One Month Dual Antiretroviral Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine

NCT ID: NCT00142337

Last Updated: 2012-01-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 244 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-12-31
• Study Completion Date: 2009-02-28

Brief Summary

The purpose of this study is to determine whether providing zidovudine (ZDV) and didanosine (ddI) during labor and for one month postpartum can reduce the selection of nevirapine (NVP) resistance mutations postpartum in women who received a single dose of nevirapine during labor and standard ZDV prophylaxis for the prevention of mother to child transmission of HIV.

Detailed Description

A single nevirapine dose to the mother, with or without a dose to the child, in addition to oral ZDV prophylaxis starting from 28 weeks gestation has been proven to be highly effective in reducing further mother-to-child HIV transmission (PMTCT).

However, post exposure nevirapine resistance mutations are observed in the mother's viral population. These mutations detectable very early after exposure tend to disappear over time.

Nevertheless, they may be associated with decrease in efficacy of non-nucleoside reverse transcriptase inhibitor (NNRTI) containing regimens subsequently given to the women for their own health.

Therefore, there is a need for research to prevent selection of resistance in the first place or to overcome the resistance in subsequent treatment of the infected mother or infant.

Nevirapine plasma levels above IC50 have been detected in women exposed to a single 200 mg dose of nevirapine in a significant number of women during the third week postpartum.

We hypothesize that giving ZDV+ddI to women exposed to nevirapine for one month as soon as possible after exposure may prevent the selection of nevirapine resistance mutations.

Conditions

HIV Infections

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Interventions

Zidovudine (ZDV)

Zidovudine 300 mg, twice daily, for one month postpartum. Note: after July 03, 2005, all women received 200 mg, twice daily, for the same duration.

Intervention Type: DRUG

Didanosine (ddI)

250 mg ddI-EC (400 mg if body weight \>60 kg) once daily, starting at the onset of labor and for one month postpartum

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Meet all pre-entry criteria;
• Consent to participate and to be followed for the duration of the study;
• Present the following laboratory values within 14 days prior to inclusion:

• Hemoglobin > 8.0 mg/dl
• Absolute neutrophil count > 1000 cells/mm3
• Platelets > 100,000 cells/mm3
• Serum creatinine < 1.5 mg/dl (women with a serum creatinine > 1.5 mg/dl must have a measured eight-hour urine creatinine clearance > 70 ml/min)
• SGPT less than 10 times the upper limit of normal
• Amylase less than 150/L IU (this upper limit may change slightly depending on the normal range at the hospital laboratory).

Exclusion Criteria

• Evidence of pre-existing fetal anomalies incompatible with life;
• Known hypersensitivity to any benzodiazepine or to NVP;
• Receipt of antiretroviral agent other than ZDV;
• Receipt of non-allowed concomitant treatment or contraindication to ddI
• Concurrent participation in another clinical trial;
• Women with a CD4 count <200/µL or history of oral candidiasis if they are not receiving pneumocystis carinii pneumonia (PCP) prophylaxis
• Any other contra-indicated drugs during ZDV+ddI treatment for the mother as well as the child (Contra-indicated drugs such as gancyclovir, isoniazid, linezolid, ethambutol, rifabutin, cidofovir are not allowed during the ZDV ddI treatment after delivery in order to prevent pharmacological interactions or overlapping toxicities.)

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

Institut de Recherche pour le Developpement

OTHER_GOV

Sponsor Role: lead

Responsible Party

Marc Lallemant

Senior Researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marc Lallemant, MD

