Good early increases in CD4 count reduce mortality risk for malnourished HIV patients

Robust early increases in CD4 cell count reduce the risk of death for patients with HIV, even those who are severely malnourished, investigators from Zambia report in the online edition of AIDS.

The large, prospective study showed that an increase in CD4 cell count of less than 100 cells/mm³ six months after starting HIV treatment was associated with an increased risk of mortality, especially for those who were malnourished.

However, the mortality risk was reduced for all patients whose CD4 cell count increased by at least 100 cells/mm³, regardless of their nutritional status.

“To our knowledge, this study is the first large cohort analysis of BMI [body mass index], early CD4 cell recovery, and subsequent mortality in a resource-limited setting”, write the investigators. They add, “the analysis indicates the importance of a robust CD4 cell count response amongst all patients starting ART [antiretroviral therapy], but especially for those with low BMI.”

Earlier research has shown that HIV-infected individuals who have a low BMI have poorer outcomes after starting antiretroviral therapy.

A slower increase in CD4 cell count after starting treatment with anti-HIV drugs has also been associated with an increased risk of mortality. However, the impact of nutritional status on immune recovery and survival has not been determined.

Therefore, investigators in Lusaka, Zambia, analysed the relationship between baseline body mass index, six-month increases in CD4 cell count, and the subsequent risk of death amongst adults starting antiretroviral therapy.

A total of 33,097 individuals who started HIV treatment between 2004 and 2009, and who were still in care six months later, were included in the study.

All had their CD4 cell count measured and their BMI calculated at baseline.

Individuals whose BMI was below 16 kg/m² were categorised as severely malnourished; those with a BMI between 16 – 16.99 kg/m² as moderately malnourished; a BMI of 17 – 18.49 kg/m² was defined as mild malnourishment, and a BMI above 18.50 kg/m² as non-malnourished.

Six-month changes in CD4 cell count were divided into strata: decline; 0-99 cells/mm³; 100-199 cells/mm³; 200-299 cells/mm³; and above 300 cells/mm³.

The median CD4 cell count increased for patients in all the nutritional groups (127 – 131 cells/mm³).

Overall, the post-six-month mortality rate was 1.79 per 100 person-years. However, this differed according to baseline BMI. It was lowest amongst patients who were not malnourished and highest for severely malnourished individuals (1.59 vs. 3.17 per 100 person years).

The investigators then examined the relationship between baseline nutritional status, six month increases in CD4 cell count, and mortality risk.

Patients of normal nutritional status at baseline and a CD4 cell count increase of 300 cells/mm³ constituted a reference group.

Individuals who were malnourished at baseline and whose CD4 cell count increased fewer than 100 cells/mm³ had a nearly four-fold increase in the risk of death than individuals in the reference group (hazard ratio [HR] = 3.93; 95% CI, 2.66-5.80), and the risk of death was even higher for severely malnourished patients whose CD4 cell count fell.

Moreover, the investigators found that regardless of baseline BMI, a CD4 cell count increase below 100 cells/mm³ was associated with an increased risk of post-six-month mortality.

However, a CD4 cell count increase above 100 cells/mm³ was protective against mortality, even for the patients who were most severely malnourished at baseline.

“A CD4 change of at least 100 cells/mm³ over the first six months of ART was not associated with a higher hazard for mortality compared to the reference group, regardless of baseline BMI”, observed the investigators.

“Given the geographical overlap of the HIV and malnutrition epidemics in sub-Saharan Africa, the success of ART programs depends on part in improving the nutritional outcomes of these particularly vulnerable [malnourished] patients”, the authors conclude.