Incidence of Immune Reconstitution Syndrome in HIV-Tuberculosis Coinfected Patients in India

HAART has led to dramatic reductions in HIV-related morbidity and mortality. HAART suppresses viral replication, allowing for partial restoration of the immune system and protection against opportunistic pathogens.

Immune reconstitution, however, can result in an inflammatory response against infectious and non-infectious antigens and an apparent clinical deterioration of the patient. This phenomenon has been described under various descriptions such as "paradoxical reaction," "immune restoration disease," "HAART attacks," "immune reconstitution syndrome (IRS)," and "immune reconstitution inflammatory syndrome."

Previous reports of IRS have primarily been published in the developed world. With declining costs in antiretroviral drugs, and production by generic manufacturers, care centers in the developing world are now able to afford and administer antiretroviral therapy to HIV patients.

With increased coprevalence of opportunistic infections and access to antiretroviral therapy in the developing world, researchers conducted this study to determine the incidence of immune reconstitution in resource-limited settings and the implications for clinicians.

In this study, 11 of 144 HIV and tuberculosis (TB)-coinfected individuals followed for 72 person-years developed IRS within 6 months of initiating generic HAART.

All of the IRS patients were male, with a median age of 29 years; median CD4 at HAART initiation was 123 cells/mm3, and 6-month median CD4 rise was 124 cells/mm3.

There was no statistical difference in CD4 rise or CD4 count and duration of TB treatment at HAART initiation between those who did and those who did not develop IRS (P = 0.8380).

The median time to development of clinical IRS was 42 days (range 10-89 days).

The incidence of IRS in this cohort is 15.2 cases per 100 patient-years.

With increased coprevalence of opportunistic infections, especially TB, and increasing access to antiretroviral therapy in the developing world, clinicians in these countries must be able to identify IRS and relieve symptoms without compromising clinical care.

Discussion

Unfortunately, the human host's enhanced ability to mount an immune reaction and protect from the destruction of infectious agents may itself cause morbidity to the host. There have been cases published of clinical "progression" despite adequate anti-TB and antiretroviral therapy, including prolonged fever, increasing respiratory symptoms, increasing lymphadenopathy, ascites, and growth of intracranial tuberculomas.

In this cohort from a resource-limited setting with a high background rate of TB, there is a high incidence of IRS. As the use of antiretroviral therapy increases in the developing world, initiation of therapy while patients have active opportunistic infections will lead to significant morbidity. An association between the duration of initiation of TB treatment and HAART initiation was seen in an earlier study for the occurrence of IRS. This association was not seen in our series. Appropriate therapy must be maintained in the face of apparently worsening clinical symptoms. The use of corticosteroids has anecdotally been successful in decreasing IRS without significantly compromising clinical care.

However, there are no definitive guidelines for care of the patient with IRS. At this center in India, patients are counseled on the condition and are advised to continue with treatment. All patients are currently stable and tolerating therapy with no further adverse events, according to the authors.

In conclusion, the authors write, “With reports of IRS growing in frequency, and now detected significantly in a tertiary HIV center in the developing world, clinical trials in developing countries need to be conducted to help physicians better understand when to initiate antiretroviral therapy in the context of opportunistic infections.

“In addition, without adequate guidelines to identify and treat IRS, clinicians treating HIV-infected individuals in the developing world will face a new set of challenges to safe and effective therapy.”

02/11/05

Reference
N Kumarasamy and others. Incidence of Immune Reconstitution Syndrome in HIV/Tuberculosis-Coinfected Patients After Initiation of Generic Antiretroviral Therapy in India. Journal of Acquired Immune Deficiency Syndromes 37(5): 1574-1576, December 15, 2004.