Role: PRINCIPAL_INVESTIGATOR

Institut de Recherche pour le Developpement

Locations

Bhumibol Adulyadej Hospital

Bangkok, Bangkok, Thailand

Health Promotion Hospital Regional Center I

Bangkok, Bangkok, Thailand

Chacheongsao Hospital

Muang, Chacheongsao, Thailand

Prapokklao Hospital

Muang, Changwat Chanthaburi, Thailand

Mae Chan Hospital

Mae Chan, Changwat Chiang Rai, Thailand

Mae Sai Hospital

Mae Sai, Changwat Chiang Rai, Thailand

Phan Hospital

Phan, Changwat Chiang Rai, Thailand

Somdej Pranangchao Sirikit Hospital

Chon Buri, Changwat Chon Buri, Thailand

Chonburi Hospital

Muang, Changwat Chon Buri, Thailand

Kalasin Hospital

Muang, Changwat Kalasin, Thailand

Kranuan Crown Prince Hospital

Kranuan, Changwat Khon Kaen, Thailand

Khon Kaen Hospital

Muang, Changwat Khon Kaen, Thailand

Regional Health Promotion Centre 6, Khon Kaen

Muang, Changwat Khon Kaen, Thailand

Srinagarind Hospital

Muang, Changwat Khon Kaen, Thailand

Lampang Hospital

Muang, Changwat Lampang, Thailand

Nong Khai Hospital

Muang, Changwat Nong Khai, Thailand

Pranangklao Hospital

Muang, Changwat Nonthaburi, Thailand

Chiang Kham Hospital

Chiang Kham, Changwat Phayao, Thailand

Buddhachinaraj Hospital

Muang, Changwat Phitsanulok, Thailand

Ratchaburi Hospital

Muang, Changwat Ratchaburi, Thailand

Rayong Hospital

Muang, Changwat Rayong, Thailand

Roi-et Hospital

Muang, Changwat Roi Et, Thailand

Hat Yai Hospital

Hat Yai, Changwat Songkhla, Thailand

Nakornping Hospital

Mae Rim, Chiang Mai, Thailand

Health Promotion Center Region 10

Muang, Chiang Mai, Thailand

Lamphun Hospital

Munag, Chiang Mai, Thailand

Chiangrai Prachanukroh Hospital

Muang, Chiangrai, Thailand

Phaholpolphayuhasena Hospital

Munag, Kanchanaburi, Thailand

Nakhonpathom Hospital

Muang, Nakhonpathom, Thailand

Maharaj Nakornratchasrima Hospital

Muang, Nakornratchasrima, Thailand

Samutprakarn Hospital

Samutprakarn, Samutprakarn, Thailand

Samutsakorn Hospital

Muang, Samutsakorn, Thailand

Countries

Thailand

References

Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, Kanshana S, McIntosh K, Thaineua V; Perinatal HIV Prevention Trial (Thailand) Investigators. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-child transmission of HIV-1 in Thailand. N Engl J Med. 2004 Jul 15;351(3):217-28. doi: 10.1056/NEJMoa033500. Epub 2004 Jul 9.

Reference Type: BACKGROUND

PMID: 15247338 (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)

Cressey TR, Jourdain G, Lallemant MJ, Kunkeaw S, Jackson JB, Musoke P, Capparelli E, Mirochnick M. Persistence of nevirapine exposure during the postpartum period after intrapartum single-dose nevirapine in addition to zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV-1. J Acquir Immune Defic Syndr. 2005 Mar 1;38(3):283-8.

Reference Type: BACKGROUND

PMID: 15735445 (View on PubMed)

Lallemant M, Ngo-Giang-Huong N, Jourdain G, Traisaithit P, Cressey TR, Collins IJ, Jarupanich T, Sukhumanant T, Achalapong J, Sabsanong P, Chotivanich N, Winiyakul N, Ariyadej S, Kanjanasing A, Ratanakosol J, Hemvuttiphan J, Kengsakul K, Wannapira W, Sittipiyasakul V, Pornkitprasarn W, Liampongsabuddhi P, McIntosh K, Van Dyke RB, Frenkel LM, Koetsawang S, Le Coeur S, Kanchana S; PHPT-4 Study Team. Efficacy and safety of 1-month postpartum zidovudine-didanosine to prevent HIV-resistance mutations after intrapartum single-dose nevirapine. Clin Infect Dis. 2010 Mar 15;50(6):898-908. doi: 10.1086/650745.

Reference Type: RESULT

PMID: 20158398 (View on PubMed)

Other Identifiers

IRD-UMI 174 PHPT-4

Identifier Type: -

Identifier Source: org_study_id