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Query: UMLS:C0019693 (HIV)
 170,526 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Growth hormone (somatotropin) is a potent anabolic protein currently being evaluated clinically in cachexia associated with malignancy and human immunodeficiency virus (HIV) disease. Growth hormone can also lead to enhancement of lectin-mediated cellular proliferation, macrophage activation, and cytokine induction, events linked to induction of latent HIV in vitro. We thus explored the ability of recombinant human growth hormone (rhGH) to affect viral replication in acute and chronic HIV infection, and to alter transcription at the HIV-1 long terminal repeat (LTR). A clone of promonocytic cells, chronically infected with HIV-1 and susceptible to viral induction by a variety of cytokines and protein kinase C activators, was unperturbed by rhGH used over broad concentrations (10 to 500 ng/mL) and time intervals. This unresponsiveness paralleled the lack of effect of rhGH on HIV-associated trans-activation in both monocytic and CD4+ T-cell lines. In contrast, rhGH enhanced viral replication in acutely infected peripheral blood mononuclear cells (PBMC) by twofold to 20-fold, albeit having no adverse effect on the antiviral efficacy of zidovudine (AZT). Augmentation of HIV growth correlated with stimulation of cellular DNA synthetic responses and an increase in tumor necrosis factor-alpha (TNF-alpha) secretion. These data are discussed in the context of ongoing clinical trials of rhGH in HIV-seropositive individuals with wasting syndromes.
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PMID:Effect of recombinant human growth hormone on acute and chronic human immunodeficiency virus infection in vitro. 173 91

Loss of body mass, or wasting, is a major cause of morbidity and a contributor to mortality in human immunodeficiency virus-1 (HIV-1) infection. Dietary supplements and appetite adjuvants have had limited effectiveness in treating this condition. GH and insulin-like growth factor I (IGF-I) have been shown to be anabolic in many catabolic conditions, and limited data suggest similar efficacy in HIV wasting. In addition, it appears that GH and IGF-I may have complementary anabolic effects with opposing glucoregulatory effects. We report results from a 12-week randomized, placebo-controlled trial of combination recombinant human GH (rhGH; Nutropin; 0.34 mg, sc, twice daily) and rhIGF-I (5.0 mg, sc, twice daily) in individuals with HIV wasting and without active opportunistic infection, cancer, or gastrointestinal disease. A total of 142 subjects (140 males and 2 females) were randomized using a 2:1, double blind treatment scheme and assigned to receive either active treatment or placebo injections. Eighty subjects completed the 12-week protocol. Nutritional intake and demographic and clinical characteristics did not differ between the groups at any study time point. At 3 weeks, the treatment group had a significantly larger weight increase (P = 0.0003), but this difference was not observed at any later time point. Similarly, fat-free mass, calculated from skinfold measurements, increased transiently in the treatment group at 6 weeks (P = 0.002). No significant differences in isokinetic muscle strength or endurance testing or in quality of life were observed between the groups. Resting heart rate was significantly higher in the treatment group at each time point post-baseline. GH and IGF-binding protein-3 levels did not change; however, IGF-I levels were higher in the treatment group at 6 and 12 weeks. There were no significant between-group differences in any of the measured biochemical or immunological parameters. rhGH plus rhIGF-I treatment was associated with an increased incidence of peripheral edema and other side-effects, possibly related to fluid retention. We conclude that the combination of rhIGF-I and low dose rhGH used in this study had no significant anabolic effect in HIV wasting.
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PMID:A randomized, placebo-controlled trial of combined insulin-like growth factor I and low dose growth hormone therapy for wasting associated with human immunodeficiency virus infection. 876 60

Immune cell death or dysfunction is induced by HIV infection and results in an immunocompromised state. Newer treatments are able to control viral replication to prevent massive cytoreduction. Attention must now focus on therapies that will rapidly reconstitute the immune system to provide defense against future HIV attacks as well as opportunistic infections. In addition to increasing the rate of differentiation of myeloid and lymphoid precursors from marrow stem cells, ideal therapies should improve thymic function as well. Growth hormone (GH), a member of the hematopoietic cytokine superfamily and its receptors, is expressed in multiple sites within the immune system. GH has been shown to have a stimulatory effect on the function of thymic cells, as well as other immune cell types. In this paper, we consider the use of GH to reconstitute the immune system following cytoreduction due to HIV infection.
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PMID:Growth hormone in immune reconstitution. 1022 23

Although effective treatment of antiretroviral-associated metabolic abnormalities ultimately depends on understanding the mechanisms involved, clinicians facing these problems are beginning to feel compelled to do something now to manage treatment-related metabolic complications. Diet and exercise should not be overlooked, because both can be effective in managing these complications without causing further side effects. Fibric acid derivatives such as gemfibrozil and statins can lower HIV-associated cholesterol and triglyceride levels, although further data are needed on problematic interactions between statins and protease inhibitors (PIs). Hypoglycemic agents may have some role in managing glucose abnormalities, although troglitazone cannot be recommended for fat abnormalities alone and metformin may cause lactic acidosis. Growth hormone and anabolic steroids may have some role in treating lipodystrophy, but the cost of growth hormone is prohibitive for many patients and definitive data on efficacy are lacking. Replacing a PI with a reverse transcriptase inhibitor has improved lipid and glucose levels in some studies. However, that strategy begs the question of how the nucleosides might contribute to lipodystrophy.
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PMID:How to manage metabolic complications of HIV therapy: what to do while we wait for answers. 1075 16

