Abstract
ObjectivesTo identify associations between specific WHO stage 3 and 4 conditions diagnosed after ART initiation and all cause mortality for patients in resource-limited settings (RLS).Design, SettingAnalysis of routine program data collected prospectively from 25 programs in eight countries between 2002 and 2010.Subjects, Participants36,664 study participants with median ART follow-up of 1.26 years (IQR 0.55–2.27).Outcome MeasuresUsing a proportional hazards model we identified factors associated with mortality, including the occurrence of specific WHO clinical stage 3 and 4 conditions during the 6-months following ART initiation.ResultsThere were 2922 deaths during follow-up (8.0%). The crude mortality rate was 5.41 deaths per 100 person-years (95% CI: 5.21–5.61). The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with increased mortality (HR: 2.21; 95% CI: 1.97–2.47). After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis (aHR: 3.54; 95% CI: 2.74–4.56), HIV wasting syndrome (aHR: 2.92; 95%CI: 2.21 -3.85), non-tuberculous mycobacterial infection (aHR: 2.43; 95% CI: 1.80–3.28) and Pneumocystis pneumonia (aHR: 2.17; 95% CI 1.80–3.28) were associated with the greatest increased mortality. Cerebral toxoplasmosis, pulmonary and extra-pulmonary tuberculosis, Kaposi’s sarcoma and oral and oesophageal candidiasis were associated with increased mortality, though at lower rates.ConclusionsA diagnosis of certain WHO stage 3 and 4 conditions is associated with an increased risk of mortality in those initiating ART in RLS. This information will assist initiatives to reduce excess mortality, including prioritization of resources for diagnostics, therapeutic interventions and research.
Highlights
Despite increasing access to HIV treatment in resource-limited settings (RLS), patients commencing anti-retroviral therapy (ART) in these settings have been shown to have an increased risk of mortality in the first months of therapy compared with those in high-income countries [1,2], this difference in mortality risk reduces with time on ART [1].A number of factors have been associated with mortality during early ART in RLS
The diagnosis of any WHO stage 3 or 4 condition during the first 6 months of ART was associated with increased mortality (HR: 2.21; 95% CI: 1.97–2.47)
After adjustment for age, sex, region and pre-ART CD4 count, a diagnosis of extrapulmonary cryptococcosis, HIV wasting syndrome, nontuberculous mycobacterial infection and Pneumocystis pneumonia were associated with the greatest increased mortality
Summary
Despite increasing access to HIV treatment in resource-limited settings (RLS), patients commencing anti-retroviral therapy (ART) in these settings have been shown to have an increased risk of mortality in the first months of therapy compared with those in high-income countries [1,2], this difference in mortality risk reduces with time on ART [1].A number of factors have been associated with mortality during early ART in RLS. Opportunistic infections have been recognized as important causes of early mortality in those initiating ART in RLS [7,8], but limited data are available regarding the relative impact of specific HIV-associated conditions on mortality. Both prevalent and incident tuberculosis (TB) have been associated with a greater than two fold increased risk of mortality during ART in a South African cohort [9] and cryptococcal meningitis has a high mortality in RLS [10,11]. The objective of this study was to determine the association between specific WHO stage 3 and 4 conditions diagnosed after initiation of ART and all cause mortality on ART
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