Acquired Rifampicin Resistance in Thrice-Weekly Antituberculosis Therapy: Impact of HIV and Antiretroviral Therapy

Narendran, Gopalan; Menon, Pradeep A.; Venkatesan, P; Vijay, Krishnamoorthy; Padmapriyadarsini, Chandrasekaran; Kumar, S. Ramesh; Bhavani, Kannabiran P.; Sekar, L; Gomathi, Sivaramakrishnan N.; Chandrasekhar, C; Kumar, Santosh; Ramaswamy, Sridhar; Swaminathan, Soumya

doi:10.1093/cid/ciu674

Cited by 31 publications

(42 citation statements)

References 19 publications

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“…(n = 50, 0% on cART) reported a faster rate of sputum smear conversion with rifabutin versus rifampicin ( p < 0.05, log rank test) . Multiple studies have shown increased rates of acquired drug resistance with intermittent dosing both for rifampicin and rifabutin , particularly in those with advanced immunosuppression and disseminated bacillary burden . There has been no evidence of increased risk of acquired rifabutin monoresistance in HIV co‐infected individuals when rifabutin is dosed daily and hence, this is recommended, subject to pharmacokinetic considerations.…”

Section: Treatment Outcomesmentioning

confidence: 99%

Global access of rifabutin for the treatment of tuberculosis – why should we prioritize this?

et al. 2019

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Introduction Rifabutin, a rifamycin of equivalent potency to rifampicin, has several advantages in its pharmacokinetic and toxicity profile, particularly in HIV co‐infected patients on combined antiretroviral therapy (cART). In this commentary, we evaluate evidence supporting increased global use of rifabutin and highlight key recommendations for action. Discussion Although extrapolation of data from HIV uninfected patients would suggest non‐inferiority, there has been no randomized controlled study comparing rifabutin versus rifampicin in the outcomes of relapse‐free cure, in drug susceptible tuberculosis (TB), in HIV co‐infected patients on currently utilized cART regimens or in paediatric populations. An important advantage of rifabutin is that compared to the dose adjustments required with rifampicin, it can be co‐administered with the integrase strand transfer inhibitors raltegravir or dolutegravir without the need for dose adjustments. This strategy would be easier to implement in a programmatic setting and would save costs. We have assessed cost incentives to utilize rifabutin and have estimated generic costs for a range of rifabutin dosage scenarios. Where facilities are present for drug re‐challenge and monitoring for drug toxicity and cross‐reactivity, rifabutin offers a switch alternative for adverse drug reactions (ADR)s attributed to rifampicin. This would negate the need to prolong treatment in the absence of a rifamycin as part of short‐course multidrug therapy. There is evidence of incomplete cross‐resistance to rifampicin and rifabutin. Rifabutin may be useful in rifampicin‐resistant TB, in an estimated 20% of cases, based on phenotypic or genotypic rifabutin susceptibility testing. Conclusions Rifabutin should be available globally as a first‐line rifamycin in HIV co‐infected individuals and as a switch option in cases of rifampicin associated ADRs. Further studies are needed to ascertain the utility of rifabutin in rifampicin‐resistant rifabutin‐susceptible TB.

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Section: Treatment Outcomesmentioning

confidence: 99%

Global access of rifabutin for the treatment of tuberculosis – why should we prioritize this?

et al. 2019

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“…by using fluoroquinolones) have proved unsuccessful, with high relapse rates . Intermittent administration of TB therapy should be avoided during the induction phase in HIV‐positive individuals, as this strategy has been associated with acquired rifamycin resistance .…”

Section: Treatment Of Active Drug‐sensitive Tbmentioning

confidence: 99%

“…Other factors that may increase the risk of treatment failure and relapse include presence or development of drug resistance or drug intolerance, use of intermittent TB therapy, malabsorption of TB drugs, extreme biological variation in the response to TB therapy and hetero‐resistance or reinfection with drug‐resistant strains. ART reduces the risk of treatment failure with acquired rifamycin resistance in HIV‐positive individuals, perhaps related to prompt diagnosis of HIV and earlier ART initiation preserving immune function .…”

