Phenotypic NNRTI resistance and genetic diversity in antiretroviral naive women
Polly Clayden, HIV i-Base
A poster from Susan Eshleman and coworkers presented findings from a study in which they used a sensitive phenotypic assay to determine the frequency of antiretroviral resistance in drug naive Ugandan women who subsequently received single dose nevirapine for prevention of HIV-1 mother to child transmission in the HIVNET 012 trial.
The investigators tested 24 subtype A and 25 subtype C samples for nevirapine and efavirenz resistance and found 38 samples (78%) to have phenotypic NNRTI resistance. They found the frequency of resistant variants ranged from 0.31.9%.
Twenty-one of the samples (half of those with phenotypic resistance) had known NNRTI resistance mutations at frequencies of 0.151.1%. Among the 13,870 RT isolates, the NNRTI-resistant mutations K101E (2), K103N (1), V106A (12), V108I (2), Y181C (6), Y188C (6), Y188H (3), Y188C (5), M230L (2), P236L (1) and L283I (1) were present.
Some isolates with phenotypic NNRTI resistance that lacked known NNRTI resistance mutations had unusual variants not present in the majority species. These variants that confer phenotypic resistance include: L100V, K102R, K103E/R, K104R, I132L/M/T/V, Y188N, M230I/R/V and L283C.
The investigators summarised their findings:
- NNRTI-resistant viruses are present at low levels in most ARV drug naive Ugandan women.
- In 35% of these samples, phenotypic NNRTI resistance was not explained by IAS-defined NNRTI resistance mutations.
- Combinations of polymorphisms result in decreased NNRTI susceptibility.
- The frequency of drug resistance varies among individuals suggesting that discrete viral populations have different levels of genetic diversity.
- A coupled reverse transcription/mutation assay identifies patient-derived RT variants that may replicate with different levels of fidelity.
Nissley DV, Church JD, LA Guay et al. Phenotypic NNRTI resistance and genetic diversity in drug-naive individuals. XV International HIV Drug Resistance Workshop, Sitges, Spain, July 2006. Abstract 138.