Genotypic HIV-coreceptor tropism prediction with geno2pheno [coreceptor]: differences depending on HIV-1 subtype

Purpose of the study : Determination of HIV-1 coreceptor tropism is a major prerequisite before starting treatment with a CCR5-antagonist. While most of the patients currently under treatment with maraviroc are probably infected with HIV-1 subtype B viruses, recently published data show differences in the distribution of coreceptor tropism in different HIV-1 subtypes. Methods : In a Germany-wide project within the HIV-GRADE society, V3-loop sequences of 2466 isolates were analysed with geno2pheno for coreceptor tropism using a FPR cut-off of 10%. HIV-1 subtype was determined by using the COMET HIV subtyping tool. Sequences consisted of at least the V3 loop fragment. The ratio of CCR5 vs CXCR4 tropic viruses was calculated for each subtype. A normalized mean for all analyzed subtypes was calculated to extrapolate the overall ratio of coreceptor usage distribution. From this the expected distribution in the particular subtype was calculated and compared to the observed one. Statistical analysis was performed using the chi2 test. Summary of Results : Most samples were classified as HIV-1 subtype B (79%, n=1952). Other subtypes present in at least 23 samples were A1 (9.5%, n=234), C (4.8%, n=118), CRF01_AE (2.2%, n=55), G (1.6%, n=39), D (1.1%, n=27), F (0.9%, n=23). The calculated normalized mean distribution over all subtypes was 71% CCR5- vs. 29% CXCR4-tropic viruses. No significant difference compared to the mean distribution could be observed for HIV-1 subtypes B (71/29%), C (76/24%) and F (70/30%). Higher rates of CXCR4 tropic virus were detected in subtypes D (52/48%, p=0.01) and CRF01_AE (49/51%, p=0.001), while in HIV-1 subtypes A1 (22/78%, p=0.02) and G (13/87%, p=0.02), a higher rate of CCR5-tropic virus was observed. Conclusions : Our analysis shows a different distribution of CCR5 and CXCR4 tropic virus in some subtypes. In contrast to other publications, we could not observe a statistically significant difference in subtype C compared to the overall mean distribution, while we could confirm a higher rate of CXCR4-tropic virus in subtype D, as previously described. Without further data on treatment success of patients with non-B subtypes under treatment with maraviroc, it remains unclear if subtype-specific differences in the distribution of tropism are biased by differences in clinical variables before test or if there is a bias in the tropism interpretation system. In the latter case, individual interpretation cut-offs for different subtypes may be necessary. (Published: 11 November 2012) Citation: Abstracts of the Eleventh International Congress on Drug Therapy in HIV Infection Obermeier M et al. Journal of the International AIDS Society 2012, 15 (Suppl 4):18214 http://www.jiasociety.org/index.php/jias/article/view/18214 | http://dx.doi.org/10.7448/IAS.15.6.18214