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. Treatment failure is considered as either clinical failure, immunological failure or virological failure.
Clinical failure :
It is defined as recurrent, persistent or new HIV related illness after at least 3 months on ART. Also lack or decline of growth rate, development of encephalopathy or neuroregression is taken as clinical failure. 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.
Immunological failure : Immunological failure is considered in following circumstances:
- 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.
- Developing or returning to the following age-related immunological thresholds after at least 24 weeks on ART, in a treatment-adherent child: CD4 count of =200 cells/mm3 or %CD4+ =10% for a child more than 2 years to less than 5 years of age and CD4 count of =100 cells/mm3 for a child 5 years of age or more.
Virologic failure : Virological failure is defined as follows:
- Inability of viral load to below undetectable levels within 6 months of initiating 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).
When to switch ARV drugs for treatment failure
There are no data on when to switch ART in children with detectable viremia in order to minimize the evolution of drug-resistant virus. Available drug regimens, viral resistance profiles, adherence issues and readiness of the family and child to switch; all need to be considered. Adding or substituting single drugs in a failing ART regimen without resistance testing risks giving the new drug as effective monotherapy which may result in rapid development of further resistanc?e. It is therefore recommended that all changes in therapy with detectable viremia be preceded by a resistance test unless it is unequivocal that there is no cross-resistance with previous drugs received. Ideally resistance testing should be performed while the patient is still on the old regimen, or within a few weeks of stopping. Expert opinion should be sought in interpreting resistance genotypes. The general rule is to change all the drugs in the regimen after first-line ART failure with resistance. Lamivudine (3TC) and Abacavir (ABC) may be switched to Zidovudine (ZDV) and Didanosine (ddl) or in adolescents, ZDV and tenofovir, which may be preferable as cross resistance, may occur between ABC and ddl. Failure of an NNRTI-based regimen is often as a result of viral drug resistance, and switching to a boosted PI is appropriate. Failure of a boosted PI-based regimen is more likely to be because of poor adherence than resistance. If resistance is detected, a switch to an NNRTI-based regimen or another PI without overlapping resistance may be appropriate. If resistance is not detected, continuing the PI with enhanced adherence support should be considered. Any change in regimen should be preceded by a thorough re-assessment of adherence, and a plan for adherence monitoring of the new regimen.