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Cutaneous Adverse Drug Reactions in Human Immunodeficiency Virus Infection

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Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions

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Abstract

CADR is more common in HIV-infected persons, although the incidence is declining because of the new safer drugs and early initiation of antiretroviral therapy. The presentation and clinical course does not seem to differ from that in the general population. Antiretrovirals, antituberculosis drugs, and drugs for treating opportunistic infections are most commonly implicated. HIV-associated CADR poses major diagnostic and management challenges because of polypharmacy, overlapping drug toxicities, drug interactions, overlap of CADR with other diseases, and limited alternative drugs. We discuss pragmatic management strategies of HIV-associated CADR focusing on resource-limited settings, where HIV infection and associated CADR are most common.

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Abbreviations

AHR:

Abacavir hypersensitivity reaction

ART:

Antiretroviral therapy

cADR:

Cutaneous adverse drug reactions

DRESS:

Drug rash with eosinophilia and systemic symptoms

FDE:

Fixed drug eruption

HIV:

Human immunodeficiency virus

IRIS:

Immune reconstitution inflammatory syndrome

MDE:

Morbilliform drug eruption

MDH:

Multiple drug hypersensitivity

OIs:

Opportunistic infections

PT:

Patch tests

SJS/TEN:

Stevens-Johnson syndrome/toxic epidermal necrolysis

References

  • Adih WK, Selik RM, Hu X (2011) Trends in diseases reported on US death certificates that mentioned HIV infection, 1996–2006. J Int Assoc Physicians AIDS Care (Chic) 10(1):5–11

    Article  Google Scholar 

  • Bezabhe WM et al (2015) Adverse drug reactions and clinical outcomes in patients initiated on antiretroviral therapy: a prospective cohort study from Ethiopia. Drug Saf 38(7):629–639

    Article  CAS  Google Scholar 

  • Boonyagars L, Hirunwiwatkul P, Hurst CP (2017) CD4 count and risk of anti-tuberculosis drug-associated cutaneous reactions in HIV-infected Thai patients. Int J Tuberc Lung Dis 21(3):338–344

    Article  CAS  Google Scholar 

  • Budamakuntla L et al (2015) A retrospective study of spectrum of nevirapine induced cutaneous drug reactions in HIV positive patients. J US-China Med Sci 12:85–89

    Google Scholar 

  • Carr DF et al (2017) Genome-wide association study of nevirapine hypersensitivity in a sub-Saharan African HIV-infected population. J Antimicrob Chemother 72(4):1152–1162

    CAS  PubMed  PubMed Central  Google Scholar 

  • Centers for Disease Control and Prevention (CDC) (2001) Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures: worldwide, 1997–2000. MMWR Morb Mortal Wkly Rep 49:1153–1156

    Google Scholar 

  • Chantachaeng W et al (2011) Cutaneous adverse reactions to sulfonamide antibiotics. Asian Pac J Allergy Immunol 29(3):284–289

    CAS  PubMed  Google Scholar 

  • Cohen MS et al (2011) Prevention of HIV-1 infection with early antiretroviral therapy. N Engl J Med 365(6):493–505

    Article  CAS  Google Scholar 

  • Coopman SA et al (1993) Cutaneous disease and drug reactions in HIV infection. N Engl J Med 328(23):1670–1674

    Article  CAS  Google Scholar 

  • Cutrell AG et al (2004) Updated clinical risk factor analysis of suspected hypersensitivity reactions to abacavir. Ann Pharmacother 38(12):2171–2172

    Article  Google Scholar 

  • Gao S et al (2012) HLA-dependent hypersensitivity reaction to nevirapine in Chinese Han HIV-infected patients. AIDS Res Hum Retrovir 28(6):540–543

    Article  CAS  Google Scholar 

  • George J et al (2012) Toxic epidermal necrolysis caused by fluconazole in a patient with human immunodeficiency virus infection. J Pharmacol Pharmacother 3(3):276–278

    Article  CAS  Google Scholar 

  • Hernandez J et al (2000) The rate of hypersensitivity reactions to abacavir is similar in under-represented populations and incarcerated subjects. AIDS 14:569

    Google Scholar 

  • Holtzer CD, Flaherty JF Jr, Coleman RL (1998) Cross-reactivity in HIV-infected patients switched from trimethoprim-sulfamethoxazole to dapsone. Pharmacotherapy 18(4):831–835

    CAS  PubMed  Google Scholar 

  • Hughes CA et al (2008) Abacavir hypersensitivity reaction: an update. Ann Pharmacother 42(3):387–396

    Article  CAS  Google Scholar 

  • Isaacs T et al (2013) Annular erythema and photosensitivity as manifestations of efavirenz-induced cutaneous reactions: a review of five consecutive cases. J Antimicrob Chemother 68(12):2871–2874

    Article  CAS  Google Scholar 

  • Kannenberg SM et al (2012) Toxic epidermal necrolysis and Stevens-Johnson syndrome in South Africa: a 3-year prospective study. QJM 105(9):839–846

