ART: TB/HIV Co-infection

Principles

Persons with TB should be started on standard TB therapy with 2 months rifampicin/isoniazid/pyrazinamide/ethambutol followed by at least 4 months rifampicin/isoniazid (choice of drugs and length of treatment depends on drug susceptibility and site of disease), see Diagnosis and Treatment of TB in Persons with HIV

All persons with TB/HIV co-infection should start ART irrespective of CD4 count. Treatment supervision and adherence evaluation are very important. If the person is already on ART, check for potential DDIs and if these are significant, consider switching to one of the recommended regimens for TB/HIV co-infection

Suggested timing of ART initiation in TB/HIV co-infection

ART should be started as soon as possible (within two weeks of initiating TB treatment) regardless of CD4 count specifically if CD4 count < 50 cells/µl 

In case of TB meningitis, see When to start ART in persons with Opportunistic Infections (OIs)

ARV regimens

Table 1. Antiretroviral regimens in TB/HIV co-infection

These recommendations are for persons initiating ART with susceptible Mycobacterium tuberculosis infection. When treating MDR-TB or XDR-TB, careful review of DDIs and potential toxicities is mandatory before initiating ART. For a wider review of potential DDIs of ART and TB treatment, see Drug-drug Interactions between Anti-tuberculosis Drugs and ARVs

Additional guidance

1. There are available generic forms of TDF, which instead of fumarate use phosphate, maleate, and succinate salts. They can be used interchangeably. In certain countries, TDF is labelled as 245 mg rather than 300 mg to reflect the amount of the prodrug (tenofovir disoproxil) rather than the fumarate salt (tenofovir disoproxil fumarate)
2. DTG should be dosed 50 mg bid when given with rifampicin since rifampicin lowers DTG exposure. This dose adjustment should be maintained for 2 weeks after stopping rimfampicin as the inducing effect persists after discontinuation of a strong inducer
3. EFV: not to be given if history of suicide attempts or mental illness; not active against HIV-2 and HIV-1 group O strains. Use EFV at the dose of 600 mg/d
4. ABC contraindicated if HLA-B*57:01 positive. Even if HLA-B*57:01 negative, counselling on HSR risk still mandatory. ABC should be used with caution in persons with a high CVD risk (> 10%)
5. RAL 400 or 800 mg bid. With RAL 400 bid a large phase 3 study showed non-inferiority at week 24 but failed to show non-inferiority at week 48 compared to EFV.
   With 800 mg bid only limited data from a phase 2 study with potential increases in liver toxicity
6. For guidance on ARV and rifabutin dosing, see TB Drug Doses, DDI table on Anti-tuberculosis drugs and ARVs

Non-rifamycin regimens

Tuberculosis can be treated with regimens that do not contain rifamycins. Their use should be contemplated only in persons with serious toxicity to rifamycins where desensitisation has failed, or in persons with rifamycin-resistant isolates. Although non-rifamycin regimens have fewer drug-drug interactions, such regimens are inferior to a rifampicin-based regimen for fully drug-sensitive TB treatment

Poorer outcomes have also been seen in cases where rifampicin is used for the initial two months before the regimen is switched to isoniazid and ethambutol in the continuation phase

In countries where neither DTG nor rifabutin are available, or there is no possibility to use RAL or EFV, following combinations could also represent a short term alternative until anti-TB treatment has been completed

• Rifampicin plus double dose LPV/r or with RTV super boosted (400 mg bid) + LPV
• For other regimens based on 2 NRTIs plus NVP, RPV, DOR, ETV or MVC, consultation with an HIV specialist is recommended