Severity of HIV illness more likely culprit in fat loss than medication

Severity of HIV disease, and not antiretroviral treatment, has the strongest association with lipoatrophy (fat loss) in people taking HAART, according to a US study published in the 1^st January 2003 edition of the Journal of Acquired Immune Deficiency Syndromes. This study contradicts an emerging consensus that certain anti-HIV drugs are primarily responsible for the fat loss seen in a growing number of HIV-positive people taking HAART.

Investigators recruited 546 people from the ongoing HIV Outpatient Study (HOPS), which is based in seven large US cities to this study. Patients were assessed in late 1998 and again in the summer of 2000. Three body areas were evaluated for fat loss: superficial thinning of the extremities; thinning of the buttocks/hips; and sunken cheeks.

The findings were first presented at the Ninth Conference on Retroviruses and Opportunistic Infections in 2002.

Study design

Only people with absolutely no evidence of lipoatrophy at the first survey were included in the prospective analysis. When the results of the follow-up visit were analysed, data from people still without fat-loss were compared to those from people who developed lipoatrophy over the two year follow-up.

The investigators were keen to see if any of the following factors could be significantly associated with fat wasting: age; HIV transmission group; gender; race; use of anti-HIV drugs by class; length and severity of HIV disease; immune profile, including CD4 count; and, HIV viral load.

Of the 546 patients enrolled to the study, 337 had no evidence of lipoatrophy at baseline. Of these, 44 developed moderate to severe fat loss by the time of the follow-up visit two years later.

Initial analysis of study data suggested that age; white race; severity of HIV infection (as measured by AIDS defining illnesses and CD4 count); HIV viral load; and, body mass index (BMI) were all predictive of the development of lipoatrophy.

However, only white race, CD4 count below 100 cells/mm³, a viral load above 1,000 copies/mL and body mass index remained significant on further analysis. The strongest predictor of lipoatrophy was CD4 count at the second visit. In addition, an increase in CD4 count of less than 50 cells/mm³ in the two years of the study was also found to be a risk factor of fat loss.

Patients with low CD4 counts at the time of the second study visit were found to be more likely to have had low CD4 counts earlier in the course of their HIV infection. Indeed, a lowest ever (nadir) CD4 count of less than 100 cells/mm³ at any time as early as 1994 was predictive of the emergence of lipoatrophy.

In addition, patients who had had a CD4 count below 100 cells/mm³, a low BMI and a viral load above 1,000 copies at any time were more likely to have fat loss. The investigators note that this finding “held throughout the subject’s HIV course, whether present at pre-HAART, Survey 1 or Survey 2 time points."

The study results were also controlled for diseases causing fat loss, including MAI, pneumonia and depression. Such illnesses occurred in 18.2% of the group with lipoatrophy, but in over 40% of patients with no fat wasting.

No relationship was found between any anti-HIV drug and fat loss. The investigators comment: “When evaluating for total time on drug, time of drug initiation, drug continuation, and drug discontinuation, we could find no clear relationship to the incidence of lipoatrophy…the incidence of lipoatrophy was consistently higher in persons with nadir CD4 counts 3 at any time in their illness regardless of the length of time on antiretroviral drugs.”

The investigators conclude “our study suggests that HIV infection or factors associated with immune reconstitution may play a greater role in the development of lipoatrophy than the use of any specific medication.” Adding, “we are unable to demonstrate any association with use or duration of time on any individual drug or class of drug with the incidence of lipoatrophy.”