Read the treatment guidelines online - Summary

BHIVA treatment guidelines for TB/HIV infection

These guidelines have been drawn up to help physicians manage adults with HIV/TB co-infection.  We recommend that co-infected patients are managed by a multi-disciplinary team which includes physicians who have expertise in the treatment of both tuberculosis and HIV. 

We recommend that the optimal regimen be used in the treatment of tuberculosis.  In the majority of cases, this will necessitate use of rifampicin and isoniazid. In the treatment of HIV, there is more flexibility of choice for many patients starting highly active anti-retroviral therapy (HAART). 

We recommend that if HIV treatment is started in patients who are on anti-tuberculosis therapy then HAART should be modified if necessary. TB treatment should only be modified when a patient has developed intolerance of, or severe toxicity from, HIV drugs or has evidence of genotypic resistance to specific HIV drugs thus limiting HAART therapy to agents whish are likely to interact with anti-tuberculosis therapy. 

These factors (intolerance, toxicity and resistance) may sometimes necessitate prolongation of duration of TB treatment.

The gold standard for diagnosis of tuberculosis is microscopy followed by culture and drug sensitivity testing.  Molecular diagnostics may be valuable in reducing the time patients spend in isolation facilities when tuberculosis is suspected clinically.  Confirmation, by molecular diagnostics, that acid-fast bacilli are not M. tuberculosis may be useful for clinical management and infection control. 

We recommend rapid detection of rifampicin resistance using molecular techniques in patients whose clinical course or initial assessment suggest multi-drug resistant tuberculosis.  These molecular tests should be used as an adjunct to standard laboratory techniques. 

TB treatment

We recommend daily tuberculosis treatment whenever possible. Treatment may be given 5 days a week, but should be intensively supervised. This option may be useful in hospital or other highly supervised settings. Three times a week directly observed therapy (DOT) should only be given to patients where local logistics enable this to be successfully undertaken.

We do not recommend twice-weekly DOT for treatment of HIV/TB co-infected patients, especially in those with CD4 counts <100 cells/uL. 

Treatment should be started with four drugs (typically rifampicin, isoniazid, pyrazinamide and ethambutol) until sensitivities are known.

We recommend a 6 months treatment regimen for drug sensitive Mycobacterium tuberculosis outside of the central nervous system (CNS) [at least 182 doses of isoniazid and rifampicin and 56 doses of pyrazinamide and ethambutol].  In drug sensitive tuberculosis affecting the CNS we recommend 12 months of treatment. This usually consists of two months of a four-drug TB regimen, followed by 10 months of isoniazid and rifampicin.  Drug resistant disease should be treated in line with BTS Guidelines.

Drug interactions and toxicities.

Rifampicin is a powerful inducer of cytochrome P450-3A4 and therefore careful attention should be paid to potential drug/drug interactions between anti-tuberculosis drugs, HAART and other concomitant therapy.  The alternative use of rifabutin may overcome some of the difficulties in co-administration of rifampicin with protease inhibitors and non-nucleosides.

Overlapping toxicity profiles, for example peripheral neuropathy with stavudine and isoniazid, or rash with non-nucleosides and rifampicin can complicate care , as ascribing a cause may be difficult.  In some patients, for example those with chronic viral hepatitis, there is an increased rate of drug toxicity.  In these patients we recommend more frequent monitoring of liver function tests.

Antiretroviral treatment

The following antiretroviral drugs may be used with rifampicin-based regimens of TB therapy. It is important to note that there is little long-term clinical outcome data to support use of these drugs in combination.

