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Growth hormone and HIV infection: Contribution to disease manifestations and clinical implications

https://doi.org/10.1016/j.beem.2010.11.001Get rights and content

In untreated HIV patients growth hormone deficiency contributes to loss of lean and fat mass. Pharmacologic doses of growth hormone successfully reverse this wasting process. In patients responding to antiretroviral therapies several non AIDS-related complications usually common among older, uninfected persons now occur more frequently in younger HIV patients. Among these conditions are cardiovascular disease and metabolic disorders. Although their etiology is multifactorial, changes in growth hormone biology reflecting relative growth hormone deficiency occur and may be involved. In these patients truncal obesity, and associated dyslipidemia and glucose homeostasis changes contribute to impaired quality of life and increased cardiovascular risk. Treatment with growth hormone and growth hormone releasing factor leads to short-term improvement of some of these abnormalities. This paper will review abnormalities of growth hormone biology and the use of growth hormone and growth hormone releasing factor as therapeutic agents in HIV patients.

Introduction

HIV is today a treatable infection in most persons with regular access to highly active antiretroviral therapy (HAART). Despite the incomplete immune reconstitution occurring on HAART, complications resulting from the severe immunosuppression (collectively termed AIDS) in untreated patients or those unresponsive to HAART occur much less frequently. The majority of treated patients have a significantly improved survival, although it is projected to be less than in uninfected persons.1 Clinically, several common, mostly ageing-related complications (termed SNARE-Serious Non AIDS Related Events) now occur more frequently in treated patients.*2, 3 These contribute to the ongoing, although significantly decreased morbidity and mortality. They include premature cardiovascular disease and metabolic disorders, bone demineralization, renal failure, hepatic disease, several primarily infection-associated malignancies, and non-dementing cognitive dysfunction.

Among the most common of these complications are the adipose tissue associated body shape changes and related metabolic abnormalities commonly known as the HIV/HAART associated Lipodystrophy (HAL) syndromes.4 These contribute to decreased quality of life (QOL)5 in otherwise stable patients and to an increased cardiovascular disease (CVD) risk.6 However, metabolic complications are not only a recently described complication. In untreated patients or those responding poorly to HAART metabolic abnormalities were identified early in the AIDS epidemic. These consist of the preferential loss of lean body mass (LBM) more so than the loss of fat mass (FM). This phenomenon occurs in patients with advanced HIV disease and is called the AIDS Wasting Syndrome (AWS).7

The etiology of these diverse metabolic disorders is multifactorial. Abnormal hormonal homeostasis contributes to these conditions. The growth hormone (GH)-insulin-like growth factor-1 (IGF-1) system has been extensively investigated in this regard.8 Other endocrinopathies may also contribute to these complications, including hypogonadism, thyroid disorders, abnormalities of adrenal and gut hormones and, possibly, recently described changes in interactions between bone and adipose tissues.9, 10, 11

HIV-related changes in GH physiology have been studied due to similarities between metabolic abnormalities occurring in GH-deficient states in the general population and HIV-related metabolic changes. These include decreased body cell mass, increased visceral adipose tissue (VAT), dyslipidemia and insulin resistance.12 This review will summarize current insight into GH physiology in HIV disease and will discuss the therapeutic effects of GH and related agents in the management of metabolic abnormalities.

Section snippets

Clinical features of AWS

Most untreated HIV patients with advanced HIV disease, or those responding poorly to ARV drugs, have decreased total body weight. Severe weight loss, more than 10% of usual body weight over a 12 month period, along with chronic diarrhea or persistent idiopathic fever, fulfills diagnostic criteria for the AWS, an AIDS-defining condition.7 It occurs in over one-third of untreated patients. The etiology includes decreased caloric intake, malabsorption, altered intermediary metabolism and diarrhea.

Clinical features

Soon after the introduction of HAART, some patients noted significant body shape changes. Atherogenic dyslipidemia and glucose homeostasis changes also developed.33 Dyslipidemia, consisting primarily of elevated triglycerides (TGs) and low HDL-cholesterol, occurs in untreated HIV patients and is thought to be of similar etiology to that seen in other chronic infectious and inflammatory states.34 The initiation of HAART is generally associated with worsening of the already elevated TGs, no

Summary

Abnormalities of growth hormone biology contribute to metabolic complications in both untreated and treated HIV patients. The AIDS Wasting Syndrome decreases survival in untreated patients. Significant weight loss occurring in patients with advanced HIV disease, and not HIV infection itself is the main cause of the growth hormone resistance that exists in these patients. Pharmacologic doses of growth hormone improve lean body mass, functional status and outcomes. Ongoing loss of lean body mass

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