Antiretroviral treatment in HIV-infected children who require a rifamycin-containing regimen for tuberculosis

ABSTRACT

Introduction: In high prevalence settings, tuberculosis and HIV dual infection and co-treatment is frequent. Rifamycins, especially rifampicin, in combination with isoniazid, ethambutol and pyrazinamide are key components of short-course antituberculosis therapy.

Areas covered: We reviewed available data, for which articles were identified by a Pubmed search, on rifamycin-antiretroviral interactions in HIV-infected children. Rifamycins have potent inducing effects on phase I and II drug metabolising enzymes and transporters. Antiretroviral medications are often metabolised by the enzymes induced by rifamycins or may suppress specific enzyme activity leading to drug-drug interactions with rifamycins. These may cause significant alterations in their phamacokinetic and pharmacodynamic properties, and sometimes that of the rifamycin. Recommended strategies to adapt to these interactions include avoidance and dose adjustment.

Expert opinion: Despite the importance and frequency of tuberculosis as an opportunistic disease in HIV-infected children, current data on the management of co-treated children is based on few studies. We need new strategies to rapidly assess the use of rifamycins, new anti-tuberculosis drugs and antiretroviral drugs together as information on safety and dosing of individual drugs becomes available.

KEYWORDS:

• Children
• drug-drug interaction
• HIV
• rifamycin
• tuberculosis

Article highlights

• Despite the prevalence of children with tuberculosis dually infected with HIV there are few pharmacokinetic studies addressing combined antituberculosis and antiretroviral treatment in children and no peer reviewed data on the newer antiretroviral drugs or antituberculosis drugs.

• Nevirapine drug-drug interaction with rifampicin can be overcome with increased dosing of nevirapine and potentially forgoing the lead-in dose.

• The efavirenz dose does not require adjustment during rifampicin co-treatment. This may be due to co-treatment with isoniazid. Efavirenz metabolism is determined by genotype.

• Doubling the dose of lopinavir/ritonovir (4:1) in children does not resolve the drug-drug interaction with rifampicin, but super-boosting does. This is a key difference between children and adults.

• There is only one study assessing the drug-drug interactions of antiretroviral drugs with rifabutin in children. Here, using rifabutin with lopinavir/ritonavir gave significant toxicity.

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Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

H Rabie, HS Schaaf and MF Cotton are supported by the National Research Foundation.