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People with HIV (PHW) are at greater risk of depression than the general population. Insight into the time-to-treatment-response and predictors of response to psychotherapy may improve implementation in primary care. We assessed depression treatment response among 80 participants in a trial of cognitive-behavioral therapy for adherence and depression (CBT-AD) for PWH with MDD and suboptimal antiretroviral therapy (ART) adherence. Participants self-reported depressive symptoms (CES D) at each therapy session. Clinicians assessed participants' depression (HAM D), along with potential predictors of response, every four months for one year. Latent class analyses examined classes of responders for the active and the post-treatment phases. Regression analyses identified predictors of class membership for each phase. During the active treatment phase (CES D) we identified an early response (at session 2 and with continued trajectory of improvement) and a non-response group. There were also two classes during post-treatment (HAM-D): early responders (4-month) and late responders (12-month). Distress aversion was associated with lower likelihood of early response to CBT-AD (aOR = 0.74, 95%CI[0.56–0.90], p =.009), and social support was associated with increased likelihood of early response (aOR = 2.24, 95%CI[1.07–5.46], p =.045). Self-reported depression during the treatment phase may have resulted from social desirability bias. Most participants responded to CBT-AD early during treatment (89 %) and had sustained improvements in depression by 4 months (80 %). Distress aversion was a risk factor for late response, and social support was protective. Future research is needed to assess the optimal dose of CBT-AD in resource limited settings. • Cognitive Behavioural Therapy effectively treats depression and adherence in Persons with HIV. It therefore improves rates of viral suppression, more than treatment as usual. • Early self-reported improvements in depression most likely are the result of being in a trial. Improvement continued to occur throughout the acute treatment phase. • Clinician-rated depression over 4, 8 and 12 months also occurred, with steep improvement seen at 4 months. • Whether or not shorter durations of therapy, delivered by nurses, is effective remains to be explored. [ABSTRACT FROM AUTHOR]