new LTBI treatment guidelines

The CDC just published new recommendations regarding treatment for latent TB infections (LTBI), highlighting shorter and less toxic regimens, see https://www.cdc.gov/mmwr/volumes/69/rr/rr6901a1.htm .

Recommendations:

--shorter course (3-4 month) rifamycin-based treatment regimens are preferred over longer isoniazid (INH) monotherapy-based ones (6-9 months)

--preferred regimens:

    --weekly INH plus rifapentine for 3 months, for those >2 yo (and including those HIV-positive, though check for drug-drug interactions: https://www.hiv-druginteractions.org/checker is a great website, or go to https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportunistic-infection/0 for an updated listing of drug interactions). adult dose INH 900mg and rifapentine 900 mg once a week

    --daily rifampin for 4 months. adult dose 600mg daily

    --daily INH plus rifampin for 3 months. adult dose INH 300mg and RIF 600mg daily

--alternative regimens:

    --INH for 6 months: can be 300mg daily for adults daily or 900mg twice a week

    --INH for 9 months: can be 300mg daily for adults daily or 900mg twice a week

Commentary:

--1/4 of global population (2 billion people) are infected with M tuberculosis, including 13 million in the US

--most are asymptomatic and have LTBI, though 5-10% with LTBI are likely to progress to TB disease over their lifetimes; 80% of cases of TB disease in the US are related to progression of LTBI

--note that there are significant drug-drug interactions between the rifamycins and other meds, and that they vary depending on the rifamycin (ie, rifampin and rifapentine have somewhat different drug-drug interactions, see websites above)

--as noted in prior blogs, I personally am hesitant to give INH without also giving vitamin B6 to prevent neuropathy. I see too many people who have neuropathy or are predisposed to it (mostly diabetics, but lots of others), and this vitamin seems to be an easy, cheap way to prevent INH-induced or aggravated neuropathy

--weekly INH and rifapentine x12 weeks:

    --it is a lot of pills at once (rifapentine comes as 150mg, so 6 pills; INH as 300mg, so 3 pills; and if you add the B6: a total of 10 pills)

    --and the patient needs to be able to remember a weekly vs daily regimen. For some patients, I have asked one of our nurse case managers to call the patient every week to remind them.

    --directly-observed therapy should be considered in some higher risk people (eg HIV-positive): completion rate of therapy has been higher in some studies with DOT 

    --and, INH hepatotoxicity is less in this combination than with 9 months of INH, though still severe reactions requiring hospitalization do occur in 0.1% of people; systemic drug reactions (including influenza-like syndrome) are usually self-limited and mild, with no reported deaths

--daily rifampin x4 months:

    --equivalent to and less toxic than 6-9 months of INH

    --recommended for all ages, though no studies in HIV-positive patients (and there are lots of drug-drug interactions with rifampin)

        --can substitute rifabutin for rifampin in those with drug-drug interactions with rifampin ("Rifabutin 300mg has fewer or less pronounced drug interactions and may be used in place of rifampin when rifampin is contraindicated due to drug-drug interactions and isoniazid cannot be used"). the NIH report (https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportunistic-infection/0 ) does say that dolutegravir (but NOT bictegravir) can be used with rifampin, but that dolutegravir should be dosed at 50mg BID and contnued for 2 weeks after the LTBI therapy (rifampin halves the dolutegravir blood levels)

    --one consideration in HIV positive patients who have low CD4 counts is that they are at higher risk of actually having an active TB infection (asymptomatic or subclinical), and giving rifampin monotherapy could lead to rifampin-resistant TB (ie, it is especially important to rule-out active TB in these patients)

--daily INH plus rifampin x3months:

    --a conditional recommendation (defined as "when uncertainty existed regarding whether the desirable consequences outweighed the undesirable consequences"). the results comparing this to >= 6 mo of INH is similar in HIV-negative, but the risk of hepatoxicity is no different. a study in HIV-positive persons found somewhat less hepatotoxicity with this shorter course

--INH regimens: the 6 mo one is strongly recommended for those HIV-negative and conditionally recommended if HIV-positive; the 9-month course is conditionally recommended for all, whether HIV-positive or negative

    --for patients with inactive TB (tuberculin positive, stable fibrotic lung disease, and negative sputum cultures, and never treated for TB), 6 and 12 month courses were better than 3 months

so, the included regimens are not so different from prior recommendations, but there is a big shift to preferring the shorter course ones (improved completion rates, similar effectiveness, and less toxic than the older INH regimens, which are now relegated to the "alternative" category).  i have been prescribing either the weekly INH/rifapentine one (for those able to take weekly meds and 10 pills on that day), or the 4 month rifampin one, in essentially everyone during the past few years, without any problems. except when there are irreconcilable issues of drug-drug interactions. 

and, i think these new recommendations remind us of the importance of testing for LTBI in higher risk patients and treating it when present, esp those coming from countries where TB is common (ie, much of the world)

geoff​

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