ART For TB-HIV Patients

Antiretroviral Therapy (ART) in People Living with HIV (PLHIV) with TB Co-infection 

ART reduces the morbidity and mortality due to TB in PLHIV.

All PLHIV diagnosed with active TB are to be initiated on ART regardless of CD4 count, after initiation of TB treatment. ART is to be started as soon as possible, keeping in mind the time needed for acceptance of the diagnosis, counselling needs, pill burden, drug interactions/ additive toxicities with Anti-tuberculosis Drugs (ATT) and TB-associated Immune Reconstitution Inflammatory Syndrome (TB-IRIS). 

Timing of ART in relation to initiation of TB treatment 

ART should be started as soon as possible within two weeks of initiating TB treatment, regardless of CD4 cell count, among PLHIV (except when signs and symptoms of meningitis are present). 

Among PLHIV with TB meningitis, ART should be delayed for at least 4 weeks (and initiated within 8 weeks) after treatment for TB meningitis is initiated. Corticosteroids should be considered as an adjuvant treatment for TB meningitis.

ART Regimen in PLHIV Receiving First-line (Rifampicin-containing) anti-TB treatment 

Current National AIDS Control Organisation (NACO) treatment guidelines for first-line ART in adults and adolescents recommend a three-drug combination therapy from two classes of Antiretroviral (ARV) drugs for initial treatment, i.e., 2 Nucleoside Reverse Transcriptase Inhibitor (NRTI) + 1 Integrase Strand Transfer Inhibitor (INSTI).

• Dolutegravir (DTG)-based regimen (with NRTI backbone) is the preferred regimen for all PLHIV on first-line (Rifampicin-containing) ATT. 

  Rifampicin (RIF) is a potent inducer of drug-metabolizing enzymes and drug transporters, and co-administration with DTG reduces the bioavailability of DTG, which can be overcome by doubling the DTG dose to 50 mg twice daily. Therefore, patients on Rifampicin-containing ATT should receive an additional tablet of DTG 50 mg (at an interval of 12 hours with the regular dose of DTG) till the completion of ATT. Once the ATT is completed, an additional tablet of DTG 50 mg should be stopped 2 weeks after the stoppage of the Rifampicin-containing treatment regimen. 

• Rifampicin is a Cytochrome p450 enzyme (CYP450) inducer and suppresses the bioavailability of Protease Inhibitors (PIs), thereby decreasing the efficacy of ART. Therefore, if a patient co-infected with HIV on first-line ATT needs to be co-administered with boosted PI (Ritonavir boosted Atazanavir (ATV/r) or Ritonavir boosted Lopinavir (LPV/r) or Ritonavir boosted Darunavir (DRV/r))-based ART regimen, Rifampicin should be replaced by Rifabutin for the entire course of ATT. 

Recommended ART regimens in PLHIV (adults and adolescents) infected with Drug Sensitive TB receiving Rifampicin-containing anti-TB treatment 

Considerations in PLHIV Already on ART at Time of Diagnosis of Active TB 

The following points are to be considered in PLHIV if TB is diagnosed in patients already receiving ART:

• In PLHIV who are already on ART at the time of TB diagnosis, appropriate modification of ART/ ATT needs to be done to maintain optimal efficacy of ATT as well as ART. 
• When a patient on ART presents with active TB, there is a possibility of suspecting treatment (ART) failure. NACO recommends the following guiding principles in this context: 
  • If an episode of TB occurs within the first 6 months of the initiation of ART, it should not be considered a failure of the treatment and IRIS should be suspected and managed accordingly. 
  • If an episode of TB develops more than 6 months after the initiation of ART, PLHIV should be assessed for the possibility of treatment failure (based on CD4 counts and viral load) with a special focus on adherence. 

Second-line ART in HIV-TB Co-infection

The patient is switched to second-line ART when first-line treatment has failed.

The current recommendation for second-line ART is based on the following principles:

 A new class of Anti-retroviral (ARV) is to be given

1.        An INSTI (DTG), if first-line was NNRTI based 
2.        A Ritonavir-boosted PI (Atazanavir/ Ritonavir or Lopinavir/ Ritonavir), if first-line was INSTI based 

 Supported by at least one new and unused NRTI (Zidovudine or Tenofovir) 

 Continued Lamivudine administration ensures reduced viral fitness

References 

•  National Guidelines for HIV Care and Treatment, NACO, MoH, GoI, 2021.
•   WHO Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring, 2021. 

Assessment