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

HIV Infections Clinical Trial

Official title:

A Phase 2, One Arm, Open Label, Feasibility Study Assessing One Month Zidovudine/Didanosine Postpartum Prophylaxis to Prevent Resistance Mutations in Mothers Exposed to Single Dose Nevirapine to Prevent Mother to Child Transmission of HIV

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00142337
• Other study ID #: IRD-UMI 174 PHPT-4
• Status: Completed
• Phase: Phase 2
• First received: September 1, 2005
• Last updated: January 4, 2012
• Start date: December 2004
• Est. completion date: February 2009

Study information

• Verified date: January 2012
• Source: Institut de Recherche pour le Developpement
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ministry of Public Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 244
• Est. completion date: February 2009
• Est. primary completion date: May 2006
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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.)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections

Intervention

Drug:
• 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.
• 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

Locations

Country	Name	City	State
Thailand	Bhumibol Adulyadej Hospital	Bangkok
Thailand	Health Promotion Hospital Regional Center I	Bangkok
Thailand	Chiang Kham Hospital	Chiang Kham	Phayao
Thailand	Somdej Pranangchao Sirikit Hospital	Chonburi
Thailand	Hat Yai Hospital	Hat Yai	Songkla
Thailand	Kranuan Crown Prince Hospital	Kranuan	Khon Kaen
Thailand	Mae Chan Hospital	Mae Chan	Chiang Rai
Thailand	Nakornping Hospital	Mae Rim	Chiang Mai
Thailand	Mae Sai Hospital	Mae Sai	Chiang Rai
Thailand	Buddhachinaraj Hospital	Muang	Pitsanuloke
Thailand	Chacheongsao Hospital	Muang	Chacheongsao
Thailand	Chiangrai Prachanukroh Hospital	Muang	Chiangrai
Thailand	Chonburi Hospital	Muang	Chonburi
Thailand	Health Promotion Center Region 10	Muang	Chiang Mai
Thailand	Kalasin Hospital	Muang	Kalasin
Thailand	Khon Kaen Hospital	Muang	Khon Kaen
Thailand	Lampang Hospital	Muang	Lampang
Thailand	Maharaj Nakornratchasrima Hospital	Muang	Nakornratchasrima
Thailand	Nakhonpathom Hospital	Muang	Nakhonpathom
Thailand	Nong Khai Hospital	Muang	Nong Kai
Thailand	Pranangklao Hospital	Muang	Nonthaburi
Thailand	Prapokklao Hospital	Muang	Chantaburi
Thailand	Ratchaburi Hospital	Muang	Ratchaburi
Thailand	Rayong Hospital	Muang	Rayong
Thailand	Regional Health Promotion Centre 6, Khon Kaen	Muang	Khon Kaen
Thailand	Roi-et Hospital	Muang	Roi-et
Thailand	Samutsakorn Hospital	Muang	Samutsakorn
Thailand	Srinagarind Hospital	Muang	Khon Kaen
Thailand	Lamphun Hospital	Munag	Chiang Mai
Thailand	Phaholpolphayuhasena Hospital	Munag	Kanjanaburi
Thailand	Phan Hospital	Phan	Chiang Rai
Thailand	Samutprakarn Hospital	Samutprakarn

Sponsors (1)

Lead Sponsor	Collaborator
Institut de Recherche pour le Developpement

Country where clinical trial is conducted

Thailand, 

References & Publications (4)

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. — View Citation

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 9. — View Citation

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. Epub 2004 Jul 9. — View Citation

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, Sitt — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with viral NNRTI mutations detectable during the 4 month follow-up compared with the incidence observed in the PHPT-2 clinical trial, who received the same antiretroviral prophylaxis but no post-partum regimen		Within 4 months postpartum	No