BackgroundKnowledge of ones HIV status is a critical step in the cascade of HIV care and prevention. Despite being available, many people at risk of HIV cannot access these services due to low uptake of HIV testing. Unsupervised HIV self-testing (HST) has potential to increase knowledge of HIV status; however, its accuracy is unknown. The main objectives were to determine the accuracy of HST and user preferences for HIV testing in Uganda.MethodsWe conducted a conjoint survey and performed a non-blinded, randomized controlled, non-inferiority trial of unsupervised compared with supervised HST among high-risk fisherfolk in three fishing communities in Uganda between July and September 2013. The study enrolled 246 participants and randomized them in a 1:1 ratio to unsupervised HST or provider-supervised HST. The primary outcome was difference in assay sensitivity and specificity, assessed with one sided Walds asymptotic test for non-inferiority with a -15% non-inferiority margin in the intent to treat and per-protocol analyses. Conjoint analyses using a hierarchical Bayes model were used to estimate utilities for HIV testing attributes. Utilities were used to simulate and estimate the shares of preference of 2 scenarios including an oral self HIV test, with price added as a key attribute. ResultsIn an intent-to-treat analysis, the HST sensitivity was 90% in the unsupervised arm and 100% among the provider-supervised, yielding a difference 0f -10% (90% CI: -21%, 1%); non-inferiority was not shown. In a per protocol analysis, the difference in sensitivity was -5.6% (90% CI: -14.4, 3.3%) and did show non-inferiority. Relative importance of HIV test attribute was highest for timeliness and accuracy (30.2%), price (29.7%) and counseling (17.5%) respectively. Given no costs of service, an oral home based self-test had the largest share of preference (24.5%), twice that of the rapid testing done at a public clinic. The share of preference drops to 9.9% when a $2 fee is included.ConclusionUnsupervised HST is feasible in rural Africa and may be non-inferior to provider-supervised HST. Highly accurate HST with oral tests and immediate results offered at no fee with counseling support could increase HIV test uptake.