HIV-infected patients have a higher burden of comorbidities than the general population and drug-drug interactions limit the choice of antiretroviral compounds, also limiting the possibility of drug sequencing in case of toxicity or failure. In our patient, affected by HIV-related pulmonary hypertension (HIV-PAH), the use of sildenafil and ambrisentan excluded the possibility of using two of the main classes of antiretrovirals, protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs). Having failed a combination regimen based on raltegravir, while awaiting the results of genotypic testing for drug resistance she was switched to dolutegravir, a brand new integrase strand transfer inhibitor (INSTI) with high genetic barrier, and in one month her HIV-1 viremia dramatically dropped to undetectable levels. The genotypic test revealed resistance to all the drugs she was taking including dolutegravir. The backbone was changed to a dual regimen including rilpivirine and viral suppression was maintained at three months. Unprecedented pharmacokinetic data are provided for the two antiviral drugs in combination with sildenafil and ambrisentan.
| [1] | D'Alonzo GE, Barst RJ, Ayres SM, Bergofsky EH, Brundage BH, Detre KM, Fishman AP, Goldring RM, Groves BM, Kernis JT, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med. 1991; 115(5): 343-349.View Article PubMed |
| [2] | Baldi F, Fuso L, Arrighi E, and Valente S. Optimal management of pulmonary arterial hypertension: prognostic indicators to determine treatment course. Therapeutics and Clinical Risk Management 2014:10 825-839. |
| [3] | Barnett CF and Hsue PY: Human Immunodeficiency Virus–Associated Pulmonary Arterial Hypertension. Clin Chest Med. 2013; 34(2): 283-292.View Article PubMed |
| [4] | Feijoo MQ et al. Relationship between endothelin-1 levels and pulmonary arterial hypertension in HIV-infected patients. AIDS. 2014 Nov 28; 28(18):2693-9.View Article PubMed |
| [5] | Pal J, et al. Effect of antiretroviral therapy on pulmonary hypertension in HIV patients J Indian Med Assoc. 2013 Dec; 111(12):845-6, 849. PubMed |
| [6] | Muirhead GJ, Wulff MB, Fielding A, Kleinermans D, and Buss N. Pharmacokinetic interactions between sildenafil and saquinavir/ritonavir. Br J Clin Pharmacol. 2000 August; 50(2): 99-107.View Article PubMed |
| [7] | Schöller-Gyüre M, Debroye C, Vyncke V, et al. Effect of TMC125 on sildenafil pharmacokinetics. Abs. 45, 7th International Workshop on Clinical Pharmacology of HIV Therapy, Lisbon, April 2006. |
| [8] | Dingemanse J, van Giersbergen PL, Patat A, and Nilsson PN. Mutual pharmacokinetic interactions between bosentan and lopinavir/ritonavir in healthy participants. Antivir Ther, 2010, 15(2): 157-163.View Article PubMed |
| [9] | Humbert M, Segal ES, Kiely DG, et al. Results of European post-marketing surveillance of bosentan in pulmonary hypertension. Eur Respir J 2007; 30: 338-344.View Article PubMed |
| [10] | Lennox JL, DeJesus E, Lazzarin A, Pollard RB, Madruga JV, Berger DS, Zhao J, Xu X, Williams-Diaz A, Rodgers AJ, Barnard RJ, Miller MD, DiNubile MJ, Nguyen BY, Leavitt R, Sklar P; STARTMRK investigators. Safety and efficacy of raltegravir-based versus efavirenz-based combination therapy in treatment-naive patients with HIV-1 infection: a multicentre, double-blind randomised controlled trial. Lancet. 2009 Sep 5; 374(9692): 796-806.View Article |
| [11] | Kobayashi M Yoshinaga T, Seki T, Wakasa-Morimoto C, Brown KW, Ferris R, Foster SA, Hazen RJ, Miki S, Suyama-Kagitani A, Kawauchi-Miki S, Taishi T, Kawasuji T, Johns BA, Underwood MR, Garvey EP, Sato A, and Fujiwara T. In vitro antiretroviral properties of S/GSK 1349572, a next generation HIV integrase inhibitor. Antimicrob Agents Chemother 2011; 55: 813-21.View Article PubMed |
| [12] | Underwood MR Johns BA, Sato A, Martin JN, Deeks SG, and Fujiwara T. The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults. J Acquir Immune Defic Syndr 2012; 61: 297-301.View Article PubMed |
| [13] | Castagna A Maggiolo F, Penco G, Wright D, Mills A, Grossberg R, Molina JM, Chas J, Durant J, Moreno S; the VIKING-3 Study group. Dolutegravir in Antiretroviral-Enperienced Patients With Raltegravir- and/or Elvitegravir-Resistant HIV-1: 24-Week Results of the Phase III VIKING-3 Study. JID 2014 Aug 1; 210(3): 354-62.View Article PubMed |
| [14] | Gulick R. HIV treatment 2020: what will it look like? Journal of the International AIDS Society 2014, 17(Suppl 3): 19528.View Article PubMed |