Incidence, clinical spectrum, risk factors and impact of HIV-associated immune reconstitution inflammatory syndrome in South Africa.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) is a widely recognised complication of antiretroviral therapy (ART), but there are still limited data from resource-limited settings. Our objective was to characterize the incidence, clinical spectrum, risk factors and contribution to mortality of IRIS in two urban ART clinics in South Africa. METHODS AND FINDINGS: 498 adults initiating ART in Durban, South Africa were followed prospectively for 24 weeks. IRIS diagnosis was based on consensus expert opinion, and classified by mode of presentation (paradoxical worsening of known opportunistic infection [OI] or unmasking of subclinical disease). 114 patients (22.9%) developed IRIS (36% paradoxical, 64% unmasking). Mucocutaneous conditions accounted for 68% of IRIS events, mainly folliculitis, warts, genital ulcers and herpes zoster. Tuberculosis (TB) accounted for 25% of IRIS events. 18/135 (13.3%) patients with major pre-ART OIs (e.g. TB, cryptococcosis) developed paradoxical IRIS related to the same OI. Risk factors for this type of IRIS were baseline viral load >5.5 vs. <4.5 log(10) (adjusted hazard ratio 7.23; 95% confidence interval 1.35-38.76) and ≤30 vs. >30 days of OI treatment prior to ART (2.66; 1.16-6.09). Unmasking IRIS related to major OIs occurred in 25/498 patients (5.0%), and risk factors for this type of IRIS were baseline C-reactive protein ≥25 vs. <25 mg/L (2.77; 1.31-5.85), haemoglobin <10 vs. >12 g/dL (3.36; 1.32-8.52), ≥10% vs. <10% weight loss prior to ART (2.31; 1.05-5.11) and mediastinal lymphadenopathy on pre-ART chest x-ray (9.15; 4.10-20.42). IRIS accounted for 6/25 (24%) deaths, 13/65 (20%) hospitalizations and 10/35 (29%) ART interruptions or discontinuations. CONCLUSION: IRIS occurred in almost one quarter of patients initiating ART, and accounted for one quarter of deaths in the first 6 months. Priority strategies to reduce IRIS-associated morbidity and mortality in ART programmes include earlier ART initiation before onset of advanced immunodeficiency, improved pre-ART screening for TB and cryptococcal infection, optimization of OI therapy prior to ART initiation, more intensive clinical monitoring in initial weeks of ART, and education of health care workers and patients about IRIS.

A high incidence of nucleoside reverse transcriptase inhibitor (NRTI)-induced lactic acidosis in HIV-infected patients in a South African context.

OBJECTIVE: To determine the incidence of and predisposing risk factors for lactic acidosis in HIV-infected patients on antiretroviral drugs in South Africa. DESIGN: Observational case series. SETTING: Sinikithemba HIV Clinic, McCord Hospital, Durban. SUBJECTS: Eight hundred and ninety-one HIV-positive patients on highly active antiretroviral therapy (HAART) during an 18-month period commencing in January 2004. MEASUREMENTS AND RESULTS: Fourteen cases of lactic acidosis (incidence rate of 19 (95% confidence interval (CI): 9-29) cases per 1,000 person-years of treatment) were reported. All cases were female, with a median age of 36 years and a median weight of 81 kg. The median time on HAART before developing lactic acidosis was 7.5 months and the median peak lactate level was 9.3 mmol/l. All cases were on stavudine (d4T), lamivudine (3TC) and 1 non-NRTI. The case mortality rate was 29% (4 patients). CONCLUSIONS: The incidence rate is higher than reported in studies in developed countries. This may be due to d4T, which is recommended as a first-line antiretroviral drug in South Africa. This implication raises the question whether it is an appropriate drug in first-line treatment of patients with predisposing risk factors such as female gender and being overweight.