Treatment Strategies for Metabolic Abnormalities: Re-Examining Our Approach to HIV Care

Bill Valenti M.D.

Recently, descriptions of the lipodystrophy syndrome have caused us to re-examine some of our approaches to HIV care.

The syndrome, still without a case definition, consists of one or more of the following: fat redistribution, muscle wasting, lipid abnormalities, and insulin resistance.

Protease inhibitors have been suggested as the cause¹, but the causes are more likely to be multifactorial. Other possibilities include non-nuceloside reverse transcriptase inhibitor (RTI) drugs, along with advanced HIV disease itself. Several recent reports have shown that lipodystrophy is related to time since HIV diagnosis, age, lower nadir CD4 count, greater viral load rebound and duration of antiretroviral therapy ²,³.

While the prevailing approach to treatment is still "treat early and treat hard" the emergence of this series of metabolic disorders has caused many of us to plan and monitor our treatment differently than in the past.

For example, treatment planning today requires a different approach to drug selection. As a minimum, a discussion of some of the metabolic complications of antiretroviral therapy is needed, along with monitoring patients receiving antiretrovirals for changes in lipids and body shape.

We now need to monitor patients with a different awareness of the significance of cholesterol and triglyceride abnormalities. In the past, during the monotherapy era, lipid abnormalities were often overlooked as being less important to the patientpis outcome. With advances in antiretroviral therapy that have changed HIV to a chronic, more manageable illness for many people, these metabolic abnormalities have become more significant. As a component of the lipodystrophy sydrome, treatment of lipid and other metabolic abnormalities has taken center stage for patients and their providers.

Even with this new awareness, certain fundamentals of HIV care still have a role in treatment, including the use of appetite stimulants, replacement of various deficiencies, and exercise.

Some of our earliest treatments such as megestrol (Megace) and dronabinol (Marinol) will be necessary for some patientspi nutritional well-being. Appetite stimulants remain an important class of drugs both as monotherapy and adjunctive therapy. Encouraging news for physicians and patients is dronabinolpis reclassification from a schedule II to a schedule III drug in most states, making it less restricted.

Metabolic treatments that have been useful in the past, including testosterone replacement, remain important treatment strategies for many patients. While testosterone deficiency has not been included within the spectrum of lipodystrophy, there is enough clinical experience to know that it occurs with some regularity, can be a cause of decreased libido, fatigue and depression, and is easily diagnosed and treated.

In addition to injectable testosterone, there are a variety of other choices for testosterone replacement, including several patch delivery systems. An even newer option is testosterone gel (Androgel), a gel delivery system, now in clinical trials that may be available soon.

While testosterone is only weakly anabolic, other, more potent agents are available to increase muscle mass. These treatments, however, also work best with exercise as outlined by Tadd Lazarus in this issue of Numedx.

Non-prescription products, such as amino acid mixtures containing beta-hydroxy-beta-methyl butyrate (HMB; Juven) have been shown to increase body weight and muscle mass in exercised patients in preliminary studies ⁴,⁵. This product has recently been approved for Medicaid reimbursement in both New York and New Jersey.

Anabolic steroids continue to play a role to increase muscle mass in HIV infected patients. Deca-durobolin is still used along with newer oral formulations including oxandrolone (Oxandrin). In addition, an agent like oxymetholone (Anandrol-50) can provide both anabolic and androgenic activity to further replenishment of lean muscle mass.

Human growth hormone (Serostim) has been used for AIDS wasting since early studies showed an increase in body cell mass and improvement in performance in exercised patients ⁶. More recently, descriptions of growth hormone and its role in lipodystrophy treatment have been presented, including improvements in dorsal fat pad (>=Buffalo hump<=) redistribution⁷ and reversal of body fat changes in an open label trial ⁸.

The approach to HIV treatment remains highly individualized with a variety of choices for antiretroviral and metabolic therapies. These choices allow us to select the best options for patients, based on individual need. These options also provide an opportunity to use these metabolic therapies in combination, just as we use combinations of antiretrovirals.

Earlier treatment for metabolic disorders should also be emphasized here. Close patient follow up will help us to monitor changes in lipids and body shape, as well as responses to treatment. Early intervention for metabolic problems is necessary if we are to manage lipodystrophy effectively, in much the same way earlier antiretroviral use has been initiated.

Other discussions in this issue of Numedx support this concept by laying the groundwork for this new treatment paradigm. This includes guidelines for early nutritional referral and baseline body compartment measurements via bioelectrical impedance analysis (BIA) and access to metabolic therapies for all patients regardless of payer source. Marcy Fenton, in her article, says it best: >=the time has come for HIV medical nutrition therapy.

1. Martinez, E and Gatell, J, - Metabolic Abnormalities and Use of HIV-1 Protease Inhibitors<= Lancet. 1998; 352: 821.

2. Romeu, J, Sirera, MJ, Rego, E et al. Cumulative risk of hyperlipidemia in patients treated with protease inhibitors. #1293 Abstracts of 39th ICAAC, San Francisco, CA Sept 26-29, 1999.

3. Ward, D, Delaney, A, Moorman, A et al. Clinical factors related to the lipodystrophy severity in the HIV oupatient study (HOPS). #1299 Abstracts of the 39th ICAAC, San Francisco, CA Sept 26-29, 1999.

4. Nissen, S.L., R.H. Clark, G. Feleke, M. Din, T. Yasmin, G. Singh, F. Khan, J.A. Rathmacher and N.N. Abumrad. Effect of supplemental beta-hydroxy-beta-methylbutyrate (HMB), glutamine, and arginine on skeletal muscle mass in AIDS patients. JPEN 23(1):S7 1999.

5. Rathmacher, J.A., S.L. Nissen, L. Panton, J. Fuller, Jr., R.H. Clark, G. Singh and N.N. Abumrad. Safety of nutritional mixture of beta-hydroxy-beta-methylbutyrate (HMB), glutamine and arginine in healthy young adults and patients with AIDS. JPEN 23(1):S10, 1999.

6. Mulligan K, Grunfeld C, Hellerstein MK, Neese RA, Schambelan M. Anabolic effects of recombinant human growth hormonein patients with wasting associated with human immunodeficiency virus infection. J Clin Endocrinol Metab. 1993;77:.

7. Torres, R. - Treatment of dorsocervical fat pads and truncal adiposity with serostim (recombinant human growth hormone) in patients with AIDS maintained on HAART. Abstract 32164. 12th World Conference on AIDS, 1998.

8. Wanke, C, Gerrior, J, Kantaros, J, Coakely, E and Albrecht, M. Recombinant human growth hormone improves the fat redistribution syndrome (lipodystrophy) in patients with HIV. AIDS; 1999: 13; . Internet resources:

Boyle, B. Lipodystrophy: A New Phenomenon. The AIDS Reader 9(1):15-17,1999.

http://www.medscape.com/SCP/TAR/1999/v09.n01/a6148.boyl/a6148.boyl-01.html

New Developments in HIV-Related Lipodystrophy. Transcript of a teleconference on the web with Donald Kotler, Andrew Carr, Ronald Baker and Roger Anderson.

http://www.hivtreatmentlive.com/html/trans915.html