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

NCT00099632 | Completed Phase 2 Results DMC

• 4 other identifiers: A520710127ACTG A5207MOMS
• Study Type: interventional
• Target: 484
• Locations: 6 countries
• Sites: 8

Brief Summary

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.

Conditions

HIV Infections

Keywords

Treatment Naive

Outcome Measures

Primary Outcomes (1)

• Number of Participants With New Circulating Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)-Resistant Variants as Detected by Standard Composite (Bulk) Genotyping

  For the 7-day treatment duration group, only the genotype results from weeks 3 and 7 contributed to the primary endpoint; For the 21-day treatment duration groups, only the genotype results from weeks 5 and 9 contributed to primary endpoint. 10 participants who did not have resistance samples available were excluded from the primary endpoint analysis.

  2 and 6 weeks after completion of treatment

Secondary Outcomes (4)

• Number of Participants With New Circulating NRTI-resistant Variants Detected by Standard Composite (Bulk) Genotyping.

  2 and 6 weeks after completion of treatment

• Number of Participants With New PI-resistant Variants as Detected by Standard Composite (Bulk) Genotyping.

  2 and 6 weeks after completion of treatment

• Severe (Grade 3) and Higher Adverse Events and Any Grade Adverse Event That Leads to a Treatment Change From First Day of Study Treatment to Week 12

  From first day of study treatment to week 12

• Number of Participants Who Discontinued Study Treatment Prematurely

  From first day of study treatment to last day of study treatment (up to 21 days)

Study Arms (6)

7-day 3TC/ZDV

EXPERIMENTAL

SD NVP and 3TC/ZDV provided at onset of active labor, followed by 7 days of 3TC/ZDV.

Drug: Lamivudine/Zidovudine; Drug: single dose Nevirapine

21-day 3TC/ZDV

EXPERIMENTAL

SD NVP and 3TC/ZDV provided at onset of active labor, followed by 21 days of 3TC/ZDV.

Drug: Lamivudine/Zidovudine; Drug: single dose Nevirapine

7-day FTC/TDF

EXPERIMENTAL

SD NVP and FTC/TDF provided at onset of active labor, followed by 7 days of FTC/TDF.

Drug: Emtricitabine/Tenofovir Disoproxil Fumarate; Drug: single dose Nevirapine

21-day FTC/TDF

EXPERIMENTAL

SD NVP and FTC/TDF provided at onset of active labor, followed by 21 days of FTC/TDF.

Drug: Emtricitabine/Tenofovir Disoproxil Fumarate; Drug: single dose Nevirapine

7-day LPV/r

EXPERIMENTAL

SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r.

Drug: Lopinavir/Ritonavir; Drug: single dose Nevirapine

21-day LPV/r

EXPERIMENTAL

SD NVP and LPV/r provided at onset of active labor, followed by 7 days of LPV/r

Drug: Lopinavir/Ritonavir; Drug: single dose Nevirapine

Interventions

Emtricitabine/Tenofovir Disoproxil Fumarate DRUG

200mg/300mg as one tablet taken orally once daily

Also known as: FTC/TDF

21-day FTC/TDF; 7-day FTC/TDF

Lamivudine/Zidovudine DRUG

150mg/300mg as one tablet taken orally twice daily

Also known as: 3TC/ZDV

21-day 3TC/ZDV; 7-day 3TC/ZDV

Lopinavir/Ritonavir DRUG

133.3mg/33.3mg as three capsules taken orally twice daily

Also known as: LPV/r

21-day LPV/r; 7-day LPV/r

single dose Nevirapine DRUG

one 200 mg tablet taken orally

Also known as: SD NVP

21-day 3TC/ZDV; 21-day FTC/TDF; 21-day LPV/r; 7-day 3TC/ZDV; 7-day FTC/TDF; 7-day LPV/r

Eligibility Criteria

• Age: 13 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 infected
• CD4 count 250 cells/mm3 or greater within 30 days of study entry
• The following laboratory values obtained within 30 days prior to study entry: absolute neutropil count \>= 750/mm3; hemoglobin \>= 8.0 g/dL; platelet count \>= 50,000/mm3; calculated creatinine clearance (Cockcroft-Gault formula) \> 60 mL/min; AST(SGOT) and ALT(SGPT) \< 5 x ULN; total bilirubin \< 1.5 X ULN.
• Pregnant with a viable fetus at 28 to 38 weeks gestation at study entry.
• Willing to give birth to baby in a hospital or clinic
• Written informed consent from parent or guardian, if applicable

