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1 December 1996 | Volume 125 Issue 11 | Pages 865-872
Objective: To increase lean body mass and improve health status in patients with wasting associated with the acquired immunodeficiency syndrome (AIDS) by treatment with recombinant human growth hormone (rhGH), recombinant human insulin-like growth factor 1 (rhIGF-1), or both.
Design: Randomized, double-blind, placebo-controlled clinical trial.
Setting: University of New Mexico Clinical Research Center and University of Texas Southwestern Medical Center.
Patients: 60 patients with AIDS and wasting as defined by the Centers for Disease Control and Prevention. Patients were divided into four groups of 15 patients each.
Intervention: Group 1 received 1.4 mg of rhGH once daily plus placebo twice daily; group 2 received 5 mg of rhIGF-1 twice daily plus placebo once daily; group 3 received 5 mg of rhIGF-1 twice daily plus 1.4 mg of rhGH once daily; and group 4 received placebo three times daily.
Measurements: Body weight, body composition, muscle strength, protein catabolism, quality of life, and immune status were assessed at baseline, and changes in these variables were measured at 6 and 12 weeks.
Results: At 6 weeks, lean body mass had increased and total fat mass had decreased in the groups receiving rhGH, rhIGF-1, or both. Group 3 had the greatest changes in lean body mass (mean ± SE, 3.2 ± 0.59 kg; P < 0.001); only in this group were changes in body mass maintained at 12 weeks. Only patients in group 1 had improvement in muscular strength of the knees and upper body (P = 0.04) and quality of life (P = 0.01). Immunologic function did not improve in any group.
Conclusions: Growth factor therapy had significantly increased lean body mass and decreased fat mass by 6 weeks, but these improvements persisted for 12 weeks only in group 3. Growth factor therapy at the dosages used in this study is not recommended because the magnitude of weight gain was modest and improvements in quality-of-life measures varied.
Deceased.
We hypothesized that treating AIDS-associated wasting with rhIGF-1, alone or in combination with rhGH, would reverse the catabolic effects characteristic of this wasting. We further hypothesized that if rhGH therapy increased lean body mass, then physical strength, immune function, and quality of life would improve. We therefore did a randomized, double-blind, placebo-controlled trial to assess the effects of rhGH and rhIGF-1 therapy in patients with AIDS-associated wasting. The primary end points were changes in weight and lean body mass. The secondary end points were changes in muscle function, immune status, quality of life, and protein catabolism.
The Institutional Review Boards of the University of New Mexico and the University of Texas Southwestern Medical Center approved the study, and all patients gave written informed consent before entering the study.
We recruited 60 patients (58 men and 2 women) with AIDS (as defined by the Centers for Discase Control and Prevention [12]), unexplained wasting (defined as weight loss
Baseline dietary histories were analyzed; at study entry, all patients were consuming at least 25 kcal/kg of body weight and none was receiving intravenous or tube feeding. None had received therapy with anabolic or catabolic agents, including interferon, megestrol, dronabinol, oxandrolone, and corticosteroids, within 30 days of study entry. No patient had received any experimental agent or procedure within 30 days of enrollment other than prophylactic antimicrobial therapy directed at fungal, bacterial, viral, mycobacterial, or parasitic infections. All patients had been receiving antiretroviral therapy for at least 3 months before study entry and received prophylaxis for Pneumocystis carinii throughout the treatment period.
Genentech, Inc. (South San Francisco, California), randomly assigned the 60 patients into four groups of 15 patients each so that balance was maintained across the groups with respect to body mass index, CD4 count, type of antiretroviral therapy, and age. The type of antiretroviral therapy was divided into five categories: zidovudine alone, didanosine alone, simultaneous administration of zidovudine and didanosine, simultaneous administration of zidovudine and zalcitabine, and other. The schedule for the subcutaneously injected therapy was as follows: Group 1 received 1.4 mg of rhGH once daily and 1 mL of placebo twice daily; group 2 received 5 mg of rhIGF-1 twice daily and 1 mL of placebo once daily; group 3 received 5 mg of rhIGF-1 twice daily and 1.4 mg of rhGH once daily; and group 4 received 1 mL of placebo three times daily. All patients received three subcutaneous injections per day for 12 weeks. Both patients and clinicians were blinded to treatment group assignments. The rhGH dosage used in this study was approximately one half the dosage used in our previous study [9]. The decision to use this dosage was based on the 2 x 2 analysis of variance (ANOVA) design and concern about the potential for increased incidence and severity of side effects if full doses of rhGH and rhIGF-1 were used in the patients receiving rhGH plus rhIGF-1.
