Role of recombinant human growth hormone in HIV-associated wasting and cachexia: pathophysiology and rationale for treatment.
BACKGROUND
Wasting, or cachexia, is a significant, debilitating, and potentially life-threatening complication of HIV infection. It is associated with reduced strength and functional ability, reduced ability to withstand opportunistic infections, and increased risk of mortality. Although the incidence of HIV-associated wasting may have declined since the introduction of highly active antiretroviral therapy (HAART), it continues to be a concern in this patient population.


OBJECTIVE
This paper reviews available data on the etiology and clinical impact of HIV-associated wasting, the role of the growth hormone/insulin-like growth factor-I axis in the pathophysiology of this condition, and the rationale for its treatment with recombinant human growth hormone (rhGH).


METHODS
MEDLINE was searched for articles published in English through August 2007 using the terms HIV, wasting (and related terms), and growth hormone. Preference was given to clinical studies (including randomized clinical studies), meta-analyses, and guidelines. Review articles were evaluated and the bibliographies examined for additional relevant articles. The analysis was restricted to studies conducted in developed countries.


RESULTS
Alterations in the growth hormone/insulin like growth factor-I axis have been observed in patients with HIV-associated wasting, including elevated levels of the former and reduced levels of insulin-like growth factor I. In randomized, placebo-controlled studies, rhGH significantly improved lean body mass by approximately 3 kg compared with placebo (P < 0.001) and total body weight by approximately 3 kg (P < 0.001), and was associated with significant improvements in physical endurance and quality of life (P < 0.001). Common adverse events with rhGH therapy include blood glucose elevations, arthralgia (36.4%), myalgia (30.4%), and peripheral edema (26.1%), but these usually respond to dose reduction or drug discontinuation.


CONCLUSIONS
Physicians should be alert to the possibility of wasting in HIV-infected patients receiving HAART and should consider treatment to improve patients' stamina and quality of life. The evidence supports a role for rhGH in the treatment of patients with HIV-associated wasting. Regular blood glucose monitoring is advised when treating wasting with rhGH.
D000293:Adolescent; D000328:Adult; D023241:Antiretroviral Therapy, Highly Active; D001823:Body Composition / Q000502:physiology; D002100:Cachexia / Q000188:drug therapy* / Q000503:physiopathology*; D002648:Child; D016207:Cytokines / Q000502:physiology; D004734:Energy Metabolism; D013006:Growth Hormone / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015658:HIV Infections / Q000503:physiopathology; D019247:HIV Wasting Syndrome / Q000188:drug therapy* / Q000453:epidemiology / Q000503:physiopathology*; D019382:Human Growth Hormone / Q000502:physiology; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology / Q000627:therapeutic use; D009135:Muscular Diseases / Q000209:etiology / Q000473:pathology; D055435:Myostatin; D011506:Proteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D012307:Risk Factors; D015398:Signal Transduction / Q000502:physiology; D013739:Testosterone / Q000097:blood; D016212:Transforming Growth Factor beta / Q000378:metabolism
D016207:Cytokines; C525911:MSTN protein, human; D055435:Myostatin; D011506:Proteins; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D019382:Human Growth Hormone; D013739:Testosterone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone