Severe anaemia complicating HIV in Malawi; Multiple co-existing aetiologies are associated with high mortality

Abstract

Background: Severe anaemia is a major cause of morbidity and mortality in HIV-infected adults living in resource-limited countries. Comprehensive data on the aetiology are lacking but are needed to improve outcomes.

Methods: HIV-infected adults with severe (haemoglobin ≤70g/l) or very severe anaemia (haemoglobin ≤ 50 g/l) were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Fifteen potential causes and associations with anaemia severity and mortality were explored.

Results: 199 patients were enrolled: 42.2% had very severe anaemia and 45.7% were on ART. More than two potential causes for anaemia were present in 94% of the patients including iron deficiency (55.3%), underweight (BMI<20: 49.7%), TB infection (41.2%) and unsuppressed HIV infection (viral load >1000 copies/ml) (73.9%). EBV/CMV co-infection (16.5%) was associated with very severe anaemia (OR 2.8 95% CI 1.1-6.9). Overall mortality was high (53%; 100/199) with a median time to death of 17.5 days (IQR 6-55) days. Death was associated with folate deficiency (HR 2.2; 95% CI 1.2-3.8) and end stage renal disease (HR 3.2; 95% CI 1.6-6.2).

Conclusion: Mortality among severely anaemic HIV-infected adults is strikingly high. Clinicians should be aware of the urgent need for a multifactorial approach including starting or optimising HIV treatment, considering TB treatment, nutritional support and optimising renal management.

Fig 1. Total number of aetiologies for severe anaemia co-existing in each patient (n = 199).

Mean is 3 factors (SD 1.3), range 1–8. Aetiologies for severe anaemia include: 1) Unsuppressed HIV-infection; viral load ≥1000 copies/ml. 2) TB: one or more of the following were present: a) positive sputum culture, b) chest X-ray with signs of pulmonary TB and/or c) on going TB treatment at time of enrolment d) clinical diagnosis by local doctor including unknown generalized lymphadenopathy and/or night sweats of > 30 days and of unknown origin e) caseating granulomata in the bone marrow trephine. 3) Malaria: presence of malaria parasites in a thick blood film. 4) Parvovirus B19: viral load of >1000 copies/ml. 5) Cytomegalovirus (CMV); load of >100 copies/ml. 6) Epstein-Barr virus (EBV); viral load >100 copies/ml. 7) Bacteraemia; a blood culture growing a potential pathogen. 8) Underweight (BMI ≤18.5). 9) Serum folate deficiency (≤3 ng/l). 10) Vitamin B12 deficiency (≤180 pg/ml). 11). Iron deficiency defined by MCV ≤ 83 fl. 12) Zidovudine usage. 13) Cotrimoxazole usage. 14) Bone marrow disorders; lympho-proliferative disease, myeloid-proliferative disease or MDS. 15) Renal impairment: a GFR which either indicated impaired (GFR 15–59 ml/min/1.73 m²) or End Stage (GFR ≤15 ml/min/1.73 m²) Renal Disease [22, 35].

Fig 2. Kaplan Meyer survival curve over time (days) for adult Malawian patients with HIV infection and severe anaemia during 365 days follow-up.

Abbreviation: 95% confidence interval (95% CI).

Fig 3. Risk factors for 365-day mortality in HIV-infected patients with severe anaemia.

Univariate and multivariate Cox regression outcome (Hazard Ratios 95% CI). Folate deficiency (≤3 ng/l) HR 2.0 95% CI 1.2–3.6 and end stage renal disease (GFR ≤15); HR 3.0 5% CI 1.5–5.9, were associated with overall mortality. Abbreviations: Hb: Haemoglobin, GFR; Glomerular filtration rate, VL Viral Load.