The study titled “A Randomized Comparison of two Regimens of Chemotherapy with Compatible Antiretroviral Therapy for Treatment of Advanced AIDS-KS in Resource-Limited Settings” is a phase III, open-label, prospective, 2-arm randomized study stratified by CD4+ lymphocyte cell count and by country. This study will estimate the difference in event (KS progression, death, entry into an additional step, or loss to follow-up, prior to week 48) rates between two “experimental” regimens (ART initiation + BV   which are considered standard of care therapies in resource limited settings) and an active control (ART initiation + Paclitaxel - PTX: a standard treatment in the United States that is sometimes used as salvage therapy for relapsed/refractory KS in resource-limited settings) for the treatment of HIV-infected, ART-naive participants presenting with advanced KS.

The target population includes males and females ³ 18 years of age with the following characteristics: documentation of HIV-1 infection, biopsy diagnostic of KS, current advanced  KS ( T1 stage KS), systemic chemotherapy for KS and radiation treatment naïve, and currently not receiving ART. A total of 706 participants, ≥18 years of age will be enrolled across all sites. Randomization will be stratified by screening peripheral blood CD4+ lymphocyte cell count (< 100 or  ³ 100 cells/mm³) and ART history (naïve or experienced). At study entry participants will be randomized in 1:1 fashion to one of the following 2 arms in Step 1: , arm 1B, co-formulated EFV/FTC/TDF with blemomycin/Vincristine(BV) and Arm 1C, Co-formulated EFV/FTC/TDF with PTX . In Step 2, at the discretion of the site investigator, after confirmation of disease progression by the IERC (Independent Endpoint Review Committee), participants who experience KS progression will receive second course of chemotherapy utilized in Step 1 (up to 6 cycles)  co-formulated EFV/FTC/TDF. In step 3, participants will receive randomly assigned chemotherapy co-formulated with EFV/FTC/TDF. In Step 4, following Clinical Management Committee (CMC) and IERC-confirmed KS progression on Step 3, or if there is dose-limiting toxicity after receiving less than 4 cycles of chemotherapy in Step 3, in the absence of a complete response (CR) or partial response (PR), participants will be assigned to the remaining study-provided chemotherapy not given in Step 1, Step 2, or Step 3. All participants will be followed for 5 years after randomization or assignment to the last step they enter.

The primary endpoint incorporates lack of KS progression, death, entry into an additional step, or loss to follow-up, prior to week 48. The main interest of the study is the outcome at 48 weeks after the treatment initiation. The primary analyses will consist of the construction in the proportion of 48-week event rates between each experimental regimen and the active control (ART initiation with PTX).