NNRTI Versus PI Containing Regimens for HIV Infected Women After They Have Taken Nevirapine to Prevent Mother-To-Child Transmission of HIV - Full Text View

Sponsors and Collaborators:	National Institute of Allergy and Infectious Diseases (NIAID) Adult AIDS Clinical Trials Group
Information provided by:	National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:	NCT00089505

Purpose

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are commonly included in anti-HIV drug regimens. However, HIV infected women who have previously taken the NNRTI nevirapine (NVP) for the prevention of mother-to-child transmission (MTCT) of HIV may not respond as well to NNRTIs as women who have never taken NVP. Another class of anti-HIV drugs, protease inhibitors (PIs), may be more effective for women who have previously taken NNRTIs. This study will compare the effectiveness of NNRTI- and PI-based regimens in women who have taken NVP for prevention of MTCT of HIV. This study will also compare regimens including an NNRTI with regimens including a PI in women who have never taken NVP.

Condition	Intervention	Phase
HIV Infections	Drug: Emtricitabine Drug: Emtricitabine/Tenofovir disoproxil fumarate Drug: Lopinavir/Ritonavir Drug: Nevirapine Drug: Tenofovir disoproxil fumarate	Phase III

MedlinePlus related topics: AIDS

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

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Optimal Combination Therapy After Nevirapine Exposure

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

Primary Outcome Measures:

Time from randomization to virologic failure or death [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Drug-resistant plasma virus as determined by virologic failure by bulk sequencing [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Tolerability and safety of drug regimens [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
CD4 count [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Time from randomization to HIV-related disease progression or death [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
NVP-associated rash or hepatitis [ Time Frame: Throughout study ] [ Designated as safety issue: Yes ]
Adherence to study drug regimens [ Time Frame: Throughout study ] [ Designated as safety issue: No ]
Measures of resource utilization [ Time Frame: Throughout study ] [ Designated as safety issue: No ]

Estimated Enrollment:	740
Study Start Date:	October 2005
Estimated Study Completion Date:	October 2009
Estimated Primary Completion Date:	October 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
A: Experimental FTC, TDF, and NVP daily the first 14 days, then twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue NVP will receive LPV/RTV twice daily plus two more NRTIs.	Drug: Emtricitabine 200 mg taken orally Drug: Emtricitabine/Tenofovir disoproxil fumarate 200/300 mg taken orally Drug: Lopinavir/Ritonavir 400/100 mg taken orally Drug: Nevirapine 200 mg taken orally Drug: Tenofovir disoproxil fumarate 300 mg taken orally
B: Experimental FTC and TDF daily and LPV/RTV twice daily. FTC and TDF may be replaced by the combination drug FTC/TDF. Participants who discontinue LPV/RTV will receive NVP daily for 14 days before taking it twice daily. plus 2 more NRTIs.	Drug: Emtricitabine 200 mg taken orally Drug: Emtricitabine/Tenofovir disoproxil fumarate 200/300 mg taken orally Drug: Lopinavir/Ritonavir 400/100 mg taken orally Drug: Tenofovir disoproxil fumarate 300 mg taken orally

Detailed Description:

NVP is the NNRTI of choice to prevent MTCT of HIV, especially in resource-limited settings. However, prolonged use of NVP may result in drug resistance, decreasing the efficacy of future anti-HIV regimens containing NVP. PIs are more expensive and cause different adverse effects than NNRTIs, but PI-containing regimens may be more effective than NNRTI-containing regimens in treating HIV infected women who previously took NVP for MTCT prophylaxis. This study will compare the efficacy of NNRTI- and PI-containing anti-HIV regimens in women who have previously taken NVP for MTCT of HIV and in women who have never taken NVP.

The study will last a minimum of 48 weeks. Participants will be grouped by previous NVP exposure: participants who have previously taken NVP as MTCT prophylaxis (Trial 1 participants), and participants who have never taken NVP (Trial 2 participants). Participants in each trial will be randomly assigned to one of two arms, A or B. At the start of the study, Arm A participants will receive emtricitabine (FTC) daily, tenofovir disoproxil fumarate (TDF) daily, and NVP daily for the first 14 days, then twice daily. Arm B participants will receive both FTC and TDF daily and lopinavir/ritonavir (LPV/RTV) twice daily. FTC and TDF may be replaced in either arm with the combination drug FTC/TDF.

If participants experience virologic failure, toxicity, or otherwise cannot tolerate their regimens, they will switch to a different regimen. Arm A participants will switch to a regimen of two or more nucleoside reverse transcriptase inhibitors (NRTIs) and LPV/RTV; Arm B participants will switch to a regimen of two or more NRTIs and NVP. Study visits will occur at entry and at Weeks 2, 4, 8, 12, 16, 24, 36, and 48. Visits will consist of a physical exam, medication assessment, and blood collection. Participants will be asked to complete adherence questionnaires at Weeks 4, 12, 24, and 28 and quality of life questionnaires at Weeks 24 and 48.