    Article  CAS  Google Scholar 

  • Knight L et al (2014) Factors associated with increased mortality in a predominantly HIV-infected population with Stevens Johnson syndrome and toxic epidermal necrolysis. PLoS One 9(4):e93543

    Article  Google Scholar 

  • Lehloenya RJ, Dheda K (2012) Cutaneous adverse drug reactions to anti-tuberculosis drugs: state of the art and into the future. Expert Rev Anti-Infect Ther 10(4):475–486

    Article  CAS  Google Scholar 

  • Lehloenya RJ, Kgokolo M (2014) Clinical presentations of severe cutaneous drug reactions in HIV-infected Africans. Dermatol Clin 32(2):227–235

    Article  CAS  Google Scholar 

  • Lehloenya RJ et al (2011) Outcomes of reintroducing anti-tuberculosis drugs following cutaneous adverse drug reactions. Int J Tuberc Lung Dis 15(12):1649–1657

    Article  CAS  Google Scholar 

  • Lehloenya RJ et al (2012) Multiple drug hypersensitivity reactions to anti-tuberculosis drugs: five cases in HIV-infected patients. Int J Tuberc Lung Dis 16(9):1260–1264

    Article  CAS  Google Scholar 

  • Lehloenya RJ et al (2016) Diagnostic patch testing following tuberculosis-associated cutaneous adverse drug reactions induces systemic reactions in HIV-infected persons. Br J Dermatol 175(1):150–156

    Article  CAS  Google Scholar 

  • Lin KY, Hung CC (2015) Clinical relevance of cross-reactivity between darunavir and trimethoprim-sulfamethoxazole in HIV-infected patients. AIDS 29(16):2213–2214

    Article  Google Scholar 

  • Lin D, Li WK, Rieder MJ (2007) Cotrimoxazole for prophylaxis or treatment of opportunistic infections of HIV/AIDS in patients with previous history of hypersensitivity to cotrimoxazole. Cochrane Database Syst Rev 2:CD005646

    Google Scholar 

  • Littera R et al (2006) HLA-dependent hypersensitivity to nevirapine in Sardinian HIV patients. AIDS 20(12):1621–1626

    Article  CAS  Google Scholar 

  • Manosuthi W et al (2006) Incidence and risk factors of rash associated with efavirenz in HIV-infected patients with preceding nevirapine-associated rash. HIV Med 7(6):378–382

    Article  CAS  Google Scholar 

  • Mittmann N et al (2012) Incidence of toxic epidermal necrolysis and Stevens-Johnson syndrome in an HIV cohort: an observational, retrospective case series study. Am J Clin Dermatol 13(1):49–54

    Article  Google Scholar 

  • Murphy RA et al (2007) Antiretroviral therapy-associated toxicities in the resource-poor world: the challenge of a limited formulary. J Infect Dis 196(Suppl 3):S449–S456

    Article  CAS  Google Scholar 

  • Naisbitt DJ et al (2002) Covalent binding of the nitroso metabolite of sulfamethoxazole leads to toxicity and major histocompatibility complex-restricted antigen presentation. Mol Pharmacol 62(3):628–637

    Article  CAS  Google Scholar 

  • Naranjo CA et al (1981) A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 30(2):239–245

    Article  CAS  Google Scholar 

  • Pascopella L et al (2011) When tuberculosis comes back: who develops recurrent tuberculosis in California? PLoS One 6(11):e26541

    Article  CAS  Google Scholar 

  • Pasmatzi E et al (2011) Short-term and low-dose oral fluconazole treatment can cause Stevens-Johnson syndrome in HIV-negative patients. J Drugs Dermatol 10(12):1360

    PubMed  Google Scholar 

  • Peter JG et al (2017) Severe delayed cutaneous and systemic reactions to drugs: a global perspective on the science and art of current practice. J Allergy Clin Immunol Pract 5(3):547–563

    Article  Google Scholar 

  • Phillips E, Mallal S (2009) Successful translation of pharmacogenetics into the clinic: the abacavir example. Mol Diagn Ther 13(1):1–9

    Article  Google Scholar 

  • Pinto A, Chan RC (2009) Lack of allergic cross-reactivity between fluconazole and voriconazole. Antimicrob Agents Chemother 53(4):1715–1716

    Article  CAS  Google Scholar 

  • Rankin BT, Jariwala S (2012) Graded challenge protocol for fluconazole hypersensitivity in a patient with cryptococcal pneumonitis. Ann Allergy Asthma Immunol 108(6):466

    Article  Google Scholar 

  • Rieder MJ et al (1995) Toxicity of sulfonamide-reactive metabolites in HIV-infected, HTLV-infected, and noninfected cells. J Acquir Immune Defic Syndr Hum Retrovirol 8(2):134–140

