Changing Antiretroviral Therapy

Changing antiretroviral therapy
ART regimen may be changed in the following circumstances:

Failure of current regimen

Toxicity or intolerance to current regimen

Treatment failure:- Poor adherence, inadequate drug levels, prior existing drug resistance or inadequate potency of the drugs chosen can all contribute to ARV treatment failure.

Clinical failure:- Recurrent, persistent or new HIV related illness after at least 3 months on ART. Symptoms of opportunistic infections occurring in the first 3 months of ART concurrent with a rapid rise of CD4 values is termed as immune reconstitution syndrome (IRIS) and is not failure of ART. Pulmonary tuberculosis alone is not indicative of treatment failure and thus does not necessitate change is second line therapy. Response to antituberculous therapy should be evaluated to determine need for changing therapy. Also lack or decline of growth rate, development of encephalopathy or neuroregression is taken as clinical failure.

Immunological failure

Persistently declining CD4 cell count measured on at least 2 separate occasions

Failure to increase age related CD4 threshold despite an adequate trial of ART.

Virologic failure

Inability of viral load to below undetectable levels within 6 months of initiating therapy. (In patients with alternative regimens, stabilization of viral load below previous baseline may be an appropriate goal of therapy).

Repeated detection of virus in plasma after initial suppression to undetectable levels. (Ensure that increase is not due to infection, vaccination or problems with test methodology. Increase should be at least 3 fold from lowest viral load level).

Choice of new antiretroviral regimen
The following principles should be follows:

When therapy is changed because of toxicity and intolerance, agents with different side effect profile should be chosen.

When changing therapy because of treatment failure, adherence should be assessed as a potential cause of failure. If patient is adherent, change at least 2 drugs and assume development of drug resistance. (Change in one drug or addition of a drug to a failing regimen is suboptimal).

The potential for cross-resistance between ARVs should be considered in choosing new drugs.

In patients on NNRTI based regimen, a regimen based on PI (boosted if possible) should be advocated.

In patients on PI, resistance testing helps to determine whether other PIs or NNRTI should be an option.