Whole blood platelet aggregometry in HIV-infected patients on treatment with abacavir

Rosario Palacios Muñoz, Jose A. González-Correa, Josefa Ruiz, Enrique Nuño, Manuel Márquez, Jose P. de la Cruz, Jesús Santos

Infectious Diseases Unit, Virgen de la Victoria Hospital, Málaga, Spain.
Pharmacology Department, Medicine School, Málaga University, Málaga, Spain.

DOI: 10.4236/ojim.2012.22013                

Abstract

Purpose: To assess platelet activity in HIV-patients with and without antiretroviral therapy (ART), analysing the influence of the presence or absence of ABC in the regimen. Methods: Observational, pilot study, including 30 asymptomatic HIV-patients: 20 on ART for at least 24 weeks and with undetectable HIV viral load - 10 on ABC, 10 on tenofovir (TDF) - and 10 na?ve patients, and a control group of 10 HIV-negative subjects. No subject was receiving drugs with antiagregant activity. Platelet activity was assessed by measuring time-dependent platelet aggregometry (electrical impedance on fasting whole blood), induced by ADP (1.25, 2.5 μM), collagen (0.5, 1 μg/mL), arachidonic acid (100, 200 μM), and U46619 (receptor agonist of the tromboxano A2) (1.25, 2.5 μM). Statistic program: SPSS, 16.0. Results: Demographic, anthropometric data, and cardiovascular risk factors were similar in all groups, but older age and longer time of HIV infection in the ABC group (50.4 vs 36.1, 34.2 and 42.7 years, respectively; p < 0.05, and 140.3 vs 88.1 and 48.3 months in the two other groups of HIV patients; p < 0.05). Mean CD4 cells count was 564/mm3. Platelet aggregation with exposure to U46619 was higher in the ABC compared with the TDF group (11.1 vs 4.4%; p = 0.007), na?ve patients (11.1 vs 5.7%; p = 0.014), and the HIV-negative group (11.1 vs 6.5%; p = 0.04). These differences remained significant when controlled for age and time of HIV infection. Conclusions: ABC increases platelet aggregability possibly in relation with the receptor of tromboxano. Wider studies are needed to confirm this hypothesis.

