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During advanced HIV infection, Human Cytomegalovirus (HCMV) has been proven to produce devitalizing end-organ diseases (EOD). The interactive co-existence of HIV and HCMV has been reported by many researchers and has been suggested to be linked with a more aggressive disease state. This study has been designed to bring forward an assessment of the clinical risk factors capable of defining the conditions of HCMV induced retinitis and gastro-enteric diseases among HIV1 seropositive patients. We also intended to analyse the phylogenetic variation if any, among the infecting virus types inducing the two separate clinical conditions. The patients were arranged in three different groups; (Group 1 with 26 individuals and group 2 and group 3 with 25 individuals each) based on their current status of HIV and HCMV infections. Serum ELISA, qualitative and quantitative detection of HCMV DNA, Real time mRNA expression study, sequencing, and phylogenetic analysis were performed. All statistical analyses and graphs were exercised using relevant software. We found that in HIV patients with HCMV induced end-organ diseases the components of the CXCL9, 10, 11-CXCR3 chemokine pathway is highly expressed with significant differences existing among patients with retinitis and gastrointestinal disease. We found that the gL gene sequences from the retinitis (HR) group clustered almost separately from that of the gastroenteritis (HG) group in the phylogenetic tree. It may be suggested that a form of natural selection pressure is working on the clinical HCMV strains creating a slight divergence in their phylogenetic lineage thereby helping them adapt to the particular tissue microenvironment they are colonizing. [ABSTRACT FROM AUTHOR]