**Author details**

230 Immunodeficiency

Some special issues must be considered:

thrombocytopenia (HIT).

**5.2. Warfarin-induced skin necrosis (WISN)** 

prothrombotic abnormalities?

**5.1. Antiretroviral therapy and warfarin drug interaction** 

Interactions between warfarin and ART (non-nucleoside reverse transcriptase inhibitors-NNRTIs and protease inhibitors-PIs), are through influence of ART on CYP2C9, the enzyme responsible for the metabolism of the more active S-enantiomer of warfarin [3]. Among the NNRTIs, induction of warfarin metabolism is likely with nevirapine. Inhibition of warfarin metabolism may occur with efavirenz o etravirine. Interactions involving ritonavir-boosted PIs are most frequent when warfarin is initiated in patients receiving concurrent efavirenz therapy [**36**]. International Normalized Ratio (INR) response should be used to guide warfarin dosage requirements; otherwise, low-molecular-weight heparin (LMWH) could be considered as a safer choice, although always keeping in mind that HIV infection may be an independent risk factor for the development of heparin-induced

The presentation of WISN, a condition due to decrease protein C levels by warfarin, in HIV-1 infected patients, is a novel clinical entity, reported recently [**37**]. Six cases of WISN occurred in 973 patients receiving warfarin therapy for venous thrombosis (0.62%, 95% CI 0.25 - 1.37%) at a referral hospital in Cape Town, South Africa. All 6 cases occurred in HIV-1 infected women (median age 30 years, range 27 - 42) with microbiologically confirmed tuberculosis (TB) and venous thrombosis. All were profoundly immunosuppressed (median CD4+ count at TB diagnosis 49 cells/microl, interquartile range 23 - 170). Of the 3 patients receiving combination ART, 2 had TB-IRIS. The occurrence of 6 WISN cases in a 40-month period may be attributed to: hypercoagulability secondary to HIV-1(above all if associated to decreased protein C levels) and TB, short concurrent heparin and warfarin therapy and high loading doses of warfarin. Active prevention and appropriate management of WISN

are likely to improve the morbidity and mortality of this unusual condition.

**6. Questions and remarks arised from clinical practice [3, 25]** 





absence of classic thrombophilic risk factors, be evaluated for HIV infection?

not females of childbearing age), who present an unsatisfactory course?.

setting, above all when patients have unexplained dyspnea or hypoxemia.

Hortensia Álvarez Díaz, Ana Mariño Callejo and José Francisco García Rodríguez *Infectious Diseases Unit, Department of Internal Medicine, Hospital Arquitecto Marcide-Profesor Novoa Santos, Sanitary Area of Ferrol, A Coruña, Spain* 

#### **7. References**


[9] Musselwhite LW, Sheikh V, Norton TD et al. Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV. AIDS. 2011 Mar 27; 25 (6): 787-95.

HIV-Infected Patients and Potential Impact on Thrombotic Events 233

[24] Kiser KL, Badowski ME. Risk factors for venous thromboembolism in patients with human immunodeficiency virus infection. Pharmacotherapy. 2010 Dec; 30 (12): 1292-

[25] Álvarez Díaz H, Mariño Callejo A and García Rodríguez JF. Non-cirrhotic portal hypertension in Human Immunodeficiency Virus-Infected patients: a new challenge in

[26] Schneider E., Whitmore S, Glynn KM et al.; Centers for Disease Control and Prevention (CDC). Revised surveillance case definitions for HIV infection among adults, adolescents, and children aged < 18 months and for HIV infection and AIDS among children aged 18 months to < 13 years-United States, 2008.MMWR Recomm Rep. 2008

[27] Asherson R.A., Gómez-Puerta J.A. and Marinopoulos G. Recurrent pulmonary thromboembolism in a patient with systemic lupus erythematosus and HIV-1 infection associated with the presence of antibodies to prothrombin: a case report. CID 2005; 41:

[28] Alcaraz I, Revelles JM, Camacho D et al. Superficial thrombophlebitis: A new clinical manifestation of the immune reconstitution inflammatory syndrome in a patient with

[29] Cilingiroglu M, Lather N, Youseff A et al. ST-elevation myocardial infarction due to a spontaneous thrombus in the left anterior descending artery in a young HIV-infected

[30] Achouh P, Jemel A, Chaudeurge A et al. Aortic biological valve thrombosis in an HIV

[31] Jedlinski I, Baralkiewicz G and Poprawski K. Acute coronary syndrome in a patient with acquired immunodeficiencysyndrome and non-bacterial thrombotic endocarditis.

