Efficacy, Safety and Pharmacokinetics of DTG with RIF

This is a Stage II, randomized, open-label study describing the efficacy and safety of DTG 50 mg OD with food and DTG 50 mg BID plus 2NRTIs in HIV/TB co-infected patients receiving RIF based anti-TB therapy. The study will be conducted in approximately 200 HIV-1 infected individuals who are ART-naïve and newly diagnosed with probable or confirmed pulmonary, pleural, or lymph node (LN) Mycobacterium TB (MTB) taking RIF-containing first-line TB treatment. Subjects should have confirmed RIF-sensitive MTB infection as determined by GeneXpert (or equivalent approved molecular test) or mycobacterial culture.

The study is comprised two different stages:

1. Stage1, investigators will test the safety and tolerability, as well as Pharmacokinetics (PK), of two different doses of dolutegravir co-administered with standard anti-TB treatment. Overall, 40 HIV/TB patients will be enrolled. They will be randomized to 2 groups (DTG 50 mg with food and DTG 50 mg BID). Intensive PK of DTG will be performed at week 4. Interim analysis will be performed if all 40 cases completed 12 weeks and 24 weeks. Premature study termination will be set for

1. proportion of HIV RNA \< 50 copies/ml at week 24 between 2 group is different \> 20% 2. DTG 50 mg with food has geometric mean DTG Ctrough \< 0.3 mg/L If there is no premature study termination met, the study will move to stage 2. Stage 2 will only be recruited if two different doses of dolutegravir are well tolerated and safe. 2. Stage 2: 160 HIV/TB patients will be enrolled. They will be randomized to 2 groups (DTG 50 mg with food and DTG 50 mg BID). DTG concentration will be performed at week 4 and 48. Interim analysis will be performed if all 200 cases completed 24 weeks.

• AUC of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID [Срок оценки: Week 4]
• Cmax of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID [Срок оценки: Week 4]
• Cmin of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID [Срок оценки: Week 4]
• Oral clearance of DTG concentration between DTG 50 mg with food OD and DTG 50 mg BID [Срок оценки: Week 4]
• Proportion of subjects with plasma HIV-1 RNA <50 c/mL at Week 24 [Срок оценки: Week 24]
• Changes in CD4+ counts from baseline to Week 24 and Week 48 [Срок оценки: Weeks 24 and 48]
• Incidence of disease progression [Срок оценки: Week 48]
• Proportion of subjects that have completed TB treatment [Срок оценки: Week 48]
• Proportion of subjects that are cured from TB [Срок оценки: Week 48]
• Proportion of subjects that have relapsed [Срок оценки: Week 48]
• Proportion of subjects that have defaulted [Срок оценки: Week 48]
• TB outcome in terms of cure [Срок оценки: Week 48]