Background: 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. Methods: 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[sbnd]D) at each therapy session. Clinicians assessed participants' depression (HAM[sbnd]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. Results: During the active treatment phase (CES[sbnd]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). Limitations: Self-reported depression during the treatment phase may have resulted from social desirability bias. Conclusions: 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.