Mengistu,Yohannes(Dr.)Meseret,Yohannis(Phd)2025-08-122025-08-122011-03https://etd.aau.edu.et/handle/123456789/6454It was not known why some people were HIV negative and others were HIV positive despite frequent sexual relationship between couples in Ethiopia. Most of the transmission of HIV is currently between discordant couples. This is a big problem as very few people know their HIV status and protection between couples during sexual intercourse is unknown. The result obtained from the study of discordant couples is very important as it enables us to know the reasons for susceptibility and resistance to HIV infection. This is especially true for policy makers as the result obtained from this study is high quality data including behavioral, biomedical and virological factors. The objectives of this study is, therefore, to investigate the reasons for susceptibility and resistance to HIV infection in discordant couples, which may involve behavioral, viral, immunological and other host and viral factors by comparing with concordant and healthy negative control subjects. The study involves discordant couples who have been in marriage relationship for more than one year, concordant couples and healthy negative couples with similar marital status with discordant couples. The study was carried out in hospitals and clinics all over Ethiopia and involved discordant and concordant couples who were on the follow up for many years in the respective hospital and clinics and were not on antiretroviral treatment. The samples were analyzed with appropriate statistical package using SPSS version 13 soft ware. To study if the difference in sexual behavior might have contributed to their serodiscordance, 325 discordant couples, 152 concordant couples and 14 healthy negative controls sexual behavior was studied. The study method involved an in-depth interview. There were known behavioral differences between discordant negatives and positives and concordant couples. There was very close similarity in behavior between discordant positives and concordant couples, showing that they shared similar risk behaviors. But the difference between discordant negatives and discordant positives was clear and big enough showing distant behavioral similarities. The healthy controls were behaviorally very much different from both discordant and concordant couples but they were similar to discordant negatives in some of their behaviors. Almost all of them were not aware of HIV before VCT and had multiple partners before marriage and were multiply married. All had unprotected sexual intercourse before and after marriage with their partners and there was no HIV test in between marriages. The majority of them were, however, satisfied in their marriages, but the reason for the satisfaction was not based on love, faithfulness and mutual respect. The reason for the dissatisfaction was also similar. The sexual frequency and number of sexual act per each contact was higher for discordant positives and concordant couple than discordant negatives and healthy control and discordant positives and concordant couples were also involved more in traumatic sex than discordant negatives. History of STDs was also higher for discordant positives and concordant couples when compared with xiii discordant negatives. Discordant positives and concordant couples were exposed to more risky behavior than concordant couples. Perceived mechanisms of HIV infection was also known risk factors for HIV infection and were associated with their sexual lives, family, occupation, social evils and injustice. When subjects were compared immunologically, discordant negative partners had adequate amount of CD4 equivalent to healthy subjects and highly significantly (P<.001) different from discordant positives. CD4 and CD8 ratio was also high indicating a healthy balance and this was also similar to healthy controls. Discordant positive partners had a significantly (P<.05) different number of CD4 cells when compared to concordant couples. Their CD8 number was very similar to discordant negatives and there was no significant difference. Increased CD8 number was associated with decreased viral load and in some subjects even to the level of below detection level. Lower viral load in discordant positives when compared to concordant couples also indicated lower or absence of transmission to uninfected partner. CD8 T cells were responsible in decreasing viral load. The evidence for this came from the observation that concordant couples showed elevated viral load and decreased CD8 T cells number while discordant positives showed elevated CD8 and very low viral load. Their CD4 number was also closer but slightly higher than the normal boundary count and might have been capable of providing the appropriate help for CD8 cells. Syphilis was a known risk factor for HIV transmission as it was diagnosed in many of discordant positives and concordant couples. This is possible because syphilis is a common STD in this country and its chronic nature might have accounted for its co-factor effect. Analysis of T cell subpopulations in discordant couples showed no activation of a specific marker between discordant positives and negatives and the expression of T cell subpopulations was comparable. The only difference observed was the expression of activation markers in significantltiy (P<.05) higher proportion in concordant couples when compared with discordant positives , indicating lower immune activation in discordant positives. In discordant positives, in addition to decreased number of activation markers there were also expression of certain markers (CD4+CD45RA-CD27-) in higher proportion(>30%), which were common in long-term-non- progressors, showing that discordant positives were long-term-non-progressors. Our study showed that there was a clear difference between discordant positives and discordant negative couples in their genetic profiles. There was also a clear difference between discordant positives and concordant couples and AIDS patients, in their genetic profiles. Ethiopian AIDS patients were different from Ethiopian concordant couples in their very significant to significant association with HLA-A*29, *18, and *41; HLA-B*0705, *1517, *4101, *5001, *7301 and *18; xiv HLA-C*0501, *0701, and *0740. AIDS patients were also very significantly different from discordant positives in their associations HLA-A*68, HLA-B*39 and HLA- DR*11. AIDS patient were also different from discordant negatives in their very highly significant to highly significant association with HLA-*0801, *1817, *352001 and *4901; HLA-C*7 and HLA-DR*40301. Concordant couples were also different from discordant positives in their very highly significant to significant associations with HLA-B* 0705, *0801 and *3910. Concordant couples were also different from discordant negatives in their significant association with HLA-DR*100101 and *110201. Discordant negatives were different from discordant positives in expressing HLA profiles of HLA-B*0801, *39, *41, *39; HLA-C*0716, HLA-DR*100101 and *110201. Overall, the differences between the different groups had a genetic background. When comparisons were made between discordant positives, concordant couples and AIDS subjects, discordant positive subjects were found to be more heterozygous at all loci (HLA-A, B, C and HLA-DR) when compared with concordant couples and HIV/AIDS subjects. This showed that discordant positives better controlled HIV and maintained HIV in check and were non- progressors due to heterozygous advantage. Overall, the results for discordant positives and AIDS subjects were clear enough to show significant difference between them. Ethiopian HIV viruses were mainly HIV type C in all discordant positives and HIV/AIDS subjects. But other subtypes such as subtype A, B and recombinant A/G subtypes were also observed. Co receptor utilization of discordant positive isolated viruses was both CCR5 and CXCR4 in equal proportion. The majority of HIV/AIDS patients used CXCR4, although about one third used CCR5 and a few also used dual co receptors. Our study showed that the majority of subtype C viruses were CXCR4/SI high/rapid subtype. And about one third was CCR5/NSI subtypes. The phylogenetic or evolutionary relationship showed that the majority of the viruses isolated from discordant positives showed subclustering in one region and those isolated from concordant couples in another region, showing that discordant positive isolated viruses were evolving independently and were related with each other but this was not seen in viruses of concordant couples and HIV/AIDS subjects.en-USHIV/AIDSHIV negativeThesis