Early mortality among adults accessing antiretroviral treatment programmes in sub-Saharan Africa

Abstract

Two-thirds of the world's HIV-infected people live in sub-Saharan Africa, and more than 1.5 million of them die annually. As access to antiretroviral treatment has expanded within the region; early pessimism concerning the delivery of antiretroviral treatment using a large-scale public health approach has, at least in the short term, proved to be broadly unfounded. Immunological and virological responses to ART are similar to responses in patients treated in high-income countries. Despite this, however, early mortality rates in sub-Saharan Africa are very high; between 8 and 26% of patients die in the first year of antiretroviral treatment, with most deaths occurring in the first few months. Patients typically access antiretroviral treatment with advanced symptomatic disease, and mortality is strongly associated with baseline CD4 cell count less than 50 cells/mul and WHO stage 4 disease (AIDS). Although data are limited, leading causes of death appear to be tuberculosis, acute sepsis, cryptococcal meningitis, malignancy and wasting syndrome. Mortality rates are likely to depend not only on the care delivered by antiretroviral treatment programmes, but more fundamentally on how advanced disease is at programme enrollment and the quality of preceding healthcare. In addition to improving delivery of antiretroviral treatment and providing it free of charge to the patient, strategies to reduce mortality must include earlier diagnosis of HIV infection, strengthening of longitudinal HIV care and timely initiation of antiretroviral treatment. Health systems delays in antiretroviral treatment initiation must be minimized, especially in patients who present with advanced immunodeficiency.

Figure 1

Kaplan Meier plot showing survival proportion over 21 months among patients (n=1235) from the time of entering a community-based antiretroviral treatment (ART) programme in South Africa. The period covered includes the interval between programme enrolment and ART initiation – a median of 33 days. The survival proportions are shown according to (a) baseline CD4 cell count and (b) baseline WHO clinical stage. The graphs show the strong unadjusted association between CD4 cell count, WHO clinical stage and mortality risk in the first year of ART and the low mortality risk in the second year. Data adapted from reference [22].

Figure 2

Hypothetical graph showing relative mortality risk (95% CI) among patients accessing ART with late HIV diagnoses and advanced symptomatic disease (diamonds) versus mortality rates among patients whose HIV was diagnosed early and who received appropriate longitudinal HIV care and timely referral for ART (squares). Mortality risk is shown broken down by period: pre-ART (the interval between enrolment in the ART programme and the time ART is started), early ART (first 4 months of ART) and late ART (beyond 4 months of ART). Data on patients with late diagnoses are based on reference [22] and data from patients with early diagnoses and care are hypothetical, being based approximately on data from references [22, 81, 96].