In Ethiopia, substance use and risky sexual behavio ur are common. High rates of substance use and unprotected sex have unintended health consequences for University students. The Objective of the research was assessment of substance abuse and sexu al risk behavior. 611 students in Dilla University were interviewed in 2011. Data were coll ected and analyses were performed to examine demographic and sexual HIV-risk behaviour. Analysis was done using SPSS version 20 and necessary ethical issues were considered. Four hund red and thirty four (71.0 %) males and one hundred and seventy seven (29.0 %) females particip ated with 94.47% response rate. The mean age was 21.39 with SD of ±1.69 years. Five hundred and seventy (93.3%) were single, two hundred and thirty six (38.6%) were first year. The prevalence of alcohol drinking, chewing khat, and cigarette smoking were 396(64.7%), 251(41.8%), and 117(19.17% ) respectively. The most common substances used were Alcohol and Khat. Daily Khat intake was a ssociated with unprotected sex: adjusted Odds Ratio= 2.28 at 95% CI (1.90-2.68). Alcohol use was also significantly associated with having three or more sexual partners as well as with having unprote cted sex with a long-term partner when compared to those not using it: adjusted Odds Ratio= 3.0 at 95% CI(2.34-3.89). Among sexually active 27(5.8%); 6(1.3%) of them had 3 life time partners; and 25( 5.4%) of them had 5,and more than 5 life time partners. Having multiple sexual partners is signif icantly associated (x 2 =23.371,df=7, p<0.001). Substance use and risky sexual practices were signi ficantly higher among study participants. Alcohol and Khat were found to be significant risk factors for HIV-risk behaviours. Government and other responsible bodies should design a strategy to cont rol the use of substances like alcohol, khat, and Shisha. Further study to identify prevalence and ro le of substance in exposure to HIV infection is recommended.
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