Patients were withdrawn from the study if they did not administer all three injections each day for 7 continuous days throughout the treatment period. Injection compliance was assessed by counting vials and interviewing the study clinician during assessment visits. In addition, IGF-1 levels were monitored in all patients and were compared with values at baseline and those in placebo recipients. The intended duration of all treatments was 12 weeks.
Body Composition
Lean body mass, fat mass, and percentage of body fat were measured by using dual-energy x-ray absorptiometry (Hologic QDR-1000/W, Waltham, Massachusetts), as described elsewhere [13].
Total Body Water
We measured total body water using bioelectric impedance analysis (model 106, bioelectrical impedance analysis, RJL Systems, Detroit, Michigan). Testing was done between 1300 and 1500 hours, and all patients were fed and well hydrated before testing. We calculated body water by fitting the impedance measurements of resistance and reactance into previously derived prediction equations [14].
Protein Catabolism
Protein catabolism was estimated by turnover of [2H5]phenylalanine (Cambridge Isotope Laboratories, Woburn, Massachusetts), as described elsewhere [15, 16]. The plasma phenylalanine level was measured by using gas chromatography mass spectrometry after being derivatized to its t-butyldimethylsilyl ester [17]. The concentration and level of [2H5]phenylalanine in plasma were analyzed by using multiple ion detection under electron-impact ionization conditions [17].
Muscle Function
Computerized isotonic dynamometry (Baltimore Therapeutic Equipment, Baltimore, Maryland) was used to evaluate maximal voluntary contraction and maximum power (20%, 40%, and 60% maximal voluntary contraction) for a knee extension and a compound movement of the upper body.
Quality of Life
We measured quality of life using a self-administered 36-item Medical Outcomes Study questionnaire, which was previously validated in HIV-positive patients with AIDS-associated complex [18]. We accounted for missing values by averaging scores across completed items in the same scale for a particular patient. Eleven domains and three generalized domains were analyzed: 1) Total score was the average of the scores for all 36 questions; 2) functional status was the average of the scores in the domains for physical functioning, role functioning, social functioning, and cognitive functioning; and 3) well-being was the average of the scores in the domains for pain, mental health, energy and fatigue, health distress, and quality of life.
Endocrine Assays
Serum insulin levels were measured by using double-antibody radioimmunoassay (Pharmacia Diagnostics AB, Piscataway, New Jersey), and growth hormone levels were measured by using Tandem-R human growth hormone immunoradiometric assay (Hybritech, Inc., San Diego, California). Total IGF-1 levels were measured by double-antibody radioimmunoassay using rabbit antihuman IGF-1 antibody generated by Peter Gluckman (Auckland, New Zealand) at Genentech, Inc.
Immunologic Studies
Levels of HIV p24 antigen were measured in serum after acid dissociation by solid-phase sand-wich-type immunoassay that used a signal amplification technique (acid dissociated enzyme-linked immunoassay, DuPont Co., Boston, Massachusetts) [19]. CD3, CD4, and CD8 counts and percentage of total lymphocytes were measured in Ficol-separated peripheral blood mononuclear cell by flow cytometry using appropriate monoclonal antibodies and FACscan IV (Becton-Dickinson, Mountain View, California). Quantitative levels of circulating HIV were assayed from purified peripheral blood mononuclear cells by using the co-culture technique [19-21].
Intake of Nutrients
Before patients were enrolled in the study, a 24-hour self-reported recall process was used to determine whether all patients were consuming at least 25 kcal/kg per day. At study entry, the patients were instructed on how to follow a diet that consisted of 35 kcal/kg per day and 1 g of protein/kg per day. Intake was determined by a 24-hour recall done at baseline, 6 weeks, and 12 weeks and was analyzed by Nutritionist III software (N2 Computing, Salem, Oregon) for kilocalories, grams of protein, grams of fat, and grams of carbohydrates.
