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Carole Wallis

DIFFERENT PREVALENCE OF SUBTYPE C PROTEASE POLYMORPHISMS IN TWO DISTINCT GEOGRAPHICAL AREAS IN SOUTHERN AFRICA. Carole Wallis. As ARV roll-out programmes increase in sub-Saharan Africa, there is going to be an increase in demand of PI-containing second-line regimens

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Carole Wallis

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  1. DIFFERENT PREVALENCE OF SUBTYPE C PROTEASE POLYMORPHISMSIN TWO DISTINCT GEOGRAPHICAL AREAS IN SOUTHERN AFRICA Carole Wallis

  2. As ARV roll-out programmes increase in sub-Saharan Africa, there is going to be an increase in demand of PI-containing second-line regimens • There is a need for an increased understanding of protease resistance in HIV-1 subtype C • The aim of this study was to determine the frequency of naturally occurring polymorphisms in subtype C from 2 geographical regions in sub-Saharan Africa • 1305 patients from Zambia and South Africa were enrolled on the PASER-M project • All patients with viral loads >1000 RNA copies/ml were sequenced using the Wits In-house method and mutation patterns determined according to the IAS-USA mutation list

  3. 6 naturally occurring polymorphisms >10% were examined Not in the hydrophobic pocket Theoretically, these polymorphisms are unlikely to reduced binding of PIs in the hydrophobic pocket; but may impact on the folding structure of the protein

  4. Statistically significant differences of polymorphisms in HIV-1 subtype C PR was observed • These may lead to: • different mutation pathways • contribute to a varied response to PIs • Coordinated cohort studies are required to evaluate the clinical impact of PR polymorphisms on: • drug susceptibility • resistance evolution • treatment outcomes in HIV-1 subtype C viruses.

  5. University of the Witwatersrand • Department of Molecular Medicine & Hematology • Wendy Stevens • Catherine Bell • Esrom Legadima • Lindiwe Skhosana • Michelle Bronze • Alexio Capovilla • PharmAccess • Tobias Rinke de Wit • Raph L. Hamers • Clinical HIV Research Unit, Helen Joseph Hospital • Francesca Conradie • Muelmed Hospital, South Africa • Mariette Botes • Trust Hospital, Lusaka, Zambia • Margaret Siwale PASER is part of the “Linking African and Asian Societies for an Enhanced Response to HIV/AIDS” (LAASER) program, a collaboration of Aids Fonds The Netherlands, amfAR TREAT Asia, PharmAccess Foundation and International Civil Society Support, and is funded by a grant from the Dutch Ministry of Foreign Affairs (12454). More information can be found at http://www.pharmaccess.org.

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