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

GENOTYPIC AND PHENOTYPIC HIV TROPISM TESTING PREDICTS THE OUTCOME OF MARAVIROC REGIMENS

Antivir Ther 2009; 14 Suppl 1:A51 (abstract no. 47)

P Braun¹, E Wolf², M Hower³, S Scholten⁴, W Köthemann⁵, A Neuwith⁵, F Wiesmann¹, C Höhn¹, A Balogh², R Ehret¹, A Trein⁶, S Christensen⁷, H Jäger² and H Knechten^1
1PZB, Aachen, Germany; ²MUC Research, Munich, Germany; ³Städt. Klinik Dortmund, Germany; ⁴Medical Practice I, Cologne, Germany; ⁵Medical Practice II, Cologne, Germany; ⁶Medical Practice, Stuttgart, Germany; ⁷Medical Practice, Münster, Germany

OBJECTIVES: Determining HIV-1 coreceptor tropism is crucial before initiating therapies with maraviroc (MVC). To date, the practicability of HIV pheno-and genotypic tropism testing and consequently therapeutical success of MVC regimens in clinical routine has not sufficiently been studied and was the subject of this work. We observed long-term efficacy of MVC-containing regimens and the effect on HIV-1 coreceptor tropism in a 48 week follow-up analysis.

METHODS: HIV-1 coreceptor tropism was determined in 337 patients by conventional sequencing of the HIV-1 V3-loop region and interpretation with the geno2pheno online tool. False-positive X4-rates (FPR) with a cutoff of 20% were used for tropism prediction. Phenotypic tropism testing was performed by using Monograms Trofile^™ assay (25.5% with TrofileES). A total of 186 patients (55.2%) were CCR5-positive. Of the 186 CCR5-positive, therapy-experienced patients, 51 (86% infected with HIV-1 subtype B) received a MVC-containing regimen (paired phenotypic and genotypic results were available for 36 patients). A median active drug score (including MVC) of 3 (range 1–5) was calculated with HIV-Grade algorithm (ver. 07/2008). Therapy success (viral load <50 copies/ml) and possible changes in viral tropism were observed at weeks 12, 24 and 48.

RESULTS: A total of 25 patients reached week 24 so far. Seventeen patients (68%) had a drop in HIV-RNA <50 copies/ml. Five patients had a decrease of at least 1 log (20%) and another three patients had no reduction or an increase in viral load. The positive predictive value for the Trofile^™ assay was 74% and 67% for geno2pheno (FPR 12.5%). Discordant viral tropism results between genotype and phenotype occurred in five patients. Despite these results, three of them showed viral loads below the detection limit after week 24.

CONCLUSIONS: Combining MVC with further active drugs is an effective option in clinical practice for heavily pretreated patients. Good treatment response was observed in 68% of patients, which is also due to combinations of new drugs. A major issue before starting MVC-containing regimens remains the correct interpretation of discordant virus tropism results. Although both methods show similar positive predictive values, an important advantage of genotype-based tropism prediction remains the capability to analyse even samples with low or no detectable viral loads.

2009-06-09
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