TB-related immune reaction to HIV therapy occurs 20 months after TB treatment first started - is this a record?

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An HIV-positive patient has experienced what appears to be an extremely delayed instance of immune restoration inflammatory syndrome (IRIS). The individual commenced HIV therapy 20 months after starting anti-tuberculosis therapy and experienced an IRIS, French doctors report in the January 2nd edition of AIDS. This case is highly unusual – most cases of IRIS occur if HIV therapy begins less than two months after TB treatment begins (which is why HIV therapy is delayed in such circumstances of coinfection unless absolutely vital).

The case concerned a 43 year-old, HIV-positive Laotian man with a CD4 cell count of 261 cells/mm3> He had pulmonary tuberculosis diagnosed in April 2004. Standard first-line tuberculosis therapy, consisting of rifampicin, isoniazid, ethambutol, and pyrazinamide was commenced. For the next six months, however, sputum samples indicated that the patient still had infectious tuberculosis and the dosage of his drugs was modified and two additional drugs were added into his regimen to prevent drug-resistant tuberculosis emerging. The investigators note that even though the patient only weighed 35kg, it was necessary to provide drug doses needed to treat an individual who weighed 60kg.

During tuberculosis therapy, a pneumothorax (a gathering of air in the cavity surrounding the lung) required surgery. In October 2004, six months after tuberculosis treatment was initiated (a duration of therapy that would normally be sufficient for a cure), the patient developed a fistula on the scar of the pneumothorax drain. This required two months of treatment with steroids.

Glossary

immune reconstitution inflammatory syndrome (IRIS)

A collection of inflammatory disorders associated with paradoxical worsening (due to the ‘waking’ and improvement of the immune system) of pre-existing infectious processes following the initiation of antiretroviral therapy.

 

sputum

Material coughed up from the lungs, which can be examined to help with diagnosis and management of respiratory diseases.

isoniazid

An antibiotic that works by stopping the growth of bacteria. It is used with other medications to treat active tuberculosis (TB) infections, and on its own to prevent active TB in people who may be infected with the bacteria without showing any symptoms (latent TB). 

immune response

The immune response is how your body recognises and defends itself against bacteria, viruses and substances that appear foreign and harmful, and even dysfunctional cells.

cure

To eliminate a disease or a condition in an individual, or to fully restore health. A cure for HIV infection is one of the ultimate long-term goals of research today. It refers to a strategy or strategies that would eliminate HIV from a person’s body, or permanently control the virus and render it unable to cause disease. A ‘sterilising’ cure would completely eliminate the virus. A ‘functional’ cure would suppress HIV viral load, keeping it below the level of detection without the use of ART. The virus would not be eliminated from the body but would be effectively controlled and prevented from causing any illness. 

In September 2005, a full 20 months after the patient first started tuberculosis treatment, anti-HIV therapy with a regimen comprising two NRTIs and efavirenz was begun. At this time the patient had a CD4 cell count of 317 cells/mm3 and a viral load of 500,000 copies/ml.

Three weeks after antiretroviral therapy was started, a fistula once again appeared on the scar of the pneumothorax drain. At thistime, the patient was responding well to HIV therapy; his CD4 cell count had increased to 422 cells/mm3 and his viral load had fallen to 500 copies/ml.

Tests revealed that concentrations for all anti-tuberculosis and antiretroviral drugs were within normal therapeutic ranges and all samples were negative for tuberculosis. A CT scan failed to show any evidence of tuberculosis reactivation and the fistula disappeared by itself without treatment in November 2005.

However, the patient experienced weight loss, cough and weakness and was hospitalised. Tests detected semi-invasive aspergillosis, which quickly responded to treatment in December 2005.

“This report is unusual in the unusually long delay between the anti-tuberculosis treatment and the initiation of combination antiretroviral therapy”, write the investigators. They add, “in the literature, we did not find any report of such latency between the initiation of anti-tuberculosis treatment and the occurrence of IRIS.”

They suggest some possible reasons for the delayed IRIS in their patient, including a weak immune response to tuberculosis, or the presence of undiagnosed disseminated tuberculosis which therapy was unable to clear promptly. They also ponder if the diagnosis of aspergillosis was also another manifestation of IRIS.

References

Cailhol J et al. A delayed immune reconstitution inflammatory syndrome. AIDS 21: 115 – 116, 2007.