This pilot study assessed the determinants of engagement in HIV care among Zambian patients new to antiretroviral (ARV) therapy, and the effect of an intervention to increase medication adherence. Participants (n = 160) were randomized to a 3-month group or individual intervention utilizing a crossover design. Psychophysiological (depression, cognitive functioning, health status), social (social support, disclosure, stigma), structural factors (health care access, patient–provider communication), and treatment engagement (adherence to clinic visits and medication) were assessed. Participants initially receiving the group intervention improved their adherence, but gains were not maintained following crossover to the individual intervention. Increased social support and patient–provider communication and decreased concern about HIV medications predicted increased clinic attendance across both arms. Results suggest that early participation in a group intervention may promote increased adherence among patients new to ARV therapy, but long-term engagement in care may be sustained by both one-on-one and group interventions by health care staff.