dc.description.abstract | CCRS antagonists have clinically been approved for prevention or treatment of HIV/AIDS.
Countries in Sub-Saharan Africa with the highest burden of HIVIAIDS are yet to adopt these
regimens. However, HIV can also use CXCR4 as a co-receptor. There is hence a need to map
out cellular tropism of Kenya's circulating HIV strains to guide the impending use of CCR5
an~s. The study aimed to determine the prevalence of CCR5- and CXCR4-trcOpicHlv-
] stIains among patients attending Kenyatta National Hospital. Blood samples were obtained
from HIV infected patients attending the comprehensive care centre, Kenyatta National
Hospital in years 2008 and 2009. The samples were separated into plasma and peripheral
blood mononuclear cells (PBMCs). Proviral DNA was extracted from PBMCs and
Pol}mmase Chain reaction (PCR) done to amplify the mv env fragment spanning the C2-V3
region. The resultant fragment was directly sequenced on an automated sequencer (ABI,
3100)_ The HIV!.l env sequences were then entered into a variety of predictivealgoritbms:
amino acids at position ] 1125 rule, V3 net charge rule, Geno2pheno [co-receptor} and
dsKemel Phylogenetic relationships were determined using CLUSTALW and Neighbour
Joining method. A total of 84 sequences were successfully amplified and sequenced. HIV-l
R5 tropic strains were more prevalent in the study population according to a11algorithms:
(71.010/0, 69-41%, 125% and 82.890/0for amino acids at positions 11/25 rule, V3 net charge
rule, Geno2pheno(co-receptor] and dsKernel respectively). Phylogenetic analysis showed
tha1 75% were subtype A, 13% subtype C and 12% subtype D. There were no significant
differmces in predicting the tropism using the four predicting tools (x,2 test, p=OJ9). The
age" sex and CD4 counts of the study participants were not associated with HIV-tropism <:X,2
test, p=O.4447, p= 1.000 and p=0.26 respectively). There was a tendency of a higher number
of X4 tropic viruses being in the treatment experienced group though not statistically
significant (x2 test, p=O.31). However, a strong association was observed between HIV
tropism and HN subtypes (x,2 test, p=O.04), with subtype D harbouring mainly X4-tropic
steams. In conclusion, HIV-l R5 tropic strains were the most prevalent in the study
PQptd'3tion and HIV infected patients in Kenya may benefit from CCR5 antagonists.
HmYe\.'m"~ there is need for caution where subtype D infection is suspected or where
antiretroviral salvage therapy is indicated. | en |
dc.description.department | a
Department of Psychiatry, University of Nairobi, ; bDepartment of Mental Health, School of Medicine,
Moi University, Eldoret, Kenya | |