Very low CD4, rural care, linked to higher risk of death on ARVs in African studies

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Very late initiation of HIV treatment, when a person's CD4 cell count has fallen below 50 cells/mm3 is strongly associated with an increased risk of death in African patients, according to findings from Kenya, South Africa and Uganda presented on Monday August 14th at the Sixteenth International AIDS Conference in Toronto, Canada. Also, patients receiving treatment at less well-resourced rural clinics may have a higher risk of death than urban patients, Kenyan researchers reported.

In the first study, data from nine HIV clinics in Western Kenya were analysed in order to determine predictors of death in patients who started antiretroviral therapy between November 2001 and December 2005.

Data from 527 deceased patients were compared with data from 1054 patients known to be alive. Whilst patients who were still alive had been taking ART for a median of 44 weeks, those who died took ART for a median of only 7.7 weeks, indicating that the majority of deaths were occurring in people soon after they started treatment, and not a s aresult of the failure of longer-term treatment. This difference was highly significant (P

Glossary

multivariate analysis

An extension of multivariable analysis that is used to model two or more outcomes at the same time.

meningitis

Inflammation of the outer lining of the brain. Potential causes include bacterial or viral infections.

 

hazard

Expresses the risk that, during one very short moment in time, a person will experience an event, given that they have not already done so.

hazard ratio

Comparing one group with another, expresses differences in the risk of something happening. A hazard ratio above 1 means the risk is higher in the group of interest; a hazard ratio below 1 means the risk is lower. Similar to ‘relative risk’.

toxicity

Side-effects.

As observed in other studies, patients with CD4 cell counts below 100 cells/mm3 at baseline had a significantly higher risk of death after starting treatment (hazard ratio 1.94, p3 (HR 1.63, p

Unlike many other studies reporting from Africa in the past year, baseline weight did not predict the risk of death, but anaemic patients and those with low haemoglobin (

Death was significantly more likely in rural patients (HR 0.35 for urban patients, p

Ugandan researchers also found that a very low baseline CD4 count was strongly associated with a greater risk of death. They analysed data from 550 patients receiving treatment at Makerere University Hospital in Kampala, and found that 72 patients died during 30 months of follow-up. Unlike the Kenyan study however, the majority of deaths occurred more than six months after starting treatment, with 19 more than one year after starting treatment.

In this cohort, the median CD4 count of those who died was 24 cells/mm3 overall, with the lowest median count in those who died within six months of starting treatment (14 cells/mm3 at baseline). In comparison, those who survived for at least 12 months had a median baseline count of 110 cells/mm3.

In Durban, South Africa, researchers from McCord Hospital and Harvard Medical School found a significant association between specific opportunistic infections and the subsequent risk of death on treatment.

Looking at a cohort of 309 patients who had received treatment up to February 2004, the researchers found that 78% were alive after one year on treatment by Kaplan-Meier analysis, and multivariate analysis showed that a history of oral candiasis prior to antiretroviral treatment was associated with an increased risk of death on treatment (HR 2.58). In univariate analysis crypotoccal meningitis wsa also predictive of death, but this disappeared after controlling for CD4 count, presumably because a CD4 count below 50 cells/mm3 (the level at which crypotoccal meningitis becomes more likely) was already strongly predictive of death (HR 3.12).

The McCord Hospital study also observed that the median patient weight at the time therapy began was 56kg, implying the importance of paying attention to the need for reducing the dose of stavudine (d4T) from 40mg to 30mg twice daily in order to reduce the risk of toxicity in individuals with lower body weight.

References

Mayanja-Kizza H et al. Very low CD4 T cell counts and low total lymphocyte counts at initiation of HAART are associated with a poor outcome in the first 6 months of antiretroviral treatment. Sixteenth International AIDS Conference, Toronto, Canada, abstract MoPdb06, 2006.

Ojikutu B et al. Predictors of mortality in patients initiating antiretroviral therapy in Durban, South Africa. Sixteenth International AIDS Conference, Toronto, Canada, abstract MoPdb05, 2006.

Siika AM et al. Predictors of mortality in HIV-infected adult African patients receiving highly active antiretroviral therapy. Sixteenth International AIDS Conference, Toronto, Canada, abstract MoPdb04, 2006.