Open Access HIV & TB drug resistance clinical cases:

Here we provide you with cases published in the HIV/TB Drug Resistance & Clinical Management Case Book. These cases have been presented to over 1000 medical doctors in southern Africa at the annual SATuRN Drug Resistance Workshops.

The objective is to capacitate doctors, nurses and allied medical staff at all levels of the health system to prevent and manage HIV and TB drug resistance.


Clinical Cases Latest Cases

TB Case 2 - HIV-infected TB suspect with household MDR-TB contact: Xpert MTB/RIF test

Authors: Richard Lessells

A 61 year old HIV-infected female on antiretroviral therapy presents with three weeks of cough, night sweats and chest pain. She has been taking TDF/3TC/LPVr (her first ART regimen commenced in the private sector) for almost two years. Her latest results are CD4 470 cells/ul and viral load <40 copies/ml. She reports a previous episode of smear negative pulmonary TB in 2009 for which she completed six months of treatment.

A sputum specimen is obtained and tested with the Xpert MTB/RIF system. In addition a chest X-ray is performed. Routine bloods include creatinine 92 micromol/L (calculated creatinine clearance 58ml/min).

Further history reveals that her co-resident 27 year old son commenced treatment for MDR-TB four months prior to her presentation. In addition her two year old grandson (who was also living with them) had recently been admitted to hospital in Durban for pneumonia.



Clinical chart

The Xpert MTB/RIF result is MTB DETECTED MEDIUM. Rif Resistance DETECTED. This molecular test has detected M. tuberculosis and at least one of the mutations in the rpoB gene which confer resistance to rifampicin, which can be considered a reliable proxy for MDR-TB.


Drug resistance

Interpretation

The chest X-ray demonstrates bilateral apical fibrosis and left lower lobe consolidation with early cavity formation. This is consistent with active TB disease.


Recommendations

Treatment recommendation
This lady has specific risk factors for MDR-TB: the history of TB treatment two years prior to this presentation and the household contact with diagnosed MDR-TB. In this context the Xpert MTB/RIF suggests a very high likelihood of MDR-TB.

She should be commenced on a standard MDR-TB regimen with at least four drugs which are expected to be active. A recommended regimen would be: kanamycin (Km), ofloxacin (Ofx), ethionamide (Eto), terizidone (Trd) and pyrazinamide (Z). If not done already, a further sputum specimen should be sent for culture and phenotypic DST.


Questions

I. Why has this individual developed TB disease whilst on suppressive antiretroviral therapy?

II. What further information regarding the son might be useful in managing the patient?

III. Is there any information given that would make you alter the dosage of any TB drugs?

IV. Should the current ART regimen be continued or changed?

V. What advice would you give regarding the grandson?


Answers

I. Unfortunately TB disease can still develop in HIV-infected individuals on suppressive ART. Indeed studies show that the incidence of TB disease on ART remains significantly higher than the background population rate (Brinkhof 2007).

II. Information should be sought regarding the susceptibility profile of the son TB isolates and his response to MDR-TB treatment. In this case it was determined that the son at baseline had pre-XDR-TB (resistance to kanamycin but not ofloxacin) and had remained smear and culture positive in the first six months of treatment. This might increase the likelihood that our patient has additional resistance and might also have an unfavourable response to standard MDR-TB treatment. This makes it critical that full phenotypic DST is performed.

III. She has chronic kidney disease stage 3 (creatinine clearance 58ml/min). The dosing frequency of the injectable agent should be reduced from five days per week to three days per week. The creatinine should be monitored at least monthly whilst on kanamycin.

IV. There is no evidence with which to guide antiretroviral regimen choice in patients on second-line TB drugs. It should be noted that ritonavir may interact with second-line TB drugs through inhibition of the cytochrome P450 (CYP450) system. Of the common second-line TB drugs, ethionamide is known to be metabolized through this CYP450 system so there is the potential for increased drug levels (no specific studies have been performed). Given the current virological suppression, it would be sensible to continue her current ART regimen but she should be monitored very closely for toxicity.

V. The report of the grandson being admitted with pneumonia should be of concern. The child needs to be assessed for active TB disease with Mantoux test, chest X-ray, gastric washings, and HIV test.


Key learning points

I. In MDR-TB cases with a household contact also on MDR-TB treatment, information should be sought about the drug susceptibility profile and response to treatment of the contact, this might help to tailor the regimen pending full DST results

II. Child contacts of MDR-TB cases should all be referred for assessment. Symptomatic contacts should undergo investigation with Mantoux test, chest X-ray, gastric aspirates, and HIV testing

Further reading

Brinkof MW, Egger M, Boulle A (2007). Tuberculosis after initiation of antiretroviral therapy in low-income and high-income countries. Clin Infect Dis 2007; 45: 1518-1521

Coyne KM, Pozniak AL, Lamorde M, Boffito M (2009). Pharmacology of second-line antituberculosis drugs and potential for interactions with antiretroviral agents. AIDS 23: 437-446

Grandjean L, Crossa A, Gilman RH et al (2011). Tuberculosis in household contacts of multidrug-resistant tuberculosis patients. Int J Tuberc Lung Dis 15: 1164-1169



Disclaimer:

Although every attempt has been made to ensure that the information in this book is accurate and up-to-date, the authors and publishers accept no responsibility for any loss or damage resulting from use of the information herein.

It is the responsibility of the individual clinician or health care worker to abide by national and local guidelines and protocols regarding management of HIV and TB. Information regarding drug indications and dosages should be checked with the national or local formulary, or with the pharmaceutical package insert.

None of the authors has declared any competing financial interests with regards to any material discussed within the HIV and TB Drug Resistance and Clinical Management Case Book.


SATuRN output, All cases...

HIV Case 1 - Adult female with virological failure on first line d4T/3TC/EFV
HIV Case 2 - Adult female patient with virological failure on first line therapy after substitution of EFV to NVP
HIV Case 3 - Adult female patient on treatment for epilepsy with virological failure on TDF/3TC/EFV; previous single dose NVP for PMTCT
TB Case 1 - HIV-infected TB suspect with previous history of TB treatment: Xpert MTB/RIF test
TB Case 2 - HIV-infected TB suspect with household MDR-TB contact: Xpert MTB/RIF test
TB Case 3 - HIV-infected adult male with a laboratory report showing extensively drug-resistant TB (XDR-TB)

SATuRN output, All cases...


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