    Article  CAS  Google Scholar 

  • Saka B et al (2013) Stevens-Johnson syndrome and toxic epidermal necrolysis in sub-Saharan Africa: a multicentric study in four countries. Int J Dermatol 52(5):575–579

    Article  Google Scholar 

  • Salami TA, Asalu AF, Samuel SO (2010) Prevalence of cutaneous drug eruptions in adult Nigerians with HIV/AIDS. Niger Postgrad Med J 17(2):160–163

    CAS  PubMed  Google Scholar 

  • Sarfo FS et al (2014) Incidence and determinants of nevirapine and efavirenz-related skin rashes in West Africans: nevirapine’s epitaph? PLoS One 9(4):e94854

    Article  Google Scholar 

  • Sassolas B et al (2010) ALDEN, an algorithm for assessment of drug causality in Stevens-Johnson syndrome and toxic epidermal necrolysis: comparison with case-control analysis. Clin Pharmacol Ther 88(1):60–68

    Article  CAS  Google Scholar 

  • Selik RM, Byers RH Jr, Dworkin MS (2002) Trends in diseases reported on U.S. death certificates that mentioned HIV infection, 1987–1999. J Acquir Immune Defic Syndr 29(4):378–387

    Article  Google Scholar 

  • Small CB et al (2017) HLA-B*57:01 allele prevalence in HIV-infected North American subjects and the impact of allele testing on the incidence of abacavir-associated hypersensitivity reaction in HLA-B*57:01-negative subjects. BMC Infect Dis 17(1):256

    Article  Google Scholar 

  • Smith KJ et al (1997) Increased drug reactions in HIV-1-positive patients: a possible explanation based on patterns of immune dysregulation seen in HIV-1 disease. The Military Medical Consortium for the Advancement of Retroviral Research (MMCARR). Clin Exp Dermatol 22(3):118–123

    Article  CAS  Google Scholar 

  • Soriano V et al (2000) Is there cross-toxicity between nevirapine and efavirenz in subjects developing rash? AIDS 14(11):1672–1673

    Article  CAS  Google Scholar 

  • Stewart A et al (2016) Severe antiretroviral-associated skin reactions in South African patients: a case series and case-control analysis. Pharmacoepidemiol Drug Saf 25(11):1313–1319

    Article  Google Scholar 

  • Su SC et al (2016) Severe cutaneous adverse reactions: the pharmacogenomics from research to clinical implementation. Int J Mol Sci 17(11):E1890

    Article  Google Scholar 

  • Suarez-Lorenzo I et al (2016) Severe reaction to emtricitabine and lamiduvine: evidence of cross-reactivity. Contact Dermatitis 74(4):253–254

    Article  CAS  Google Scholar 

  • Takaki I, Quirelli L, Cuman RK (2017) Adverse drug reaction in HIV-infected people treated with HAART in Maringá, Southern Brazil. Trop J Pharm Res 16(4):939–945

    Article  Google Scholar 

  • Todd G (2006) Adverse cutaneous drug eruptions and HIV: a clinician’s global perspective. Dermatol Clin 24(4):459–472 vi

    Article  CAS  Google Scholar 

  • Yunihastuti E, Widhani A, Karjadi TH (2014) Drug hypersensitivity in human immunodeficiency virus-infected patient: challenging diagnosis and management. Asia Pac Allergy 4(1):54–67

    Article  Google Scholar 

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Author information

Authors and Affiliations

  1. Division of Dermatology, Department of Medicine, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa

    Rannakoe J. Lehloenya

  2. Groote Schuur Hospital, Cape Town, South Africa

    Rannakoe J. Lehloenya

  3. Division of Allergy and Clinical Immunology, Department of Medicine, University of Cape Town, Cape Town, South Africa

    Jonny Peter

  4. Allergy and Immunology Unit, University of Cape Town Lung Institute, Cape Town, South Africa

    Jonny Peter

Authors
  1. Rannakoe J. Lehloenya
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  2. Jonny Peter
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Corresponding author

Correspondence to Rannakoe J. Lehloenya .

Editor information

Editors and Affiliations

  1. University of Toronto Medical School, Sunnybrook Health Sciences Centre, Toronto, ON, Canada

    Neil H. Shear

  2. Department of Dermatology, Emek Medical Center, Afula, Israel

    Roni P. Dodiuk-Gad

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Lehloenya, R.J., Peter, J. (2019). Cutaneous Adverse Drug Reactions in Human Immunodeficiency Virus Infection. In: Shear, N., Dodiuk-Gad, R. (eds) Advances in Diagnosis and Management of Cutaneous Adverse Drug Reactions. Adis, Singapore. https://doi.org/10.1007/978-981-13-1489-6_13

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  • DOI: https://doi.org/10.1007/978-981-13-1489-6_13

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  • Publisher Name: Adis, Singapore

  • Print ISBN: 978-981-13-1488-9

  • Online ISBN: 978-981-13-1489-6

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