Published in the Bulletin of Experimental Treatments for AIDS Summer 1999 issue, by the San Francisco AIDS Foundation.

Summer 1999 Table of Contents

Main Page

beta@sfaf.org

Global Perspectives on Nutrition and HIV

A Special Report

By Mary Romeyn, MD, and Nathan Gunn

Lipodystrophy, HIV-associated lipodystrophy (HAL), and fat redistribution syndrome (FRS) were titles proposed by investigators for the syndrome. Many speakers called for a case definition and uniform agreement on what features make up the syndrome. This report will primarily use fat redistribution syndrome (FRS), the name proposed by Donald Kotler, MD, of St. Luke's-Roosevelt Hospital in New York, who discussed the changing face of malnutrition in HIV infection.

Current Knowledge of FRS

In his opening speech, Dr. Kotler reviewed HIV malnutrition before and after highly active antiretroviral therapy (HAART). Pre-HAART fat loss has been replaced by post-HAART variable weight change. Body cell mass depletion has given way to altered fat distribution: increases in visceral fat, deposited deep within the abdominal cavity (visceral adipose tissue, or VAT) and the chest cavity; loss of subcutaneous fat in arms, legs, buttocks, and face (lipoatrophy); and increased breast size and reduced thigh and hip fat in women.

Metabolism (the way the body takes in nutrients, breaks them down, and directs how they are used to make substances or drive reactions), particularly fat metabolism, has also changed. Former (i.e., pre-HAART) HIV-associated decreases in low-density lipoprotein (LDL, or "bad" cholesterol) have been replaced by increases. A rise in triglycerides (hypertriglyceridemia) is seen especially with protease inhibitor therapy; some protease inhibitors appear to cause hypertriglyceridemia more than others. Resistance to insulin (used for the metabolism of glucose, or sugar), not seen before HAART, is now widespread.

While prior metabolic changes predicted reduced survival, insulin resistance and current changes in fat metabolism are associated with a better prognosis and greater viral suppression. New adverse events include decreased adherence; some people may not accept survival at the cost of a change in appearance. In addition, viral suppression and improved survival bring with them increased risk of heart disease. Carl Grunfeld, MD, PhD, of the San Francisco Veterans Affairs Medical Center estimates this risk to be less than two cardiac events per ten years per 100 people, however-much less than the former risk of dying from AIDS. This cardiac risk increases significantly, however, if more than one risk factor (e.g., smoking, high blood pressure, diabetes, family history of early heart attacks) is present.

Changes in fat metabolism and insulin regulation are associated with increased intra-abdominal fat and other aspects of central fat accumulation. The nature of the relationship is not clear, nor is their relationship to protease inhibitor therapy. Table III looks at the association between high cholesterol and triglyceride levels and central fat accumulation in Dr. Kotler's retrospective study. Table IV relates protease inhibitor use to the presence of a dorsocervical fat pad ("buffalo hump").

Table II

Table III

Table IV

While serum cortisol levels have not been found to be related, Joan Lo, MD, of San Francisco General Hospital (SFGH) and R.L. Hengel report increases in 24-hour urine-free cortisol; therefore there may be a role for increased glucocorticoids (steroid hormones which are increased as part of the body's response to stress) in this syndrome. Levels of complement, a substance active in the immune response, are not altered. It is therefore hard to determine the roles played by immune activity, drug effects, and hormonal changes in FRS.

Dr. Kotler noted that the following are still needed to better understand FRS: a case definition, determination of prevalence, causative agents, pathogenesis (how FRS develops), reversibility, effects of protease inhibitor and other anti-HIV therapy, and treatment options. In other words, "all we know now is what we don't know," he noted, recommending head-to-head protease inhibitor trials as a starting point.

On the second day of his presentation, Dr. Kotler reviewed a study comparing HIV positive subjects from his clinic since 1996 with pre-1996 HIV positive subjects and HIV negative controls in an attempt to understand changes since the advent of HAART. Multiple factors appear to act on fat distribution; there seems to be an HIV effect, a gender effect, and-particularly interesting-an HIV RNA effect. Better viral load suppression correlates with more aggressive fat redistribution changes.

