Comparison of Three Anti-HIV Regimens to Prevent Nevirapine Resistance in Women Who Take Nevirapine During Pregnancy - 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:	NCT00099632

Purpose

HIV infected pregnant women may take single-dose nevirapine (SD NVP) prior to giving birth to prevent mother-to-child transmission (MTCT) of HIV. However, SD NVP may cause NVP resistance in the mother, potentially ruling out some treatment options in the future. The purpose of this study is to determine which of three anti-HIV drug regimens most effectively reduces the development of maternal NVP resistance in HIV infected pregnant women. The effectiveness of short-term (7 day therapy) versus long-term (21-day therapy) regimens will also be compared.

The study hypotheses are: 1) intrapartum SD NVP with a 21-day course of antiretroviral therapy (ART) results in less frequent selection of NVP-resistant HIV-1 variants than intrapartum SD NVP with a 7-day course of ART, and 2) a 7- or 21-day course of lamivudine/zidovudine (3TC/ZDV), emtricitabine/tenofovir disoproxil fumarate (FTC/TDF), or lopinavir/ritonavir (LPV/r) following SD NVP will not select nucleoside reverse transcriptase inhibitor (NRTI)- or protease inhibitor (PI)- resistant HIV-1 variants.

Condition	Intervention	Phase
HIV Infections	Drug: Emtricitabine/tenofovir disoproxil fumarate Drug: Lamivudine/zidovudine Drug: Lopinavir/ritonavir Drug: Nevirapine	Phase II

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Maintaining Options for Mothers Study (MOMS): A Phase II Randomized Comparison of Three Antiretroviral Strategies Administered for 7 or 21 Days to Reduce the Emergence of Nevirapine Resistant HIV-1 Following a Single Intrapartum Dose of Nevirapine

Resource links provided by NLM:

MedlinePlus related topics: AIDS AIDS and Pregnancy

Drug Information available for: Zidovudine Nevirapine Lamivudine Tenofovir Ritonavir Lopinavir Tenofovir disoproxil Tenofovir Disoproxil Fumarate

U.S. FDA Resources

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

Primary Outcome Measures:

Proportion of participants with new circulating nonnucleoside reverse transcriptase inhibitor (NNRTI)-resistant variants as detected by standard composite (bulk) genotyping [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Proportion of participants with new circulating NRTI- and new PI- resistant variants [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Proportion of participants with new circulating NNRTI-, NRTI-, or PI- resistant virus [ Time Frame: Through Week 24 ] [ Designated as safety issue: No ]
Time from emergence of new circulating NNRTI-, NRTI-, or PI- resistant virus to a reduction to less than 2% [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Pattern of emergence of new circulating resistance mutations [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Change in viral load [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Grade 3 and higher adverse events and any grade adverse event that leads to a treatment change [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Time from delivery to early permanent discontinuation of randomized therapy [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
HIV-1 infection status of the infant [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Pharmacokinetic parameters [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	420
Study Start Date:	January 2007
Estimated Study Completion Date:	January 2010
Estimated Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
1: Experimental Prior to labor, participants will be randomly assigned to receive NVP at the onset of labor. All participants in Group 1 will receive 3TC/ZDV after delivery for the duration of the trial unless otherwise specified by the investigator	Drug: Lamivudine/zidovudine 150 mg lamivudine/300 mg zidovudine tablets taken orally daily Drug: Nevirapine 200 mg tablet taken orally daily for the first 14 days before taking 200 mg tablet orally twice daily
2: Experimental Prior to labor, participants will be randomly assigned to receive NVP at the onset of labor. All participants in Group 2 will receive FTC/TDF after delivery for the duration of the trial unless otherwise specified by the investigator	Drug: Emtricitabine/tenofovir disoproxil fumarate 200 mg emtricitabine/300 mg tenofovir disoproxil fumarate tablet taken orally daily Drug: Nevirapine 200 mg tablet taken orally daily for the first 14 days before taking 200 mg tablet orally twice daily
3: Experimental Prior to labor, participants will be randomly assigned to receive NVP at the onset of labor. All participants in Group 3 will receive LPV/r after delivery for the duration of the trial unless otherwise specified by the investigator	Drug: Lopinavir/ritonavir 200 mg lopinavir/50 mg ritonavir tablet taken orally daily Drug: Nevirapine 200 mg tablet taken orally daily for the first 14 days before taking 200 mg tablet orally twice daily

Detailed Description:

The World Health Organization (WHO) currently recommends giving HIV infected pregnant women SD NVP prior to birth to prevent MTCT of HIV. However, a major disadvantage of giving SD NVP is the potential for maternal development of NVP resistance and additional resistance to other nonnucleoside reverse transcriptase inhibitors (NNRTI) in the mother; as a result, future treatment options may be limited for these HIV infected women. The purpose of the study is to determine which of three ART regimens most effectively deters the development of maternal NVP resistance in HIV infected pregnant women postpartum. This study will also compare the effectiveness of short-term versus long-term ART in discouraging the development of maternal NVP resistance.

