After first-line ART: towards an evidence-based SECOND-LINE.

2062 www.thelancet.com Vol 381 June 15, 2013 Access to antiretroviral therapy in low-income and middle-income countries has been scaled-up eff ectively in the past decade; however, failure of the fi rst-line regimen is increasing. In The Lancet, the SECOND-LINE Study Group provide a high-quality evidence-based strategy for safe and eff ective treatment of patients in whom fi rstline treatment has failed. They did a randomised clinical trial to compare a WHO-recommended second-line treatment regimen—a ritonavir-boosted protease inhib itor (lopinavir) plus two or three nucleoside or nucleotide reverse transcriptase inhibitors (NtRTIs)— with a novel dual-treatment approach that combined ritonavir-boosted lopinavir with the integrase inhibitor raltegravir. The investigators showed that the effi cacy of the new regimen was non-inferior to standard treatment: 223 (83%) of 270 patients in the raltegravir group versus 219 (81%) of 271 in the control group had a plasma viral load of less than 200 copies per mL at week 48 (diff erence 1·8%, 95% CI –4·7 to 8·3). No major safety issues emerged in either group. Patients who took raltegravir had signifi cantly larger increases in CD4 T-cell count than patients who took the control regimen. These fi ndings are important because they show that the WHO-recommended second-line treatment is an effi cacious rescue regimen. Furthermore, they suggest that the new regimen has equal effi cacy, but with other potential advantages. First, use of a single treatment based on only two diff erent compounds for all the patients failing fi rst-line treatment will ease demand on drug supply and stocks. Second, simple regimens might enable treatment to be delivered by trained, but non-medical, health-care workers, improving access to HIV care in settings with limited resources. Third, because the rescue treatment consists of two drugs from antiretroviral classes to which patients have not been previously exposed, genotypic resistance testing is not needed, saving time, money, and eff ort. Finally, the raltegravir regimen is likely to cause fewer toxic eff ects than NtRTI-based treatments. Nevertheless, these advantages are counterbalanced by the higher cost of raltegravir—at present, it is prohibitively expensive in many low-income and middle-income countries. The study by Boyd and colleagues provides a tradeoff , instead of settling for only what is readily available at a reasonable price in resource-constrained settings. However, although the cost of raltegravir will hopefully drop owing to competition with other integrase inhibitors soon to be licensed, new mechanisms to provide wider access to raltegravir are needed if it is to be included in second-line regimens. Progress in expanding HIV care in the past decade has been based on a public health approach, especially the introduction of a simple, eff ective, safe, and toler able standardised fi rst-line antiretroviral treatment regimen. According to guidelines, three regimens could be used sequentially, with exponentially increas ing costs, in case After fi rst-line ART: towards an evidence-based SECOND-LINE injecting drug users. The introduction of PrEP for HIV prevention in injecting drug users should be considered as an additional component to accompany other proven prevention strategies like needle exchange pro grammes, methadone programmes, promotion of safer sex and injecting practices, condoms, and HIV counselling and testing. PrEP as part of combination prevention in injecting drug users could make a useful contribution to the quest for an AIDS-free generation.