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
“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
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
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
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
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%
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.”