ALTHOUGH IMPORTANT DEVELOPMENTS in antiretroviral treatment have occurred, the ability to durably suppress HIV replication is still quite limited. Current guidelines recommend the introduction of at least two compounds not included in the discontinued regimen for treatment failures.1–3 This approach is based on the assumption that resistance mutations may be present at the time of failure, and thus, the new combination would be effective only if there were enough new drugs in the regimen. However, drug resistance is not always found in patients with treatment failure.4–6 Taking into account that responses to second and third lines of therapy are usually poorer than to initial treatment,7,8 it is expected that after one failure, subsequent treatment changes will be necessary. Moreover, adverse effects can contribute to drug discontinuation,9,10 narrowing the availability of treatment options. An increasing number of individuals have exhausted most or all available drugs, and have limited options to control HIV replication. The broadly accepted principle “the more (drugs) you change the better” needs to be reconsidered in view of economizing the available antiretroviral agents.11 In this context, certain clinical scenarios might merit consideration. In particular, the addition of one or two more drugs to an active but insufficient regimen might achieve the goal of durable HIV suppression without compromising other drugs that might be valuable for the future. While this “intensification” approach is not recommended in any of the published guidelines, it could be considered a reasonable option in some circumstances.