Statistical Analysis
The power analysis was calculated on the basis of an attrition rate of 30% and a mean ±SD increase in body weight of 4 ± 5.3 kg. This increase was seen in a previous study in which rhGH treatment alone was given for 12 weeks [9]. Therefore, because we had planned for an augmented effect of rhGH plus IGF-1, 15 patients per treatment group (corresponding to four cells in a 2 x 2 factorial design) were required to detect such differences with 80% power and a 5% probability of a type I error. The initial choice of a factorial design instead of a one-way design was based on the ability of the factorial design to allow conclusions to be drawn even if an interaction is seen between the two factors (in this case, rhIGF-1 and rhGH); in addition, the factorial design has superior power for comparing the main effects [22]. The method of analysis was a two-way ANOVA of 6-week and 12-week changes in the outcome variables from the baseline values. The 6-week and 12-week changes were also assessed by paired t-tests for each treatment group. To remedy a lack of normality, logarithms of some measurements or Kruskal-Wallis tests were used as appropriate. Logistic regressions were used to access dropouts in our intention-to-treat analysis [23-25]. Regression methods were used to assess the association between outcome variables and changes in lean body mass, measured IGF-1 levels, and percentage of weight loss before study entry. We used SAS software for all statistical analyses (SAS Institute, Cary, North Carolina).
The number of patients per treatment group at 6 and 12 weeks was as follows: rhGII plus rhIGF-1, 13 and 9, respectively; rhGH plus placebo, 12 and 11, respectively; rhIGF-1 plus placebo, 10 and 4, respectively; and placebo, 14 and 11, respectively. At 12 weeks, the dropout rate in the rhIGF-1 plus placebo group was significantly greater than that in the other treatment groups and was primarily attributable to intercurrent illness (P = 0.006; Fisher exact test). The patients who dropped out of the study did not differ from the total study sample by CD4 count, percentage of weight loss, or total number of opportunistic infections before study entry. Analysis of the characteristics of the patients who dropped out indicated that drop out occurred randomly; our intention-to-treat analysis considered only the patients who received treatment for at least 6 weeks [23-25].
Assessment of Variability Due to Dropout
Although the analysis used in our study is the best estimate of treatment effects, these results might vary because of attrition. We therefore did a last-value-carried-forward analysis and a worst-case analysis on the data.
In the last-value-carried-forward analysis, values at baseline or 6 weeks were carried forward as 12-week values. In the rhGH plus rhIGF-1 group, this analysis caused the P value for increases in lean body mass between baseline and 12 weeks to change from 0.006 to 0.003; the P value for decreases in fat mass in the same period changed from 0.02 to 0.002.
In the worst-case analysis, patients who dropped out were assigned 12-week values equal to the worst-case value (baseline to 12 weeks) obtained in their treatment group. In the rhGH plus rhIGF-1 group, this analysis changed the P value for increases in lean body mass from 0.006 to 0.004; the P value for decreases in fat mass changed from 0.02 to 0.34.
Patient Characteristics
Baseline demographic and clinical characteristics did not differ among the treatment groups (Table 1). The total sample consisted of 46 white persons, 14 Hispanic persons, 1 black person, and 1 Native American person. The mean age (± SE) of all patients was 37 ± 7 years (range, 24 to 53 years). The acquired immunodeficiency syndrome was diagnosed a median of 24 months before study entry (interquartile range, 18 months). The mean weight loss was 13 ± 0.8 kg, which represented an average reduction of 17% ± 1% from the weight before diagnosis. ARTICLE
Recombinant Human Growth Hormone, Insulin-like Growth Factor 1, and Combination Therapy in AIDS-Associated Wasting
A Randomized, Double-Blind, Placebo-Controlled Trial
Wasting associated with the acquired immunodeficiency syndrome (AIDS) is a serious complication of human immunodeficiency virus (HIV) infection that causes progressive loss of both lean body mass and, more variably, fat mass [1-4]. The pathogenesis is probably multifactorial and includes the underlying viral infection, tissue cytokines, intercurrent infections, and poor intake of calories [1, 2]. Recombinant human insulin-like growth factor 1 (rhIGF-1) alone and recombinant human growth hormone (rhGH) alone have been administered to humans during various catabolic states, including fasting, the period immediately after surgery, and trauma, and have had positive effects on lean body mass [5-7]. The beneficial effects of rhGH on body composition and metabolism are reportedly mediated by increased levels of IGF-1 [4, 5]. Furthermore, animal studies have shown that rhIGF-1 has beneficial effects on lymphopoieses [8]. Limited studies of rhGH or rhIGF-1 treatment alone in patients with AIDS have also been promising, resulting in an increase in circulating IGF-1 levels, lean body mass, and muscle function [9-11].
