Improvement of HIV-related pulmonary hypertension after the introduction of an antiretroviral therapy

To the Editors:

The potential impact of combination antiretroviral therapy (CART) on HIV-related pulmonary arterial hypertension (PAH) remains controversial 1–4. We herein report the case of a dramatic improvement in PAH at the time of the inception of CART in a 19-yr-old female with HIV-1 infection due to mother-to-child transmission. HIV-related PAH was diagnosed in January 2006, when she was stable in stage A2 of the US Centers for Disease Control and Prevention classification without any antiretroviral therapy (table 1⇓). Specific PAH therapy with bosentan was started in January 2006, in combination with oral anticoagulant and diuretic therapy. CART was indicated at that time, but not prescribed owing to patient refusal. Her clinical condition slowly deteriorated (onset of major bilateral lower limb oedema and functional New York Heart Association (NYHA) class IV) until June 2006, leading to hospitalisation: right heart catheterisation revealed further haemodynamic deterioration (table 1⇓). Continuous intravenous epoprostenol therapy was added, and a dose of 15 ng·kg⁻¹·min⁻¹ was reached in September 2006. At that time, it was decided to commence antiretroviral therapy, including lopinavir, ritonavir, emtricitabine and tenofovir disoproxil. Simultaneously, the epoprostenol dose was increased to 25 ng·kg⁻¹·min⁻¹, reached in March 2007. A sustained improvement in her clinical condition was observed from the end of November 2006. Since January 2007, the viral load has been undetectable and the CD4 count has gradually risen to >500 cells·mm⁻³. Treatments for PAH and HIV infection have remained unchanged and a right heart catheterisation, performed in September 2007, demonstrated a dramatic improvement (table 1⇓). As the patient was in functional NYHA class I, it was decided to cautiously decrease the i.v. epoprostenol doses until its interruption, achieved in February 2008. Bosentan and CART were maintained unchanged. A right heart catheterisation, performed a few weeks after epoprostenol interruption, confirmed the stable results (table 1⇓).

This case report is remarkable, because first, in contradiction with previous reports on the effectiveness of these drugs in such a setting, a flare-up of PAH occurred despite the step-up in specific therapy with the combination of oral bosentan and i.v. epoprostenol. As an example, in the open-label study by Sitbon et al. 2, which evaluated the administration of bosentan in HIV-related PAH, an improvement in the 6-min walk distance was observed in all patients at week 16. Secondly, a dramatic clinical and haemodynamic improvement paralleled the introduction of CART and, furthermore, the withdrawal of epoprosterol was achieved. Data on the impact of CART on PAH are scarce and conflicting, with reports of either improvement 5, 6 or worsening 7, 8. One open-label 6-month study compared, in 36 previously untreated HIV-infected patients with PAH, the effect of the introduction of CART alone and the combination of CART and bosentan 9: at week 24, a significant decrease in mean pulmonary artery pressure from baseline was observed in the subgroup receiving the combination of CART and bosentan; this was not observed in the subgroup receiving CART alone. As case reports point to variable therapeutic responses of PAH to antiretroviral therapies, larger studies including HIV-related PAH patients with high CD4 counts are needed 10.

Statement of interest

None declared.