Some mothers in this study may receive ZDV monotherapy prior to SD NVP administration; initiation of ZDV monotherapy will be at the discretion of the site investigator and will not be provided by this study. Prior to labor, mothers will be randomly assigned to receive SD NVP at the onset of labor and one of three postpartum ART regimens: Group A will receive 3TC/ZDV; Group B will receive FTC/TDF; and Group C will receive LPV/r. In addition, participants will be randomly assigned to receive 7 or 21 days of their assigned postpartum treatment.

Mothers will be followed for 96 weeks following delivery; there will be 11 study visits for mothers during the study. At the onset of labor, medical and medication history, a targeted physical exam, and an obstetrical exam will occur. Additional physical exams will occur on Day 1 and Weeks 1 and 3. Blood collection will occur at 8 study visits between Weeks 3 and 96. Infants will be followed for up to 96 weeks after birth; there will be 8 study visits for infants during the study. Infants who have ever been breastfed will have study visits at Weeks 16, 24, 48, and 96, and at about 1 and 2 years of age. A physical exam, medication history, and blood collection will occur at each infant visit. Mothers and infants may be prescribed continuing ART, but such ART will not be provided by this study. Breastfeeding mothers are encouraged to enroll their infants in ACTG A5190, an observational study of the effects of maternal ART on infants born to HIV infected women.

Eligibility

Ages Eligible for Study:	13 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria for Mothers:

HIV infected
CD4 count 250 cells/mm3 or greater within 30 days of study entry
Pregnant with a viable fetus at 28 to 38 weeks of pregnancy
Willing to give birth to baby in a hospital or clinic
Written informed consent from parent or guardian, if applicable

Exclusion Criteria for Mothers:

Any ART, including single-dose NVP, prior to study entry. Mothers who receive ZDV monotherapy prior to labor under the supervision of the site investigator are not excluded.
Known allergy or sensitivity to study drugs or their formulations
Current drug or alcohol abuse that may interfere with the study
Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 14 days prior to study entry are not excluded.
Hepatitis B surface antigen positive within 180 days prior to study entry
Active tuberculosis infection requiring treatment
Prior enrollment in this study
Expect to use ART, except ZDV monotherapy, prior to onset of labor
Expect to use ART other than study medications from delivery to 9 weeks postpartum
Require certain medications

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00099632

Locations

Haiti
Institut National de Laboratoire et de Recherches Les Centres GHESKIO	Recruiting
Port-au-Prince, Haiti
Contact: Patrice Severe, MD 509 222 2241 patsevere@gheskio.org
India
YRG Center for AIDS Research and Education	Recruiting
Chennai, India, 60001-7
Contact: Aylur Kailasom Srikrishnan, MBA 91 442 254 2929 krish@yrgcare.org
India, Maharashtra
BJ Medical College CRS	Not yet recruiting
Pune, Maharashtra, India, 411001
Contact: Nishi Suryavanshi, PhD 91-020-26052419 nishi@jhumitpune.com
Principal Investigator: Gowri Sastry, MD, MPH
Malawi
Univ. of Malawi	Recruiting
Blantyre, Malawi
Contact: Sima TM Berendes, MPH (265) 018-60132 sberendes@jhu.medcol.mw
South Africa
University of Witwatersrand, CTU	Recruiting
Johannesburg, South Africa
Contact: Pauline S. Vunandlala, BSc 27 11 717 2810 idsyndicate@witshealth.co.za
Principal Investigator: Ian M. Sanne, MD, FCP
University of KwaZulu-Natal, Nelson Mandela School of Medicine	Recruiting
Durban, South Africa, 4013 SF
Contact: Fawzia Williamson 27 31 260 4365 amodf1@nu.ac.za
Principal Investigator: Umesh Gangaram Lalloo, MD

