13th International HIV Drug Resistance Workshop


8–12 June 2004, Tenerife Sur-Costa Adeje, Canary Islands, Spain


SURVEILLANCE OF RESISTANCE IN KZN SOUTH AFRICA, INCLUDING MOTHER-INFANT PAIRS 6 WEEKS AFTER SINGLE-DOSE NVP

Antiviral Therapy 2004; 9:S80 (abstract 71)

M Gordon1, N Graham1, R Bland2, N Rollins2, T De Oliveira1, B Monosi1, K Van Laethem3, A Vandamme3 and S Cassol1,2
1HIV Molecular Virology and Bioinformatics Unit, University of KwaZulu-Natal; 2Africa Centre for Health and Population Studies, Mtubatuba; and 3Rega Institute, Katholieke Universiteit Leuven, Belgium

BACKGROUND: To ensure that drug programs remain effective, it is essential that the rate and pattern of drug resistance development is closely monitored.

METHODS: Resistance patterns were determined using the Viroseq kit. Phylogenetic subtyping and sequence analysis was performed using PAUP*, PAML, MEGA and Prosite.

RESULTS: Of 30 HIV-1 C-infected mother-infant pairs 6 weeks after pMTCT prophylaxis, 40% of the mothers and 40% of the infants harboured resistant virus. Y181C was present in 11/12 (92%) of the children (including one of twin infants). In addition to Y181C, two infants (17%) had a K103N mutation, and a third infant (8%) carried an HIV-1 C-associated V106M mutation. K103N was the most common mutation in 10/12 mothers (83%). Other mutations in the mothers included Y181C in 3/12 (25%), Y188C in 3/12 (25%), V106M in 2/12 (17%) and G190A in 1/12 (8%). Two or more mutations were found in 4/12 (33.3%) mothers. The K103N mutation resulted in the loss of a protein kinase phosphorylation site at codons 102 to 105 in RT. This was replaced with a myristoylation site at codons 99 to 104 and a glycosylation site at codons 103 to 106. All resistant infants lacked a tyrosine kinase phosphorylation site at codons 174 to 181, near the RT active site.

CONCLUSIONS: Taken together, these findings suggest that the pattern of resistance in African patients will be similar to that observed for the treatment of subtype B infection. However, given the high rate of resistance in mothers and infants after single-dose NVP, the search for safer regimens to prevent MTCT should be intensified.

PRESENTING AUTHOR: M Gordon

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2004-06-08
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