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Patients
10% of the weight before diagnosis or body mass index 
19.8 kg/m2), and a CD4 count less than 200 cells/mm3. Weight before diagnosis was defined as the weight that an adult patient maintained for at least 2 years during the time the patient believed that he or she was healthy. In New Mexico, patients were recruited by postings at the University of New Mexico Hospital Infectious Disease Clinic and Veterans Administration Hospital and by physician referral from private practices in Albuquerque and Santa Fe. In Texas, patients were recruited from the University of Texas Southwestern Medical Center at Dallas, a collaborating institution, and private practices throughout the Southwest. In addition, an advertisement was placed in the directory of the American Federation for AIDS Research. The patients were admitted to the University of New Mexico Clinical Research Center for a 2-day inpatient screening assessment. This assessment included physical examination, neurologic examination, electrocardiography, and chest radiography. Additional inclusion criteria were a hematocrit of 0.28 or greater, negative result of a pregnancy test (in women), negative 7-day blood culture for Mycobacterium avium intracellulare within 4 weeks before study entry, negativity for cryptococcal antigen in serum within 4 weeks before study entry, and a chest radiograph showing no evidence of acute cardiopulmonary disease within 28 days before study entry. Exclusion criteria were body mass index of 26.0 kg/m2 or greater, opportunistic infection that resolved less than 4 weeks before study entry, diarrhea (defined as five or more bowel movements per day or identification of an enteric pathogen), history of endocrine disease associated with hypoglycemia or hyperglycemia, any disorder associated with moderate or severe edema, history of cancer within 3 years of study entry, active Kaposi sarcoma, diagnosed cardiovascular disease (including congestive heart failure and cardiomyopathy), medically significant liver dysfunction (serum alanine aminotransferase level > 200 IU, total bilirubin level > 51.3 mmol/L) and renal dysfunction (creatinine level > 176.8 mmol/L).
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Eleven patients withdrew during the first 6 weeks of the study, and an additional 14 patients withdrew during the second 6 weeks. Two patients receiving rhGH plus rhIGF-1, 1 receiving rhGH plus placebo, 4 receiving rhIGF-1 plus placebo, and 2 receiving placebo withdrew because of intercurrent illness. One patient in the rhGH plus rhIGF-1 group and 1 patient in the rhGH plus placebo group withdrew because of protocol violations. Two patients in the rhGH plus IGF-1 group, 2 in the rhGH plus placebo group, 4 in the rhIGF-1 plus placebo group, and 1 in the placebo group withdrew by patient request. One patient in the rhGH plus rhIGF-1 group and 3 in the rhIGF-1 plus placebo group were lost to follow-up.
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Body Composition
Body weight had significantly increased in the rhGH plus placebo group and the rhGH plus rhIGF-1 group at 6 weeks (P = 0.02; ANOVA) Figure 1, but no significant differences among the groups were noted at 12 weeks. Lean body mass had significantly increased in the active treatment groups at 6 weeks (rhGH plus placebo and rhGH plus rhIGF-1, P = 0.002; rhIGF-1 plus placebo, P = 0.005; ANOVA) (Figure 1). Although lean body mass had increased at 12 weeks in the rhIGF-1 plus placebo group, only 4 patients still remained in the analysis at this assessment; the difference was not statistically significant. Thus, only the rhGH plus rhIGF-1 group had statistically significant increases in lean body mass from baseline to 12 weeks (mean change, 3.2 ± 0.59 kg; P = 0.006). At the same time, fat mass had significantly decreased at 6 weeks in all active treatment groups (P < 0.001; ANOVA); the decrease was significantly greater in the rhIGF-1 plus placebo and rhGH plus rhIGF-1 groups (P < 0.001; ANOVA) (Figure 1). In the rhGH plus rhIGF-1 group, fat mass was significantly decreased at week 12 (mean change, –1.7 kg ± 0.56; P = 0.02).
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The rhGH plus placebo group showed significant increases in total body water at week 6 (P = 0.04; paired t-test). However, no significant differences were seen between the groups for changes in this variable at 6 weeks. The rhGH plus rhIGF-1 group had a significant increase in total body water at 6 weeks (P = 0.02; paired t-test). At week 12, the rhIGF-1 plus placebo and rhGH plus rhIGF-1 groups showed significant increases in this variable (P = 0.03; ANOVA). The rhGH plus rhIGF-1 group had a significant increase in total body water at 12 weeks (P = 0.03; paired t-test)
Protein catabolism was not significantly decreased in any treatment group at 6 weeks. At 12 weeks, however, there was a trend toward a significant decrease in protein catabolism in the rhGH plus rhIGF-1 group (mean change, –1.0± 0.4 g/kg per day; P = 0.052; paired t-test). No significant differences were seen between the rhGH treatment groups or the rhIGF-1 treatment groups at 6 or 12 weeks (P > 0.05; ANOVA).
