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This study is based on evidence that (1) HIV\u2010PIs can improve pulmonary hemodynamics in experimental models; (2) both Toll\u2010like receptor 4 and high\u2010mobility group box 1 (HMGB1) participate in the pathogenesis of experimental pulmonary hypertension; and (3) a high\u2010throughput screen for inhibitors of HMGB1\u2010induced macrophage activation yielded HIV\u2010PIs as potent inhibitors of HMGB1\u2010induced cytokine production. In this proposed open\u2010label, pre\u2010post study, micro, low, and standard doses of SQV+RIT will be given to IPAH patients for 14\u00a0days. Patients will receive follow\u2010up for the next 14\u00a0days. The primary outcome to be evaluated is change in HMGB1 level from baseline at 14\u00a0days. The secondary outcome is changes in tumor necrosis factor \u03b1, interleukin 1\u03b2, interleukin 6, C\u2010reactive protein, pulmonary arterial pressure based on echocardiography parameters and New York Heart Association\/World Health Organization functional class, and Brog dyspnea scale index from baseline at 14\u00a0days. Other secondary measurements will include N\u2010terminal pro\u2010brain natriuretic peptide, atrial natriuretic peptide, and 6\u2010minute walk distance. We propose that SQV+RIT treatment will improve inflammatory disorders and pulmonary hemodynamics in IPAH patients. If the data support a potentially useful therapeutic effect and suggest that SQV+RIT is safe in IPAH patients, the study will warrant further investigation. 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