5. When to start ART in patients with active tuberculosis

 

ART initiation is recommended for all patients with TB, regardless of their CD4 cell count. However, the first priority is to initiate standard antituberculous treatment (in accordance with the respective national TB policy and guidelines). Case-fatality rates in patients with TB during the first two months of TB treatment are high, particularly in settings with high HIV prevalence, suggesting that ART should be initiated early.

Although ART reduces case-fatality rates, the risk of developing TB as well as the risk of recurrent TB in HIV-positive patients, concerns about drug interactions, tolerability, and the potentially life-threatening immune reconstitution inflammatory syndrome (IRIS) are key reasons why the initiation of antiretroviral therapy is often postponed in patients with tuberculosis.

From the the WHO 2013 HIV treatment and prevention guidelines

1. Start ART in all HIV-infected individuals with active tuberculosis (TB) irrespective of CD4 cell count.

2. Initiate TB treatment first, followed by ART as soon as possible within the first 8 weeks of TB treatment.

3. In severely immunosuppressed patients with CD4 count< 50 cells/mm3, ART should be initiated immediately within first two weeks of treatment.

4. Efavirenz (EFV) should be used as the preferred non-nucleoside reverse transcriptase inhibitor (NNRTI) in patients starting ART while on TB treatment.

IRIS is rarely life threatening in patients with pulmonary tuberculosis though it can be fatal in more severe forms of disease, such as tuberculosis meningitis. In a randomised controlled trial from Vietnam involving patients with tuberculosis meningitis, in whom ART was given within 1 week or was deferred until 8 weeks after presentation, the outcome was worse in patients who started early (no reduction of mortality and more side effects).

Thus, the evidence provides support for earlier initiation of ART in HIV/TB co-infected patients with advanced immunosuppression, except in TB meningitis.

For further reading, we recommend the following link:

In summary we can say that more and more evidence is accumulating that early start of ART is beneficial in patients with TB. If we have to select one group in which it really makes a difference in survival it is the group of patients with a very low CD4 count (< 50 cells/µl). Toxicity and TB-IRIS is more common in the early start group but does not increase mortality.


Blanc FX et al

Death after

Median FU of 25 months

Havlir DV et al

Death or AIDS at 48 weeks

Abdool Karim SS et al

AIDS or death

Study sites

Cambodia


Multi-- countries


South Africa


Number pts

included

661


809


642


Inclusion criteria

in HIV patients

Confirmed TB and CD4 <200


Confirmed or probable TB

and CD4 <250


Confirmed TB and CD4 <500


Intervention

Start ART after

TB treatment


Start ART after

TB treatment


Start ART after

TB treatment


All CD4 groups

Early

2 weeks

18%

< 2 weeks of

TB treatment

12.9%

<4 weeks of TB treatment

6.9/100 person-years

Late

8 weeks

27%

(HR=0.62; CI:0.44- 0.86; p=0.0006)

8--‐12 weeks of TB treatment

16.1%

(95%CI:1.8-8.1; p=0.45).

>8--‐12 weeks of TB treatment

7.8/100 person-years

(incidence-rate: 0.89; 95%CI:, 0.44 -1.79; p= 0.73)

CD4 <50cells/μl

Early


NA


15.5%


8.5/100 person-years

Late


NA


26.6%

(95%CI:1.5-

20.5; p=0.02)


26.3/100 person-years

(incidence-rate: 0.32; 95%CI: 0.07-1.13; p= 0.06)

To access the studies mentioned above for further additional reading, click on the following links: