Summary
Definition
History and exam
Key diagnostic factors
- no antiretroviral treatment (ART) or failure of ART
- fever
- headache and altered mental status
- dyspnoea or cough
- abdominal pain, diarrhoea, weight loss
- dysphagia
- lymphadenopathy
- visual floaters, eye pain, and blindness
- ocular haemorrhage
- mucosal changes
Other diagnostic factors
- hepatosplenomegaly
- exercise-induced oxygen desaturation
- blurred vision and photophobia
- papilloedema
- meningismus, focal neurological findings
- pain and weakness
- bone or joint pain
- skin lesions
Risk factors
- post-HIV seroconversion with any CD4 count
- CD4 count below 250 cells/microlitre
- CD4 count below 200 cells/microlitre
- CD4 count below 150 cells/microlitre
- CD4 count below 100 cells/microlitre
- CD4 count below 50 cells/microlitre
- no antiretroviral treatment (ART) or failure of ART
- men who have sex with men (MSM)
- black or Hispanic race
- intravenous drug use
- socio-economic factors (poverty, over-crowding, homelessness, poor nutrition)
- dust inhalation in areas endemic for Coccidioides and Histoplasma
Diagnostic investigations
1st investigations to order
- CD4 cell count
- sputum stain and culture
- blood cultures
- adenosine deaminase
- Toxoplasma gondii serology
- Coccidioides serology
- cryptococcal polysaccharide antigen
- Histoplasma capsulatum antigen
- Histoplasma capsulatum culture
- FBC
- LFT
- LDH
- ABG
- CXR
- head CT
Investigations to consider
- tuberculosis (TB) nucleic acid amplification
- lateral flow urine lipoarabinomannan (LF-LAM) assay
- bronchoalveolar lavage (BAL)
- oropharyngeal scrapings (KOH preparation) and culture
- cerebrospinal fluid (CSF) analysis
- polymerase chain reaction (PCR): cerebrospinal fluid (CSF), bronchoalveolar lavage (BAL) fluid, and vitreous and aqueous humor specimen for Toxoplasma gondii
- bone marrow aspirate and culture
- lymph node aspirate or biopsy
- tissue biopsy
- brain biopsy
- abdominal CT
- high-resolution CT (HRCT) of the chest
- polymerase chain reaction (PCR) for Pneumocystis jirovecii pneumonia (PCP)
- beta-D-glucan
- brain MRI
- thallium single photon emission tomography and PET
- upper gastrointestinal endoscopy and colonoscopy
- coccidioidal antigen testing
- polymerase chain reaction (PCR) for Coccidioides
- polymerase chain reaction (PCR) for Histoplasma
Treatment algorithm
Contributors
Authors
Jake Scott, MD
Clinical Associate Professor
Infectious Diseases and Geographic Medicine
Stanford University School of Medicine
Antimicrobial Stewardship Program Medical Director
Stanford Health Care Tri-Valley
Pleasanton
CA
Disclosures
JS declares that he has no competing interests.
Acknowledgements
Dr Jake Scott would like to gratefully acknowledge Dr, Ruth Byrne, Dr Mark Nelson, and Dr Irene Alexandraki, previous contributors to this topic.
Disclosures
RB, MN, and IA declare that they have no competing interests.
Peer reviewers
Thomas B. Campbell, MD
Professor of Medicine
University of Colorado Anschutz
Aurora
CO
Disclosures
Unpaid member of the US DHHS Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV and the National Comprehensive Cancer Network Guidelines for Cancer in People with HIV and Kaposi Sarcoma.
Ellen Kitchell, MD, FIDSA, AAHIVM-S
Associate Professor
University of Texas Southwestern
Dallas
TX
Disclosures
EK declares that she has no competing interests.
Colm O'Mahony, MD, FRCP, BSc, DIPVen
Consultant in Sexual Health
Department of Sexual Health
Countess of Chester Hospital NHS Foundation Trust
Chester
UK
Disclosures
CO declares that he has no competing interests.
Nicola Steedman, MRCP, DipGUM, DipHIV
Consultant Physician in Sexual Health and HIV
Department of Sexual Health
Countess of Chester Hospital NHS Foundation Trust
Chester
UK
Disclosures
NS declares that she has no competing interests.
William R. Rodriguez, MD
Assistant Professor of Medicine
Massachusetts General Hospital
Charlestown
MA
Disclosures
WRR declares that he has no competing interests.
Peer reviewer acknowledgements
BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.
Disclosures
Peer reviewer affiliations and disclosures pertain to the time of the review.
References
Key articles
National Institutes of Health, Centers for Disease Control and Prevention, HIV Medicine Association, and Infectious Diseases Society of America. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents with HIV. 2025 [internet publication].Full text
World Health Organization. Guidelines for diagnosing, preventing and managing cryptococcal disease among adults, adolescents and children living with HIV. Jun 2022 [internet publication].Full text
Griffith DE, Aksamit T, Brown-Elliott BA, et al. An official ATS/IDSA statement: diagnosis, treatment, and prevention of nontuberculous mycobacterial diseases. Am J Respir Crit Care Med. 2007 Feb 15;175(4):367-416.Full text Abstract
Wheat LJ, Freifeld AG, Kleiman MB, et al. Clinical practice guidelines for the management of patients with histoplasmosis: 2007 update by the Infectious Diseases Society of America. Clin Infect Dis. 2007 Oct 1;45(7):807-25.Full text Abstract
Chang CC, Harrison TS, Bicanic TA, et al. Global guideline for the diagnosis and management of cryptococcosis: an initiative of the ECMM and ISHAM in cooperation with the ASM. Lancet Infect Dis. 2024 Aug;24(8):e495-512.Full text Abstract
Pappas PG, Kauffman CA, Andes DR, et al. Clinical practice guideline for the management of candidiasis: 2016 update by the Infectious Diseases Society of America. Clin Infect Dis. 2016 Feb 15;62(4):e1-50.Full text Abstract
Reference articles
A full list of sources referenced in this topic is available here.
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