Modest weight and muscle gains seen with HAART

A year of highly active antiretroviral therapy (HAART) leads to only modest gains in weight and lean body mass in HIV-positive individuals, according to a United States study published in he October 15^th edition of Clinical Infectious Diseases. The study also found that increases in weight and lean body mass accompanied falls in viral load, and that weight gains were better in antiretroviral-naïve patients than individuals with previous experience of antiretroviral therapy, particularly if this involved adefovir (a drug which was investigated, but not licensed for use against HIV).

Weight loss and decreases in lean body mass are commonly observed in HIV-positive patients, with weight often falling before the onset of AIDS-defining illnesses. Studies have found an association between viral load and weight loss, but few prospective studies have investigated the relationship between the impact of viral suppression with HAART and changes in weight and lean body mass.

The AIDS Clinical Trials Group (ACTG) 892 study was a prospective, multicentre 48-week study designed to assess changes in weight, lean body mass and functional performance in 143 HAART-naïve and -experienced patients.

Changes in weight, lean body mass and performance were assessed in both the short term (16 weeks of HAART), and the longer term (48 weeks of antiretroviral therapy).

There were no significant differences between the 83 treatment-experienced and 120 antiretroviral-naïve patients at baseline with respect to gender, ethnicity, injection drug use or CD4 cell count. However, treatment-naïve patients were significantly younger (median age 35 versus 38 years, p = 0.005), had a higher median HIV viral load (160,000 versus 64,000 copies/ml, p = 0.004) and had a higher median Karnofsky score (100 versus 90, p = 0.002).

After 16 weeks of HAART, overall the patients’ weight had increased by a median of 1.9kg. There was no further weight gain by week 48. The median gain in lean muscle was 0.6kg at week 16 and 0.9kg at week 48.

A significantly greater gain in body weight was observed at week 16 in patients who has achieved a viral load below 500 copies/ml than in those who had not (p = 0.045). Similarly, at week 48 individuals who were virologically suppressed had greater gains in lean body mass than patients with a viral load above 500 copies/ml (p = 0.035).

When the investigators looked at changes in weight according to whether a patient was antiretroviral-naïve or -experienced, they found that naïve patients gained significantly more weight (p

A CD4 cell count below 200 cells/mm³ and a viral load above 100,000 copies/ml at baseline were associated with greater gain in weight and lean muscle at week 16, but by week 48 the difference was no longer significant.

At week 48, functional activity scores were higher for treatment- naive patients who had gained 1.5kg or more of weight than those who had not (p = 0.039). No significant changes were observed for treatment-experienced patients at any time point.

“The initiation of HAART was associated with modest median body weight increases…and modest lean body mass increases”, write the investigators. They add, “a relationship was found between decreases in HIV-1 RNA loads and increases in weight at week 16 and between decreases in HIV-1 RNA loads and increases in lean body mass at week 48.” They note that their findings support the hypothesis that immunological factors affect weight, with the magnitude of gains in weight and lean muscle correlated to the degree of immunosuppression at baseline.

Regarding the poorer gains seen in treatment-experienced patients, the investigators stress that many of these individuals were recruited from studies investigating adefovir, a nucleotide analogue which, because of safety reasons, was not licensed for use as part of HAART in HIV-positive patients.

“Future studies of body composition in HIV should consider the potential existence of other factors that affect weight and lean body mass increase other than simple virological control”, conclude the investigators. “In particular, those factors that may differ between antiretroviral naïve and antiretroviral-experienced subjects should be considered.”