Post-1996 HIV positive subjects had increased visceral adipose (fat) tissue (VAT) relative to pre-1996 subjects. This was masked by a reduction in subcutaneous adipose tissue (fat just beneath the skin), or SAT. When compared with HIV negative controls, HIV-infected subjects had 23% less fat overall and 59% less subcutaneous fat, but almost twice as much visceral fat (see table IV). Changes were less exaggerated when studied in women alone.

Body composition in the Kotler studies is measured by magnetic resonance imaging (MRI). VAT is calculated by measuring abdominal radius to estimate total adipose tissue, then subtracting the radius of the subcutaneous fat; visceral fat is then calculated from the remaining radius. Dr. Kotler reports that dual x-ray absorptiometry (DEXA) incorrectly estimates visceral fat. Bioimpedance analysis, which overreports extremity composition, is also limited in its ability to evaluate redistribution.

Eric Ravussin, MD, from Lilly Research Labs reviewed normal mechanisms of energy balance and compared them to HIV-associated mechanisms. In healthy HIV negative subjects, weight gain or loss is largely genetically determined. Body shape is determined about 2/3 by genetics and 1/3 by environment. Resting metabolic rate (the rate at which energy is spent without movement), is proportional to lean body mass. It does not account for maintenance of body weight during fluctuations in dietary intake. When dieting fails in overweight people and when overfeeding fails in thin people, it is not because of the metabolic rate. Rather, changes in involuntary movements (i.e., fidgeting) tend to balance caloric intake. If people predisposed to thinness eat a big meal, they will, for example, pace, tap their feet, twirl their pencils, get out of their chairs, stretch, and stroll around the office-thereby burning the excess calories away. People predisposed to being overweight will not. In fact, in the face of dieting, their normal fidgeting will be reduced.

In HIV, however, wasting is associated with an increased metabolic rate-a rate not matched by added intake. The degree of wasting parallels the severity of infection.

According to Dr. Ravussin, 33% of normal obesity is due to "gluttony and sloth," 42% to inappropriately increased appetite, 5% to failure of metabolic regulation, and 10% to the fidget factor. People with HIV do not alter their fidgeting to balance their intake but do have metabolic dysregulation and rarely have hyperphagia (excessive appetite). Gluttony and sloth are subject to individual variation, but rarely differ before and after infection.

Morris Schambelan, MD, of the University of California at San Francisco (UCSF) noted that FRS was seen before the protease inhibitor era and that protease inhibitor-naive persons experience similar body composition changes (see table IV). He suggested that FRS may reflect an underlying HIV-associated defect in metabolism among HIV positive persons that becomes apparent only when they are no longer wasted. If so, the syndrome may be associated with HAART simply because such therapy allows people to regain weight.

Body habitus in FRS is remarkably similar to one seen in Cushing's syndrome, a state of elevation in blood cortisol (stress steroid) levels. However, serum cortisol levels in FRS are not reported to be elevated. Seven of Dr. Schambelan's eight subjects with a dorsocervical fat pad had normal urine-free cortisol; the remaining person had a normal dexamethasone suppression test, suggesting no cortisol-related disorder. Dorsocervical fat pad subjects were also more likely to have increased visceral fat.

In contrast, Per Bjorntorp of the University of Gothenburg, Sweden, continued to suspect a role for modest elevations of cortisol in FRS. A body that is chronically stressed will have chronic cortisol elevation, leading to reductions in sex steroids such as testosterone as well as growth hormone. Problems with this theory include a lack of significant cortisol elevation in HIV, the absence of FRS in other stressed states, and no "burnout" effect, as is seen in Cushing's when excess cortisol production over time leads to reduction. Bjorntorp hypothesized that elevations too subtle and immediate to be considered important may play a role. (Referring to Bjorntorp's work in a speech June 3, 1999, Dr. Kotler noted that studies in the community such as he and Dr. Bjorntorp have done did appear to show cortisol elevations in HIV, where those in the controlled hospital setting such as Dr. Schambelan's did not. He suggested that inpatient studies may falsely reduce the stress of life with HIV, and hence falsely reduce cortisol levels in that population also.)