Muscle Function
In the rhGH plus placebo group, knee power and upper-body power were significantly increased at 6 weeks (P = 0.04 and 0.02, respectively; paired t-test) and upper-body strength was significantly increased at 12 weeks (paired t-test; P = 0.008). However, ANOVA did not show that changes in muscle function at 6 or 12 weeks differed between the groups. At 12 weeks, strength had significantly decreased in the rhGH plus rhIGF-1 group; this decrease may have been related to the increased number of reports of arthralgia and myalgia (P = 0.05; ANOVA).
Quality of Life
Changes in quality of life at 6 weeks did not significantly differ between groups. No changes in quality of life were associated with changes in weight or with treatment group. Changes in lean body mass were significantly related to improvements in quality of life at 6 weeks (r = 0.50; P = 0.003). Increased pain was reported at 6 weeks in patients who received rhGH plus rhIGF-1 (P = 0.01; paired t-test). The total quality-of-life score had increased at 12 weeks only in the rhGH plus placebo group (P = 0.02; paired t-test). However, no significant differences were seen between treatment groups (Figure 2).
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Endocrinologic Measures
At 6 weeks, IGF-1 levels were significantly increased from the baseline value in all three active treatment groups (P < 0.04 for all comparisons; paired t-test). Changes in IGF-1 levels were 183 ± 50 ng/mL in the rhGH plus rhIGF-1 group, 144 ± 40 ng/mL in the rhGH plus placebo group, 70 ± 28 ng/mL in the rhIGF-1 plus placebo group, and 9 ± 8 ng/mL in the placebo group. At 12 weeks, levels of IGF-1 had increased only in the rhGH plus placebo group (86 ± 22 ng/mL; P = 0.003). In the placebo group, levels of IGF-1 did not significantly change between baseline and week 6 or week 12. Levels of IGF-1 in the rhGH treatment groups were significantly greater than those in the placebo group (P = 0.003; ANOVA).
At 6 weeks, insulin levels were significantly decreased in the two groups that received rhIGF-1 (P < 0.001; ANOVA). In all groups, insulin levels at baseline did not significantly differ from levels at week 12.
Immunologic and Virologic Findings
After 6 or 12 weeks of treatment, values for none of the following variables differed from the baseline values in any group: CD3, CD4, or CD8 counts in peripheral blood; serum HIV p24 antigen levels; and HIV levels associated with peripheral blood mononuclear cells, quantitated by co-culture technique (P > 0.05; ANOVA).
Nutrition
During the study, nutrition intake did not significantly differ within or between the groups. Average caloric intake was 2115 kcal/d (35.5 kcal/kg per day) and 80 g of protein/d (1.3 g/kg per day).
Side Effects
Edema and arthralgia or myalgia were the most frequently reported side effects. Jaw pain occurred in 9 patients receiving rhGH plus IGF-1, 4 receiving rhGH plus placebo, and 2 receiving placebo. Edema developed in 7 patients receiving rhGH plus IGF-1, 2 receiving rhGH plus placebo, and 1 receiving placebo. Myalgias and arthralgia occurred in 10 patients receiving rhGH plus IGF-1, 4 receiving rhGH plus placebo, 2 receiving rhIGF-1 plus placebo, and 3 receiving placebo. Two patients receiving rhIGF-1 plus placebo developed gynecomastia. Hypoglycemia occurred in 2 patients in the rhGH plus IGF-1 group, 3 in the rhGH plus placebo group, and 1 in the rhIGF-1 plus placebo group. Headaches developed in 2 patients in the rhGH plus IGF-1 group, 1 in the rhIGF-1 plus placebo group, and 1 in the rhGH plus placebo group. Most adverse events developed in the rhGH groups during the initial weeks of anabolic hormone therapy. Some side effects were treated with diuretics, and others resolved after therapy during the washout phase.
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Previous studies that administered rhGH to patients with AIDS-associated wasting [9, 10] used higher dosages than those used in our study; one of these studies [10] also strictly controlled the patients' diet through the use of an inpatient study design. An inpatient clinical trial of rhIGF-1 treatment in AIDS-associated wasting found only transient effects of IGF-1 on nitrogen retention despite a controlled diet and intravenous administration of therapy [11]. In all of these studies, total body water increased along with lean body mass, and a plateau in the effect on nitrogen retention and lean body mass was rapidly reached [within 1 to 6 weeks]. Thus, our modest increases in lean body mass and the rapid plateaus in lean body mass gain may be attributable to several factors: 1) the lower total dose of growth hormone; 2) changes in total body water during continued treatment; 3) development of IGF-1 or growth hormone resistance to prolonged hormonal exposure; and 4) inadequate intake of protein.
