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 outcome measures
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:
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Study | Strategy | Number of people | Outcomes |
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Agudelo et al. (41) | Itraconazole + RHZE | At initiation n = 10 | After switch n = 7 | Loss to follow-up: 1/7
Detectable itraconazole levels: 0/3 measured
Treatment success: 4/6
Death: 1/6
Relapse (TB + progressive disseminated histoplasmosis): 1/6 |
Itraconazole + quinolone + HZE | At initiation n = 4 | After switch n = 7 | Loss to follow-up: 1/7
Detectable itraconazole levels: 2/2 measured
Treatment success: 4/5 (one switched from RHZE to quinolone HZE because of clinical failure) |
Drayton et al. (40) | Itraconazole + RHZE | 1 | Undetectable serum itraconazole levels during rifampicin administration.
Discontinuation of R led to improvement in progressive disseminated histoplasmosis. |