NNRTI vs PI Regimens for HIV Infected Women After They Have Taken Nevirapine to Prevent Mother-To-Child HIV Transmission
NCT ID: NCT00089505
Last Updated: 2018-10-12
Study Results
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View full resultsBasic Information
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COMPLETED
PHASE3
745 participants
INTERVENTIONAL
2006-11-30
2011-02-28
Brief Summary
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Detailed Description
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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, NVP-containing arm(NVP/NVP for trial 1 participants and NoNVP/NVP for trial 2 participants) or PI-containing arm(NVP/LPV\_r for Trial 1 participants and NoNVP/LPV\_r for Trial 2 participants). At the start of the study, Arm NVP/NVP and NoNVP/NVP participants will receive emtricitabine (FTC) daily, tenofovir disoproxil fumarate (TDF) daily, and NVP daily for the first 14 days and then twice daily. Arm NVP/LPV\_r and NoNVP/LPV\_r 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 NVP/NVP and NoNVP/NVP participants will switch to a regimen of two or more nucleoside reverse transcriptase inhibitors (NRTIs) and LPV/RTV; Arm NVP/LPV\_r and NoNVP/LPV\_r 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, and then every 12 weeks thereafter. 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 every 24 weeks thereafter, and quality of life questionnaires at Weeks 24 and ever 24 weeks thereafter. Study drugs will be provided for all participants through 48 weeks after the final participant is randomized.
As per an amendment (dated April 13, 2009), participants will be asked to take part in an extension of this study. Enrollment in the extension is completely voluntary. The purpose of the extension is to monitor, in greater extent, the participants' health as they transition from study treatment to local, clinical care. During the study extension participants will not receive any medications through the study; it is expected that participants will receive their treatments through a local clinic.
Participants enrolling in the extension will enter the extension at the same time as their last visit in the current study. For the extension, participants will be asked to come back to the clinic two times for study visits: at 12 and 72 weeks after entry into the extension. Because there will be a long time between these study visits, participants will also be contacted by phone (or through some other means) close to 48 weeks after entry into the extension.
At each of these visits, participants will be asked about their health and medications, including current anti-HIV drugs. Participants will also be asked about any HIV care received outside of the study. As part of this study, investigators may need to review participants' non-study medical records and speak with their non-study care providers, to find out more about their HIV care and medical problems, and also to check results of lab tests.
During the study extension period, participants will have blood drawn and also be tested for pregnancy.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
NONE
Study Groups
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NVP/NVP
For participants who had SD NVP exposure prior to study entry. 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.
Emtricitabine
200 mg taken orally
Emtricitabine/Tenofovir disoproxil fumarate
200/300 mg taken orally
Nevirapine
200 mg taken orally
Tenofovir disoproxil fumarate
300 mg taken orally
NVP/LPV_r
For participants who had SD NVP exposure prior to study entry. 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.
Emtricitabine
200 mg taken orally
Emtricitabine/Tenofovir disoproxil fumarate
200/300 mg taken orally
Lopinavir/Ritonavir
400/100 mg taken orally
Tenofovir disoproxil fumarate
300 mg taken orally
NoNVP/NVP
For participants who did NOT have SD NVP exposure prior to study entry.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.
Emtricitabine
200 mg taken orally
Emtricitabine/Tenofovir disoproxil fumarate
200/300 mg taken orally
Nevirapine
200 mg taken orally
Tenofovir disoproxil fumarate
300 mg taken orally
NoNVP/LPV_r
For participants who did NOT have SD NVP exposure prior to study entry. 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.