Section: Management Of Relapse Treatment Failure and Drug‐resistant mentioning

confidence: 99%

British HIV Association guidelines for the management of tuberculosis in adults living with HIV 2019

et al. 2019

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“…Narendran et al () in the cross‐protocol analyses comparing three cohorts – TB without HIV, TB with HIV infection in the pre‐HAART era and HIV–TB with ART – found that pretreatment INH resistance and HIV infection at baseline were significantly associated with the emergence of rifampicin resistance, when an intermittent regimen of ATT is used with concomitant HAART.…”

Section: Antituberculosis Therapy In Hiv Co‐infectedmentioning

confidence: 99%

“…Currently, the global WHO recommendation is to use a 6-month regimen of INH, rifampicin, ethambutol and pyrazinamide, with daily dosing at least in the intensive phase followed by INH and rifampicin given daily or thrice weekly (Standards of TB Care in India, 2014). Narendran et al (2014) in the cross-protocol analyses comparing three cohorts -TB without HIV, TB with HIV infection in the pre-HAART era and HIV-TB with ARTfound that pretreatment INH resistance and HIV infection at baseline were significantly associated with the emergence of rifampicin resistance, when an intermittent regimen of ATT is used with concomitant HAART.…”

Section: Antituberculosis Therapy In Hiv Co-infectedmentioning

confidence: 99%

TB–HIV co‐infection: a catastrophic comradeship

Narendran

Swaminathan

2016

Oral Diseases

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The symbiotic association of tuberculosis (TB) and HIV poses a challenge to human survival. HIV complicates every aspect of TB including presentation, diagnosis and treatment. HIV–TB patients encounter unique problems like drug–drug interactions, cumulative toxicity, immune reconstitution inflammatory syndrome (IRIS), lower plasma drug levels and emergence of drug resistance during treatment despite adherence. TB may also be overdiagnosed in HIV due to a number of diseases that closely resemble TB. Notable among them are non‐tuberculous mycobacteria, Pneumocystis Jirovecii and Nocardia. Even though diagnostic procedures have improved over the years, patients in developing countries usually seek health care at later stage of the disease. Research data ascertains the duration of therapy for TB to be 6 months with rifampicin and isoniazid, reinforced with ethambutol and pyrazinamide in the first 2 months. The schedule of therapy is still debatable with daily regimens being preferred in the context of HIV. Many reasons exist for persistence of Mycobacterium Tuberculosis (M.TB) in sputum, or delayed‐clearance of TB from sputum smears in HIV, apart from emergence of drug resistance and non‐compliance. Acquired rifampicin resistance (ARR) is a unique phenomenon complicating HIV‐associated TB when an intermittent regimen of antituberculosis therapy (ATT) is used without timely initiation of highly active antiretroviral therapy (HAART), especially in patients harbouring isoniazid‐resistant strains Immune restoration is often incomplete (‘swiss cheese’ pattern) even with effective HAART if not started early. Immune reconstitution inflammatory syndrome (IRIS) is the paradoxical worsening of the patient's condition often with radiological deterioration, due to an enhanced immune response with HAART. IRIS occurs despite an effective virological suppression and a favourable response to ATT. The incidence of IRIS in HIV has reached up to 54%, requiring utilization of experts and tertiary care which forms an obstacle to the decentralization of patients in the ART programme. Research in HIV–TB immunology and management needs further exploration in order to understand the diseases and offer appropriate treatment. The following paragraphs provide scientific evidences generated through research that could potentially guide management.

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Acquired Rifampicin Resistance in Thrice-Weekly Antituberculosis Therapy: Impact of HIV and Antiretroviral Therapy

Abstract: HIV-infected patients with tuberculosis treated with a thrice-weekly antituberculosis regimen are at a higher risk of ARR, compared with HIV-uninfected patients, in the presence of baseline isoniazid resistance. HAART reduces but does not eliminate the risk of ARR.

Cited by 31 publications

References 19 publications

Global access of rifabutin for the treatment of tuberculosis – why should we prioritize this?

Global access of rifabutin for the treatment of tuberculosis – why should we prioritize this?

British HIV Association guidelines for the management of tuberculosis in adults living with HIV 2019

TB–HIV co‐infection: a catastrophic comradeship

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