HIV Drug therapies that combat wasting
by Tadd Scott Lazarus, M.D. and David W. Purdy
There are a variety of options in the treatment of HIV-related wasting syndrome. Probably the most important concept to remember is that one must diagnose and treat what is treatable. Specifically, wasting is often a result of undiagnosed mycrobacterial infection or cytomegalovirus that has become disseminated (extra-ocular).
One should never abandon investigating an infectious, neoplastic or mechanical etiology for wasting. During the investigative process, wasting must be treated through a directed effort concentrating on addressing both symptoms and etiology.
Wasting and the nutritional problems associated with HIV/AIDS have for too long been placed as back-burner issues of concern of the dietician or the patient but not the clinician. In 1989, Dr. Donald Kotler and associates published a pivotal study in the American Journal of Clinical Nutrition (50(3);444-447) wherein they described the “magnitude of body-cell-mass depletion and the timing of death from wasting in AIDS.”
They noted that there was progressive depletion of body cell mass as patients neared death. The extrapolated and observed values for body cell mass at death were 54% of normal. Body weight had a similar relationship to death, with a projected body weight at death of 66% of ideal.
We conclude that death from wasting in AIDS is related to the magnitude of tissue depletion and is independent of the underlying cause of wasting. The degree of wasting seen in this study is similar to historical reports of semistarvation, with or without associated infections. This observation suggests that successful attempts to maintain body mass could prolong survival in patients with AIDS.”
Since that time, multiple studies have clearly shown the correlation between decreased body cell mass and an increase in morbidity and mortality. Yet little of this knowledge has found its way into the practice of HIV medicine.
At the heart of wasting syndrome is the inappropriate use of lean muscle as an oxidative fuel and the inability of the body to appropriately oxidize fat stores.
Only anabolic agents can effectively address this conundrum and correct the metabolic course. Agents—such as appetite stimulants—have an important place in the treatment armamentarium as the intake of calories and nutrients is crucial in replenishing lean body mass.
The following is not meant as an exhaustive treatise on this subject but a place for clinicians and patients unfamiliar with these therapies to augment their knowledge base.
Thousands of people with HIV are currently being treated successfully with anabolic-androgenic steroids for HIV-associated wasting and hypogonadism.
Androgenic steroids (male sex hormones), like anabolic steroids, have a long history of use in treating wasting conditions associated with infectious diseases and cancer.1,2 An article published as early as 1968 strongly supported the use of anabolic steroids in the management of chronic wasting diseases.3
Studies clearly show that anabolic agents may produce far superior and more enduring lean body mass increases than any other available treatment for wasting.4 Anabolic steroids improve muscle bulk, body weight, overall strength and sense of well being in HIV-positive patients.5
Anabolic steroids also improve nutritional status, stimulate appetite6, combat anemia, control depression and significantly improve the patient’s overall quality of life.
Anabolic steroids possess anti-catabolic properties in that they can abolish a negative nitrogen balance brought about by the administration of corticosteroids and anti-androgens.7,8 In placebo-controlled studies using anabolic steroids, not only was there a significant effect on lean body mass, but also muscle strength.9
Anabolic-androgenic steroids act directly on skeletal muscle by binding to the androgen receptors.10
Testosterone and Other Anabolic Steroids
All anabolic-androgenic steroids are derivatives of the human body’s natural testosterone. Synthetic preparations of testosterone used in medicine are in fact anabolic-androgenic steroids. All anabolic steroids have anabolic (muscle building) and androgenic (masculinizing) properties.
Testosterone has the highest level of androgenic properties. Anabolic steroids were developed for clinical use with the expectation that they would be relatively less androgenic than testosterone.11
Because all anabolic steroids contain androgenic properties which are considered undesirable and unnecessary for many patients, and also may lead to potential side effects, efforts have been made to separate the two properties, with emphasis on creating synthetic anabolic steroids which have higher anabolic than androgenic properties.12 The anabolic steroids recommended for the treatment of HIV wasting are in fact higher in anabolic properties than androgenic properties.
One study successfully demonstrated that testosterone analogues, like Deca-Durabolin (nandrolone decanoate, Organon) may be more appropriate to prescribe than testosterone itself for HIV wasting.13
Oral Anabolic Steroids
There are two oral anabolic steroids that experts recommend in the treatment of HIV-associated wasting. The two medications are Oxandrin (oxandralone, BTG) and Winstrol (stanozolol, Sanofi Winthrop).
Oxandrin appears to be one of the few oral anabolic steroids with a history of use in treating wasting disorders. It differs from other testosterone analogues in that it contains an oxygen rather than a carbon atom. This may account for its anabolic potency that is approximately three to 13 times that of testosterone.14
Oxandrin is indicated as adjunctive therapy to promote weight gain after weight loss following extensive surgery, chronic infections or severe trauma.15 Clinical trials have demonstrated that Oxandrin is a safe and effective oral anabolic steroid with low androgenic properties. It appears that unlike other oral anabolic steroids, Oxandrin undergoes little overall metabolic transformation in the liver and is well tolerated in men and women.16
A 1995 double-blind study conducted at six different U.S. sites concluded that HIV-positive men who were severely wasting (10% or below their normal body weight), experienced significant and sustained weight gain with Oxandrin. The study subjects were prescribed 15 mg/day or 140 mg a week, for 16 weeks. There were no apparent side effects.17 In other studies, Oxandrin has been prescribed at much higher dosages than 15 mg/day without significant side effects. Oxandrin appears to be one of the few safe oral anabolic steroids, because unlike other anabolic-androgenic steroids, Oxandrin undergoes little metabolism and is not aromatized into estrogen.18
Winstrol, the other anabolic steroid recommended for HIV-associated wasting, has a history of use in wasting disorders as well, but appears to be slightly more androgenic than Oxandrin. When prescribed at small therapeutic dosages, however, as recommended in the treatment of wasting, this should not be a problem or cause negative side effects.
Anabolic Steroid Patches
Some health care providers and patients prefer the anabolic steroid patch as a convenient alternative to injections or oral anabolic steroid preparations.
There are currently two anabolic steroid patches. One is Testoderm (testosterone transdermal system, ALZA). The patch is a thin flexible film that adheres to the scrotum by utilizing a heat-activated adhesive. Testosterone passes from the system through the scrotal skin and into the bloodstream. The scrotal skin appears to allow 10 times more testosterone to pass through than other skin sites on the body trunk and arm.
Another anabolic steroid patch is Androderm (testosterone transdermal system, SmithKline Beecham). Unlike Testoderm, Androderm is applied as two patches to the back of the arm or shoulder upon retiring.
Anabolic Steroid Gels
Dihydrotestosterone Gel is in development as a novel delivery mechanism for testosterone. It is applied to the patient’s abdominal area. The appropriate dosage of this product for the treatment of HIV-associated wasting is not yet clear, but it could be a convenient and effective alternative hormone therapy for the future.
Human Growth Hormone
Much attention has been focused on the use of Serostim (recombinant human growth hormone, Serono) for the treatment of HIV-associated wasting. Serostim is an effective agent causing prompt reversal of negative nitrogen balance and increases in lean body mass. Unfortunately, the cost of therapy has made it difficult to justify this agent as first-line therapy for wasting. Serostim requires a daily injection during the course of therapy and side-effects can include flu-like symptoms including myalgias and arthralgias as well as peripheral edema. In trials of Serostim in the elderly, there was evidence of reversal of gains in lean body mass with cessation of the agent. it should be remembered the Serostim has no androgenic activity and a hypogonadal male will still need exogenous testosterone replacement.