Managing Drug Interactions in the Treatment of HIV-Associated TB

Salim S. Abdool Karim, MD, PhD reviewing Centers for Disease Control and Prevention (CDC). Morb Mortal Wkly Rep MMWR 2014 Mar 28.

 

These updated guidelines provide recommendations for managing drug interactions between rifamycin antibiotics and four classes of antiretrovirals and for co-treatment of tuberculosis and HIV infection in children and pregnant women.

 

Sponsoring Organization: CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention, Division of Tuberculosis Elimination

Target Population: Primary care providers, HIV/tuberculosis (TB) treatment providers

Background and Objective

Co-treatment of TB and HIV infection is often complicated by adherence challenges, overlapping side effects, immune reconstitution inflammatory syndrome, and drug–drug interactions.

What’s Changed

Recommendations for use of newer antiretrovirals, including CCR5-receptor antagonists and integrase inhibitors, are now provided. Other new features include the following:

  • Summaries of clinical experience with use of specific antiretroviral therapy (ART) regimens during TB treatment, together with pharmacokinetic data

  • A table summarizing clinical experience with key ART regimens and providing suggested regimens

  • Recommendations on treatment for special populations (i.e., patients with latent TB infection, those with drug-resistant TB, young children, pregnant women)

Key Recommendations

  • Efavirenz (600 mg for adults; standard weight-based dosing for children aged >3 years) plus two nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs), along with rifampin-based TB therapy, is the preferred strategy for co-treatment of HIV infection and TB.

  • If efavirenz cannot be used (e.g., during the first trimester of pregnancy and in children aged <3 years), then a nevirapine- or protease inhibitor (PI)-based ART regimen can be used in combination with rifampin.

  • Rifampin should not be coadministered with the second-generation nonnucleoside reverse transcriptase inhibitors (NNRTIs) rilpivirine or etravirine.

  • High-dose lopinavir/ritonavir regimens should be used together with rifampin-based treatment only if hepatotoxicity is closely monitored.

  • Patients who are unable to take NNRTIs can use rifampin in conjunction with triple- or quadruple-NRTI regimens if their HIV RNA levels are <100,000 copies/mL.

  • Doubling the dose of raltegravir to 800 mg twice daily is recommended for adults taking rifampin, but this drug combination should not be used in individuals with high HIV viral loads.

  • Although clinical data are limited, increasing the dose of maraviroc to 600 mg twice daily is recommended if the drug is coadministered with rifampin.

  • A 150-mg daily dose of rifabutin, with careful monitoring for rifabutin-related toxicities, is recommended if this drug is coadministered with boosted PIs.

  • Rifabutin can be used in patients on nevirapine-based ART and in those taking standard-dose raltegravir (400 mg twice daily).

  • Nevirapine-based HIV treatment can be used in pregnant women receiving rifampin-based TB treatment. A nucleotide/nucleotide-only regimen with rifampin, or lopinavir/r with rifabutin, can also be considered for pregnant patients. More-frequent HIV RNA monitoring is recommended during pregnancy.

  • For children on rifampin-based TB treatment, super-boosted lopinavir plus appropriate NRTIs is recommended. Alternatives include standard-dose efavirenz–based ART for children aged >3 years and a triple-nucleoside regimen for those aged <3 years.

COMMENT

These revisions provide long-awaited clarity on the coadministration of antiretrovirals, especially nonnucleoside reverse transcriptase inhibitors, and tuberculosis treatment. Although studies have shown a highly variable effect of rifampin on efavirenz concentrations, the recommendation of a 600-mg dose balances the needs for maintaining therapeutic levels of efavirenz and reducing the risk for neurological side effects. The doses of raltegravir and maraviroc that should be used in conjunction with TB treatment are clarified. Finally, helpful guidance (including the use of super-boosted lopinavir) is provided for co-treatment of HIV infection and TB in children.

CITATION(S):

  1.  

  2. Centers for Disease Control and Prevention (CDC).Managing drug interactions in the treatment of HIV-related tuberculosis. June 2013. (http://www.cdc.gov/tb/publications/guidelines/TB_HIV_Drugs/pdf/tbhiv.pdf)

– See more at: http://www.jwatch.org/na34266/2014/05/02/managing-drug-interactions-treatment-hiv-associated-tb#sthash.oNrY0fBZ.dpuf