P26. Monophylogenetic HIV-1C epidemic in Ethiopia is dominated by CCR5-tropic viruses – an analysis of a prospective country-wide cohort

Amare W. Kalu1,2, Nigus F Telele1,2, Solomon Gebreselasie2, Daniel Fekade3, Samir Abdurahman4, Gaetano Marrone5, Anders Sönnerborg1,5
Affiliates: 1Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, Stockholm, Sweden; 2Department of Microbiology, Immunology and Parasitology, Addis Ababa University, Ethiopia; 3Department of internal Medicine, Addis Ababa University, Ethiopia; 4Department of Science and Technology, Örebro University, Örebro, Sweden; 5Unit of Infectious Diseases, Department of Medicine Huddinge, Karolinska Institutet, Stockholm, Sweden

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Background
CCR5 coreceptor using HIV-1 subtype C (HIV-1C) has been reported to dominate the Ethiopian epidemic. However, almost all data have been obtained from the central and north-west region and recent data is lacking. Reports regarding impact of baseline tropism on antiretroviral therapy (ART) outcome vary in different settings.

Methods
The envelope region of HIV-1 from plasma of 420 treatment naïve patients recruited 2009-2011 to a large country-wide Ethiopian cohort (Figure 1) was sequenced by population sequencing. Subtype was determined by online methods: REGA subtyping tool v2.0, RIP 3.0, and COMET HIV. Co-receptor tropism was predicted by the genotypic Geno2Pheno online tool. The impact of baseline tropism on outcome of ART was evaluated.

Results
V3 loop sequencing was successful in 352 (84%) samples. HIV-1C was found in 350 (99.4%) and HIV-1A in two (0.6%) patients. Using the Geno2Pheno[FPR 10%] clonal and clinical model, X4- or R5/X4 tropic virus was predicted in 17% and 19.0%, respectively. Altogether, 75.6% of the 352 predictions were concordant between the two models (Figure 2). No statistically significant difference found in prevalence of X4 tropism across the geographical regions. In bivariate intention to treat analysis, X4 virus infected patients achieved plasma HIV RNA levels of <1000 copies/mL less frequently than R5 virus infected patients, at month six and 12 (Figure 3). However, no difference was found in therapy outcome and CD4+ cell gain between R5-tropic and X4-tropic virus infected patients by multivariate analysis. At viral failure, R5 to X4 switch was rare while X4 to R5 switch occurred more frequently (month six: p= 0.006; month 12: p= 0.078). Comparison of 387 Ethiopian V3 loop sequences dated from 1984-2003 with those of ours showed an increase in the proportions of X4/R5X4 tropic virus from 5.6% to 17.3% (P<0.001).

Conclusion
The HIV-1C epidemic is monophylogenetic in all regions of Ethiopia and R5-tropic virus dominates, although the proportion of X4-tropic virus have increased over the last two decades. Geno2pheno clinical and clonal prediction models showed a large discrepancy. Hence further studies are needed to assess the utility of genotypic tropism testing in HIV-1C.

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