Abstract
Limited access to virological monitoring has led to a high prevalence of resistance to nucleoside reverse transcriptase inhibitors (NRTIs) at the time of first line failure in most studies from low- and middle-income countries (LMIC). Nevertheless, the current standard of care is to include NRTIs in second line regimens. The activity of tenofovir/emtricitabine following failure of stavudine/lamivudine or zidovudine/lamivudine is dependent on the sensitivity of the monitoring strategy used during first line therapy and the threshold for switching, whereas these factors are less important if the opposite sequencing strategy is used. Boosted protease inhibitors (PIs) are the foundation of effective second-line therapy with demonstrated efficacy in early salvage regimens and high barrier to resistance. Lopinavir/ritonavir and ritonavir-boosted atazanavir have recently been described by the World Health Organization as preferred boosted PIs for use in LMIC. Alternative approaches currently under investigation include boosted PI monotherapy, dual boosted PIs, and the combination of raltegravir (an HIV integrase inhibitor) and a boosted PI.