Keywords

Antiretroviral Therapy; Abacavir; Cardiovascular Risk; Platelet Activity

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1]	Santos, J., Palacios, R., González, M., Ruiz, J. and Márquez, M. (2005) Atherogenic lipid profile and cardiovascular risk factors in HIV-infected patients (Nétar Study). International Journal of STD & AIDS, 16, 677-680.
[2]	Jericó, C., Knobel, H., Sorli, M.L., Montero, M., Guelar, A. and Pedro-Botet, J. (2006) Prevalencia de factores de riesgo cardiovascular en pacientes con infección por el VIH. Revista Clínica Espa?ola, 206, 556-559.
[3]	Friis-M?ller, N., Reiss, P., Sabin, C.A., et al., Data Collection on Adverse Events of Anti-HIV Drugs (DAD) Study Group (2007) Class of antiretroviral drugs and the risk of myocardial infarction. The New England Journal of Medicine, 356, 1723-1735. doi:10.1056/NEJMoa062744
[4]	Holmberg, S.D., Tong, T.C., Ward, D.J., et al., HIV Outpatient Study (HOPS) (2002) Protease inhibitor drug use and adverse cardiovascular outcomes in ambulatory HIV-infected persons. Lancet, 360, 1747-1748. doi:10.1016/S0140-6736(02)11672-2
[5]	Mary-Krause, M., Cotte, L., Simon, A., et al., Clinical Epidemiology Group from the French Hospital Database (2003) Increased risk of myocardial infarction with duration of protease inhibitor therapy in HIV-infected men. AIDS, 17, 2479-2486. doi:10.1097/00002030-200311210-00010
[6]	Grinspoon, S., Grunfeld, C., Kotler, D.P., Currier, J.S., Lundgren, J.D., Dubé, M.P., et al. (2008) State of the science conference: Initiative to decrease cardiovascular risk and increase quality of care for patients living with HIV/AIDS: Executive summary. Circulation, 118, 198-210. doi:10.1161/CIRCULATIONAHA.107.189622
[7]	D’Arminio, A., Sabin, C.A., Phillips, A.N., Reiss, P., Weber, R., Kirk, O., et al. (2004) Cardio- and cerebro- vascular events in HIV-infected persons. AIDS, 18, 1811-1817. doi:10.1097/00002030-200409030-00010
[8]	Worm, S.W., Sabin, C., Weber, R., Reiss, P., El-Sadr, W., Dabis, F., et al. (2010) Risk of myocardial infarction in patients with HIV infection exposed to specific individual antiretroviral drugs from the 3 major drug classes: The data collection on adverse events of anti-HIV drugs (D: A:D) study. The Journal of Infectious Diseases, 201, 318-330. doi:10.1086/649897
[9]	Baker, J.V., Neuhaus, J., Duprez, D., et al., for the INSIGHT SMART Study Group (2011) Changes in inflammatory and coagulation biomarkers: A randomized comparison of immediate versus deferred antiretroviral therapy in patients with HIV infection. The Journal of Infectious Diseases, 56, 36-43.
[10]	Calmy, A., Gayet-Ageron, A., Montecucco, F., et al., STACCATO Study Group (2009) HIV increases markers of cardiovascular risk: Results of a randomized, treatment interruption trial. AIDS, 23, 929-939. doi:10.1097/QAD.0b013e32832995fa
[11]	Sabin, C.A., Worm, S.W., Weber, R., et al., D:A:D Study Group (2008) Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the D:A:D study: A multi-cohort collaboration. Lancet, 371, 1417-1426. doi:10.1016/S0140-6736(08)60423-7
[12]	Marin, A., Amin, J., Cooper, D., et al., STEAL Study Group (2010) Abacavir does not affect circulating levels of inflammatory or coagulopathic biomarkers in suppressed HIV: A randomized clinical trial. AIDS, 24, 2657-2663. doi:10.1097/QAD.0b013e32833f147f
[13]	Lang, S., Mary-Krause, M., Cotte, L., et al., Clinical Epidemiology Group of the French Hospital Database on HIV (2010) Impact of individual antiretroviral drugs on the risk of myocardial infarction in human immunodeficiency virus-infected patients: A case-control study nested within the French Hospital Database on HIV ANRS cohort CO4. Archives of Internal Medicine, 170, 1228-1238. doi:10.1001/archinternmed.2010.197
[14]	Brothers, C.H., Hernández, J.E., Cutrell, A.G., Curtis, L., Ait-Khaled, M., Bowlin, S.J., et al. (2009) Risk of myocardial infarction and abacavir therapy: No increased risk across 52 GlaxoSmithKline-sponsored clinical trials in adult subjects. Journal of Acquired Immune Deficiency Syndromes, 51, 20-28. doi:10.1097/QAI.0b013e31819ff0e6
[15]	Benson, C., Ribaudo, H., Zheng, E., et al. (2009)No association of Abacavir use with risk of myocardial infarction or severe cardiovascular disease events: Results from ACTG A5001. Program and Abstracts of the 16th Conference on Retroviruses and Opportunistic Infections, February 8-11 2009, Montreal, Abstract 721.
[16]	Costagliola, D., Lang, S., Mary-Krause, M. and Boccara, F. (2010) Abacavir and cardiovascular risk: Reviewing the evidence. Current HIV/AIDS Reports, 7, 127-133. doi:10.1007/s11904-010-0047-3
[17]	Behrens, G.M. and Reiss, P. (2010) Abacavir and cardiovascular risk. Current Opinion in Infectious Diseases, 23, 9-14. doi:10.1097/QCO.0b013e328334fe84
[18]	Daví, G. and Patrono, C. (2007) Platelet activation and atherothrombosis. The New England Journal of Medicine, 357, 2482-2494. doi:10.1056/NEJMra071014
[19]	Kottke-Marchant, K. (2009). Importance of platelets and platelet response in acute coronary syndromes. Cleveland Clinic Journal of Medicine, 76, S2-S7. doi:10.3949/ccjm.76.s1.01
[20]	Li Z, Delaney MK, O’Brien KA, et al. (2010) Signaling during platelet adhesion and activation. Arteriosclerosis, Thrombosis, and Vascular Biology, 30, 2341-2349. doi:10.1161/ATVBAHA.110.207522
[21]	Cardinal, D.C. and Flower, R.J. (1980) The electronic aggregometer: A novel device for assessing platelet behaveior in blood. Journal of Pharmacological Methods, 3, 135-158. doi:10.1016/0160-5402(80)90024-8
[22]	Moyle, G.J., Sabin, C.A., Cartledge, J., et al., RAVE (Randomized Abacavir versus Viread Evaluation) Group UK (2006) A randomized comparative trial of tenofovir DF or abacavir as replacement for a thymidine analogue in persons with lipoatrophy. AIDS, 20, 204-250. doi:10.1097/01.aids.0000247574.33998.03
[23]	Jones, R., Sawleshwarkar, S., Michailidis, C., Jackson, A., Mandalia, S., Stebbing, J., et al. (2005) Impact of antiretroviral choice on hypercholesterolaemia events: The role of the nucleoside reverse transcriptase inhibitor backbone. HIV Medicine, 6, 396-402. doi:10.1111/j.1468-1293.2005.00325.x
[24]	Satchell, C., O’Connor, E., Peace, A., et al. (2009) Platelet Hyper-Reactivity in HIV-1-infected Patients on Abacavir-containing ART. Program and Abstracts of the 16th Conference on Retroviruses and Opportunistic Infections, February 8-11 2009, Montreal, Canada, Abstract 151LB.
[25]	Satchell, C.S., Cotter, A.G., O’Connor, E.F., Peace, A.J., Tedesco, A.F., Clare, A., et al. (2010) Platelet function and HIV: A case-control study. AIDS, 24, 649-657. doi:10.1097/QAD.0b013e328336098c
[26]	Graff, J., Von Hentig, H., Kuczka, K., Angioni, C., Gute, P., Klauke, S., et al. (2008) Significant effects of tipranavir on platelet aggregation and thromboxane B2 formation in vitro and in vivo. Journal of Antimicrobial Chemotherapy, 61, 394-399. doi:10.1093/jac/dkm486