Higher Body Mass Index Predicts Greater CD4 Count Gain After Starting HIV Treatment

A body mass index (BMI) at the threshold of obesity predicted greater CD4+ T-cell gains when antiretroviral therapy (ART) began in an 8000-person North American analysis. CD4+ counts rose more in heavier women than in heavier men.

Adipose tissue can affect the cellular immune system, and prior research indicated that heavier people gain more CD4+ cells when they start ART. But the results of previous trials -- usually involving single cohorts -- have proved inconsistent. To get a better understanding of how BMI affects CD4+ cell gains after ART begins, researchers working with the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) conducted this study.

The analysis involved 8381 adults in 13 NA-ACCORD cohorts who started their first ART regimen from 1998 through 2010 and maintained a viral load below 400 copies/mL for at least six of their first 12 months of therapy. The researchers excluded people who died or dropped out of care before completing 12 months of ART, and they excluded women who had more than a 10% change in weight, which could indicate pregnancy. To assess relationships between pre-ART variables and CD4+ change, the NA-ACCORD team used linear regression adjusted for age; sex; race; initial ART regimen; year ART began; and pre-ART BMI, CD4+ cell count and viral load.

Most of the 8381 study participants (85%) were men and 52% were nonwhite.

While 52% of participants were underweight or normal weight, 32% were overweight (25 to 29.9 kg/m²) and 15% were obese (>30 kg/m²).

Pretreatment BMI was significantly associated with a 12-month change in CD4+ count (P < 0.001), but the relationship was nonlinear: An S-curve described the relationship between baseline BMI and CD4+ change, with one inflection point around 30 kg/m². Compared with a BMI of 22 kg/m² (approximately halfway through the normal BMI range), a BMI of 30 kg/m² (the threshold of the obese range) was associated with a 36-cell/mm³ greater 12-month gain in women and a 19-cell/mm³ greater gain in men. The CD4-cell increase persisted in women through baseline BMIs of 35 versus 22 kg/m² (+36 cells/mm³) and 40 versus 22 kg/m² (+31 cells/mm³). But in men the association with baseline BMI dwindled at higher baseline BMIs: +16 cells/mm³ at 35 versus 22 kg/m² and +10 cells/mm³ at 40 versus 22 kg/m². Women underweight when starting ART (<18.5 kg/m²) had 12-month CD4-cell gains approximately 60% as high as those of women with a baseline BMI of 30 kg/m².

As in much previous research, older age when starting ART meant a better CD4-cell gain 12 months after therapy began (for example, +18 cells/mm³ for 30 versus 40 years old, and -16 cells/mm³ for 50 versus 40 years). Lower pre-ART viral load also meant a better 12-month CD4-cell change in the multivariate model (+44 cells/mm³ for 4 versus 5 log copies/mL, and -43 cells/mm³ for 6 versus 5 log copies/mL). Race did not affect 12-month CD4-cell change in this model.

The authors observe that research in the general population confirms a positive association between greater BMI and higher CD4+ count, total lymphocyte count and total T helper CD4+ cells. The reasons for these associations remain unclear, the NA-ACCORD team notes, though poor nutrition is linked to reduced circulating lymphocytes.

No one suggests encouraging normal-weight people to gain weight before starting ART to promote a more robust CD4-cell response; overweight and obesity certainly carry more health risks than a slower CD4+ recovery on ART. But the NA-ACCORD researchers suggest that the link between greater adiposity and greater CD4-cell gains "should be explored further in translational studies to understand the mechanisms and potential therapeutic implications."

Mark Mascolini is a freelance writer focused on HIV infection.