Pediatric Nevirapine Resistance Study

Clinical Relevance of Nevirapine Resistance

This study is designed to test if a sequential protease-inhibitor (PI) - / nevirapine (NVP) -based regimen is effective for the treatment of HIV-infected children when previous NVP exposure has occurred as part of programs to prevent mother-to-child transmission (pMTCT).

Study Overview

• Status: Unknown
• Conditions: HIV Infections; AIDS
• Intervention / Treatment: Drug: nevirapine

Detailed Description

The wide use of NVP in pMTCT-prophylaxis may result in resistance to NNRTI and concomitantly limits the use of these drugs for the treatment of HIV-infected children. To avoid restricting treatment options for children, it is desirable to preserve NVP for both pMTCT and first line treatment. This study will therefore test whether resistance-caused treatment failures of HIV-infected and previously NVP-exposed children can be avoided if the NVP treatment is preceded by an initial PI-based regimen.

Comparison: HIV-infected children less than 24 months of age, exposed to any pMTCT regimen that included NVP and who achieve and maintain viral suppression for at least 3 months with a PI-based regimen will be randomized to one of the two groups: (1) to continue on PI-containing regimen or (2) to be switched off the PI-containing regimen onto the NVP-containing regimen. The study outcome will be proportions in the two groups who have complete virologic suppression at 6 months after randomization.

• Study Type: Interventional
• Enrollment (Anticipated): 250
• Phase: Phase 3

Contacts and Locations

Study Locations

• South Africa
  • Johannesburg, South Africa
    • Recruiting
    • Coronation Hospital
    • Contact: Ashraf Coovadia, MD; Phone Number: +27 (0) 11 470 9290/9317; Email: coovadiaah@paedshiv.wits.ac.za

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 2 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• NVP-exposure as part of pMTCT-prophylaxis around delivery
• HIV-positive
• Eligible for treatment
• Plans to stay in the area for the next 6 months

Exclusion Criteria:

• Already on anti-retroviral treatment
• History of toxicity to perinatal NVP
• Grade 3 or greater elevation of liver function tests
• Being treated for a severe acute opportunistic infection or tumor

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Virologic suppression at 6 months after randomization

Secondary Outcome Measures

Outcome Measure
To compare the time to virologic failure up to 18 months post randomization
to examine the associations between detection of drug resistance mutation and virologic response to treatment
to compare the toxicity profiles and adherence in the two groups
to describe the emergence of genotypic resistance in the two groups

Collaborators and Investigators

• Sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Collaborators: Columbia University; University of Witwatersrand, South Africa
• Investigators: Principal Investigator: Louise Kuhn, Ph.D., Columbia University

Publications and helpful links

General Publications

• Strehlau R, Kuhn L, Abrams EJ, Coovadia A. HIV-associated neurodevelopmental delay: prevalence, predictors and persistence in relation to antiretroviral therapy initiation and viral suppression. Child Care Health Dev. 2016 Nov;42(6):881-889. doi: 10.1111/cch.12399. Epub 2016 Aug 22.
• Shiau S, Kuhn L, Strehlau R, Martens L, McIlleron H, Meredith S, Wiesner L, Coovadia A, Abrams EJ, Arpadi SM. Sex differences in responses to antiretroviral treatment in South African HIV-infected children on ritonavir-boosted lopinavir- and nevirapine-based treatment. BMC Pediatr. 2014 Feb 12;14:39. doi: 10.1186/1471-2431-14-39.
• Kuhn L, Coovadia A, Strehlau R, Martens L, Hu CC, Meyers T, Sherman G, Hunt G, Persaud D, Morris L, Tsai WY, Abrams EJ. Switching children previously exposed to nevirapine to nevirapine-based treatment after initial suppression with a protease-inhibitor-based regimen: long-term follow-up of a randomised, open-label trial. Lancet Infect Dis. 2012 Jul;12(7):521-30. doi: 10.1016/S1473-3099(12)70051-8. Epub 2012 Mar 16.
• Coovadia A, Abrams EJ, Stehlau R, Meyers T, Martens L, Sherman G, Hunt G, Hu CC, Tsai WY, Morris L, Kuhn L. Reuse of nevirapine in exposed HIV-infected children after protease inhibitor-based viral suppression: a randomized controlled trial. JAMA. 2010 Sep 8;304(10):1082-90. doi: 10.1001/jama.2010.1278.

Study record dates

Study Major Dates

• Study Start: April 1, 2005
• Study Completion (Anticipated): September 1, 2010

Study Registration Dates

• First Submitted: July 6, 2005
• First Submitted That Met QC Criteria: July 7, 2005
• First Posted (Estimate): July 8, 2005

Study Record Updates

• Last Update Posted (Estimate): June 29, 2007
• Last Update Submitted That Met QC Criteria: June 28, 2007
• Last Verified: January 1, 2006

More Information

Terms related to this study

• Keywords: HIV Seronegativity; Treatment Naive; Drug Resistance; Non-nucleoside reverse transcriptase inhibitor
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; Nevirapine
• Other Study ID Numbers: 5R01HD047177 (U.S. NIH Grant/Contract)