Nevena Christeff of the Hôpital Bichat in Paris reported on a prospective study comparing HIV positive subjects, nine with and nine without lipodystrophy or FRS, with nine matched HIV negative controls. Seventeen out of 18 HIV positive subjects were on antiretroviral treatment, using a total of nine different regimens. Cortisol levels were higher in HIV positive subjects than in the controls, but cycled appropriately. The ratio of cortisol to DHEA (a testosterone precursor that may have other actions) was increased with progression of disease. Laboratory changes in fat metabolism were seen without associated body shape changes; the author hypothesized that metabolic changes precede body shape changes. All increases in serum lipids (cholesterol and triglycerides) were associated with decreases in DHEA; thus subjects with lipid abnormalities had increased DHEA/cholesterol ratios. They also had higher CD4 cell counts, again stressing the better prognosis associated with FRS.

Lipid metabolism is a balance between fat breakdown, or lipolysis, and fat manufacture, or lipogenesis. The process of lipolysis is regulated by the enzyme lipoprotein lipase and triggered by increased cortisol. Reduced DHEA, which also increases the cortisol/DHEA ratio, increases insulin resistance. People can have DHEA reduction by itself, without a change in the cortisol/DHEA ratio, and appear normal. Perhaps a high cortisol level, when matched to a high DHEA level, may also be protective.

Antiretroviral therapies act on enzymes also involved in the making of sex steroids like DHEA; DHEA collapse in the setting of lipodystrophy is most likely related to antiretroviral therapy, and pushes up the cortisol/DHEA ratio.

Kathleen Mulligan, PhD, of SFGH reported that FRS is masked in women. Prior to HAART, women lost and regained fat and lean mass proportionately, rather than favoring lean mass, as do men. After initiation of protease inhibitors, what comes back first is fat.

Treating FRS-Related Metabolic Abnormalities

While FRS as currently defined appears to carry with it an improved survival outlook, the metabolic changes that accompany or precede body shape abnormalities require adjustments in treatment priorities. Insulin resistance may progress to diabetes. High cholesterol and triglyceride levels can cause premature heart disease. If these are carefully managed, there may be additional survival benefit. Since metabolic changes appear to predate changes in body composition, metabolic treatments may help to prevent or reverse those changes. Metabolic treatments have the added benefit of addressing the changes that increase the risk of heart and vascular (blood vessel) disease.

Dr. Schambelan reviewed possible approaches to dietary and exercise interventions as well as medications. Treatment of glucose intolerance/insulin resistance may be done with metformin (Glucophage), keeping in mind the risk of metabolic acidosis (life-threatening alteration in the blood) and the risk to the kidneys if contrast dye is used for imaging studies while on the drug. Troglitazone has also been advanced as a possible solution, but the risk of liver damage makes it especially problematic in people with HIV, given the use of many other medications metabolized by the liver as well as the high frequency of coinfection with hepatitis B or C virus. Rosiglitazone, a newly approved insulin-sensitizing drug, appears to reduce the risk of liver toxicity. High triglycerides have been safely treated with gemfibrozil (Lopid). High cholesterol has been successfully addressed with the HMG CoA reductase inhibitors, or "statins" (most of the experience reported has been with atorvastatin, or Lipitor). Note the report below, however, on severe reductions in saquinavir (Fortovase) levels. Dr. Schambelan advocated watching for elevations in CPK (creatine phosphokinase, a muscle enzyme), as high levels of statins can cause myositis (inflammation of the skeletal muscle) and metabolism may be impaired, particularly by protease inhibitors. No myositis in HIV-associated hyperlipidemia has been reported to date, however. While atorvastatin has not yet shown toxicity in this population and is known to be highly effective, there may be a role for reducing the job of the liver where possible.

Marijka Batterham, MD, of the Royal Prince Alfred Hospital in Camperdown, Australia, discussed the relationship of dietary fat and serum lipids in people with HIV in the era of HAART. Forty-four subjects with self-reported peripheral fat wasting and central fat accumulation (41 of whom were on protease inhibitors and none of whom were antiretroviral-naive) had intake monitored using a previously validated "food frequency event instrument." There was no significant correlation between saturated fat or caloric intake and serum parameters associated with glucose, total cholesterol, high-density lipoprotein (HDL, or "good" cholesterol), LDL, triglycerides, insulin, or insulin resistance. The author concluded that, given the lack of correlation between diet and laboratory values and the enormous demands for dietary adherence already posed by treatment of HIV, people with HIV should not be asked to modify their diet as part of a lipid lowering or metabolic regulation strategy.

