Antiretroviral therapy (ART) inhibits HIV replication, allowing recovery of CD4+ T cell numbers and the restoration of immune function; its introduction has led to improved outcomes for individuals with HIV infection. However, it has been observed that some individuals responding to ART experience a clinical deterioration with symptoms and signs of an inflammatory illness. Immune reconstitution inflammatory syndrome (IRIS) results from pathological immune responses occurring during immune reconstitution. IRIS is best considered a group of disorders with a wide range of clinical manifestations, incorporating disease resulting from pathological inflammation to pathogens, immune-mediated inflammatory disease and autoimmune disease. Clinical effects range from a mild, self-limiting illness to severe morbidity and mortality. Clinicians working in the field of HIV medicine can expect to encounter individuals with IRIS. In this review, we discuss definitions, describe clinical presentations, summarize research relating to pathogenesis and identify risk factors, preventive and management strategies.

Altogether 42 million people worldwide have been infected with HIV, and 12 million have died over the last 20 years. Effective antiretroviral therapy has lead to sustained HIV viral suppression and immunological recovery in patients who have been infected with the virus. The incidence of AIDS has declined in the Western world with the introduction of effective antiretroviral therapy. Questions on When to start treatment?, What to start with?, How to monitor patients?, remain heavily debated. Adherence to antiretroviral treatment remains the cornerstone of effective treatment, and failure to adhere is the strongest predictor of virological failure. Long term therapy can lead to metabolic complications. Resource poor countries are dealing with difficult issues such as mother to child prevention of HIV transmission. Other treatment options are now available, with the recent introduction of fusion inhibitors, second generation non-nucleoside reverse transcriptase inhibitors, and nucleotide reverse transcriptase inhibitors to clinical practice.

Bloodstream infection is associated with significant short-term mortality, but less is known about long-term outcome. We describe factors affecting mortality up to 3 years after bloodstream infection in a cohort of patients reviewed at the bedside by an infection specialist. Patients seen by the bacteraemia service of our infectious diseases department between June 2005 and November 2008 were included in analyses. Routine clinical data collected at the time of consultation, together with laboratory, demographic and outcome data were analysed to identify factors predicting death at 30 days and 3 years after bloodstream infection. Cox regression models for both time-points were constructed, together with Kaplan-Meier survival curves. In all, 322 bloodstream infections were recorded in 304 patients. The 30-day mortality was 15%, with a 3-year mortality of 49%. At 30 days after bacteraemia, in the Cox regression model, increasing age (p 0.003) and lower serum albumin (p 0.014) were predictive of death. At 3 years, age (p <0.0001) and albumin (p 0.004) remained significant predictors of death, with the presence of vascular disease (p 0.05) also significantly associated with mortality. If temperature was treated as a continuous variable then urea was significant (p 0.044); however, if temperature was categorized into hypothermia and non-hypothermia, then the presence of hypothermia (p 0.008) and chronic renal disease (p 0.034) became significant. There is an appreciable and gradual increase in mortality after an episode of bloodstream infection. Although many factors may not be amenable to intervention, patients at high risk of long-term mortality might require further follow up and assessment for potentially modifiable factors.

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