Overweight patients have best gains in CD4 cell count twelve months after starting HIV therapy

Patients who would normally be classified as overweight have the biggest increases in their CD4 cell counts during the first year of HIV therapy, US investigators report in the online edition of Clinical Infectious Diseases. Immune restoration after twelve months of antiretroviral therapy was greatest among individuals with a baseline body mass index (BMI) in the range 25 to 29.9 kg/m², which is usually described as overweight.

In contrast, patients who were seriously underweight or obese at the time they initiated HIV therapy had significantly poorer CD4 cell gains.

“These epidemiological findings suggest that a BMI in the range of 25 – 30 kg/m² may be associated with optimal immune reconstitution in the first year of ART [antiretroviral therapy].”

Being obese (a BMI above 30 kg/m²) is a risk factor for metabolic and cardiovascular complications that are being seen with increased frequency in patients with HIV. In the US it is estimated that between a fifth and a third of all HIV-positive patients are obese, a prevalence approaching that seen in the general population.

However, studies conducted before the introduction of effective HIV therapy showed that a higher BMI (click here for the NHS BMI calculator) was associated with a lower risk of disease progression. Little is known about the impact of baseline BMI on immune reconstitution during antiretroviral treatment.

Therefore investigators from Vanderbilt University School of Medicine, Tennessee, undertook a study involving 915 of their patients who started HIV therapy between 1998 and 2008.

Information was available on the patients’ BMI at the time they initiated antiretroviral therapy, and the investigators conducted a series of analysis to see if this was associated with twelve-month changes in CD4 cell count. They adjusted their results for factors such as age, race, baseline CD4 cell count, viral load, type of HIV treatment, and the year therapy was initiated.

Approximately three-quarters (78%) of patients were men and their median age was 39 years. The median baseline BMI was 24 kg/m², with 16% of patients having a BMI below 20 kg/m² (underweight) and 15% a BMI above 30 kg/m². Overall, the patients had advanced immune suppression at the time they started HIV therapy, as the median CD4 cell count was just 171 cells/mm³.

Baseline BMI was associated with changes in CD4 cell count after a year of HIV therapy (p = 0.03). However, the relationship was not linear, and a BMI at both extremes was associated with diminished CD4 cell gains.

Patients were categorised according to their baseline BMI (20, 25, 30, and 40 kg/m²).

Compared to patients with a BMI in the range 25 to 29.9 kg/m², individuals with a BMI below 20 kg/m² gained significantly fewer CD4 cells (-65 cells/mm³ women; -18 cells/mm³ men).

Similarly, obese women and men had lower twelve-month CD4 cell gains than patients who were overweight (-17 and -12 cells/mm³ respectively).

Baseline viral load, non-white race, the year therapy was started (all p < 0.05) and longer duration of infection with HIV (p = 0.03) were also associated with poorer CD4 cell gains.

The investigators took these findings into account, but their analysis still showed a significant relationship between baseline BMI and immune restoration, with optimum increases observed in patients in the overweight range.

Restricting their analysis to patients whose weight remained stable after starting HIV therapy did not affect their findings (p < 0.01).

Subgroup analyses showed that severely underweight patients with a baseline BMI below 18.5 kg/m² were significantly less likely to have a CD4 cell count of 350 of above after a year of HIV therapy than individuals in the BMI 25 to 29.9 kg/m² reference group, as were morbidly obese patients with a BMI above 40 kg/m² (p = 0.05).

“The magnitude of immune reconstitution 12 months after ART initiation increased with rising BMI and seemed to reach a plateau in the range of BMI 25 to 30 kg/m²”, write the investigators. “The relationship between BMI and CD4 lymphocyte count changes persisted and the strength of the association increased when the cohort was limited to those with a less than 10% weight change.”

The investigators were unclear about the reasons underlying their findings. However, they speculate that patients who were under or overweight were “more likely to have other health conditions or physiologic derangements that impair peripheral CD4 lymphocyte repopulation. They also note, “abdominal obesity is associated with increased cellular immune activation in HIV-uninfected individuals.”

Possible limitations of the study include its observational design and sample size. The researchers also note that they lacked data on their patients’ socio-economic circumstances, factors which could affect both weight and overall health. Moreover, the investigators did not undertake DEXA scans to determine the exact body composition of their patients.

Nevertheless, they conclude, “12-month CD4 lymphoctye recovery was greatest among patients commonly classified as overweight, suggesting an appropriate pretreatment BMI range of 25-30 kg/m² may promote optimal immune reconstitution on ART.”

Koethe JR et at. An optimal body mass index associated with improved immune reconstitution among HIV-infected adults initiating antiretroviral therapy. Clin Infect Dis, online edition, doi: 10.1093/cid/cir606, 2011 (click here for the free abstract).