Primary antifungal prophylaxis for cryptococcal disease in HIV‐positive people


Ajibola A Awotiwon1, Samuel Johnson2, George W Rutherford3, Graeme Meintjes4, Ingrid Eshun‐Wilson5

1 Knowledge Translation Unit, University of Cape Town Lung Institute, Observatory, Cape Town, South Africa

2 Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK

3 Global Health Sciences, University of California, San Francisco, San Francisco, USA

4 Department of Medicine, University of Cape Town, Cape Town, South Africa

5 Centre for Evidence Based Health Care, Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa

 Primary antifungal prophylaxis for cryptococcal disease in HIV‐positive people. Cochrane Database of Systematic Reviews 2018, Issue 8. Art. No.: CD004773. DOI: 10.1002/14651858.CD004773.pub3

Access the full-text here: DOI:10.1002/14651858.CD004773.pub3/full

What is the aim of this review?

The aim of this Cochrane Review was to find out if taking an antifungal drug regularly, such as fluconazole, prevented HIV‐positive people who have low cluster of differentiation 4 (CD4) cell counts, from getting cryptococcal disease, and what the potential complications were. Cochrane researchers collected and analysed all relevant studies to answer this question, and found nine trials that looked at this question.

Key messages

We found that regularly taking antifungal medication prevented HIV‐positive people who had low CD4 counts from developing cryptococcal disease. We also found that primary prophylaxis probably reduced the number of people dying specifically from cryptococcal disease. However it probably did not reduce the number of people dying overall.

What was studied in the review?

Cryptococcal disease is one of the leading causes of death for HIV‐positive people who have low CD4 counts. The current recommended strategy in most countries to prevent people from developing cryptococcal disease, is to screen eligible patients with a blood test that picks up early signs of disease. We looked at trials that studied whether taking antifungal prophylaxis stopped people from dying or developing cryptococcal disease. We also looked at the side effects of the antifungal drug and whether it caused resistance to antifungal drugs in other fungal infections, such as thrush.

What are the main results of the review?

We found nine trials that included 5426 participants. These trials were conducted in Australia, Canada, South Africa, the UK, the USA,Thailand, and sub‐Saharan Africa. Seven trials were conducted before the availability of modern antiretroviral therapy. The participants in two large trials received modern HIV treatment regimens.

We found that antifungal prophylaxis may have no effect on death overall, although it reduced the risk of those with low CD4 counts developing cryptococcal disease by 71%. Prophylaxis with an antifungal probably also reduced deaths specifically from cryptococcal disease. There may be an increased risk of the vaginal tract becoming colonized with fluconazole‐resistant Candidaorganisms if someone takes prophylaxis, however, this may not necessarily result in an increased risk of clinical disease that doesn't respond to treatment. Generally, there were few side effects of taking antifungal prophylaxis, and it was well‐tolerated when compared to placebo.

How up to date is this review?

The review authors searched for studies that had been published up to 31 August 2017.