evaluate the safety and effectiveness of adding daily infant NVP to standard prevention measures to decrease vertical transmission of HIV.

According to current statistics from the study site, approximately 70% of the pregnant HIV infected women in this study will have begun antenatal ZDV prior to the initiation of NVP at labor. The remaining 30% of the HIV infected women enrolled in this trial will have been previously undiagnosed. These women will be diagnosed with HIV infection either at the time they present to the delivery room in stage 1 of labor or immediately postpartum if they present for delivery late in labor and cannot provide informed consent for HIV screening prior to delivery.

All infants will receive the standard does of NVP at 72 hours postpartum. Infants will then be randomized to receive either daily NVP and a daily multivitamin (MVI) or a daily MVI alone. Infants will take NVP/MVI or MVI alone during Weeks 2 to 6 postpartum. The primary outcome measure is infant HIV infection rates at 6 months.

Two additional related cohorts of women will be followed for comparison: 1) an equal number of HIV uninfected women and their children will be enrolled for comparison of postpartum morbidity and mortality; and 2) consenting HIV infected women and their children who choose not to enroll in the clinical trial or are ineligible because they are not breastfeeding will be enrolled in an ancillary cohort.

Eligibility

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

Criteria

Inclusion Criteria for Pregnant or Postpartum Mothers

HIV infected
Planning to breastfeed
Able to tolerate oral drugs and available for 12 months of postpartum follow-up

Exclusion Criteria

Significant physical or emotional distress
Infant with serious or life threatening disease or severe fetal abnormality
Obstetrical complications affecting maternal health
Prior antiretroviral drugs (except antenatal ZDV or intrapartum (NVP)

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00061321

Locations

India
BJ Medical College
Pune, India

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Principal Investigator:

Robert C. Bollinger, MD, MPH

Johns Hopkins University

More Information

Click here for more information about nevirapine This link exits the ClinicalTrials.gov site

Click here for more information on after birth care for HIV positive women and their babies This link exits the ClinicalTrials.gov site

Publications of Results:

Bhore AV, Sastry J, Patke D, Gupte N, Bulakh PM, Lele S, Karmarkar A, Bharucha KE, Shrotri A, Pisal H, Suryawanshi N, Tripathy S, Risbud AR, Paranjape RS, Shankar AV, Kshirsagar A, Phadke MA, Joshi PL, Brookmeyer RS, Bollinger RC Jr. Sensitivity and specificity of rapid HIV testing of pregnant women in India. Int J STD AIDS. 2003 Jan;14(1):37-41.

Suryavanshi N, Jonnalagadda S, Erande AS, Sastry J, Pisal H, Bharucha KE, Shrotri A, Bulakh PM, Phadke MA, Bollinger RC, Shankar AV. Infant feeding practices of HIV-positive mothers in India. J Nutr. 2003 May;133(5):1326-31.

Phadke MA, Gadgil B, Bharucha KE, Shrotri AN, Sastry J, Gupte NA, Brookmeyer R, Paranjape RS, Bulakh PM, Pisal H, Suryavanshi N, Shankar AV, Propper L, Joshi PL, Bollinger RC. Replacement-fed infants born to HIV-infected mothers in India have a high early postpartum rate of hospitalization. J Nutr. 2003 Oct;133(10):3153-7.

Shankar AV, Pisal H, Patil O, Joshi A, Suryavanshi N, Shrotri A, Bharucha KE, Bulakh P, Phadke MA, Bollinger RC, Sastry J. Women's acceptability and husband's support of rapid HIV testing of pregnant women in India. AIDS Care. 2003 Dec;15(6):871-4.

Shrotri A, Shankar AV, Sutar S, Joshi A, Suryawanshi N, Pisal H, Bharucha KE, Phadke MA, Bollinger RC, Sastry J. Awareness of HIV/AIDS and household environment of pregnant women in Pune, India. Int J STD AIDS. 2003 Dec;14(12):835-9.

Sastry J, Pisal H, Sutar S, Kapadia-Kundu N, Joshi A, Suryavanshi N, Bharucha K, Shrotri A, Phadke M, Bollinger R, Shankar A. Optimizing the HIV/AIDS informed consent process in India. BMC Med. 2004 Aug 2;2(1):28.

Bharucha KE, Sastry J, Shrotri A, Sutar S, Joshi A, Bhore AV, Phadke MA, Bollinger RC, Shankar AV. Feasibility of voluntary counselling and testing services for HIV among pregnant women presenting in labour in Pune, India. Int J STD AIDS. 2005 Aug;16(8):553-5.

