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

Phase 2

Completed

• Conditions: HIV Infections

• Registration Number: NCT00142337
• Lead Sponsor: Institut de Recherche pour le Developpement

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.

Study Timeline

• Study Start: 2004-12
• Study First Submitted: 2005-09-01
• Study First Submitted QC: 2005-09-01
• Study First Posted: 2005-09-02
• Primary Completion: 2006-05
• Study Completion: 2009-02
• Status Verified: 2012-01
• Last Update Submitted: 2012-01-04
• Last Update Posted: 2012-01-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 244

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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Primary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (32)

Mae Chan Hospital; 🇹🇭 Mae Chan, Chiang Rai, Thailand

Maharaj Nakornratchasrima Hospital; 🇹🇭 Muang, Nakornratchasrima, Thailand

Rayong Hospital; 🇹🇭 Muang, Rayong, Thailand

Health Promotion Center Region 10; 🇹🇭 Muang, Chiang Mai, Thailand

Chonburi Hospital; 🇹🇭 Muang, Chonburi, Thailand

Nong Khai Hospital; 🇹🇭 Muang, Nong Kai, Thailand

Bhumibol Adulyadej Hospital; 🇹🇭 Bangkok, Thailand

Mae Sai Hospital; 🇹🇭 Mae Sai, Chiang Rai, Thailand

Pranangklao Hospital; 🇹🇭 Muang, Nonthaburi, Thailand

Roi-et Hospital; 🇹🇭 Muang, Roi-et, Thailand

Samutsakorn Hospital; 🇹🇭 Muang, Samutsakorn, Thailand

Chiangrai Prachanukroh Hospital; 🇹🇭 Muang, Chiangrai, Thailand

Hat Yai Hospital; 🇹🇭 Hat Yai, Songkla, Thailand

Somdej Pranangchao Sirikit Hospital; 🇹🇭 Chonburi, Thailand

Chiang Kham Hospital; 🇹🇭 Chiang Kham, Phayao, Thailand

Phaholpolphayuhasena Hospital; 🇹🇭 Munag, Kanjanaburi, Thailand

Lampang Hospital; 🇹🇭 Muang, Lampang, Thailand

Health Promotion Hospital Regional Center I; 🇹🇭 Bangkok, Thailand

Prapokklao Hospital; 🇹🇭 Muang, Chantaburi, Thailand

Nakornping Hospital; 🇹🇭 Mae Rim, Chiang Mai, Thailand

Phan Hospital; 🇹🇭 Phan, Chiang Rai, Thailand

Chacheongsao Hospital; 🇹🇭 Muang, Chacheongsao, Thailand

Kalasin Hospital; 🇹🇭 Muang, Kalasin, Thailand

Khon Kaen Hospital; 🇹🇭 Muang, Khon Kaen, Thailand

Regional Health Promotion Centre 6, Khon Kaen; 🇹🇭 Muang, Khon Kaen, Thailand

Nakhonpathom Hospital; 🇹🇭 Muang, Nakhonpathom, Thailand

Srinagarind Hospital; 🇹🇭 Muang, Khon Kaen, Thailand

Samutprakarn Hospital; 🇹🇭 Samutprakarn, Thailand

Lamphun Hospital; 🇹🇭 Munag, Chiang Mai, Thailand

Ratchaburi Hospital; 🇹🇭 Muang, Ratchaburi, Thailand

Kranuan Crown Prince Hospital; 🇹🇭 Kranuan, Khon Kaen, Thailand

Buddhachinaraj Hospital; 🇹🇭 Muang, Pitsanuloke, Thailand