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Investigators

Study Chair:	Gyrlande Bois, MD	Institute National de Laboratoire et de Recherches, Les Centres GHESKIO
Study Chair:	Jane Hitti, MD, MPH	Department of Obstetrics/Gynecology, Perinatal Medicine, University of Washington Medical Center
Study Chair:	Deborah McMahon, MD	Division of Infectious Diseases, Department of Medicine, University of Pittsburgh

More Information

Additional Information:

Click here for more information about emtricitabine/tenofovir disoproxil fumarate This link exits the ClinicalTrials.gov site

Click here for more information about lamivudine/zidovudine This link exits the ClinicalTrials.gov site

Click here for more information about lopinavir/ritonavir This link exits the ClinicalTrials.gov site

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

Click here for more information about ACTG A5910 This link exits the ClinicalTrials.gov site

Click here for more information on HIV and pregnancy This link exits the ClinicalTrials.gov site

Haga clic aquí para más información acerca del VIH y el embarazo This link exits the ClinicalTrials.gov site

Click here for more information on medication regimens for HIV positive pregnant women This link exits the ClinicalTrials.gov site

Haga clic aquí para ver información sobre este ensayo clínico en español. This link exits the ClinicalTrials.gov site

Haga clic aquí para más información acerca de los tratamientos para las mujeres embarazadas infectadas por el VIH This link exits the ClinicalTrials.gov site

Publications:

Cunningham CK, Chaix ML, Rekacewicz C, Britto P, Rouzioux C, Gelber RD, Dorenbaum A, Delfraissy JF, Bazin B, Mofenson L, Sullivan JL. Development of resistance mutations in women receiving standard antiretroviral therapy who received intrapartum nevirapine to prevent perinatal human immunodeficiency virus type 1 transmission: a substudy of pediatric AIDS clinical trials group protocol 316. J Infect Dis. 2002 Jul 15;186(2):181-8.

Eshleman SH, Jackson JB. Nevirapine resistance after single dose prophylaxis. AIDS Rev. 2002 Apr-Jun;4(2):59-63. Review.

Jourdain G, Ngo-Giang-Huong N, Le Coeur S, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M; Perinatal HIV Prevention Trial Group. Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med. 2004 Jul 15;351(3):229-40. Epub 2004 Jul 09.

Lyons FE, Coughlan S, Byrne CM, Hopkins SM, Hall WW, Mulcahy FM. Emergence of antiretroviral resistance in HIV-positive women receiving combination antiretroviral therapy in pregnancy. AIDS. 2005 Jan 3;19(1):63-7.

Sullivan JL. Prevention of mother-to-child transmission of HIV--what next? J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S67-72. Review.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5207, MOMS
Study First Received:	December 17, 2004
Last Updated:	February 6, 2009
ClinicalTrials.gov Identifier:	NCT00099632 History of Changes
Health Authority:	United States: Food and Drug Administration

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

Treatment Naive

Study placed in the following topic categories:

Antimetabolites
Anti-Infective Agents
HIV Protease Inhibitors
Sexually Transmitted Diseases, Viral
Anti-HIV Agents
Acquired Immunodeficiency Syndrome
Zidovudine
Lamivudine
Antiviral Agents
Immunologic Deficiency Syndromes
Protease Inhibitors
Reverse Transcriptase Inhibitors

Virus Diseases
Nevirapine
Anti-Retroviral Agents
Lopinavir
Emtricitabine
HIV Infections
Ritonavir
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

Additional relevant MeSH terms:

Antimetabolites
Anti-Infective Agents
Sexually Transmitted Diseases, Viral
Slow Virus Diseases
Molecular Mechanisms of Pharmacological Action
Zidovudine
Lamivudine
Infection
Reverse Transcriptase Inhibitors
Anti-Retroviral Agents
Lopinavir
Emtricitabine
Therapeutic Uses
Tenofovir
Retroviridae Infections

Nucleic Acid Synthesis Inhibitors
Tenofovir disoproxil
HIV Protease Inhibitors
RNA Virus Infections
Anti-HIV Agents
Immune System Diseases
Acquired Immunodeficiency Syndrome
Enzyme Inhibitors
Antiviral Agents
Immunologic Deficiency Syndromes
Pharmacologic Actions
Protease Inhibitors
Virus Diseases
Nevirapine
HIV Infections

ClinicalTrials.gov processed this record on September 11, 2009