SUMMARY  

• Clinical studies specifically designed to investigate the efficacy and/or safety of UPTRAVI in the treatment of pulmonary arterial hypertension (PAH) associated with human immunodeficiency virus (HIV) infection (HIV-PAH) have not been performed.
• In the phase 3, randomized, multicenter, double-blind, placebo-controlled, event-driven, GRIPHON (Prostacyclin (PGI2) Receptor Agonist In Pulmonary Arterial HypertensiON) study evaluating the long-term efficacy, safety and tolerability of oral UPTRAVI in 1156 patients with symptomatic PAH, 5 (0.9%) patients in the UPTRAVI arm and 5 (0.9%) patients in the placebo arm had HIV-PAH. However, no subgroup analysis was performed for this population of patients with HIV-PAH.¹
• A search of the scientific literature identified limited information of relevance from 1 publication describing the administration of UPTRAVI to a patient with HIV-PAH²; 3 additional citations are provided in the reference list.^3,4,5

CLINICAL DATA

Phase 3 Study

GRIPHON

The phase 3 GRIPHON study was a randomized, multicenter, double-blind, parallel group, placebo-controlled, event-driven trial evaluating the efficacy and safety of oral UPTRAVI in adult patients with PAH. UPTRAVI or matching placebo was initiated at 200 mcg twice daily (BID) and up-titrated, usually at weekly intervals, until the individual highest tolerated dose was attained (maximum up to 1600 mcg BID).¹

A total of 1156 patients were enrolled in the study and randomized 1:1 to receive either UPTRAVI (200–1600 mcg BID; n=574) or matching placebo (n=582). The number of patients with different PAH etiologies at baseline in the GRIPHON study is reported in Table: Number of Patients with Different PAH Etiologies at Baseline in the GRIPHON Study below. Five (0.9%) patients in the UPTRAVI arm and 5 (0.9%) patients in the placebo arm had HIV-PAH. No subgroup analysis was performed for this population of patients with HIV-PAH.¹

Case Report

Sargent et al (2020)² described a patient with HIV-PAH who had been treated with a triple therapy including intravenous (IV) epoprostenol attaining a low-risk status and was then switched to a triple therapy including oral UPTRAVI instead of IV epoprostenol by following a specific 20-week transition protocol. The patient’s UPTRAVI dose reached 1600 mcg BID in April 2017. Twelve weeks later, right heart catheterization (RHC) showed a mildly increased mean pulmonary arterial pressure (mPAP=37 mmHg), but the patient had unchanged 6-minute walk distance (6MWD=420 meters). Three months later, the patient’s 6MWD had improved to 540 meters. In October 2018 RHC showed an mPAP of 28 mmHg, pulmonary vascular resistance of 2.20 Wood units, cardiac index of 3.0 L/min/m2. At the last reported evaluation in February 2019, the patient presented with New York Heart Association Functional Class I to II symptoms with a 6MWD of 530 meters. No information on safety outcomes is reported.

Literature Search

A literature search of MEDLINE^®, EMBASE^®, BIOSIS Previews^®, DERWENT^® (and/or other resources, including internal/external databases) was conducted on 08 June 2024.