comparison with HIV-unrelated mortality.

Mortality of HIV-infected patients starting antiretroviral therapy in sub-Saharan Africa: comparison with HIV-unrelated mortality.

Mortality in HIV-infected patients who have access to highly active antiretroviral therapy has declined in sub-Saharan Africa, but it is unclear how mortality compares to the non-HIV-infected population. Brinkhof and colleagues compared mortality rates observed in HIV-1-infected patients starting ART with non-HIV-related background mortality in four countries in sub-Saharan Africa. Patients enrolled in antiretroviral treatment programmes in Côte d’Ivoire, Malawi, South Africa, and Zimbabwe were included. They calculated excess mortality rates and standardised mortality ratios (SMRs) with 95% confidence intervals (CIs). Expected numbers of deaths were obtained using estimates of age-, sex-, and country-specific, HIV-unrelated, mortality rates from the Global Burden of Disease project. Among 13,249 eligible patients 1,177 deaths were recorded during 14,695 person-years of follow-up. The median age was 34 years, 8,831 (67%) patients were female, and 10,811 of 12,720 patients (85%) with information on clinical stage had advanced disease when starting antiretroviral treatment. The excess mortality rate was 17.5 (95% CI 14.5-21.1) per 100 person-years in patients who started antiretroviral treatment with a CD4 cell count of less than 25 cells/microl and World Health Organization (WHO) stage III/IV, compared to 1.00 (0.55-1.81) per 100 person-years in patients who started with 200 cells/microl or above with WHO stage I/II. The corresponding standardised mortality ratios were 47.1 (39.1-56.6) and 3.44 (1.91-6.17). Among patients who started antiretroviral treatment with 200 cells/microl or above in WHO stage I/II and survived the first year of antiretroviral treatment, the excess mortality rate was 0.27 (0.08-0.94) per 100 person-years and the standardised mortality ratios was 1.14 (0.47-2.77). Mortality of HIV-infected patients treated with combination antiretroviral treatment in sub-Saharan Africa continues to be higher than in the general population, but for some patients excess mortality is moderate and reaches that of the general population in the second year of antiretroviral treatment. Much of the excess mortality might be prevented by timely initiation of antiretroviral treatment.

This study, the first to compare mortality among people starting antiretroviral treatment in sub-Saharan Africa to non-HIV-related mortality in the general population, cannot determine the CD4 count at which antiretroviral treatment should be started in order to minimise mortality. What is clear though is that much of the excess mortality during the first two years of antiretroviral treatment – 18 times higher than the general population not infected with HIV - could be reduced by more timely initiation of treatment. Patients with very low CD4 counts and advanced clinical disease had mortality 300 times higher in the first 3 months of treatment than the general population. These results are likely applicable to many other patients receiving antiretroviral treatment in diverse settings in Africa south of the Sahara.