In resource-poor settings, the resistance pattern of a patient who is failing therapy will most likely not be known; however, it is reasonable to assume that the following resistance patterns will be present: the N103 mutation, which confers resistance to both NVP and EFV; the 184 mutation, which confers resistance to 3TC; and multiple NRTI mutations that confer resistance to AZT and d4T. Because a high cross-resistance between AZT and d4T is manifested when one of these drugs is used in the first-line regimen, including the other drug in a second-line regimen is not recommended.¹⁶

Based on the aforementioned mutations and as indicated in Table 3.1, the WHO recommends the use of an empiric second-line regimen consisting of TDF as the nucleoside backbone; ABC, 3TC, or an AZT/3TC combination as the second agent; and the potent combination of LPV/RTV as the third agent. Protocol 3.3 presents an algorithm for determining the necessity of switching to second-line treatment.