Rheumatologic symptoms after ART may be due to immune reconstitution inflammatory syndrome (IRIS)

New or worsening rheumatologic symptoms that follow antiretroviral therapy may be due to immune reconstitution inflammatory syndrome (IRIS), according to findings reported at the Fourth South African AIDS Conference in Durban.

IRIS is a collection of symptoms that frequently emerge soon after antiretroviral therapy is started in HIV-positive people. IRIS is believed to result from a rejuvenated immune system mounting an inflammatory response.

Despite a well-defined case definition, there is debate within the medical community about which symptoms should fall under an IRIS classification.

British and South African researchers attempted to determine whether joint pain should be regarded as an IRIS symptom by closely monitoring the onset of joint symptoms in patients undergoing antiretroviral treatment.

The study, which was conducted in Durban, South Africa, involved 498 adult HIV-infected patients who were due to begin antiretroviral treatment at two clinics during 2006 and 2007. Participants were subjected to normal clinical health checks before treatment started and also at two, four, eight, twelve, 16, 20 and 24 weeks following the start of treatment.

Patients who reported joint symptoms were assessed clinically and alternative diagnoses of their joint pains explored. In each patient, baseline and CD4 cell counts were tracked alongside C-reactive protein (CRP), which is present in blood during inflammatory responses and which, accordingly, allows doctors to measure the extent of inflammation.

Laboratory analysis of the patients’ blood revealed a median CD4 cell count of 106 (interquartile range of 53 to 165) and a baseline viral load of 5 log (interquartile range of 4.4 to 5.6 log).

Seventy-seven (15%) of the patients reported joint symptoms before or during the study period. Of these, some were excluded as IRIS cases because alternative explanations existed for their joint symptoms. Eleven patients, for example, were found to have mechanical causes of joint pain and six were found to be suffering from the side-effects of other drug treatments. After correcting for alternative diagnoses, 23 cases (30%) remained, presumably an inflammatory side-effect of antiretroviral therapy.

The median onset period for joint symptoms occurred at eleven weeks (range one week to 22 weeks) after anti-HIV treatment started, within the normal IRIS onset period. Only one patient had elevated levels of rheumatoid factor.

The researchers highlight that joint pain is common in many HIV-TB co-infected patients during the first six months of antiretroviral treatment. In the absence of other diagnoses, these symptoms may be part of the IRIS spectrum.