7.5.1 Second-line ART for adults and adolescents

Consolidated ARV guidelines, June 2013

NRTI backbone

The Guidelines Development Group maintained the rationale adopted in 2010, recommending drug sequencing consistent with ART-optimizing principles (in particular, availability as fixeddose combinations and tolerability) and resistance mutation risk, based on the NRTIs used in the first-line regimen. If a thymidine analogue NRTI (AZT or d4T) was used in the failing firstline regimen, TDF should be used in the second-line regimen. If a non-thymidine analogue NRTI was used in first-line ART (that is, TDF), AZT should be used in second-line ART. Other NRTI drugs such as ABC and ddI are acceptable as potential back-up options in special situations but are not recommended as preferred alternatives, since they have no specific advantage and add complexity and cost.

For individuals coinfected with HIV and HBV whose first-line regimen contained TDF + 3TC (or FTC), these NRTIs should be continued in the second-line regimen for the anti-HBV activity and to reduce the risk of hepatic flares, regardless of the selected second-line regimen, which should be AZT + TDF + 3TC (or FTC) + a boosted PI.

For people with active TB disease receiving rifampicin, all boosted PIs in standard doses are contraindicated because of drug interactions and significant reductions in PI plasma concentrations (227–230). In this situation, LPV/r and SQV/r may be used with an adjusted, superboosted dose of RTV (LPV/r 400 mg/400 mg twice daily or SQV/r 400 mg/400 mg twice daily) or doubling the LPV/r daily dose (LPV/r 800 mg/200 mg twice daily), but this is associated with high levels of toxicity and requires close clinical and laboratory monitoring. The recommendation to use LPV/r 800 mg/200 mg twice daily is based on evidence graded as low-quality, and it is associated with a similar level of toxicity as LPV/r 400 mg/400 mg twice daily (230,231). However, this option may be less complex and more feasible, since LPV/r is widely available as a single formulation, whereas RTV is not. However, when rifabutin is used in place of rifampicin, all boosted PIs can be concomitantly administered in their standard doses (Table 7.19).