Emtricitabine
200 mg taken orally
Emtricitabine/Tenofovir disoproxil fumarate
200/300 mg taken orally
Lopinavir/Ritonavir
400/100 mg taken orally
Tenofovir disoproxil fumarate
300 mg taken orally
Interventions
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Emtricitabine
200 mg taken orally
Emtricitabine/Tenofovir disoproxil fumarate
200/300 mg taken orally
Lopinavir/Ritonavir
400/100 mg taken orally
Nevirapine
200 mg taken orally
Tenofovir disoproxil fumarate
300 mg taken orally
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* CD4 count less than 200 cells/mm\^3 within 90 days prior to study entry
* Plasma HIV-1 RNA using standard Roche Amplicor HIV-1 Monitor Assay within 45 days prior to study entry
* the following laboratory values obtained within 45 days prior to study entry: absolute neutrophil count\>=750/mm\^3;Hemoglobin\>=7.0g/dL;platelet count\>=50000/mm\^3;aspartate aminotransferase (AST),Alanine aminotransferase (ALT), and alkaline phosphatase \<=2.5 x ULN; total bilirubin \<=2.5 x ULN
* Normal renal function within 45 days prior to study entry
* Willing to use acceptable forms of contraception
* Karnofsky performance score \>=70 on at least one occasion within 45 days prior to study entry
* 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
* 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
* Use of systemic cancer chemotherapy, systemic investigational agents, immunomodulators, or rifampin within 30 days of study entry
* Pregnant or breastfeeding
* 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
* Use of any prohibited medications within 30 days prior to study entry
* 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
13 Years
FEMALE
No
Sponsors
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National Institute of Allergy and Infectious Diseases (NIAID)
NIH
Advancing Clinical Therapeutics Globally for HIV/AIDS and Other Infections
NETWORK
Responsible Party
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Principal Investigators
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Shahin Lockman, MD, MSc
Role: STUDY_CHAIR
Brigham and Women's Hospital and Infectious Diseases Division, Department of Immunology and Infectious Diseases, Harvard School of Public Health
Frederick Sawe, MD
Role: STUDY_CHAIR
The Walter Reed Project/WRAIR
Locations
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The Gaborone BHP Study Clinic
Bontleng, Gaborone, Botswana
Molepolole BHP Study Clinic, Scottish Livingstone Hospital
Bontleng Gaborone, , Botswana
Moi University International Clnical Trials Unit
Eldoret, , Kenya
KMRI / Walter Reed Project Clinical Research Center
Kericho, , Kenya
University of North Carolina Project (UNC Project)
Lilongwe, , Malawi
University of KwaZulu Natal
Durban, KwaZulu-Natal, South Africa
Chris Hani Baragwanath Hospital, Johannesburg
Johannesburg, , South Africa
University of Witwatersrand
Johannesburg, , South Africa
Joint Clinical Research Centre (JCRC)
Kampala, , Uganda
Centre for Infectious Disease Research in Zambia (CIDRZ)
Lusaka, , Zambia
University of Zimbabwe
Avondale, Harare, Zimbabwe
Countries
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References
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Eshleman SH, Jackson JB. Nevirapine resistance after single dose prophylaxis. AIDS Rev. 2002 Apr-Jun;4(2):59-63.
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. doi: 10.1097/00002030-200110190-00006.
Harris M. Efficacy and durability of nevirapine in antiretroviral-experienced patients. J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S53-8. doi: 10.1097/00126334-200309011-00008.
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. doi: 10.1056/NEJMoa041305. Epub 2004 Jul 9.
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. doi: 10.1093/tropej/fml033. No abstract available.
Turner D, Wainberg MA. HIV transmission and primary drug resistance. AIDS Rev. 2006 Jan-Mar;8(1):17-23.
Boltz VF, Shao W, Bale MJ, Halvas EK, Luke B, McIntyre JA, Schooley RT, Lockman S, Currier JS, Sawe F, Hogg E, Hughes MD, Kearney MF, Coffin JM, Mellors JW. Linked dual-class HIV resistance mutations are associated with treatment failure. JCI Insight. 2019 Oct 3;4(19):e130118. doi: 10.1172/jci.insight.130118.
