Abstract

Survival and Causes of Death, 2 years after introduction of Antiretroviral Therapy in Africa: a historical cohort comparison in Entebbe, Uganda

Munderi P.¹, Watera C.¹, Nakiyingi J.¹, Kasirye A.¹, Walker S.², French N.³, Gilks C.⁴, Grosskurth H.¹

¹MRC/UVRI Uganda Research Unit on AIDS, Entebbe, Uganda, ²Medical Research Council Clinical Trials Unit, London, United Kingdom, ³London School of Hygiene and Tropical Medicine, London, United Kingdom, ⁴World Health Organisation, Department of HIV/AIDS, Geneva, Switzerland

Background: Over 800,000 adults are taking first-line anti-retroviral therapy (ART) in Africa. Evidence on effectiveness is limited

Methods: From 1995, the Entebbe cohort (EC) has enrolled and followed HIV-infected adults. Since 2003, ART has been available through the DART (Development of ART in Africa) trial. ART impact was assessed by comparing mortality and causes of death, before 2000, in EC participants fulfilling DART entry criteria with that observed in 2 years of DART.

Results: Overall mortality Rate Ratio 16.9 (12.9 0 221.1) p<0.001. Mortality was highest in patients with CD4<50 cells/mm3 at enrolment though survival was still significantly higher (rates 953 versus 60.4 per 1000 person-years; RR 15.8). The leading specific cause of death in EC was Cryptococcus (64 deaths; 16.8%) followed by Cryptosporidium(18 deaths; 4.7%) and tuberculosis (16 deaths; 4.2%). HIV wasting was the predominant syndrome (111 deaths; 29.2%). The leading specific cause of death in DART was tuberculosis (10 deaths; 16.1%), followed by malignancy (6 deaths; 9.7%) and bacteraemia (5 deaths; 8.1%). Acute fever was the leading syndrome (12 deaths; 19.3%) and HIV wasting virtually disappeared as a cause of death (an estimated 234-fold reduction).

Conclusions: First-line ART guided by clinical and immunological monitoring is highly effective: two year survival is 94% with overall mortality reduced 17-fold compared to a matched pre-ART cohort. Significant benefit accrues even in adults with very advanced disease.

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