BackgroundIntimate partner violence (IPV), alcohol use, and depression are key vulnerabilities for HIV in Uganda, and taken together may have a synergistic effect on risk. Our objective was to investigate the associations between depression, IPV, and alcohol use and HIV-risk indicators among a sample of outpatients in rural Uganda, and the effect of co-occurrence of these factors on HIV-risk indicators.MethodsIn a structured interview we collected data on high-risk sexual behavior, depression symptoms, emotional and physical IPV, and alcohol use, as well as a blood sample for HIV and syphilis tests and a urine sample for chlamydia and gonorrhea tests from 325 male and female outpatients receiving provider-initiated HIV testing and counseling (PITC) at a public hospital outpatient clinic in rural Uganda. We used logistic regression and generalized linear modeling to test independent associations between depression, IPV, and alcohol use and HIV-risk indicators, as well as the effect of co-occurrence on HIV-risk indicators.ResultsTwelve percent of men and 15% of women had two or more of the following conditions: depression, IPV, and alcohol use; another 29% of men and 33% of women had 1 condition. Each condition was independently associated with HIV risk behavior for men and women, and for women, depression was associated with testing positive for HIV or a sexually transmitted infection (STI). Men with one condition (AOR 2.32, 95% CI 1.95–2.77) and two or more conditions (AOR 12.77, 95% CI 7.97–20.47) reported more high risk sex acts compared to those with no potential co-occurring conditions. For men, experiencing two or more conditions increased risky sex more than one alone (χ
2 24.68, p < 0.001). Women experiencing one condition (AOR 3.33, 95% CI 137–8.08) and two co-occurring conditions (AOR 5.87, 95% CI 1.99–17.35) were more likely to test positive for HIV or an STI and women with two co-occurring conditions were also at increased risk for risky sex (AOR 2.18, 95% CI 1.64–2.91). We also found preliminary evidence suggesting synergistic effects between depression and emotional IPV and between alcohol use and depression.ConclusionsThis study demonstrates the co-occurrence of depression, IPV, and alcohol use in men and women in an outpatient setting in rural Uganda. The co-occurrence of these factors was associated with greater HIV risk, highlighting the need for a more holistic approach to HIV prevention and care research and programming.