NNRTI-associated mutations in the HIV-genome

Every year, 700.000 children are infected with HIV worldwide, most of them through vertical transmission in sub-Saharan Africa. If at all, in the resource-limited areas in sub-Saharan Africa the prophylaxis with the antiretroviral drug nevirapine is the only measure available to reduce mother-to-child transmission.

 

 

 

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Summary

In Uganda, a cohort of 100 mother-child pairs who received a nevirapine single dose regimen was formed and followed regularly over a period of 18 months from the beginning of drug intake. Body secretions such as blood, breast milk, cervicovaginal- and oropharyngeal secretions have been collected at specific intervals. Nevirapine carries a high risk of resistance formation. Possible implications are the transmission of a resistant virus to the child and an impaired treatment response to antiretroviral longtern treatment with nevirapine or other substances of the NNRTI-drug class. The aim of this project is to assess the extent of NNRTI-associated resistance mutations of the HIV-genome after nevirapine single dose administration in different compartments. Specific questions concern the emergence and temporal development of HIV- RNA mutations in blood and breast milk, the transmission of resistant virus to the child and the influence of the concentration and course of nevirapine on the resistance formation in mother and child.

Project Details

Project Co-ordinator:
Andrea Kunz

Co-workers:
Andrea Hauser
Dr. Claudia Kücherer
Prof. Dr. Gundel Harms-Zwingenberger

Co-operation:
Robert Koch-Institut Berlin, Germany

Doctoral students:
NN

Project duration:
2007-2008

Project status:
ongoing

Funding:
Hector Stiftung

Papers

Publications:
Kunz A, Frank M, Mugenyi K, Kabasinguzi R, Weidenhammer A, Kurowski M, Kloft C, Harms G. 
Persistence of nevirapine in breast milk and plasma of mothers and their children after single-dose administration. 
J Antimicrob Chemother 2009; 63:170-177.

Presentations:
"Allele-specific, subtype A and subtype D specific real-time PCR for the detection of minor drug-resistant populations after nevirapine single-dose". XVII Internationalen AIDS Konferenz, Mexiko, 2008.
"Detection of minor drug-resistant populations in plasma of HIV-infected children and their mothers after single-dose nevirapine". XVII Internationalen AIDS Konferenz, Mexiko, 2008.
"Population Pharmacokinetics in Black Newborns for Nevirapine to Prevent HIV Transmission". 2nd World Conference on Magic Bullets (Ehrlich II), Nürnberg, 2008.
Poster "Nevirapine - Population pharmacokinetic model building and simulation for mothers and newborns". Page-Meeting, Marseille 2008.
"Population pharmacokinetics of nevirapine for HIV prevention in newborns". Jahrestagung der Deutschen Pharmazeutischen Gesellschaft, Bonn, 2008.