Drug resistance testing is used to identify gene mutations that suggest reduced drug susceptibility. There are 2 types of resistance testing available predominantly.
1. Genotype tests:- They detect specific genetic mutations. They are based on amplification procedures and can detect mutations in plasma samples with move than 1000 copies/ml of HIV RNA.
2. Phenotype tests:- Phenotypic assays measure the IC50 of the drug against the virus in vitro. Although, the sensitivity patterns of the virus tested can be determined, it may not detect minor species of resistant viruses.
In children, resistance testing may be advised when the child has multiple regimen failure or suboptimal viral load response to therapy. In patients in whom an antiretroviral regimen is failing, it is preferable that blood sample for resistance testing should be obtained while the patient is taking the failing regimen. Resistance testing should be performed by laboratories that have appropriate operator training, certification and proficiency assurance.
ART resistance:- For some drugs such as 3TC and all available NNRTI, a single mutation induces high grade resistance. For other drugs such as AZT, ABC, TDF and most PIs, high-grade resistance requires the serial accumulation of multiple mutations and is thus slower to emerge. Other drugs such as ddI & d4T are associated only with low level of resistance as measured in phenotypic assays predicting decreased efficacy.
NRTI resistance mutations:- Three patterns of multi-NRTI resistance mutations have been identified:
1. Q 151 M complex
2. Mutation at codon 69
3. Thymidine associated mutations (TAMs).
TAMs lead to multi NRTI resistance with reduced susceptibility to all NRTIs.
Note:- Certain single mutations such as M 184 V may confer resistance to lamivudine and didanosine but enhance sensitivity to zidovudine, stavudine and tenofovir.
NNRTI resistance:- Two patterns of multi-NNRTI resistance have been described.
1. K 103 N mutations – confers resistance to all currently available NNRTIs.
2. Accumulation of multiple mutations.
PI resistance:- Several drugs in this class have distinctive major resistance mutations. One strategy to avoid accumulations of multiple mutations is to use low dose ritonavir to “boost” other PIs.
Thus genotypic and phenotypic results should be interpreted by individuals who are knowledgeable in antiretroviral therapy and drug resistance patters.
