A randomised open-label study comparing the safety and efficacy of ritonavir boosted lopinavir and 2-3 nucleoside reverse transcriptase inhibitors (NRTI) backbone versus ritonavir boosted lopinavir and raltegravir in participants virologically failing first-line non-nucleoside reverse transcriptase inhibitors (NNRTI)/2 NRTI therapy (the SECOND-LINE study). This study is for Human Immunodeficiency Virus (HIV) infection.

Research Hypothesis: In HIV-infected subjects who have virologically failed first-line antiretroviral therapy comprising 2NRTI + NNRTI a regimen of second-line therapy incorporating ritonavir-boosted lopinavir and raltegravir provides comparable (i.e. non-inferior) antiretroviral efficacy over 48 weeks to a regimen containing ritonavir-boosted lopinavir and 2-3NRTIs. Study Design: This is a Phase IIIb/IV, international, randomised, open label study comparing two regimens of combination antiretroviral therapy in people living with HIV with confirmed virological failure of first-line NNRTI/2 NRTI regimens. The study will run for 96-weeks but the primary analysis will take place at the week 48 time point. Eligible participants will be randomised in equal proportions to one of two regimens of combination ART as follows: I. ritonavir boosted lopinavir (LPV/r) + 2-3NRTIs II. ritonavir boosted lopinavir (LPV/r) + raltegravir Number of Subjects per Group: Approximately 275 eligible subjects will be randomly allocated to each of the two treatment arms giving a study total of 550 participants.