PROGRESS is a 96-week , open-label, randomised study for first-line therapy in HIV-infected adults. 206 patients were randomised 1 :1 to lopinavir/ritonavir 400/100 mg twice daily plus raltegravir 400 mg twice daily (n = 101) or lopinavir/ritonavir 400/100 mg twice daily plus fixed dose tenofovir/emtrictabine 300/200 mg once daily (n = 105). At baseline, mean plasma HIV-1 RNA was 4.25 log10 copies/ml and mean CD4 cells count 294/mm3. At week 96, proportion of patients with plasma HIV-1 RNA < 40 copies/ml with the intent to treat-TLOVR analysis was 66.3% for lopinavir/ritonavir + raltegravir and 68.6% for lopinavir/ritonavir + tenofovir/emtricitabine. In the observed data analysis, proportions were 88.9% and 85.2%, respectively. Discontinuation prior to week 96 was seen in 18.8% in the lopinavir/ritonavir + raltegravir group and 14.3% in lopinavir/ritonavir + tenofovir/emtricitabine. Among the 13 subjects who met protocol-defined virologic failure, 3/8 had resistance mutations detected at faiulre in the lopinavir/ritonavir +raltegravir (3 with integrase resistance of whom 1 had also protease resistance) and 1/5 in the lopinavir/ritonavir + tenofovir/emtricitabine (M184V). Diarrhea was the most common adverse event in both groups, 7.9% vs 16.2%. No difference in changes in lipid parameters was seen between groups at week 96. Mean decrease in eGFR was significantly greater at week 96 in the lopinavir/ritonavir + tenofovir/emtricitabine group ( -7.33 vs – 1.43 ml/min, p = 0.035). In a subset of 160 patients with DXA analysis, fat increase through 96 weeks was significantly higher in the arms and legs, but not in the trunk in the lopinavir/ritonavir + raltegravir group, while mean change in total bone mineral density was highly significant between groups (+0.68% in the lopinavir/ritonavir + raltegravir group vs -2.48% in the lopinavir/ritonavir + tenofovir/emtricitabine (p < 0.001).