HIV protease inhibitors in pulmonary hypertension: Rationale and design of a pilot trial in idiopathic pulmonary arterial hypertension

Ying Li, Xiao Hui Li, Zai Xin Yu, Jing Jing Cai, Timothy R. Billiar, Alex F. Chen, Ben Lv, Zi Ying Chen, Zhi Jun Huang, Guo Ping Yang, Jie Song, Bin Liu, Hong Yuan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


We propose an exploratory clinical study, the first of its kind to our knowledge, to determine the safety and potential clinical benefit of the combination of the HIV protease inhibitors (HIV-PIs) saquinavir and ritonavir (SQV+RIT) in patients with idiopathic pulmonary arterial hypertension (IPAH). This study is based on evidence that (1) HIV-PIs can improve pulmonary hemodynamics in experimental models; (2) both Toll-like receptor 4 and high-mobility group box 1 (HMGB1) participate in the pathogenesis of experimental pulmonary hypertension; and (3) a high-throughput screen for inhibitors of HMGB1-induced macrophage activation yielded HIV-PIs as potent inhibitors of HMGB1-induced cytokine production. In this proposed open-label, pre-post study, micro, low, and standard doses of SQV+RIT willbe given to IPAH patients for 14 days. Patients will receive follow-up for the next 14 days. The primary outcome to be evaluated is change in HMGB1 level from baseline at 14 days. The secondary outcome is changes in tumor necrosis factor α, interleukin 1β, interleukin 6, C-reactive 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 days. Other secondary measurements will include N-terminal pro-brain natriuretic peptide, atrial natriuretic peptide, and 6-minute 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.

Original languageEnglish
Pages (from-to)538-546
Number of pages9
JournalPulmonary Circulation
Issue number3
StatePublished - 21 Jul 2015
Externally publishedYes


  • Clinical trial
  • HIV protease inhibitors
  • Inflammation
  • Pulmonary hypertension


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