Treatment of DR-TB with HIV Coinfection

Principles of treating Drug-resistant TB (DR-TB) in People Living with HIV (PLHIV):

1. Initiate an appropriate second-line anti-tuberculosis treatment (ATT) regimen, depending on the drug-sensitivity profile

2. Initiate anti-retroviral therapy (ART) as early as possible, preferably as soon as ATT is tolerated, maximum within two weeks. HIV-infected DR-TB patients without the benefit of ART may experience mortality rates exceeding 90%

3. When choosing the drug regimens, keep in mind the drug-drug interactions and adverse event profile of the drugs. Certain combinations have to be avoided/used with caution. Dose adjustments may be required. Indicators of adverse events should be closely monitored

4. Appropriate prophylactic medication for opportunistic infections (OI), co-trimoxazole prophylaxis therapy (CPT) can be provided to all patients with HIV as per World Health Organisation (WHO) recommendation

5. Provide support for TB and anti-retroviral (ARV) medication adherence

6. Closely monitor biomarkers of immune status

Drug interactions

1. Some drugs used in ART can affect the blood levels of Bedaquiline. Examples:

• Ritonavir --> causes increased blood levels of bedaquiline (Bdq) and thus drug toxicity. Therefore, intense monitoring of adverse drug reaction (ADR) is required in these cases. 
• Efavirenz --> reduces the blood levels of bedaquiline and thus decreases the efficacy of Bdq

Dolutegravir (DTG)-based ART is the ART regimen of choice in PLHIV with Drug-resistant TB (DR-TB).

2. Linezolid (Lzd), when used for multi/ extensively drug-resistant TB (M/XDR-TB) with HIV-coinfected patients, requires close monitoring for bone-marrow depression, when co-administered with Zidovudine. Complete blood cell counts should be performed regularly. 

3. Fluoroquinolones (FQs) and Clofazimine (Cfz) may increase the risk of cardiotoxicity when co-administered with Bdq. Ritonavir-containing regimens can cause QT prolongation. Therefore, monitoring of patients for cardiac dysrhythmias or QT interval prolongation (i.e. using ECG), and for electrolyte imbalances (especially serum potassium) is important while co-administration of these drugs with Bedaquiline.

ADR management

1. Ensure good pre-treatment evaluation to assess the patient's eligibility for any drug regimen

2. Bedaquiline should be used with caution in PLHIV treated with ARVs that have drug interactions with Bdq. In such cases, patient monitoring is required.

3. Persons with suspected ADRs should be referred by healthcare staff to the medical officer for evaluation.

References

• Guidelines for PMDT in India, WHO, MoHFW, GoI, 2021.
• National Guidelines for HIV Care and Treatment, NACO, MoH, GoI, 2021.

Assessment