[32] Álvarez Díaz H, Mariño Callejo A and García Rodríguez JF. Non-cirrhotic portal hypertension in Human Immunodeficiency Virus-Infected patients: a new challenge in

[33] Jansen JM, Lijfering WM, Sprenger HG et al. Venous thromboembolism in HIV-positive women during puerperium: a case series. Blood Coagul Fibrinolysis. 2008 Jan; 19(1): 95-

[34] De Larrañaga G, Bottaro E, Martinuzzo M et al. Thrombophilia in human immunodeficiency virus-infected patients with osteonecrosis: Is there a real connection? The first case-control study. Clin Appl Thromb Hemost. 2009 May-Jun; 15(3): 340-7.

[35] Hirsh J., Guyatt G, Albers GW. et al. Antithrombotic and thrombolytic therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th

[36] Welzen ME, van den Berk GE, Hamers RL et al. Interaction between antiretroviral

antiretroviral therapy era. The Open AIDS Journal 2011, 5: 59-61.

HIV infection. Am J Dermatopathol. 2010 Dec;32(8):846-9.

patient. Arch Turk Soc Cardiol 2011; 39 (4): 308-311.

positive patient. Ann Thorac Surg. 2011 Jun; 91(6): e90-1.

antiretroviral therapy era. The Open AIDS Journal 2011, 5: 59-61.

drugs and acenocoumarol. Antivir Ther. 2011; 16 (2): 249-52.

302.

89-92.

7.

Epub 2007 Dec 26.

Edition). Chest 2008 Jun; 133: 71S-105S.

Dec 5; 57 (RR-10): 1-12.

Eur Heart J (2010) 31 (8): 935.


[24] Kiser KL, Badowski ME. Risk factors for venous thromboembolism in patients with human immunodeficiency virus infection. Pharmacotherapy. 2010 Dec; 30 (12): 1292- 302.

232 Immunodeficiency

(6): 508-14.

2010; 201: 285-292.

2008 Oct; 22 (10): 771-8.

AIDS. 2011 Mar 27; 25 (6): 787-95.

[9] Musselwhite LW, Sheikh V, Norton TD et al. Markers of endothelial dysfunction, coagulation and tissue fibrosis independently predict venous thromboembolism in HIV.

[10] Kurz K, Teerlink T, Sarcletti M et al. Plasma concentrations of the cardiovascular risk factor asymmetric dimethylarginine (ADMA) are increased in patients with HIV-1 infection and correlate with immune activation markers. Pharmacol Res 2009 Dec; 60

[11] Saif M, Bona R, Greenberg B et al. AIDS and thrombosis: retrospective study of 131

[12] Rasmussen LD, Dybdal M, Gerstoft J et al. HIV and risk of venous thromboembolism: a Danish nationwide population-based cohort study.HIV Med. 2011 Apr; 12(4):202-10.

[13] Becker AC, Jacobson B, Singh S et al. The thrombotic profile of treatment-naive HIVpositive Black South Africans with acute coronary syndromes. Clin Appl Thromb

[14] Baker J, Ayenew W, Quick H et al. High-density lipoprotein particles and markers of inflammation and thrombotic activity in patients with untreated HIV infection. JID

[15] Basavanagowdappa H, Babu MS, Karuturi S. HIV infection and thromboembolism.J

[16] Mulder R, Tichelaar YI, Sprenger HG et al. Relationship between cytomegalovirus infection and procoagulant changes in human immunodeficiency virus-infected

[17] Lyonne L, Magimel C, Cormerais L et al.Thromboembolic events at the time of highly active antiretroviral therapies against human immunodeficiency virus.Rev Med Interne.

