Laboratoire de virologie, Hôpital Necker-Enfants malades, 149, rue de Sèvres, 75015 Paris
Resistance to non-nucleoside reverse transcriptase inhibitor (NNRTI) has been found to develop rapidly after initiation of NNRTI therapy with high level of phenotypic resistance and large cross-resistance to all licensed NNRTI. NNRTI-selected mutations confer little damage to viral fitness and persist in absence of drug. In HIV-1 non-B subtype, resistance profile could differ and survey is needed. Single dose of nevirapine in the prevention of HIV mother-to-child transmission was associated with selection of resistance and loss of virologic response to NNRTI including-regimen. Furthermore, with continued therapy, viral evolution persists, creating species with greater numbers of mutations and higher level of phenotypic resistance that limits future treatment options. Absence of immunologic and virologic effect when NNRTI interruption was proposed in patients with resistant virus suggest that these compounds have lost all their in vivo antiviral activity. Taken together, strong consideration should be given to discontinuing NNRTI after virologic failure is confirmed.