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 5 - HIV-infected TB case with smear non-conversion on regimen 1 despite good adherence

Authors: Richard Lessells

A 35 year old male patient is referred to clinic because of smear non-conversion on TB regimen 1 (HRZE). He was started on treatment for smear positive pulmonary TB two months previously. His baseline smears were +++/++ and his smears at two months were +++/+++. No specimen was sent for culture/DST at baseline. He remains symptomatic with cough, night sweats, chest pain, and has not gained weight on treatment.

He reports good adherence to TB treatment with no significant side-effects. He had one previous episode of smear positive TB ten years ago, for which he received six months of treatment and was cured. He reports that his brother who works as a miner in Johannesburg had TB the previous year but apparently had improved with standard TB treatment.

He is HIV-infected with recent CD4+ cell count of 187 cells/ul but has not yet started ART. He plans to start ART in the private sector through his medical aid scheme.

Sputum is obtained and tested with the Xpert MTB/RIF assay


Clinical chart

Interpretation

The clinical history alone gives a high degree of suspicion for MDR-TB. His sputum smears show no response to standard TB treatment in the face of apparently good adherence. He has reported risk factors for MDR-TB both in terms of his previous TB episode (albeit ten years ago) and the contact with his brother who reportedly developed TB disease whilst working as a miner (drug-resistant TB is highly prevalent in the mines around Johannesburg)


Drug resistance


Recommendations

Treatment recommendation

It is important to ensure that a specimen is sent for culture/DST to confirm the drug resistance and to obtain the full susceptibility profile.


The patient should be commenced on a standardised MDR-TB regimen consisting of and injectable agent (kanamycin or amikacin), a fluoroquinolone (ideally moxifloxacin), ethionamide, terizidone and pyrazinamide and should continue isoniazid. This regimen should be re-evaluated in 2-3 months based on the DST results and the initial response to treatment.

Case resolution

The patient was commenced on isoniazid, kanamycin, ofloxacin, ethionamide, terizidone and pyrazinamide. Culture was positive for M. tuberculosis and the Genotype MTBDRplus assay was reported as showing resistance to both rifampicin and isoniazid. Isoniazid was discontinued and the standard MDR-TB regimen was continued. He commenced ART through the private sector as planned.


Questions

I. What are the potential reasons for sputum smear non-conversion?

II. What is meant by the term amplification of drug resistance?


Answers

I. Drug resistance is only one cause of sputum smear non-conversion. Most patients under normal circumstances (in the absence of drug resistance) should have negative smears at two months. Table 1 illustrates other potential causes to be considered in any case where the sputum smears have not converted. It should be noted that HIV infection per se is not a reason for non-conversion.

II.Amplification of drug resistance means the development of further drug resistance whilst receiving anti-TB treatment. In this case, for example, if MDR-TB was present prior to treatment initiation, then effectively whilst on HRZE the patient was receiving dual therapy (ZE).

This increases the likelihood of the development of mutations conferring ethambutol and pyrazinamide resistance. In addition further RIF or INH drug-resistance mutations may develop, which might have consequences in terms of cross-resistance, e.g. inhA mutations and resistance to ethionamide. This underscores the importance of moving to a system whereby rapid drug susceptibility testing is available for all TB cases.


Key learning points

Smear non-conversion should prompt full re-assessment of the patient to explore potential causes

Treatment of undiagnosed drug-resistant tuberculosis with standardised first-line drug regimens could lead to the amplification of drug resistance, which in turn compromises future treatment options

Further reading

Rieder HL. Sputum smear conversion during directly observed treatment for tuberculosis. Tuberc Lung Dis 1996; 77: 124-129

Temple B, Ayakaka I, Ogwang S, et al. Rate and amplification of drug resistance among previously-treated patients with tuberculosis in Kampala, Uganda. Clin Infect Dis 2008; 47(9): 1126-1134

Calver AD, Falmer AA, Murray M, et al. Emergence of increased resistance and extensively drug-resistant tuberculosis despite treatment adherence, South Africa. Emerg Infect Dis 2010; 16: 264-271



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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