[18] Crum-Cianflone NF., Weekes J. and Bavaro M. Thromboses among HIV-infected patients during the highly active antiretroviral therapy era. AIDS Patient Care STDS.

[19] Mata F., Yaekoub AY and Stein PD. Human immunodeficiency virus infection and risk

[20] Jong E, Louw S, Meijers JC et al. The hemostatic balance in HIV-infected patients with and without antiretroviral therapy: partial restoration with antiretroviral therapy. AIDS

[21] 19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seatle.

[22] 19th Conference on Retroviruses and Opportunistic Infections, March 5-8, 2012, Seatle.

[23] Malek J, Rogers R, Kufera J, Hirshon JM. Venous thromboembolic disease in the HIVinfected patient. Am J Emerg Med. 2011 Mar; 29 (3): 278-82. Epub 2010 Mar 26.

of venous thromboembolism. Am J Med Sci. 2008 Nov; 336 (5): 402-6.

HIV-infected patients. Aids Patient Care STDS 2001; 15 (6): 311-320.

doi: 10.1111/j.1468-1293.2010.00869.x. Epub 2010 Aug 18.

Hemost. 2011 Jun; 17 (3):264-72. Epub 2010 May 11.

patients. Clin Microbiol Infect. 2011 May; 17(5):747-9.

Assoc Physicians India. 2011 Jun; 59:380-2.

2008 Feb;29(2):100-4. Epub 2007 Nov 26.

Patient Care STDS. 2009 Dec;23(12):1001-7.

Zangerle R., Parikh R. Posters 831, 832, 833.

Martínez E. Poster 834 (SPIRAL study)


[37] Bhaijee F, Wainwright H, Meintjes G et al. Warfarin-induced skin necrosis in HIV-1 infected patients with tuberculosis and venous thrombosis. S Afr Med J. 2010 Jun 1; 100(6): 372-7.

**Chapter 11** 

© 2012 Duri, licensee InTech. This is an open access chapter distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2012 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

of antiretroviral therapy of coreceptor antagonists will also be highlighted.

**Coreceptor Usage in HIV Infection** 

Chemokines are small low molecular weight proteins or cytokines secreted by cells that function as chemical messengers. They were originally found to attract leukocytes to site(s) of inflammation. As ligands they activate and signal through their respective chemokine receptors triggering an influx of intracellular calcium (Ca2+) ions causing a process known as chemotaxis. Chemokine receptors are integral membrane proteins that specifically bind and respond to chemokines. They are members of the class A subfamily of G-protein coupled receptor (GPCRs) superfamily, a name derived from the characteristic cysteine motif of the group of chemokines they interact with. Despite their pivotal roles in the immune system and angiogenesis, chemokines as well as their receptors have been associated with a number of pathologies including autoimmune disorders, pulmonary diseases, transplant rejection, cancers, vascular diseases and human immunodeficiency virus (HIV) infection. Scientists have noted that while the CD4 receptor is necessary for the successful infection of host immune cells by all naturally occurring HIV-1 strains it is not sufficient. Thus, another specific cell surface molecule called chemokine receptor is required. The recent introduction of entry inhibitors in the clinic as components of antiretroviral treatment has increased the research interest of coreceptor usage in HIV infection. Chemokine receptors are subjects of significant medical importance which not only provide new insights into the mechanisms of viral entry, tropism and pathogenesis, but have also culminated into new control strategies from the host's perspective influencing HIV transmission along with disease progression. Identification of the different phenotypes of HIV-1 strains with different prevalence during various stages of disease progression and the role of these phenotypes in treatment outcome has further revolutionalised research in this field. This chapter seeks to depict a simple and clear understanding of the basics of HIV phenotypes or genotypes and the respective current as well as prospective diagnostic tools. Milestones and challenges in this relatively new class

Additional information is available at the end of the chapter

Kerina Duri

http://dx.doi.org/10.5772/52060

**1. Introduction** 
