Treatment failure can be defined as virologic, immunologic and/or clinical. Treatment failure results from failure to suppress viral replication with the development of viral resistance. Primary virologic failure is less than 10 fold drop in viral load after 6-8 weeks of therapy. Secondary virologic failure is 10 fold increase from lowest recorded level. Immunologic failure is defined as a 30% drop in CD4 count from peak value or a return to pre-ART baseline or lower. Clinical failure is progression of disease with the development of opportunistic infections or malignancy occurring 3 months or more after initiation of ART.
In Tanzania, immunological and clinical parameters will be used to identify failure. However, in light of dropping costs of performing viral load measurements, along with simplification of the processes, where available, viral load parameters should also be applied.
Clinical failure must be distinguished from Immune Reconstitution Syndrome. A favourable CD4 T-cell response can occur with incomplete viral load suppression and might not indicate an unfavourable prognosis. Continuation of existing therapy does not lead to rapid accumulation of drug-resistant virus in every patient. A reasonable strategy is maintenance of the regimen, with redoubled efforts at optimising adherence and increased monitoring. If it is determined that a patient should switch regimens due to treatment failure, there should be a switch from their first-line combination to a completely new standardized second-line regimen.