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Therapeutic guidelines advise that 200–350 × 106 cells/l may approximate an irreversible threshold beyond which response to therapy is compromised. We evaluated whether non-immune-based factors such as physician experience and adherence could affect survival among HIV-infected adults starting HAART.Analysis of 1416 antiretroviral naive patients who initiated triple therapy between 1 August 1996 and 31 July 2000, and were followed until 31 July 2001. Patients whose physicians had previously enrolled six or more patients were defined as having an experienced physician. Patients who received medications for at least 75% of the time during the first year of HAART were defined as adherent. Cumulative mortality rates and adjusted relative hazards were determined for various CD4 cell count strata.Among patients with < 50 × 106 cells/l the adjusted relative hazard of mortality was 5.07 [95% confidence interval (CI), 2.50–10.26] for patients of experienced physicians and was 11.99 (95% CI, 6.33–22.74) among patients with inexperienced physicians, in comparison to patients with ≥ 200 × 106 cells/l treated by experienced physicians. Similarly, among patients with < 50 × 106 cells/l, the adjusted relative hazard of mortality was 6.19 (95% CI, 3.03–12.65) for adherent patients and was 35.71 (95% CI, 16.17–78.85) for non-adherent patients, in comparison to adherent patients with ≥ 200 × 106 cells/l.Survival rates following the initiation of HAART are dramatically improved among patients starting with CD4 counts < 200 × 106 cells/l once adjusted for conservative estimates of physician experience and adherence. Our results indicate that the current emphasis of therapeutic guidelines on initiating therapy at CD4 cell counts above 200 × 106 cells/l should be re-examined.