Objectives
To evaluate the safety of available treatment strategies for TB and histoplasmosis coinfection among people living with HIV.
The evidence base is limited, and we therefore adapted our objectives to the following:
- to describe recognized drug–drug interactions between first-line therapies for histoplasmosis, TB, and HIV; and
- to describe clinical approaches to TB, histoplasmosis, and HIV infection
Methods
Criteria for considering studies for this review
Types of studies
- Randomized controlled trials
- Quasi-randomized controlled trials and non-randomized controlled trials
- Prospective cohort studies, including single-arm cohort studies
- Retrospective cohort studies, including single-arm cohort studies
- Case series
- Case reports
Types of participants
Children, adolescents, and adults living with HIV with coexisting progressive disseminated histoplasmosis and TB.
Types of interventions
- Itraconazole with rifampicin-based anti-TB regimen
- Itraconazole with non-rifampicin-based anti-TB regimen
Types of outcome measures
Primary outcomes
- All-cause mortality
- Treatment failure of HIV
- Treatment failure of TB
- Treatment failure of histoplasmosis
Secondary outcomes
- Serious adverse events
- Duration of hospital stay
Methods
We developed our search strategy with the assistance of Vittoria Lutje, Information Specialist. We searched the following: Cochrane Infectious Diseases Group Specialized Register; Central Register of Controlled Trials (CENTRAL), published in The Cochrane Library; MEDLINE (PubMed, from 1966 to present); EMBASE (OVID, from 1947 to present); Science Citation Index Expanded (SCI-EXPANDED, from 1900), Conference Proceedings Citation Index-Science (CPCI-S, from 1900), and BIOSIS Previews (from 1926), all three using the Web of Science platform. We also searched the WHO International Clinical Trials Registry Platform (http://www.who.int/ictrp/search/en), ClinicalTrials.gov, and the ISRCTN registry (www.isrctn.com) to identify ongoing studies.
One reviewer (Marylou Murray) selected studies from the search results and extracted data.
We do not present GRADE evidence profiles, since all the evidence presented is of very low certainty due to the design of the contributing studies.
Results
Results of the search
We found only two studies that could directly inform the PICO. In addition, we report anticipated drug–drug interactions from established databases, but this does not represent a pharmacokinetic review.
Effects of interventions
One retrospective cohort study (41) compared outcomes for different treatment strategies for comorbid disseminated histoplasmosis and people with both TB and HIV. The authors do not comment on antiretroviral drug choices.
One case report (40) indicated outcomes for a single person treated with rifampicin and itraconazole.
One person in ACTG120 receiving rifampicin for Mycobacterium avium-intracellulare – undetectable itraconazole levels, died.
These are summarized in the following table:
Table
Loss to follow-up: 1/7 Detectable itraconazole levels: 0/3 measured
Publication Details
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Publisher
Pan American Health Organization, Washington (DC)
NLM Citation
Guidelines for Diagnosing and Managing Disseminated Histoplasmosis among People Living with HIV [Internet]. Washington (DC): Pan American Health Organization; 2020 Apr. ANNEX 6, SYSTEMATIC REVIEW PICO 3: HISTOPLASMOSIS AND TB COINFECTION.