Eligibility

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

Criteria

Inclusion Criteria for All Participants:

HIV infected
CD4 count less than 200 cells/mm3
Willing to use acceptable forms of contraception
Parent or guardian willing to provide informed consent, if applicable
Planning to remain in the same geographical area of residence and are willing to attend study visits as required

Inclusion Criteria for Trial 1 Participants:

Previously received NVP for prevention of MTCT of HIV
Has documentation of all prior doses of NVP used for prevention of MTCT of HIV
Last dose of NVP for prevention of MTCT of HIV taken at least 6 months prior to study entry

Exclusion Criteria for All Participants:

Previously received any antiretrovirals, excluding NVP for MTCT prophylaxis for Trial 1 participants. Participants who have received up to 10 weeks of zidovudine alone and completed this course at least 6 months prior to study entry are not excluded.
Use of systemic cancer chemotherapy, systemic investigational agents, immunomodulators, or rifampin within 30 days of study entry
Known allergy or sensitivity to study drugs or their formulations
Any condition, including drug or alcohol abuse, that, in the opinion of the investigator, may interfere with adherence to study regimens
Serious illness requiring systemic treatment or hospitalization. Participants who complete therapy or are clinically stable on therapy for at least 30 days prior to study entry are not excluded.
Tuberculosis (TB) treatment within 30 days prior to study entry
Require certain medications
Involuntary incarceration in a correctional facility, prison, or jail for legal reasons or in a medical facility for treatment of either a psychiatric or physical illness
Pregnant or breastfeeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00089505

Locations

Botswana
Molepolole BHP Study Clinic, Scottish Livingstone Hospital
Bontleng Gaborone, Botswana
Botswana, Gaborone
The Gaborone BHP Study Clinic
Bontleng, Gaborone, Botswana
Kenya
KMRI / Walter Reed Project Clinical Research Center
Kericho, Kenya
Moi University International Clnical Trials Unit
Eldoret, Kenya, 30100
Malawi
University of North Carolina Project (UNC Project)
Lilongwe, Malawi, (265) 175-5056
Kamuzu Central Hospital, Tidziwe Centre
Lilongwe, Malawi
South Africa
University of Witwatersrand
Johannesburg, South Africa
Chris Hani Baragwanath Hospital, Johannesburg
Johannesburg, South Africa
South Africa, KZN
University of KwaZulu Natal
Durban, KZN, South Africa, 4013
Uganda
Joint Clinical Research Centre (JCRC)
Kampala, Uganda
Zambia
Centre for Infectious Disease Research in Zambia (CIDRZ)
Lusaka, Zambia
Zimbabwe, Harare
University of Zimbabwe
Avondale, Harare, Zimbabwe

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)

Adult AIDS Clinical Trials Group

Investigators

Study Chair:

Shahin Lockman, MD, MSc

Brigham and Women's Hospital and Infectious Diseases Division, Department of Immunology and Infectious Diseases, Harvard School of Public Health

More Information

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

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

Click here for more information about nucleoside reverse transcriptase inhibitors 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

Publications:

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

Eshleman SH, Mracna M, Guay LA, Deseyve M, Cunningham S, Mirochnick M, Musoke P, Fleming T, Glenn Fowler M, Mofenson LM, Mmiro F, Jackson JB. Selection and fading of resistance mutations in women and infants receiving nevirapine to prevent HIV-1 vertical transmission (HIVNET 012). AIDS. 2001 Oct 19;15(15):1951-7.

Harris M. Efficacy and durability of nevirapine in antiretroviral-experienced patients. J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S53-8. 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.

Nightingale S, Dabis F. Evidence behind the WHO guidelines: hospital care for children: what antiretroviral agents and regimens are effective in the prevention of mother-to-child transmission of HIV? J Trop Pediatr. 2006 Aug;52(4):235-8. Review. No abstract available.

Turner D, Wainberg MA. HIV transmission and primary drug resistance. AIDS Rev. 2006 Jan-Mar;8(1):17-23. Review.

Responsible Party:	DAIDS ( Rona Siskind )
Study ID Numbers:	ACTG A5208, OCTANE
Study First Received:	August 5, 2004
Last Updated:	January 5, 2009
ClinicalTrials.gov Identifier:	NCT00089505
Health Authority:	United States: Federal Government

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

Treatment Experienced
Treatment Naive
MTCT
HIV Seronegativity

Study placed in the following topic categories:

Sexually Transmitted Diseases, Viral
Acquired Immunodeficiency Syndrome
Immunologic Deficiency Syndromes
Virus Diseases
Nevirapine
Emtricitabine
Lopinavir

HIV Infections
Ritonavir
Sexually Transmitted Diseases
Tenofovir
Retroviridae Infections
Tenofovir disoproxil

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 January 16, 2009