The reasons for altering an initial antiretroviral regimen include intolerance leading to poor adherence, drug toxicity, the occurrence of active tuberculosis or pregnancy, and treatment failure.

A. Changing because of failure

When considering a complete regimen switch for treatment failure, the first point for discussion is the definition of failure. Treatment failure can be defined as clinical, immunological and/or virological. Clinical failure is clinical disease progression with the development of an opportunistic infection or malignancy when the drugs have been given sufficient time to induce a protective degree of immune restoration. This needs to be differentiated from an immune reconstitution syndrome, which can be seen within the first several weeks after the institution of therapy if a subclinical infection is present at baseline ⁸⁸. Although the management of immune reconstitution syndromes can be difficult, changing the antiretroviral regimen in this circumstance is not indicated. Immunological failure can be defined as a fall of over 30% in CD4 counts from the peak value or a return to or below the pre-therapy baseline ¹⁶. There is no accepted definition of immunological failure which can be used if CD4 counts are not available. Virological failure has no uniformly accepted definition but repeated, continued detectable viraemia is indicative of incomplete viral suppression. As measuring viral load is not an option in the majority of resource-constrained settings, and is not recommended for the routine monitoring of treatment in the present guidelines, the reader is referred to other guidelines ¹⁶ on the use of viral load monitoring of ARV treatment. However, it is to be hoped that this situation will change as less expensive approaches to viral load quantitation are developed.

B. Changing because of toxicity

In the setting of a good therapeutic response, the development of a clearly definable toxicity permits single drug substitutions without compromising the overall regimen. For example, d4T can be substituted for ZDV in the event of ZDV-related symptoms or anaemia, and NVP can be substituted for EFZ if EFZ-related symptoms affecting the central nervous system are unremitting. In respect of other toxicities for which a specific causal agent cannot be identified, and/or of low-grade but intolerable side-effects that frequently compromise adherence, a complete regimen switch may be the most adequate and broadly implementable approach. The choice of approach partly depends on the formulary that is available in the country concerned. If an interruption in therapy is indicated in order to deal with toxicity the entire regimen should be temporarily stopped so as to prevent the emergence of drug resistance (see Chapter XV, Table 10 and Annex 11).