A case series of emtricitabine-induced pure red cell aplasia.

BACKGROUND: Anaemia is common in patients with retroviral disease. New or worsening anaemia after initiation of antiretroviral (ARV) treatment has a broad differential diagnosis. OBJECTIVES: We describe six patients who developed transfusion-dependent anaemia on first-line therapy (tenofovir, emtricitabine and efavirenz) and, by exclusion, implicated emtricitabine in the aetiology of the anaemia. METHOD: We conducted a retrospective chart review of patients seen at the Infectious Diseases specialist clinic at King Edward VIII Hospital in KwaZulu-Natal between 2014 and 2016. We focused on patients with isolated, refractory and transfusion-dependent anaemia occurring after initiation of ARVs, in whom bone marrow biopsies were consistent with pure red cell aplasia (PRCA) without an identifiable secondary cause. RESULTS: All the patients were female, with a median (range) age and baseline CD4 cell count of 42.5 (23-61) years and 237 (83-329) cells/mm3, respectively. Before presenting with symptomatic anaemia, the duration on emtricitabine was 4.5 (2-8) months. At presentation, all patients had an HIV viral load of < 1000 copies/mL and a CD4 cell count of 314 (213-389) cells/mm3. The median time to recovery following the discontinuation of emtricitabine was 2 (1-4) months. After a median of 12 months, all patients were successfully rechallenged with emtricitabine and remained well for a follow-up period of 24 (7-36) months. CONCLUSION: This study provides strong circumstantial evidence that emtricitabine plays an important role in the pathogenesis of reversible PRCA. The mechanisms through which emtricitabine induces PRCA remain unclear and require further study.

Emtricitabine-induced pure red cell aplasia.

INTRODUCTION: Anemia is common in HIV. Parvo B19 infection is a well-recognised cause of red cell aplasia. Other causes of persistent pure red cell aplasia (PRCA) include anti-retroviral drugs such as zidovudine and lamivudine. We describe a case of PRCA that strongly implicates emtricitabine as the probable cause. PATIENT PRESENTATION: Patient was HIV positive and on treatment with a fixed drug combination consisting of tenofovir, emtricitabine and efavirenz for 3 months when she developed severe transfusion dependent anemia. The anemia, attributed to PRCA, was persistent and transfusion dependent for about one year. MANAGEMENT AND OUTCOME: Replacement of emtricitabine with abacavir resulted in a prompt, complete and lasting resolution of the anaemia, suggesting an etiologic role of emtricitabine in the PRCA. CONCLUSION: Emtricitibine is a rare cause of pure red cell aplasia.

Tuberculous Drug-induced Liver Injury and Treatment Re-challenge in Human Immunodeficiency Virus Co-infection.

BACKGROUND: Tuberculosis drug-induced liver injury (TB-DILI) is the most common adverse event necessitating therapy interruption. The optimal re-challenge strategy for antituberculous therapy (ATT) remains unclear, especially in human immunodeficiency virus (HIV) co-infected individuals in high-prevalence settings such as South Africa. OBJECTIVE: To determine the incidence of and risk factors for the recurrence of TB-DILI with different ATT re-challenge strategies. MATERIALS AND METHODS: We conducted a retrospective chart review of patients managed for TB-DILI from 2005 to 2013 at King Edward VIII Hospital in Durban, South Africa. Relevant clinical and laboratory data at the presentation of TB-DILI, time to recovery of liver function, method of ATT re-challenge and outcome of re-challenge were documented. RESULTS: 1016 charts were reviewed, and 53 individuals with TB-DILI (48 HIV-co-infected) were identified. Following discontinuation of ATT, the median time to alanine aminotransferase normalization was 28 days (interquartile range 13-43). Forty-two subjects were re-challenged (30 regimen re-challenges and 12 step-wise re-challenges). 5 (12%) cases of recurrent TB-DILI were noted. Recurrences were not associated with the method of re-challenge. CONCLUSION: Based on the data available, it appears that full ATT can be safely restarted in the majority of subjects with a recurrence of DILI occurring in about 12% of subjects. The method of re-challenge did not appear to impact on the risk of recurrence. Ideally, a prospective randomized trial is needed to determine the best method of re-challenge.