Is Stopping Secondary Prophylaxis Safe in HIV-Positive Talaromycosis Patients?

Experience from Myanmar

N Tun; A Mclean; X Deed; M Hlaing; Y Aung; E Wilkins; E Ashley; F Smithuis

Disclosures

HIV Medicine. 2020;21(10):671-673. 

In This Article

Abstract and Introduction

Abstract

Objectives: The aim of the study was to determine whether it is safe to stop secondary prophylaxis in patients with talaromycosis after immune reconstitution with a sustained increase in CD4 count to ≥ 100 cells/μL after antiretroviral therapy (ART).

Methods: A retrospective cohort analysis was performed in HIV-infected patients treated for talaromycosis between June 2009 and June 2017 in Medical Action Myanmar (MAM) clinics.

Results: Among a cohort of 5466 HIV-infected patients, 41 patients were diagnosed with and treated for clinical talaromycosis. All the patients were on ART and had a CD4 count < 100 cells/μL. Of these 41 patients, 24 patients (71%) were skin smear positive for talaromycosis, while results were negative in 17 patients. Median CD4 count and haemoglobin concentration were 24 cells/μL and 7.7 g/dL, respectively. Seventy-three per cent (30) were male. Among the 41 patients, 11 (27%) died and six (15%) were transferred to other centres. Twenty-four patients (58% of the total diagnosed) stopped itraconazole secondary prophylaxis after starting active ART with CD4 counts > 100 cells/μL for at least 1 year. Throughout the duration of follow-up post itraconazole cessation, the observed incidence of relapse was zero with a total follow-up of 93.8 person-years (95% confidence interval 0–4 per 100 person-years). The median (25th, 75th percentile) duration of follow-up post-prophylaxis discontinuation was 2.8 (2.1, 6.3) years.

Conclusions: Secondary prophylaxis can be safely stopped in patients with talaromycosis after immune reconstitution with a sustained increase in CD4 count to ≥ 100 cells/μL after highly active antiretroviral therapy.

Introduction

Talaromycosis, a systemic mycosis caused by Talaromyces marneffei, is most commonly found in Southeast Asian countries. It develops most commonly in HIV-positive patients with CD4 counts of ≤ 100 cells/μL. Common clinical manifestations include fever, nonproductive cough, hepato-splenomegaly, weight loss, anaemia, and generalized skin papules with central umbilication. A presumptive diagnosis can be made following the identification of characteristic septate yeast-like organisms under microscopic examination of Wright or Giemsa-stained samples with a sensitivity of approximately 70%.[1] This can be confirmed by culture if facilities are available. Treatment with intravenous amphotericin B for 2 weeks followed by oral itraconazole for 10 weeks is effective and safe but the mortality rate can still be > 25%.[2] Relapse rates as high as 57% were described without itraconazole maintenance therapy in the pre-antiretroviral therapy (ART) era.[3] The optimal duration of antifungal prophylaxis to prevent relapse remains unclear.[4] Studies reporting the discontinuation of antifungal prophylaxis in HIV-infected patients responding to ART are few and involved small case numbers.[5–8]

Medical Action Myanmar (MAM) is a nonprofit medical organization which operates 10 HIV integrated out-patient clinics for the poor, marginalized and vulnerable population in Myanmar. A retrospective cohort analysis was conducted to determine the relapse rate of talaromycosis after the discontinuation of itraconazole secondary prophylaxis in ART-treated patients between June 2009 and June 2017 in MAM clinics. Diagnosis was clinical with confirmation by Giemsa staining of a skin slit smear from characteristic papular skin lesions where possible. Culture was not available. All patients were treated with amphotericin (0.7 mg/kg/day) for 2 weeks and itraconazole (400–600 mg/day) for 8 to 10 weeks, followed by itraconazole 200 mg as secondary prophylaxis until they had maintained a CD4 count of > 100 cells/μL for at least 1 year on ART.

Among a cohort of 5466 HIV-infected patients, 41 patients were diagnosed with and treated for clinical talaromycosis. All the patients were on ART and had CD4 counts < 100 cells/μL. Of these 41 patients, 24 patients (71%) were skin smear positive for talaromycosis while results were negative in 17 patients. The median CD4 count and haemoglobin concentration were 24 cells/μL and 7.7 g/dL, respectively. Seventy-three per cent (30) were male. The demographic and clinical characteristics of skin smear positive and negative patients were similar (Table 1). Among 41 patients, 11 (27%) died and six (15%) were transferred to other centres, from which no clinical data could be obtained. Twenty-four patients (58% of the total diagnosed) stopped itraconazole secondary prophylaxis. The mean CD4 count of discontinued patients was 296 cells/μL, with a maximum of 751 cells/μL and a minimum of 132 cells/μL. Throughout the duration of follow-up post itraconazole cessation, the observed incidence of relapse was zero with a total follow-up of 93.8 person-years (95% confidence interval 0–4 per 100 person-years). The median (25th, 75th percentile) duration of follow-up post-prophylaxis discontinuation was 2.8 (2.1, 6.3) years with a range of 0.5–7.3 years for smear-positive and 1–6.5 years for smear-negative patients.

These findings contribute to the evidence that secondary prophylaxis can be discontinued safely in patients with talaromycosis after immune reconstitution with a sustained increase of the CD4 count to ≥ 100 cells/μL after highly active antiretroviral therapy.

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