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (8)

Les Centres GHESKIO Clinical Research Site (GHESKIO-INLR) CRS

Port-au-Prince, 6110, Haiti

Location

Byramjee Jeejeebhoy Government Medical College CRS

Pune, Maharashtra, 411001, India

Location

Chennai Antiviral Research and Treatment (CART) CRS

Chennai, Tamil Nadu, 600113, India

Location

Blantyre CRS

Blantyre, Malawi

Location

Wits Helen Joseph Hospital CRS (Wits HJH CRS)

Johannesburg, Gauteng, 2092, South Africa

Location

Durban International CRS

Westville, KwaZulu-Natal, 3610, South Africa

Location

Kilimanjaro Christian Medical CRS

Moshi, Tanzania

Location

Joint Clinical Research Center (JCRC)/Kampala CRS

Kampala, Uganda

Location

Related Publications (8)

• 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. doi: 10.1086/341300. Epub 2002 Jun 26.

  PMID: 12134253 BACKGROUND

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

  PMID: 12152519 BACKGROUND

• 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.

  PMID: 15247339 BACKGROUND

• 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. doi: 10.1097/00002030-200501030-00007.

  PMID: 15627034 BACKGROUND

• Sullivan JL. Prevention of mother-to-child transmission of HIV--what next? J Acquir Immune Defic Syndr. 2003 Sep;34 Suppl 1:S67-72. doi: 10.1097/00126334-200309011-00010.

  PMID: 14562860 BACKGROUND

• McMahon D, Noel F, Zheng L, Kabanda J, Halvas E, Taulo F, Kumarasamy N, Wallis C, Hughes M, Mellors J. Suppression of NVP Resistance with 7- vs 21-day ARV Regimens after Single-dose NVP: Results of A5207. Presented at 18th Conference on Retroviruses & Opportunistic Infections (CROI 11) on 03/01/2011 at Boston, MA

  RESULT

• Hong F, Halvas E, Chan E, Zheng L, Hughes M, Hitti J, McMahon D, Mellors J. Suppression of Minor NVP-Resistant Variants With 7- vs. 21-Day Antiretroviral Regimens After Single Dose Nevirapine. Presented at 20th Anniversary of the International Workshop on HIV & Hepatitis Virus Drug Resistance and Curative Strategies on Jun 9, 2011, Los Cabos, Mexico

  RESULT

• McMahon DK, Zheng L, Hitti J, Chan ES, Halvas EK, Hong F, Kabanda J, Taulo F, Kumarasamy N, Bonhomme J, Wallis CL, Klingman KL, Hughes MD, Mellors JW. Greater suppression of nevirapine resistance with 21- vs 7-day antiretroviral regimens after intrapartum single-dose nevirapine for prevention of mother-to-child transmission of HIV. Clin Infect Dis. 2013 Apr;56(7):1044-51. doi: 10.1093/cid/cis1219. Epub 2013 Jan 8.

  PMID: 23300238 DERIVED

MeSH Terms

Conditions

HIV Infections

Interventions

Emtricitabine, Tenofovir Disoproxil Fumarate Drug Combination; lamivudine, zidovudine drug combination; Lopinavir; Nevirapine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Tenofovir; Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Emtricitabine; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides; Drug Combinations; Pharmaceutical Preparations; Pyrimidinones; Pyridines

Results Point of Contact

• Title: ACTG Clinicaltrials.gov Coordinator
• Organization: ACTG Network Coordinating Center, Social and Scientific Systems, Inc.

ACTGCT.Gov@s-3.com

(301) 628-3313

Study Officials

• 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

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2004
• First Posted: December 20, 2004
• Study Start: March 1, 2006
• Primary Completion: April 1, 2010
• Study Completion: November 1, 2011
• Last Updated: November 4, 2021
• Results First Posted: January 19, 2012

Record last verified: 2019-01

Locations

MA (1); ZA (2); HA (1); UG (1); IN (2); TA (1)