An Update on Adverse Cutaneous Drug Reactions in HIV/AIDS

Abstract

Background: The global mortality from HIV and the cutaneous burden of infective, inflam-matory and malignant diseases in the setting of AIDS have significantly declined following the advent of highly active antiretroviral therapy. Regrettably, there has been a contemporaneous escalation in the incidence of adverse cutaneous drug reactions (ACDR), with studies attesting that HIV-positive individuals are a hundred times more susceptible to drug reactions than the general population, and advanced immunodeficiency portending an even greater risk. Several variables are accountable for this amplified risk in HIV. Summary: Adverse reactions to trimethoprim-sulfamethoxazole are the most common, increasing from approximately 2-8% in the general population over to 43% amongst HIV-positive individuals to approximately 69% in subjects with AIDS. Antituberculosis drugs and antiretrovirals are also well-known instiga-tors of ACDR. Cutaneous reactions range from mild morbilliform eruptions to severe, life-threatening manifestations in the form of Stevens-Johnson syndrome/toxic epidermal necrol-ysis. Histological features vary from vacuolar interface changes to full-thickness epidermal necrosis with subepidermal blister formation. A precipitous diagnosis of the ACDR, clinically and histologically if necessary, together with the isolation of the causative drug is critical. The identification process, however, is often complex and multifaceted due to polypharmacy and inconclusive data on which drugs are the most likely offending agents, especially against the background of tuberculosis co-infection. Key Messages: Whilst milder cutaneous reactions are treated symptomatically, severe reactions mandate immediate treatment discontinuation without rechallenge. Further studies are required to establish safe rechallenge guidelines in resource-limited settings with a high HIV and tuberculosis prevalence. Introduction Drug reactions are a significant cause of morbidity and mortality worldwide. Studies have established that HIV-positive individuals are a hundred times more susceptible to drug reactions than the general population, and advanced immunodeficiency portends an even greater risk [1]. Multiple heterogeneous factors are responsible for the substantial risk in HIV, including polypharmacy, slow acetylator status, relative glutathione deficiency, CD4+ T-cell counts of < 200 cells/mm 3 or > 25 cells/mm 3 [2], latent cytomegalovirus and Epstein-Barr virus infections [3] and high CD8+ T-cell counts > 460 cells/mm 3. The majority of adverse drug reactions are due to trimethoprim-sulfamethoxazole (TMP/ SMX), other sulphonamide drugs and penicillins, accounting for 75% of all reported cases, of which adverse reactions to TMP/SMX are the most common, increasing from approximately 2-8% in the general population over 43% amongst HIV-positive individuals to approximately 69% in subjects with AIDS [4-6]. One of the postulated reasons for the discernible incidence of reactions to TMP/SMX is the systemic glutathione deficiency in these individuals, which increases the probability of circulating toxic intermediates like hydroxylamine derivatives which play a key role in inciting drug reactions [7]. Other drugs that are renowned for engendering adverse reactions include antituberculosis (anti-TB) drugs, antiretrovirals, non-steroidal anti-inflammatory drugs and anticonvulsants. In this review, adverse cutaneous drug reactions (ACDR) due to the most commonly prescribed medications (including TMP/SMX, anti-TB drugs and antiretrovirals) in the setting of HIV will be discussed. Prompt diagnosis of the ACDR-together with the identification and immediate removal of the offending drug where applicable, as well as treatment of the reaction-is crucial for preventing further progression of the adverse reaction whilst simultaneously ensuring appropriate alternative treatment, where necessary, for the underlying disorder, bearing in mind that HIV-positive patients are often co-infected with opportunistic infections [8].