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The goal of the study was to investigate moderators of intervention effect of a guided Internet-based self-help cognitive behavioral intervention for people with HIV and depressive symptoms. This study was part of a randomized controlled trial where the intervention was found to be effective in reducing depressive symptoms, compared to an attention-only control group. Demographic characteristics (e.g., age), HIV characteristics (e.g., duration of HIV), and psychological characteristics (e.g., coping self-efficacy) were investigated as potential moderators of intervention effect. In 2015, 188 people with HIV and depressive symptoms were included in the study: 97 were randomized to the intervention group and 91 to the control group. Two moderators of intervention effect were found: coping self-efficacy and baseline depression severity. Participants with low coping self-efficacy and baseline depression severity improved more in the intervention group than in the control group, and participants with high coping self-efficacy and baseline depression severity improved in both groups. The results indicate that the intervention may be provided to all people with HIV and depressive symptoms. It may be especially important for people with HIV and low coping self-efficacy to start with the intervention since they show less improvement in the control group with only attention. Trial registration: Nederlands Trialregister NTR5407, September 11, 2015. [ABSTRACT FROM AUTHOR]