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MDR-TB in HIV — DTM&H MCQ

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ModerateTropical Bacterial InfectionsMDR-TB in HIVDTM&H

A 42-year-old HIV-positive man in South Africa with CD4 150 has a 2-month cough and weight loss. Sputum is smear-negative but GeneXpert detects M. tuberculosis with rifampicin resistance. What is the most appropriate next step?

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Correct answer: BRequest full DST and start WHO-recommended MDR-TB regimen

The correct answer is B, request full drug susceptibility testing (DST) and start a WHO-recommended MDR-TB regimen. A GeneXpert MTB/RIF result showing rifampicin resistance is a validated surrogate marker for multidrug-resistant TB, since over 90 percent of rifampicin-resistant strains are also isoniazid-resistant. NICE guidance mirrors WHO practice: once rifampicin resistance is detected on a rapid molecular test, the patient should be managed with a multidisciplinary team experienced in MDR-TB, started on a regimen of at least six drugs likely to be effective, and tested for resistance to second-line agents (fluoroquinolones, injectables/bedaquiline) to refine therapy. Waiting for further testing before treating, or treating with a regimen that assumes rifampicin susceptibility, both risk amplifying resistance and clinical deterioration in a patient who is already immunosuppressed with CD4 150. Why the other options are wrong: A. Start standard RHZE: this regimen contains rifampicin, which is already known to be ineffective against this isolate, so continuing it selects for further resistance and delays effective treatment. C. Repeat GeneXpert in 2 weeks: rifampicin resistance detection by GeneXpert has excellent sensitivity and specificity via rpoB probes; repeating the same assay does not add second-line resistance information and simply delays appropriate therapy. D. Treat with fluoroquinolone empirically: fluoroquinolone susceptibility is unknown until DST is performed, and monotherapy-style empirical escalation without a full regimen risks generating additional resistance and treatment failure. E. Defer TB treatment until ART established: with active MDR-TB and a low CD4 count, TB treatment must start promptly; ART is introduced within 2 to 8 weeks of starting TB treatment (sooner if CD4 is very low), not the reverse sequence. Key point: rifampicin resistance on GeneXpert should be treated as MDR-TB until proven otherwise, prompting immediate initiation of a WHO-recommended regimen alongside full DST, not delay or single-drug substitution.

Reference: NICE guideline NG33, Tuberculosis: prevention, diagnosis, management and service organisation, Recommendations section (updated 2024), www.nice.org.uk/guidance/ng33/chapter/Recommendations