18th International HIV Drug Resistance Workshop Basic Principles & Clinical Implications June 9–13 2009, Fort Myers, Florida, USA

DRUG RESISTANCE PATTERNS AMONG HIV-INFECTED CHILDREN AND ADULTS FAILING KALETRA-BASED REGIMENS IN SOUTH AFRICA

Antivir Ther 2009; 14 Suppl 1:A39 (abstract no. 37)

G Hunt¹, J Ledwaba¹, Z El-Khatib^1,2, A Coovadia³, L Kuhn⁴, D Katzenstein⁵ and L Morris^1
1AIDS Research Unit, National Institute for Communicable Diseases, Johannesburg, South Africa; ²Division of Global Health (IHCAR), Karolinska Institutet, Sweden; ³Empilweni Clinic, Coronation Women and Children Hospital, Enhancing Childhood HIV Outcomes (ECHO), University of the Witwatersrand, Johannesburg, South Africa; ⁴Gertrude H Sergievsky Center and Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY, USA; ⁵School of Medicine, Stanford University, Stanford, CA, USA

INTRODUCTION: The South African Department of Health HIV treatment guidelines recommend the use of a Kaletra (LPV/r)-based regimen for all HIV-infected children under 3 years of age and for adults failing NNRTI-based first line regimens. We examined patterns of drug resistance mutations among children and adults failing Kaletra-based regimens in Johannesburg, South Africa.

METHODS: All 44 children included in the analysis had been treated with LPV/r+3TC+d4T. Adults were treated with LPV/r+ddI+AZT (n=18, DOH recommended therapy), LPV/r+3TC+d4T or AZT (n=9), LPV/r+AZT+TDF (n=3), LPV/r+ddI+ABC (n=1) or LPV/r+AZT+ABC (n=1). The reverse transcriptase and protease genes were genotyped using a validated in-house methodology. Genotypic resistance was defined using the Stanford Genotypic Resistance Interpretation Algorithm and the December 2008 International AIDS Society drug resistance mutation list.

RESULTS: Children: of 44 sequences from failing patients, 15 (34%) had detectable PI mutations, 32 (73%) had NRTI mutations, 2 (5%) had NNRTI mutations and 10 (23%) were wild-type. The predominant PI mutations were V82A (30%), I54V (20%) and M46I (7%), whereas M184V was detected in 68% of samples and K103N and Y181C were detected in one sample each. The mean viral load (VL) among these patients was 30,154 copies/ml (1,158→750,000) and there was no difference in VL between patients with or without resistance (29,023 versus 33,964 copies/ml). Adults: of 32 sequences from failing patients, none (0%) had detectable major PI mutations (2 had minor PI mutations Q58E and T74P), 10 (31%) had NRTI mutations, 18 (53%) had NNRTI mutations and 11 (34%) were wild-type. M184V/I was detected in 28% of samples. The predominant NNRTI mutations detected were K103N (44%), P225H (16%) and V106M (6%). The mean VL among adult patients was 33,474 copies/ml (1480→750,000) and no difference between patients with or without mutations (25,102 versus 57,992 copies/ml) was noted.

CONCLUSIONS: Children failing Kaletra-based regimens had more frequently detectable PI and M184I/V mutations, whereas adults had high levels of NNRTI-associated mutations and no detectable PI mutations. The NNRTI mutations were likely selected and archived during first-line therapy, but their persistence on a PI-based therapy and the absence of PI resistance mutations is unexpected.

2009-06-09
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