Asmelash A, Zheng Y, Kaloustian KW, Shaffer D, Sawe F, Ogwu A, Salata R, Currier J, Hughes MD, Lockman S. Predictors of suboptimal CD4 response among women achieving virologic suppression in a randomized antiretroviral treatment trial, Africa. BMC Infect Dis. 2014 Jun 17;14:331. doi: 10.1186/1471-2334-14-331.
Boltz VF, Bao Y, Lockman S, Halvas EK, Kearney MF, McIntyre JA, Schooley RT, Hughes MD, Coffin JM, Mellors JW; OCTANE/A5208 Team. Low-frequency nevirapine (NVP)-resistant HIV-1 variants are not associated with failure of antiretroviral therapy in women without prior exposure to single-dose NVP. J Infect Dis. 2014 Mar 1;209(5):703-10. doi: 10.1093/infdis/jit635. Epub 2014 Jan 16.
Lockman S, Hughes M, Sawe F, Zheng Y, McIntyre J, Chipato T, Asmelash A, Rassool M, Kimaiyo S, Shaffer D, Hosseinipour M, Mohapi L, Ssali F, Chibowa M, Amod F, Halvas E, Hogg E, Alston-Smith B, Smith L, Schooley R, Mellors J, Currier J; OCTANE (Optimal Combination Therapy After Nevirapine Exposure) ACTG A5208/OCTANE Study Team. Nevirapine- versus lopinavir/ritonavir-based initial therapy for HIV-1 infection among women in Africa: a randomized trial. PLoS Med. 2012;9(6):e1001236. doi: 10.1371/journal.pmed.1001236. Epub 2012 Jun 12.
Skinner-Adams TS, Butterworth AS, Porter KA, D'Amico R, Sawe F, Shaffer D, Siika A, Hosseinipour MC, Stringer E, Currier JS, Chipato T, Salata R, Lockman S, Eron JJ, Meshnick SR, McCarthy JS. The frequency of malaria is similar among women receiving either lopinavir/ritonavir or nevirapine-based antiretroviral treatment. PLoS One. 2012;7(4):e34399. doi: 10.1371/journal.pone.0034399. Epub 2012 Apr 3.
Dong BJ, Zheng Y, Hughes MD, Frymoyer A, Verotta D, Lizak P, Sawe F, Currier JS, Lockman S, Aweeka FT; AIDS Clinical Trials Group Study 5208 Team. Nevirapine pharmacokinetics and risk of rash and hepatitis among HIV-infected sub-Saharan African women. AIDS. 2012 Apr 24;26(7):833-41. doi: 10.1097/QAD.0b013e328351a521.
Porter KA, Cole SR, Eron JJ Jr, Zheng Y, Hughes MD, Lockman S, Poole C, Skinner-Adams TS, Hosseinipour M, Shaffer D, D'Amico R, Sawe FK, Siika A, Stringer E, Currier JS, Chipato T, Salata R, McCarthy JS, Meshnick SR. HIV-1 protease inhibitors and clinical malaria: a secondary analysis of the AIDS Clinical Trials Group A5208 study. Antimicrob Agents Chemother. 2012 Feb;56(2):995-1000. doi: 10.1128/AAC.05322-11. Epub 2011 Nov 28.
Lockman S, Hughes MD, McIntyre J, Zheng Y, Chipato T, Conradie F, Sawe F, Asmelash A, Hosseinipour MC, Mohapi L, Stringer E, Mngqibisa R, Siika A, Atwine D, Hakim J, Shaffer D, Kanyama C, Wools-Kaloustian K, Salata RA, Hogg E, Alston-Smith B, Walawander A, Purcelle-Smith E, Eshleman S, Rooney J, Rahim S, Mellors JW, Schooley RT, Currier JS; OCTANE A5208 Study Team. Antiretroviral therapies in women after single-dose nevirapine exposure. N Engl J Med. 2010 Oct 14;363(16):1499-509. doi: 10.1056/NEJMoa0906626.
Other Identifiers
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OCTANE
Identifier Type: -
Identifier Source: secondary_id
ACTG A5208
Identifier Type: -
Identifier Source: org_study_id
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