MediCal will now provide reimbursement for the recombinant human growth hormone (Serostim) from Serono Laboratories through an Food and Drug Administration (FDA)-sanctioned Treatment Investigational New Drug program. The drug has shown promise in the treatment of AIDS-related wasting. California has appropriated $10 million for Serostim for MediCal clients. Patients qualify to receive the drug if they have failed either Megace or Marinol. Patient reimbursement advocacy activities and the distribution of Serostim are now handled by Stadtlanders Pharmacy, a mail-order business that has high visibility among people living with HIV infection and AIDS.
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PMID:Wider access to human growth hormone. 1136 98

Data from a recent study of the testosterone patch do not support its use for treating HIV-related weight loss. Testosterone as a therapy may require higher doses than the body normally produces. Currently, the only approved therapies are megestrol (Megace), dronabinol (Marinol), and recombinant human growth hormone (Serostim). More encouraging results come from data on thalidomide. Specifics will be forthcoming. Interested parties can call the Project Inform Treatment Hotline for updates.
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PMID:HIV-related weight loss. 1136 11

Even with the introduction of highly active antiretroviral therapy (HAART), the expected eradication of HIV wasting syndrome has not materialized. Patients who gain weight on HAART seem to gain it as fat, with the body apparently unable to restore lean body mass, even with strenuous exercise programs. It may be that in addition to HAART, an anabolic or anti-inflammatory agent may be needed to reset body chemistry that was damaged by HIV. Serostim, Serono's brand of growth hormone, has been approved to treat wasting, and although it does seem to increase lean body mass and decrease fat in some patients, many patients were not compliant with taking the drug. Testosterone and anabolic steroids were also effective in causing weight gain. Thalidomide is being studied to attack the underlying cause of wasting, namely the overproduction of tumor necrosis factor alpha. In studying thalidomide, however, viral load went up slightly, and reduction of tumor necrosis factor levels was not documented; side effects included skin rash and sleepiness. Research is continuing in this area, with the need to use body composition measurements as a means to gain faster approval of therapies for wasting.
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PMID:No attrition in research on wasting therapies. 1136 78

Growth hormone is one of the latest tools against AIDS. Serono's Serostim (somatropin) is the only growth hormone to receive Food and Drug Administration (FDA) approval to treat wasting. HIV-positive individuals show a dramatic suppression of growth hormone, and people with AIDS have practically none. The decrease in growth hormone is also associated with decreasing T-cell counts. The mechanisms in growth hormone production and their role in metabolism and nutrition are described. Serostim is very expensive, and the Serono SeroCare program has limited the cost to $36,000 per year. The program is managed by the National Organization for Rare Diseases. The method of creating growth hormone from the recombinant DNA proteins (rDNA) family is described.
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PMID:The panacea of growth hormone. 1136 26

AIDS wasting is characterized by a loss of lean body mass, including muscle and organ tissue, coupled with increased fat production. Loss of lean body mass can lead to muscle weakness, organ failure, and sometimes death, making AIDS wasting a leading contributor to HIV-related deaths. Manufacturers first developed injected treatments such as Serostim, a recombinant human growth hormone marketed by Serono Laboratories for the treatment of wasting. More recently, MTI Biotech has begun manufacturing Juven, an over-the-counter supplement that has been shown to increase muscle mass and reverse the side effects of AIDS wasting. Serono Laboratories answers some common questions, regarding how AIDS wasting differs from other forms of weight loss and the causes and consequences of AIDS wasting. The company also addresses specific concerns related to Serostim. Serostim dosage recommendations are provided.
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PMID:What you need to know about AIDS wasting. 1136 22

Lipodystrophy is one of the most common and distressing side effects associated with combination therapy. Some aspects of the phenomenon were reported several years ago, but the frequency of reports has greatly increased with the introduction of protease inhibitors in 1996. Lipodystrophy is a redistribution of fat, and the cause of the change is uncertain. It is not known if it is a signal of disease progression, or a result of anti-HIV therapy. A report on three separate cases conveys success in treating lipodystrophy associated with the use of protease inhibitors. All cases switched people from protease inhibitors to non-nucleoside reverse transcriptase inhibitors (NNRTI), however 10 percent of the group had increases in HIV levels. Serostim, a human growth hormone, has also had some effect in reducing central obesity and buffalo hump, but does not seem to be effective on facial and limb wasting or on decreasing lipid levels. To date, most studies on lipodystropy have been driven by AIDS activists, with pharmaceutical companies and the research community being slow to follow. There is very little information on treating this syndrome, and it is unclear how widespread its effects are. Reports on incidence levels range from 15 percent to 75 percent.
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PMID:Lipodystrophy. 1136 31


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