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

NCT ID: NCT00099632

Last Updated: 2021-11-04

Study Results

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

484 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Study Completion Date

2011-11-30

Brief Summary

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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.

Detailed Description

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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 also compared the effectiveness of short-term versus long-term ART in discouraging the development of maternal NVP resistance.

Some mothers in this study received ZDV monotherapy prior to SD NVP administration; initiation of ZDV monotherapy was at the discretion of the site investigator and was be provided by this study. Randomization was stratified by receipt of ZDV monotherapy during the pregnancy.

Prior to labor, mothers were randomly assigned to receive SD NVP at the onset of labor and one of three postpartum ART regimens: 3TC/ZDV, FTC/TDF, and LPV/r. In addition, participants were randomly assigned to receive 7 or 21 days of their assigned postpartum treatment.

Mothers were followed for 96 weeks following delivery; there were 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 occurred. Additional physical exams occurred on Day 1 and Weeks 1 and 3. Blood collection occurred at 8 study visits between Weeks 3 and 96. Infants were followed for up to 96 weeks after birth; there were 8 study visits for infants during the study. Infants who had ever been breastfed had 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 occurred at each infant visit. Mothers and infants could be prescribed continuing ART, but such ART was be provided by this study.

Conditions

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HIV Infections

Keywords

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Treatment Naive

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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7-day 3TC/ZDV

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

Group Type EXPERIMENTAL

Lamivudine/Zidovudine

Intervention Type DRUG

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

single dose Nevirapine

Intervention Type DRUG

one 200 mg tablet taken orally

21-day 3TC/ZDV

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

Group Type EXPERIMENTAL

Lamivudine/Zidovudine

Intervention Type DRUG

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

single dose Nevirapine

Intervention Type DRUG

one 200 mg tablet taken orally

7-day FTC/TDF

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

Group Type EXPERIMENTAL

Emtricitabine/Tenofovir Disoproxil Fumarate

Intervention Type DRUG

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

single dose Nevirapine

Intervention Type DRUG

one 200 mg tablet taken orally

21-day FTC/TDF

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

Group Type EXPERIMENTAL

Emtricitabine/Tenofovir Disoproxil Fumarate

Intervention Type DRUG

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

single dose Nevirapine

Intervention Type DRUG

one 200 mg tablet taken orally

7-day LPV/r

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

Group Type EXPERIMENTAL

Lopinavir/Ritonavir

Intervention Type DRUG

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

single dose Nevirapine

Intervention Type DRUG

one 200 mg tablet taken orally

21-day LPV/r

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

Group Type EXPERIMENTAL

Lopinavir/Ritonavir

Intervention Type DRUG

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

single dose Nevirapine

Intervention Type DRUG

one 200 mg tablet taken orally

Interventions

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Emtricitabine/Tenofovir Disoproxil Fumarate

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

Intervention Type DRUG

Lamivudine/Zidovudine

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

Intervention Type DRUG

Lopinavir/Ritonavir

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

Intervention Type DRUG

single dose Nevirapine

one 200 mg tablet taken orally

Intervention Type DRUG

Other Intervention Names

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FTC/TDF 3TC/ZDV LPV/r SD NVP

Eligibility Criteria

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Inclusion Criteria

* 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

Exclusion Criteria

* 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
Minimum Eligible Age

13 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jane Hitti, MD, MPH

Role: STUDY_CHAIR

Department of Obstetrics/Gynecology, Perinatal Medicine, University of Washington Medical Center

Deborah McMahon, MD

Role: STUDY_CHAIR

Division of Infectious Diseases, Department of Medicine, University of Pittsburgh

Locations

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

Port-au-Prince, , Haiti

Site Status

Byramjee Jeejeebhoy Government Medical College CRS

Pune, Maharashtra, India

Site Status

Chennai Antiviral Research and Treatment (CART) CRS

Chennai, Tamil Nadu, India

Site Status

Blantyre CRS

Blantyre, , Malawi

Site Status

Wits Helen Joseph Hospital CRS (Wits HJH CRS)

Johannesburg, Gauteng, South Africa

Site Status

Durban International CRS

Westville, KwaZulu-Natal, South Africa

Site Status

Kilimanjaro Christian Medical CRS

Moshi, , Tanzania

Site Status

Joint Clinical Research Center (JCRC)/Kampala CRS

Kampala, , Uganda

Site Status

Countries

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Haiti India Malawi South Africa Tanzania Uganda

References

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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.

Reference Type BACKGROUND
PMID: 12134253 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 12152519 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15247339 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15627034 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14562860 (View on PubMed)

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

Reference Type 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

Reference Type 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.

Reference Type DERIVED
PMID: 23300238 (View on PubMed)

Other Identifiers

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10127

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG A5207

Identifier Type: -

Identifier Source: secondary_id

MOMS

Identifier Type: -

Identifier Source: secondary_id

A5207

Identifier Type: -

Identifier Source: org_study_id