HIV-Associated Wasting in the HAART ERA

An Overlooked and Under-Diagnosed Condition

With an expanding list of approved and experimental treatments, new complications have emerged from the use of HAART.11 These include abnormal fat accumulation (lipohypertrophy), lipoatrophy, dyslipidemia, insulin resistance, diabetes, life-threatening lactic acidosis, and osteopenia. The shift in attention to these complications has overshadowed the fact that HIV-associated wasting occurs in patients today despite the use of HAART. In addition, the development of fat redistribution clearly makes wasting more difficult to diagnose. Patients with wasting do not always display the characteristics that were so typical of the wasting syndrome observed during the pre-HAART era.

Today's patient with HIV-associated wasting may be maintaining adequate virologic control and immunologic indices. When patients do gain weight on HAART, it is primarily fat with no change in lean body mass.12 They may, for example, still have abnormal fat accumulation, such as dorsocervical fat deposits and/or visceral adiposity.13-16 The diagnosis should also include other factors such as gender and psychosocial issues. These include depression, anxiety, substance use, income, access to food, and the home environment.

Incidence of HIV-Associated Wasting in the HAART Era

The most recent evidence of wasting in patients receiving HAART comes from baseline and prospective data analysis of a large cohort of HIV-infected individuals (N=633) who are participating in the Nutrition for Health Living (NFHL) longitudinal study.17 Begun in 1995, the NFHL has conducted nutritional and health assessments at baseline and then every six months on men and women who are enrolled. Monthly telephone calls collected information on health status, current weight, and changes in medications. Three definitions of HIV-associated wasting were applied to the cohort. At the time of their enrollment in the cohort, 88 individuals (13.9%) reported wasting at baseline. This group was not analyzed further. Of the remaining 466 men and women, 156 (33.6%) met at least one or more of the three criteria for wasting.

Relationship Between HAART and HIV-Associated Wasting

The study also examined the use of HAART and the development of wasting in the 633 individuals enrolled in the entire cohort. Of these, 422 (67%) subjects had used HAART, consisting of a protease inhibitor (PI) and two nucleosides (NRTIs), at some point in time. Of the remaining 211 subjects who had never used HAART, 16 (7.5%) reported wasting at the time of their study enrollment, 37 (17.0%) had insufficient follow-up data to determine wasting, and 41 (25.9%) met at least one of the wasting definitions during the course of the study.

Within the group of 422 subjects who had used HAART at some point in time, 72 (17.2%) reported wasting at the time of their study enrollment, 22 (5.2%) had insufficient follow-up data to determine wasting, and 95 (28.9%) met at least one of the wasting definitions during the course of the study. Of the 64 individuals who were not receiving HAART at the time of study entry and who met at least one wasting definition during the course of the study, 31 (48.4%) did so after starting HAART therapy. Therefore, HIV-associated wasting can occur in patients who are treatment-naïve, actively being treated with HAART, or who are already HAART-experienced.

Distinguishing Between HIV-Associated Wasting and Lipoatrophy

When examining weight loss in patients with HIV infection, it is often difficult to determine if they are losing lean body mass or fat mass. A separate analysis of 497 cohort patients from the NFHL longitudinal study found 289 individuals (58%) had lost >1.5 kg between any two study visits six months apart. In this group, the mean weight loss was 4.0 kg. Using bioelectric impedance analysis (BIA), 1.3 kg of this weight loss was lean body mass, while the remaining 2.7 kg was fat mass.

The type of tissue lost during HIV-related wasting depends on the patient's existing percentage of body fat. In general, patients who have body fat >15% will preferentially lose more fat than lean body mass. Those patients with an initial body fat percentage of <15% will have lean body mass as the predominant tissue loss.18 Although distinguishing between actual HIV-associated wasting and lipoatrophy can be difficult, some general guidelines serve as reference points to distinguish between the two.

The Impact of Wasting in the HAART Era

As noted above, associated wasting occurs even in patients on HAART.17,19-21 Loss of body cell mass still takes place in patients who receive protease inhibitors. Although many clinicians believe patients gain weight after receiving HAART, no placebo-controlled trials demonstrate such weight gain.22 In addition, there is no correlation between increased body weight changes and improved viral load.23,24

The diagnosis of wasting has become more confusing in the wake of other morphologic complications associated with HAART. For example, patients can have both wasting and fat redistribution, in the form of lipoatrophy or lipohypertrophy, at the same time. Many clinicians do not include wasting in their routine diagnostic evaluation of patients, do not obtain and record weight histories, and do not monitor body composition. Consequently, often wasting is simply overlooked.

When wasting is severe, it can be quite stigmatizing to the patient. However, one should not view HIV-associated wasting as solely a cosmetic issue. Since it involves the loss of lean body mass, body cell mass, and skeletal muscle, it can have deleterious and sometimes life- threatening physiologic effects. These include the following:

› increased weakness;
› decreased physical functioning;
› decreased quality of life;
› impaired immune functioning;
› increase in disease complications; and
› decreased survival.

HIV-associated wasting is an important disease marker, with the magnitude of weight loss related directly to the risk of death for the patient.5 The loss of lean body mass and body weight are associated with poorer survival rates in end-stage AIDS.4,5 Moderate-to-severe weight loss, before the onset of other symptoms, predicts decreased survival after the onset of symptomatic AIDS.7 Given the significance and impact of HIV-associated wasting in the post-HAART era, clinicians need to assess patients effectively for signs of wasting and treat the condition with proven therapies and interventions.