Gupta A, Nayak U, Ram M, Bhosale R, Patil S, Basavraj A, Kakrani A, Philip S, Desai D, Sastry J, Bollinger RC; Byramjee Jeejeebhoy Medical College-Johns Hopkins University Study Group. Postpartum tuberculosis incidence and mortality among HIV-infected women and their infants in Pune, India, 2002-2005. Clin Infect Dis. 2007 Jul 15;45(2):241-9. Epub 2007 Jun 4.

Gupta A, Gupte N, Sastry J, Bharucha KE, Bhosale R, Kulkarni P, Tripathy S, Nayak U, Phadke M, Bollinger RC; BJMC-JHU MIT Study Team. Mother-to-child transmission of HIV among women who chose not to exclusively breastfeed their infants in Pune, India. Indian J Med Res. 2007 Aug;126(2):131-4.

Gupta A, Gupte N, Bhosale R, Kakrani A, Kulkarni V, Nayak U, Thakar M, Sastry J, Bollinger RC; Byramji Jeejeebhoy Medical College-Johns Hopkins University Study Group. Low sensitivity of total lymphocyte count as a surrogate marker to identify antepartum and postpartum Indian women who require antiretroviral therapy. J Acquir Immune Defic Syndr. 2007 Nov 1;46(3):338-42.

Gupte N, Sastry J, Brookmeyer R, Phadke MA, Bhosale RA, Bollinger RC; BJ Medical College-National AIDS Research Institute-Johns; Hopkins Univeristy Mother-to-Child Study Group. Declining HIV infection rates among recently married primigravid women in Pune, India. J Acquir Immune Defic Syndr. 2007 Aug 15;45(5):570-3.

Sinha G, Choi TJ, Nayak U, Gupta A, Nair S, Gupte N, Bulakh PM, Sastry J, Deshmukh SD, Khandekar MM, Kulkarni V, Bhosale RA, Bharucha KE, Phadke MA, Kshirsagar AS, Bollinger RC; Maternal Infant Transmission Study in Pune, India. Clinically significant anemia in HIV-infected pregnant women in India is not a major barrier to zidovudine use for prevention of maternal-to-child transmission. J Acquir Immune Defic Syndr. 2007 Jun 1;45(2):210-7.

Other Publications:

Shankar AV, Sastry J, Erande A, Joshi A, Suryawanshi N, Phadke MA, Bollinger RC. Making the choice: the translation of global HIV and infant feeding policy to local practice among mothers in Pune, India. J Nutr. 2005 Apr;135(4):960-5.

Pisal H, Sutar S, Sastry J, Kapadia-Kundu N, Joshi A, Joshi M, Leslie J, Scotti L, Bharucha K, Suryavanshi N, Phadke M, Bollinger R, Shankar AV. Nurses' health education program in India increases HIV knowledge and reduces fear. J Assoc Nurses AIDS Care. 2007 Nov-Dec;18(6):32-43.

Publications indexed to this study:

Moorthy A, Gupta A, Bhosale R, Tripathy S, Sastry J, Kulkarni S, Thakar M, Bharadwaj R, Kagal A, Bhore AV, Patil S, Kulkarni V, Venkataramani V, Balasubramaniam U, Suryavanshi N, Ziemniak C, Gupte N, Bollinger R, Persaud D. Nevirapine resistance and breast-milk HIV transmission: effects of single and extended-dose nevirapine prophylaxis in subtype C HIV-infected infants. PLoS ONE. 2009;4(1):e4096. Epub 2009 Jan 1.

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.

Responsible Party:	Johns Hopkins School of Medicine ( Robert C. Bollinger MD, MPH )
Study ID Numbers:	5R01AI045462-04
Study First Received:	May 23, 2003
Last Updated:	July 30, 2008
ClinicalTrials.gov Identifier:	NCT00061321
Health Authority:	United States: Federal Government

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

Nevirapine
Pregnancy
Maternal to Infant transmission

Infant
Breastfeeding
HIV Seronegativity

Study placed in the following topic categories:

Virus Diseases
Nevirapine
Sexually Transmitted Diseases, Viral
HIV Infections

Sexually Transmitted Diseases
Acquired Immunodeficiency Syndrome
Retroviridae Infections
Immunologic Deficiency Syndromes

Additional relevant MeSH terms:

Anti-Infective Agents
RNA Virus Infections
Slow Virus Diseases
Anti-HIV Agents
Molecular Mechanisms of Pharmacological Action
Immune System Diseases
Enzyme Inhibitors
Infection

Antiviral Agents
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Therapeutic Uses
Lentivirus Infections
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on February 04, 2009