We hypothesized that increases in lean body mass would be reflected in improved muscle function. Muscle strength and power significantly increased only in the rhGH plus placebo group, but the rhGH plus rhIGF-1 group had the greatest increases in lean body mass. This lack of a linear association between physical changes of muscle mass and performance after growth factor therapy has been reported previously [30, 31] and may indicate that additional studies are needed to elucidate the type of tissue whose mass increases with growth factor therapy (that is, collagen or skeletal muscle protein). The lack of significant improvement in muscle function despite significant increases in lean body mass in the rhGH plus rhIGF-1 group may have reflected the increased arthralgia and myalgia seen during muscle function testing.
Effects of growth factor therapy on immunologic function and circulating HIV levels were sought because recent studies had shown that rhGH and rhIGF-1 affected lymphopoiesis, lymphocyte function, and HIV replication in rodents [8, 32]. No beneficial effects were documented in these studies, but only cell-associated HIV, not plasma HIV RNA, was quantitiated.
Quality of life improved only in the rhGH plus placebo group. Recent trials of megestrol acetate [23, 33] showed that quality of life improved as weight increased, but investigators for these studies did not report whether their instrument had been validated. We used a quality-of-life questionnaire that had been validated in HIV-positive patients with AIDS-related complex but not in patients with AIDS-associated wasting. We may have experienced a floor phenomenon (insensitivity to detecting worsening health in patients who are already very ill) with this particular instrument that prohibited the recognition of larger changes in quality of life during the follow-up assessments [34].
Our study had several limitations. Eleven enrolled patients dropped out before the 6-week assessment, and another 13 patients dropped out before the final assessment at 12 weeks. This 41% attrition rate was not unexpected because of the severely impaired immune status of the patients at baseline and because of rates of attrition reported in other AIDS studies [33, 35]. The dropout rate was significantly higher in the rhIGF-1 group, but logistic regression analysis showed that the withdrawals from the study occurred randomly and therefore did not bias our results. The improvements in the P values mentioned in the section on assessment of variability due to dropout were qualitatively unchanged in a last-value-carried-forward analysis; these improvements could be attributable to increased sample size. By using the worst-case analysis, the significant decrease in fat mass became nonsignificant. However, with a large number of dropouts, this worst-case analysis could maintain significance only if the distribution of differences for each treatment were totally positive or negative.
The rhGH dosage used in our study was 1.4 mg/d; other investigations used 0.1 mg/kg per day [10] or 5 mg every other day [9]. The dosage we used was approximately half that used previously and may not have been sufficient to elicit the responses shown by other investigators.
Nutritional recommendations for patients with AIDS or HIV infection vary, but increased caloric and protein intakes are suggested for these patients [36]. A cited guideline is 3.35 kcal/kg per day (total calories) and 2.0 to 2.5 g/kg per day (protein) [36]. Although our patients met minimum caloric requirements, they did not meet the recommendation for protein intake.
In conclusion, growth factor therapy that includes rhGH (alone or in combination with rhIGF-1) may increase lean body mass in patients with AIDS-associated wasting. In the absence of consistent improvements in muscle function, immunologic measures, and quality of life, sustained therapy with these recombinant hormones cannot be recommended at the dosages we studied.
The authors dedicate this article to their valued friend and colleague, Donna Nickell (8 September 1966-28 October 1996).
From the University of New Mexico School of Medicine, Albuquerque, New Mexico; and the University of Texas Southwestern Medical Center, Dallas, Texas.
Mr. Danska and Dr. Koster: Department of Medicine/Infectious Diseases, University of New Mexico School of Medicine, 5th Floor Ambulatory Care Center, Albuquerque, NM 87131.
Dr. Hardy: Department of Endocrine and Metabolic Diseases, Metabolic Unit, Western General Hospital, Crewe Road, Edinburgh, Scotland EH4 2XU.
Dr. Qualls and Ms. Nickell: Clinical Research Center 5E, University of New Mexico School of Medicine, Albuquerque, NM 87131.
Dr. Nightingale: 480 North McClurg #401, Chicago, IL 60611.
Dr. Gesundheit: VIVUS, Inc., 545 Middlefield Road, Suite 200, Menlo Park, CA 94025.
Mr. Watson: ID Associates, 5939 Harry Hines Boulevard #545, Dallas TX 75235.
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