ABSTRACT
@#Introduction: Early studies have suggested the role of C-C chemokine receptor type 5 (CCR5) polymorphisms in influencing HIV pathogenesis and phenotypes, including the protection against HIV infection and delaying disease progression to AIDS. This study aimed to further determine the impact of CCR5 variants (CCR5-Δ32 and CCR5- R223Q) on HIV susceptibility, viral load suppression and CD4 recovery during highly active antiretroviral therapy (HAART) among Malaysian HIV patients. Methods: This cross-sectional study involved 182 HIV-infected who were recruited from three out-patient clinics, and 150 non-HIV subjects from Malay, Chinese and Indian ethnicities. CD4 count and viral load data at 4-6 months (t1) and 8-12 months (t2) after starting HAART were gathered from hospital records. Chi-square test was used to analyse the correlation between CCR5 variants with dependent variables. Results: Heterozygous CCR5-Δ32 and CCR5-R223Q occurred in a percentage of 0.5% (1/182) and 1.7% (3/182) among HIV patients respectively, while none of homozygous mutant for CCR5-Δ32 and CCR5-R223Q were found. CCR5-R223Q was found more frequently in non-HIV as compared to the HIV group (P=0.018). However, both polymorphisms were not found to be correlated with CD4 recovery to ≥500 cells/mm3 (P>0.05) and viral load suppression ≤50 copies/mL (P>0.05). Conclusion: CCR5-R223Q and CCR5-Δ32 alleles probably have no modifying effects on HIV susceptibility virological and immunological recoveries in the first 12 months of HAART, partially due to the low prevalence of these mutations in the studied population.
ABSTRACT
Aims: To characterize the genotypic distribution of mec complex, bla complex, methicillin-resistance level (cefoxitinMIC) and β-lactamase activity in carriage methicillin-resistant Staphylococcus species for a potential correlation. Methodology and results: Biochemical test, 30 µg cefoxitin diffusion disc test, cefoxitin E-test, mec and bla complexes distributions, Pbp2a and β-lactamase assays were conducted to characterize phenotypic and genotypic of MRSA and MRCoNS in our collection. Phylogenetic tree was constructed using MEGA6 software to trace the diversity of blaZ gene of MRSA and MRCoNS. Sixteen MRSA and nineteen MRCoNS were identified by biochemical tests followed by 30 µg cefoxitin antibiotic disc susceptibility test and mecA gene screening. Twenty nine isolates carry complete mecA genes (2.1 kb), incomplete mec regulator (negative or truncated) and positive Pbp2a assay for both MRSA and MRCoNS. Only MRCoNS SC177 isolate with cefoxitin MIC of 32 µg/mL carries complete mec complex. Thirty-one of thirty-five isolates carry complete bla complex (blaZ, blaRI, blaI) with 10 MRSA produce strong β-lactamase and cefoxitin MIC of ≥12 µg/mL. Only 4 MRCoNS with cefoxitin MIC of ≤8 µg/mL produce strong β-lactamase. The diversity of blaZ gene was demonstrated by phylogenetic analysis and unusual amino acid mutation at position 145 for MRSA SA60 isolate may compromise its β-lactamase activity with low cefoxitin MIC level (2 µg/mL). Conclusions, significance and impact of the study: Isolates that carry complete complete mecA gene were largely consistent with the expression of Pbp2a. Nevertheless, there is no clear correlation of mec regulator genes in relation to cefoxitin-MIC in both methicillin resistant (MR) Isolates that carry Staphylococcus species. On the other hand, various expression level of β-lactamase may correlate with cefoxitin-MIC level in MRSA as compared to MRCoNS.