OBJECTIVE: To assess the positive predictive value (PPV) of a clinical score for viral failure among patients fulfilling the WHO-criteria for anti-retroviral treatment (ART) failure in rural Lesotho. METHODS: Patients fulfilling clinical and/or immunological WHO failure-criteria were enrolled. The score includes the following predictors: Prior ART exposure (1 point), CD4-count below baseline (1), 25% and 50% drop from peak CD4-count (1 and 2), hemoglobin drop>/=1 g/dL (1), CD4 count/=6 months, 134 (11.8%) had immunological and/or clinical failure, 104 (78%) had blood drawn (13 died, 10 lost to follow-up, 7 did not show up). From 92 (88%) a result could be obtained (2 samples hemolysed, 10 lost). Out of these 92 patients 47 (51%) had viral failure (>/=5000 copies), 27 (29%) viral suppression (/=5. A score>/=5 had a PPV of 100% to detect a VL>40 copies (95%CI: 84-100), and of 90% to detect a VL>/=5000 copies (70-97). Within the score, adherence/=5 and 4 (5%) if score/=5 among patients fulfilling WHO-criteria had a PPV of 100% for a detectable VL and 90% for viral failure. In settings without regular access to VL-testing, this PPV may be considered high enough to switch this patient-group to second-line treatment without confirmatory VL-test.