Effect of BMI on Immune Status, and Virologic Control of HIV
In the general population, multiple negative effects of being overweight or obese have been well documented. Prior studies have suggested that obese individuals have poorer immune functioning. However, the role of obesity (and BMI in general) among HIV-infected individuals remains unclear. This is a salient issue, as obesity among HIV-infected individuals has increased with trends largely mirroring those of the general population. Because HIV-infected individuals already possess some level of immunocompromise and chronic inflammation, understanding the relationship of weight to disease progression is of importance.
The main findings from the current study indicated that over time, overweight HIV-infected MSM possessed higher CD4 counts than normal weight HIV-infected MSM (neither category statistically differed from obese men in the longitudinal analysis). Among the handful of studies conducted in the HAART era, findings regarding obesity and CD4 count have been varied and contradictory. However, the current study is one of only 2 that assessed this relationship prospectively over several time points.
The current study also assessed viral load, which is novel among the HAART era studies published on this topic. Prospectively, overweight and obese men possessed significantly lower viral loads compared with normal weight men. Given that men with elevated BMI possessed higher CD4 counts, perhaps it is not surprising that their viral loads were also relatively lower compared with normal weight men. Indeed, there is a strong negative association between CD4 and viral load.
Despite the novel findings from the current study that heavier than normal HIV-infected patients have better control of their HIV infection, the behavioral and/or pathophysiological mechanism is not clear. It is plausible that leptin may be involved in the pathway of overweight and obesity to immune functioning among HIV-infected individuals. Leptin is an adipocyte-derived hormone that influences body weight (among other biological functions). Overweight and obese individuals have been found to have higher levels of serum leptin compared with normal weight individuals. Among some samples, increased levels of leptin have been found to be related to improved immunological health. Although obesity in the general population has been linked to worse immune functioning, among HIV-infected individuals, if there is actually a protective effect, it may be that higher concentrations of leptin provide a specific protective function by improvements in CD4 count, as leptin treatment has been associated with T-cell proliferation among mice and humans. However, some studies among HIV-infected individuals have failed to find a relationship between leptin treatment and CD4 count or viral load, although these studies were not designed to test intervention effects on disease progression, per se. Clearly, further studies evaluating the role of leptin and T-cell number and function in HIV-infected individuals are warranted to evaluate this hypothesis further.
Alternative explanations may be considered. Two variables that were not fully assessed in this study were the CD4 nadir when patients initiated HAART and their duration of treatment. If normal weight patients were more immunosuppressed when they initiated treatment, their ability to control viral replication and to restore immune function would be compromised, limiting their ability to achieve higher CD4 counts compared with patients who started treatment at higher CD4 counts. However, supplemental analyses revealed nonsignificant differences at baseline, and at each time point, in virological suppression as a function of BMI category.
Although the current study yielded novel findings, it is not without limitations. For instance, the nature of the sample may limit generalizability of the results, as the sample exclusively constituted MSM and was primarily white. Thus, translating these findings to women and nonwhite races should be done with caution. It is also quite possible that the patients in the CNICS cohort, by virtue of using an electronic medical record (from which the data were obtained) have a higher degree of integration of care compared with that of the typical HIV-infected patient.
In summary, prospective analyses found that elevated BMI among HIV-infected MSM is associated with better CD4 counts and viral load compared with normal weight men. It is important to note that being overweight and obese is associated with a plethora of health problems; although these findings highlight the possibility that elevated BMI may have a specific protective factor for HIV-infected MSM, it does not suggest that overweight and obesity should be clinically ignored (or for that matter encouraged) in MSM living with HIV. However, future research is needed to understand the casual mechanisms of being overweight and obese and disease progression among this population, perhaps through the role of increased levels of serum leptin and other potential immune factors.
Discussion
In the general population, multiple negative effects of being overweight or obese have been well documented. Prior studies have suggested that obese individuals have poorer immune functioning. However, the role of obesity (and BMI in general) among HIV-infected individuals remains unclear. This is a salient issue, as obesity among HIV-infected individuals has increased with trends largely mirroring those of the general population. Because HIV-infected individuals already possess some level of immunocompromise and chronic inflammation, understanding the relationship of weight to disease progression is of importance.
The main findings from the current study indicated that over time, overweight HIV-infected MSM possessed higher CD4 counts than normal weight HIV-infected MSM (neither category statistically differed from obese men in the longitudinal analysis). Among the handful of studies conducted in the HAART era, findings regarding obesity and CD4 count have been varied and contradictory. However, the current study is one of only 2 that assessed this relationship prospectively over several time points.
The current study also assessed viral load, which is novel among the HAART era studies published on this topic. Prospectively, overweight and obese men possessed significantly lower viral loads compared with normal weight men. Given that men with elevated BMI possessed higher CD4 counts, perhaps it is not surprising that their viral loads were also relatively lower compared with normal weight men. Indeed, there is a strong negative association between CD4 and viral load.
Despite the novel findings from the current study that heavier than normal HIV-infected patients have better control of their HIV infection, the behavioral and/or pathophysiological mechanism is not clear. It is plausible that leptin may be involved in the pathway of overweight and obesity to immune functioning among HIV-infected individuals. Leptin is an adipocyte-derived hormone that influences body weight (among other biological functions). Overweight and obese individuals have been found to have higher levels of serum leptin compared with normal weight individuals. Among some samples, increased levels of leptin have been found to be related to improved immunological health. Although obesity in the general population has been linked to worse immune functioning, among HIV-infected individuals, if there is actually a protective effect, it may be that higher concentrations of leptin provide a specific protective function by improvements in CD4 count, as leptin treatment has been associated with T-cell proliferation among mice and humans. However, some studies among HIV-infected individuals have failed to find a relationship between leptin treatment and CD4 count or viral load, although these studies were not designed to test intervention effects on disease progression, per se. Clearly, further studies evaluating the role of leptin and T-cell number and function in HIV-infected individuals are warranted to evaluate this hypothesis further.
Alternative explanations may be considered. Two variables that were not fully assessed in this study were the CD4 nadir when patients initiated HAART and their duration of treatment. If normal weight patients were more immunosuppressed when they initiated treatment, their ability to control viral replication and to restore immune function would be compromised, limiting their ability to achieve higher CD4 counts compared with patients who started treatment at higher CD4 counts. However, supplemental analyses revealed nonsignificant differences at baseline, and at each time point, in virological suppression as a function of BMI category.
Although the current study yielded novel findings, it is not without limitations. For instance, the nature of the sample may limit generalizability of the results, as the sample exclusively constituted MSM and was primarily white. Thus, translating these findings to women and nonwhite races should be done with caution. It is also quite possible that the patients in the CNICS cohort, by virtue of using an electronic medical record (from which the data were obtained) have a higher degree of integration of care compared with that of the typical HIV-infected patient.
In summary, prospective analyses found that elevated BMI among HIV-infected MSM is associated with better CD4 counts and viral load compared with normal weight men. It is important to note that being overweight and obese is associated with a plethora of health problems; although these findings highlight the possibility that elevated BMI may have a specific protective factor for HIV-infected MSM, it does not suggest that overweight and obesity should be clinically ignored (or for that matter encouraged) in MSM living with HIV. However, future research is needed to understand the casual mechanisms of being overweight and obese and disease progression among this population, perhaps through the role of increased levels of serum leptin and other potential immune factors.
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