The immune reconstitution inflammatory syndrome: a cause of death in persons on antiretroviral therapy?

The availability of antiretroviral therapy (ART) has significantly improved the quality of life of persons with HIV infection. However, new problems have arisen as a consequence of this treatment. An immune reconstitution inflammatory syndrome (IRIS) in which patients experience a paradoxical worsening of their clinical condition may occur during recovery of the immunity. Thus far, there is no laboratory test available to diagnose IRIS. The diagnosis therefore remains clinical and by exclusion. In this paper, we describe the autopsy findings of three HIV-infected patients who died at the Antwerp University hospital directly or indirectly related to IRIS. One patient died following a disseminated cryptococcocal and Mycobacterium avium complex (MAC) infection. Two other patients died with a disseminated aspergillosis infection after receiving corticosteroids to decrease IRIS induced inflammatory signs. These three patients show the difficulties faced by clinicians in diagnosing IRIS and the importance of performing autopsies in persons with HIV infection who die despite receiving ART.

Low prevalence of vitamin D deficiency in Ugandan HIV-infected patients with and without tuberculosis.

OBJECTIVE: To examine whether hypovitaminosis D is a risk factor for the development of tuberculosis (TB) associated immune reconstitution inflammatory syndrome (IRIS). METHODS: We measured serum 25-hydroxyvitamin D (25D) concentrations in four groups of patients at Mulago Hospital, Kampala, Uganda: 1) patients co-infected with TB and the human immunodeficiency virus (HIV) receiving anti-tuberculosis treatment (HIV+TB+; n = 92) who did and did not develop TB-IRIS after starting antiretroviral treatment (ART), 2) HIV-infected patients without TB (HIV+TB-; n = 20) starting ART, 3) non-HIV-infected individuals with TB (HIV-TB+; n = 27), and 4) those without TB (HIV-TB-; n = 23). RESULTS: The prevalence of optimal 25D levels (>75 nmol/l) was as follows: 59% in HIV+TB+, 65% in HIV+TB-, 63% in HIV-TB+ and 35% in HIV-TB- patients. 25D concentrations decreased during the first 3 months of ART in HIV+TB+ individuals who developed IRIS (P = 0.005) and those who did not (P = 0.002), and in HIV+TB- individuals (P = 0.015); however, 25D concentration in patients who did or did not develop TB-IRIS did not differ. CONCLUSION: The prevalence of optimal vitamin D status was relatively high in HIV-infected patients with and without TB living near the equator. No difference in 25D concentrations was observed between TB-IRIS and non-IRIS. However, 25D concentrations decreased during ART.

Tuberculosis in human immunodeficiency virus infected Ugandan children starting on antiretroviral therapy.

OBJECTIVE: To identify the incidence of tuberculosis (TB) in human immunodeficiency virus (HIV) infected children in a resource-limited setting before and after initiation of antiretroviral therapy (ART), and to assess the impact of TB screening by tuberculin skin testing and clinical history. METHODS: A retrospective cohort study of 1806 HIV-infected children and adolescents (age <18 years) initiating ART from 2003 to 1 July 2006 in Kampala, Uganda. A TB screening program was instituted clinic-wide in January 2006. RESULTS: Of 311 (17.2%) HIV-infected children, 171 had been diagnosed with TB before and 140 after ART initiation. During the first 100 days of ART, risk of a new TB diagnosis was 2.7-fold higher compared to the pre-ART period (RR 2.7, 95%CI 2.1-3.5, P < 0.001). After 100 days of ART, the TB incidence rate decreased to below pre-ART levels (RR 0.41, 95%CI 0.30-0.54, P = 0.002). After TB screening was instituted in 2006, the proportion of new TB cases diagnosed after starting ART decreased by 70% (95%CI 51-82, P < 0.001), abating the early excess risk. CONCLUSIONS: TB is common among African children and adolescents initiating ART in sub-Saharan Africa. More aggressive screening for active TB before starting ART can diminish the rate of TB during immune reconstitution. Future studies are needed to determine optimal screening practices for HIV-infected children.