What are DHHS guidelines for antiretroviral therapy of HIV infection with comorbid tuberculosis?

Updated: Apr 18, 2019
  • Author: R Chris Rathbun, PharmD, BCPS (AQ-ID), AAHIVP; Chief Editor: John Bartlett, MD  more...
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Answer

The overall rate of morbidity and mortality associated with MTB coinfection in patients with HIV infection is significant. Worldwide, an estimated 374,000 HIV positive people died from MTB infection in 2016; however, this statistic is difficult to fully elucidate due to the frequent classification of HIV as the cause of death regardless of other, possibly more contributory, comorbidities. [117]

Significant overlap exists in the patient populations who are exposed to MTB and are at risk for HIV infection. Disease progression rates of each are accelerated with coinfection and require swift and aggressive management strategies. Screening for MTB infection is recommended at HIV diagnosis in an attempt to capture the infection as quickly as possible to reduce morbidity and mortality. [118]

Current recommendations suggest that treatment for M tuberculosis infection and HIV infection be initiated separately because of additive adverse effects, overlapping toxicities, and risk for poor adherence with two multi-drug regimens. The ideal timeframe is dependent on the patient’s CD4 count. Treatment for MTB should be initiated first, followed by ART within 2 weeks for those with a CD4 count below 50 cells/mm3 and within 8 weeks for those with higher CD4 counts. Patients already on antiretroviral treatment should be initiated on MTB treatment immediately following an assessment of potential drug interactions and antiretroviral adjustments as needed. [118]  

Treatment selection for latent or active MTB infection is generally straightforward; however, significant drug-drug interactions are possible with antiretroviral medications when a rifamycin is included in the treatment plan because of their strong inductive effects on the cytochrome P450 system. [119]  Due to the potency of the rifamycins against MTB, however, this class should not be substituted. Rifabutin is usually selected over rifampin because of its less-potent metabolic induction when antiretroviral therapy is required, but dose adjustments are necessary when protease inhibitors and NNRTIs are administered concomitantly. [118]

For treatment-naïve patients (antiretroviral therapy initiation within the MTB infection treatment period), the preferred treatment is a 2 NRTI backbone with standard-dose efavirenz. This recommendation is based on the relatively extensive literature describing the low rates of adverse effects and pharmacokinetic stability leading to positive clinical outcomes. [118]

One alternative to the efavirenz component of the antiretroviral regimen is raltegravir at a standard (400 mg PO BID) or increased dose (800 mg PO BID). It should be noted that multi-class antiretroviral resistance has been noted with the concomitant use of raltegravir 800mg po BID (as part of triple-drug therapy for HIV) and the rifampin component of MTB treatment. [120] Raltegravir should be used cautiously and with close monitoring of HIV viral load.

Another alternative is ritonavir-boosted protease inhibitors. Rifabutin is preferred over rifampin when a PI is used; however, PIs can increase the concentration of rifabutin. Therefore, the dose of rifabutin should be reduced from 300 to 150 mg po daily or given as 300 mg three times per week during PI coadministration. [8]

Specific considerations by ARV class, applicable to treatment-naïve and treatment-experienced patients are listed below. [8]

  • NRTIs: Tenfofovir AF is contraindicated with rifamycins.
  • NNRTIs: Etravirine, rilpivirine, and nevirapine are contraindicated with rifampin.  Dose adjustments necessary when efavirenz and rilpivirine are used with rifabutin. Etravirine should not be used with a boosted PI and rifabutin.
  • PIs: Contraindicated with rifampin; use reduced-dose rifabutin instead.
  • INSTIs: When using rifampin, increase raltegravir to 800 mg BID and use cautiously. Increase dolutegravir to 50 mg BID. Elvitegravir/cobicistat and once daily raltegravir are contraindicated. Rifabutin may be safely used with standard doses of raltegravir and dolutegravir but is contraindicated with elvitegravir/cobicistat. The use of bictegravir with either rifampin or rifabutin is contraindicated. [84]
  • CCR5 antagonist: Dose adjustment required when maraviroc is used with rifampin. No change necessary when used with rifabutin.

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