  • There are no major interactions with rifampicin or rifabutin.
  • Efavirenz may be used at a dose of 800mg/day in patients weighing >50kg and the standard dose of 600mg/day in patients weighing <50kg.  In patients experiencing side effects on these doses, therapeutic drug monitoring may be of value.  We recommend that daily rifampicin should not be used with nevirapine.
  • NNRTI may be used with rifabutin, but the rifabutin dose is increased to 450mg/day when used with efavirenz.  No dose modification is required when rifabutin is used with nevirapine, however we do not recommend use of this combination.
  • Rifampicin should not be used with un-boosted protease inhibitors (PI). Data on boosted PI regimens eg lopinavir/ritonavir with rifampicin show an increased risk of hepatotoxicity and the need in some patients (based on therapeutic drug monitoring [TDM]) to increase the dose of lopinavir to 4 tablets bd.  There is a lack of good clinical and virological outcomes using these combinations Boosted saquinavir should not be used with rifampicin as 11/28 (39.3%) subjects exposed to rifampicin 600 mg daily taken together with ritonavir 100 mg and saquinavir 1000 mg given twice daily (ritonavir boosted saquinavir) developed significant hepatocellular toxicity.
  • Rifabutin can be used with un-boosted PI but dose modifications of PI are needed and the dose of rifabutin halved to 150mg/day.  There are few data to support use of rifabutin with a boosted PI but if it is used the dose of rifabutin needs to be reduced to 150mg three times a week.  The dose of boosted PI remains unaltered.  In these situations TDM should be used.
  • We recommend that TDM of NNRTI and PI should be performed when drug regimens are complex.  Drug levels of anti-tuberculosis drugs should be measured when there is clinical concern regarding absorption or response to TB therapy.
  1. Nucleoside / nucleotide reverse transcriptase inhibitors
  2. Non-nucleoside reverse transcriptase inhibitors
  3. Protease inhibitors

Starting HAART

When to start anti-retroviral therapy in patients who have tuberculosis is a balance between potential overlapping toxicities, drug interactions and possible immune reconstitution versus the risk of further immune suppression with its associated increase in morbidity and mortality.  We recommend that patients who have a CD4 count consistently >200 cells/uL while receiving treatment of tuberculosis should wait until their anti-tuberculosis therapy is completed before starting HIV therapy [see BHIVA HIV treatment guidelines].

For patients with CD4 counts between 100 and 200 cells/uL we recommend deferring starting HIV therapy until completion of the intensive phase of anti-tuberculosis treatment (after 2 months). 

For patients with CD4 counts <100 cells/uL there are no data to support either immediate or deferred HAART.  In this situation we recommend that patients should be recruited to clinical trials, which address this question.  If that is not possible then patients should be started on HAART as soon as is practical after starting anti-tuberculosis therapy.   

DOT

This is regarded as a gold standard for treatment of TB but it may not be possible to deliver all elements of the DOT package.  Witnessed supervision of treatment may be impracticable in every case and it is important to remember that patient-centred management is the core of successful TB treatment.  We recommend that DOT be used in all cases of multi-drug resistant TB.

Tuberculin skin test

Tuberculin skin testing is less useful in patients with HIV infection compared with HIV uninfected patients.  We do not recommend tuberculin skin testing in patients with suspected HIV/TB co-infection or as a screening test for tuberculosis in HIV infected patients. New immune-based detection tests [such as those using gamma interferon production from TB specific T cells] appear to have better sensitivity than tuberculin tests, however correlation of positive results with outcome in patients with low CD4 counts is required.

Chemopreventative therapy

We do not recommend routine chemo-preventative therapy for HIV infected patients. Close contacts of people who have infectious TB should be followed up and offered chemo-preventative therapy [see BTS guidelines].  Data suggest that HAART is effective in reducing the incidence of new tuberculosis and we recommend that all HIV positive patients should be offered HAART  [based on BHIVA HIV treatment guidelines].

Relapse and treatment failure

Patients with tuberculosis, with or without HIV infection, who appear to fail treatment or who relapse despite therapy pose particular management problems and should be referred to and discussed with clinical colleagues who have expertise in the management of HIV/TB. 

Control & prevention of TB failure

Every hospital/Trust should have in place a policy for the control and prevention of TB.  Specific consideration should be made to establishing protocols for prevention of transmission of TB to and from immunosuppressed patients.