ART: TB/HIV Co-infection

Principles

PLWH with TB should be started on standard TB therapy with 2 months rifampicin/isoniazid/pyrazinamide/ethambutol followed by 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 PLWH

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

However, if TB meningitis signs and symptoms are present ART initiation may be delayed. See When to start ART in PLWH with Opportunistic Infections (OIs)

Be aware of IRIS reaction in persons starting ART at low CD4 count levels and with early initiation of ART. Prophylactic prednisone for 4 weeks at the time of ART initiation (prednisone 40 mg qd for 14 days, then 20 mg qd for 14 days) can prevent paradoxical TB-associated IRIS in persons with CD4 < 100 cells/μL receiving TB treatment Corticosteroids should be considered for treatment of symptomatic IRIS, with dosages and duration tailored according to response

ARV regimens

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

These recommendations are for PLWH 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

Regimen Main requirements Footnotes (Additional guidance)
Recommended regimens with rifampicin
2 NRTIs + NNRTI
TDF/XTC + EFV or
TDF/FTC/EFV
At bed time or 2 hours before dinner   (tenofovir salts)
II  (EFV: suicidality. HIV2 or HIV-1 group 0)
ABC/3TC + EFV HLA-B*57:01 negative
HBsAg negative
HIV-VL < 100,000 copies/mL
At bed time or 2 hours before dinner
III (ABC: HLA-B*57:01)
II  (EFV: suicidality. HIV-2 or HIV-1 group 0)
Alternative regimens with rifampicin
2 NRTIs + INSTI
TDF/XTC + DTG bid     (tenofovir salts)
IV (DTG: dosing)
TDF/XTC + RAL bid     (tenofovir salts)
V  (RAL: dosing)
ABC/3TC + RAL bid HBsAg negative
HLA-B*57:01 negative
III (ABC: HLA-B*57:01)
  (RAL: dosing)
Other combinations with rifabutin
2 NRTIs + PI/r

TDF/XTC + DRV/r,
ATV/r or LPV/r

With food VI (rifabutin dosing)

ABC/3TC + DRV/r,
ATV/r, or LPV/r

HLA-B*57:01 negative
HBsAg negative
HIV-VL < 100,000 copies/mL
With food
III (ABC: HLA-B*57:01)
VI (rifabutin dosing)

 

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. EFV: not to be given if history of suicide attempts or mental illness; not active against HIV-2 and HIV-1 group O strains
  3. 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 PLWH with a high CVD risk (> 10%)
  4. 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
  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 date 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 shortterm 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