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.

Paraquat poisoning: Acute lung injury - a missed diagnosis.

Paraquat is a herbicide of great toxicological importance because it is associated with high mortality rates, mainly due to respiratory failure. We report the case of a 28-year-old man admitted to the casualty department at Ngwelezana Hospital, Empangeni, KwaZulu-Natal, South Africa, with a history of vomiting and abdominal pain after ingestion of ~100 mL of an unknown substance, later identified as paraquat, together with an unknown amount of alcohol, in a suicide attempt. He developed respiratory distress associated with lung parenchymal infiltrates that required ventilatory support and later a spontaneous pneumothorax, and died in the intensive care unit. We discuss the importance of a high index of suspicion of paraquat poisoning in rural areas, where paraquat is readily available as a herbicide on farms, in patients with a similar presentation. We further stress the importance of identifying the classic radiological progression after paraquat poisoning, to help avoid a delay in diagnosis if the culprit substance is not known (as happened in our case). Lastly, we look at the importance of avoiding oxygen supplementation, and early administration of immunosuppressive therapy, to improve outcome.

Hepatitis B immune reconstitution syndrome in a patient with HIV infection.

South Africa has a high rate of HIV and hepatitis B co-infection. The national HIV treatment guidelines include anti-retrovirals that treat both viruses. We describe a HIV-positive patient who presented with liver histology-confirmed hepatitis B immune reconstitution inflammatory syndrome whilst on a regimen containing lamivudine and tenofovir.

Challenges in the management of disseminated progressive histoplasmosis in human immunodeficiency virus-infected patients in resource-limited settings.

The diagnosis of histoplasmosis in patients with human immunodeficiency virus in southern Africa is complicated by the nonspecific presentation of the disease in this patient group and the unavailability of sensitive diagnostics including antigen assays. Treatment options are also limited due to the unavailability of liposomal amphotericin and itraconazole, and the inability to perform therapeutic drug monitoring further confounds management. We present 3 clinical cases to illustrate the limits of diagnosis and management in the southern African context, and we highlight the need for additional diagnostic tools and treatment options in resource-limited settings.

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.

Southern African HIV Clinicians Society adult antiretroviral therapy guidelines: Update on when to initiate antiretroviral therapy.

The most recent version of the Southern African HIV Clinicians Society's adult antiretroviral therapy (ART) guidelines was published in December 2014. In the 27 August 2015 edition of the New England Journal of Medicine, two seminal randomised controlled trials that addressed the optimal timing of ART in HIV-infected patients with high CD4 counts were published: Strategic timing of antiretroviral therapy (START) and TEMPRANO ANRS 12136 (Early antiretroviral treatment and/or early isoniazid prophylaxis against tuberculosis in HIV-infected adults). The findings of these two trials were consistent: there was significant individual clinical benefit from starting ART immediately in patients with CD4 counts higher than 500 cells/µL rather than deferring until a certain lower CD4 threshold or clinical indication was met. The findings add to prior evidence showing that ART reduces the risk of onward HIV transmission. Therefore, early ART initiation has the public health benefits of potentially reducing both HIV incidence and morbidity. Given this new and important evidence, the Society took the decision to provide a specific update on the section of the adult ART guidelines relating to when ART should be initiated.