CROI: Wasting and anaemia predict higher risk of death when starting ART in low-income countries

Low haemoglobin levels and wasting caused by AIDS before starting treatment appear to be the strongest predictors of death in people receiving antiretroviral therapy (ART) in Senegal and Haiti, according to research presented at the Thirteenth Conference on Retroviruses and Opportunistic Infections in Denver earlier this month. An international cohort analysis also found that the risk of illness was almost two and a half times higher in the first year of treatment in developing countries.

Background

Despite numerous reports of successful antiretroviral therapy in low-income countries, clinicians and treatment advocates remain concerned by the high death rates being seen in patients who qualify for antiretroviral therapy when compared with higher income countries. In general, clinicians have explained the higher death rate by pointing to the advanced HIV disease of patients in their care, but three studies presented at the Thirteenth Conference on Retroviruses and Opportunistic Infections were able to provide much more precise information about the factors that predict an increased risk of death or illness after starting antiretroviral therapy.

Mortality risks in the Senegal cohort

Eric Delaporte of the University of Montpellier in France reported on predictors of death in patients initiating antiretroviral therapy in the Senegal national cohort. This was a prospective observational cohort that began in 1998, and follow-up was available on 404 patients who had received treatment for a median of four years. Fifty-five per cent had CDC stage C disease (the equivalent of WHO stage 4 disease) at the time they started treatment, and the median CD4 cell count at this time was 128 cells/mm³.

Death was ascertained by hospital chart or post-mortem interview with a relative.

The cumulative probability of death was 7.2% at month 6, 11.7% at month 12, 17.4% by 24 months and 23.2% at 60 months, indicating that the risk of death was highest in the first year of treatment. Mortality was reduced from 12.5 deaths per 100 patient years of follow-up to 0.9 deaths per 100 patient years of follow-up.

The study found that a baseline body mass index below 19, a baseline haemoglobin below 10g/dl or a CD4 cell count below 200 were the only significant predictors of an increased risk of death.

Mortality risks in a Haitian community cohort

The first study reported on the GHESKIO cohort – 1,882 patients receiving antiretrovirals at community clinics in Haiti.

The study looked for predictors of early mortality in patients who had started antiretroviral therapy and who had been followed for up to one year.

The study found that only two factors remained significant predictors after adjusting for gender, CD4 cell count, development of TB and age.

These were the presence of AIDS wasting at the time of ART initiation (hazard ratio 2.36, p=0.001), and a haemoglobin below 9.5g/dl at the time of ART initiation (hazard ratio 2.14, p=0.003). Baseline CD4 cell count did not remain significant in the multivariate analysis.

A Kaplan-Meier analysis showed that almost a third of patients with AIDS wasting were likely to have died after twelve months of follow-up, compared to less than one in ten of those without wasting.

Commenting on the findings, a member of the research team from Cornell University in New York said: “These findings are important because they show that with just a haemoglobin measure and a scale we can identify the patients at high risk of dying during the first few months of treatment.”

Morbidity risks in the ART-LINC cohort collaboration

The largest analysis of outcomes presented at the meeting came from the ART-LINC cohort collaboration (Antiretroviral Treatment in Low Income Countries), which combines data on cohorts at 23 centres in developing countries and in Brazil, comprising information on 4540 patients. Dr Paula Braitstein of the University of Berne in Switzerland presented the findings on behalf of the ART-LINC group, and compared them to outcomes in the ART Cohort Collaboration, which links a large number of cohort studies in the developed world.

The ART-LINC analysis looked at the risk of developing opportunistic infections rather than death after starting ART, but its results are a useful complement to the findings on predictors of mortality from Haiti and Senegal.

The study found that the risk of death was approximately four times higher in the first year of antiretroviral treatment in the ART LINC compared with the ART Cohort Collaboration (ART CC). However the rate at which the risk of death declined during the first year of treatment was very similar between the two cohorts.

Unlike the studies looking at predictors of death, the ART-LINC study also found that baseline CD4 count influenced the risk of illness on ART, as did the type of drug regimen use. Patients who took NNRTIs were significantly less likely to develop an opportunistic infection on treatment. However, a previous history of OIs, whether off treatment or on treatment, significantly increased the risk of illness.