Background:  HIV programs benefit from knowing risk factors associated with HIV acquisition. However, prevalence data poorly reflect incidence in countries with changing epidemics.

Methods:  We analyzed data from a 2004 to 2005, nationally representative, population-based survey of 15- to 59-year-old adults in Uganda. Blood specimens were tested for HIV, syphilis, and herpes simplex virus type 2 (HSV-2). We tested HIV-seropositive specimens with the BED IgG capture-based enzyme immunosorbent assay to identify seroconversions that occurred on average within the past 155 days. We calculated incidence values using a normalized optical density of 0.8 and established adjustments. Multivariate logistic regression models were developed for sexually active, married participants and the entire population.

Results:  Of the 11,454 women and 9,905 men, aged 15–59 years, who were eligible, 90% of women and 84% of men provided blood specimens. Of the 1092 HIV infections, 172 (16%) tested as recent. Accounting for sampling design and variation in specificity due to stage of infection, weighted incidence was 1.9 infections per 100 person-years (95% confidence interval [CI] 1.6 to 2.2). 65% of incident infections occurred among married people, 26% among divorced or widowed, and 9% among never married; 77% occurred in people ≥25 years old. In multivariate analysis, recent HIV infection was associated with number of sexual partners in the past year (>2 partners compared with none (adjusted odd ratio [AOR] 2.5 [1.3 to 4.6]), HSV-2 (AOR 3.9 [2.6 to 5.8]), and being an uncircumcised man (AOR 2.5 [1.2 to 5.5]). Among married participants, 84% of recent infections occurred in people who reported no sexual partners outside of marriage in the previous year. The risk of recent infection was similar for people who used condoms with partners outside of marriage and those without outside partners (AOR 1.0 [0.3 to 2.7]). Among 74 married participants with recent infection for whom HIV testing was also conducted for their spouse, 38% of recent infections occurred among people whose spouse had long-standing HIV infection, 13% had a spouse with recent HIV infection, and 49% had an HIV-uninfected spouse.

Conclusions:  Most incident HIV infections in Ugandan adults occurred among married people and those ≥25 years. At least half of new infections among married participants were acquired from their spouse. National prevention efforts should include married people because of HIV-discordance and sexual partnerships outside of marriage.