HIV-1 Coreceptor Tropism among Kenyans Under Highly Active Antiretroviral Therapy.

Abstract

Despite the scale up of the use of combined highly active antiretroviral (ARV) therapy, many HIV-1 infected patients are still failing treatment in Kenya. In 2007, the Food Drug and Administration (FDA) approved the use of CCR5 antagonists in treatment experienced patients. CCR5 antagonists work by inhibiting the entry of HIV-1 that uses CCR5 as a coreceptor to gain entry into cells. CCR5 59029 A/G (promoter region—rs1799987) is a polymorphism that leads to the upregulation of the expression of the CCR5 protein thereby affecting the rate of HIV-1 infection. The use of these CCR5 antagonists in Kenya is limited partly because of minimal data on host genetics and coreceptor tropism among HIV-1 infected patients. In this study, we aimed at determining the prevalence of CCR5 tropic variants and CCR5 59029AG promoter polymorphism known to influence HIV-1 infection. We sequenced the V3 region of the env gene and inferred the HIV-1 tropism using clonal model of Geno2Pheno algorithm (FPR= 5%).   Also, we assessed the frequency of the CCR5 promoter polymorphisms among the patients by sequencing the polymorphic region of the CCR5 promoter. Majority of the patients (77.27%) had R5 tropic viruses whereas 22.73% of the study subjects had detectable CCR4 using viruses. The frequencies of the CCR5 59029 AA, AG, and GG genotypes were 14 (31.82%), 9 (20.45%) and 21(47.73%), respectively. Taken together, these results indicate that CCR5 antagonists could have potential therapeutic effects in the clinical management of HIV-1 among the infected patients in Kenya.

Key words: CCR5 antagonists, CCR5 59029AG, HAART, HIV-1, Polymorphism, Tropism