HIV treatment and management is constantly evolving. This is as a result of more treatment options coming on stream, tolerance changes and progress in treatment management. HIV infection today, in resource-rich countries and in the presence of combination therapies, is experienced as lifelong treatment punctuated by adjustments to antiretroviral therapy (ART) regimens. People who are diagnosed as HIV positive face a number of challenges and changes around the decision to commence treatment, responses to treatment and changes in treatment regimens. This study was set up to examine the experience of switching treatments and the impact of such switches on psychological parameters. The method used was a cross-sectional questionnaire study. A group of 779 HIV-positive clinic attendees at four clinics in London and South East England participated in the study (86% response rate). They provided detail of their treatment switching experiences as well as demographic details, risk and optimism evaluations, quality of life, symptom burden, adherence and disclosure information. The sample (n=779) comprised 183 (24%) females, 76 (10%) heterosexual males and 497 gay males (66%). Self-reported ethnicity was 67% white, 25% black, 3% Asian and 5% mixed/other ethnicity. One hundred and fifty-five (21%) were ART-naïve and 624 (79%) were ART experienced; 161 (22%) were receiving their first regimen, 135 (18%) had experienced one regimen switch, 196 (26%) had multiple switches and 99 (13.3%) had stopped treatment. Treatment naïve, non-switchers and single switchers generally reported lower symptom burden and higher quality of life. Multiple switchers reported higher physical symptom burden and higher global symptom distress scores. Those who had stopped treatment had significantly lower quality-of-life scores than all other groups. Suicidal ideation was high across the groups and nearly a fifth of all respondents had not disclosed their HIV status to anyone. Reported adherence was suboptimal -- 79% of subjects were at least 95% adherent on self-report measures of doses taken over the preceding week. In conclusion, nearly half this clinic sample will have switched treatments. A holistic approach is needed to understand the psychological effects of such switches if lifelong treatment is to be maintained and those on antiretroviral treatment are to attain good quality of life and minimize symptom burden.