AIDS SOCIETY OF INDIA

Risk factors for IRIS

• An active or sub-clinical infection by opportunistic pathogens.
  • The antigens of non-viable micro-organisms (e.g. Cryptococci and CMV) are all possible targets for an immunopathological response.
  • Cd4 T count below 50 / mm3 prior to initiation of HAART is a major risk factor for IRIS.65
  • Being ART naïve is an important risk factor for development of IRIS.64
  • Starting ART in close proximity to the diagnosis & initiation of treatment for an OI.64

Table 9 depicts various types of IRIS seen in clinical practice.

Non-infectious IRIS includes GBS, autoimmune thyroiditis and sarcoidosis. The differential diagnosis for IRIS includes active OI, ARV drug failure, ARV Drug toxicity or failure of anti-microbial therapy if patient is already on the same. Culturing the microorganism in body fluids may provide a clue for an active OI, which would warrant antimicrobial therapy.

Treatment of IRIS

There are no standard guidelines for treatment of IRIS. There is very limited information on the effectiveness of various interventions to manage IRIS, with lack of evidence from randomized clinical trials. Most cases will resolve without any additional treatment. Milder forms of IRIS resolve with continuing anti-infective therapy and HAART. In the majority of cases, HAART can be safely continued without need for interruption. In general, most clinicians prefer to continue ART if CD4 count is<100/µL or if IRIS manifests months after initiation of HAART. On the other hand, discontinuation of ART should be considered if inflammatory responses are considered life-threatening (e.g. intracranial IRIS leading to encephalitis, cerebritis, perilesional cerebral edema, pulmonary IRIS with ARDS etc), unresponsive to steroids, or if the involved pathogens are no amenable to specific antimicrobials (e.g. parvovirus B 19, polyomavirus JC causing PML) or if ART toxicity is the main differential diagnosis(e.g. hepatitis).

Nonsteroidal anti-inflammatory drugs (NSAIDs) are also helpful in controlling inflammation and fever associated withIRIS.63 However, in severe IRIS a short course of oral prednisoloneis required to alleviate symptoms. The dose and duration required is very variable and should be judged clinically. Severe disease will require at least 1–2 mg/kg of prednisolone. Thalidomide has also been tried effectively in some patients.

SPECIAL SITUATIONS

Tuberculosis (TB) is one of the commonest OI and is a leading cause of death amongst HIV infected patient in developing countries. Management of HIV and TB co-infection is complicated because of drug-Drug interactions, overlapping toxicities, additional pill burden, and problems relating to adherence and development of IRIS.66

Treatment of Tuberculosis

• All HIV/ TB patients should be treated with standard 4 Drug anti-TB combinations as per TB treatment guidelines. Once weekly and twice weekly intermittent therapy should be avoided; especially in patients with advanced HIV infections.67 Duration of anti-TB treatment in HIV is not well defined, but Drug susceptible TB not involving the CNS should be treated with a 6month regimen.68-70 In patients with slow response (cultures positive at 2 months) treatment should be prolonged for a total of 9months. Tuberculosis involving the CNS should be treated for 1year.
• Two important questions need to be answered while managing concomitant HIV and TB infections.