One late-breaker presentation by M.C. Meyohas of the Hôpital Tenon in Paris also reported on the utility of combined nutritional counseling (recommending dietary change), exercise, and smoking cessation. She found such counseling reduced triglycerides in HIV positive subjects with hypertriglyceridemia, most of whom had untreated diabetes. Whether or not subjects exercised was not known. Initial diets had been very high in saturated fats and sugars as well as calories. Despite these initially encouraging results, a statistically different change was observed in the first month only.

Presenter David Zucman, MD, of the Hôpital Foch in Saresnes, France, stated that he "would not treat people with any statin without [monitoring] protease inhibitor levels before and after." Treatment of hyperlipidemia with atorvastatin in 12 HIV positive persons on HAART for two months reduced cholesterol and did not cause myositis or liver damage. However, those people on saquinavir, even when combined with ritonavir, showed deep reductions in saquinavir levels, sometimes to below the IC90 (i.e., below the therapeutic range). Studies are needed to evaluate the effects of the statin drugs (HMG-CoA reductase inhibitors) on antiretroviral levels.

Ravi Walli of the University of Munich, Germany, reported on a study treating insulin resistance in people with FRS. Within this study, no drug-naive persons developed insulin resistance, while 27% taking only reverse transcriptase inhibitors (RTIs) and 55% of those taking a protease inhibitor-containing regimen did so. Walli used troglitazone, a medication that increases insulin sensitivity. Insulin resistance was independently associated with body mass index (BMI), age, and cholesterol, but not related to viral load or CD4 cell count. It appeared to be reversible with changes in therapy, and did respond to troglitazone. With treatment, subjects had better glucose control but increased LDL cholesterol. This therapy may ameliorate HAART-associated insulin resistance. Reservations were expressed by endocrinologists about the use of troglitazone, due to potential liver toxicity in the setting of HIV and its treatment. A similar, and safer, drug is currently pending FDA approval.

Treating FRS-Related Body Composition Changes

Dr. Schambelan also briefly reviewed currently available direct treatments for FRS. While treatment with recombinant human growth hormone (HGH, or Serostim) and anabolic steroids does work, cessation of treatment seems to result in recurrence. Surgery and liposuction of accessible fat (not visceral fat) are also followed by reaccumulation.

Christine Wahnke, MD, of Tufts University in Boston reported on the use of HGH in her study on antiretroviral effects on body composition. In her experience, women are more affected by body shape changes than men are. She studied 39 subjects (30 men, nine women) either self-referred or referred by their physicians for FRS. Ninety percent were taking protease inhibitors, 50% exercised at least 30 minutes three times per week, and 23% had a dorsocervical fat pad. Ten of the persons taking protease inhibitors (seven male, three female) also received HGH. These ten had a mean age of 41 years, a mean HIV RNA viral load of 96,000 copies/mL (50% undetectable), and had been diagnosed with HIV for a mean of seven years. After these subjects started HGH therapy, body mass index rose, waist-to-hip ratio fell, and mid-thigh circumference rose. Joint pains and muscle aches (2/10) resolved with every-other-day dosing. One person stopped treatment because of elevated glucose levels. Another subject who stopped treatment returned to baseline in all parameters two months after stopping. Similar reports of growth hormone success with body composition were offered by Stefan Mauss, MD, of Germany who showed reductions in visceral fat with HGH. Improvements reversed with cessation of treatment, requiring reinitiation of treatment.

Esteban Martinez, MD, of the Autonomous University of Barcelona, Spain, reported on the effects of changing a protease inhibitor drug combination in people with FRS to a combination based on nevirapine (Viramune). Twenty-three subjects (43% female) on a protease inhibitor and double nucleoside analog therapy were switched to nevirapine while maintaining the same double nucleoside drugs. Thirty-eight had been placed on a protease inhibitor combination as initial therapy. Most had mixed lipoatrophy (loss of fat from arms, legs, and/or face) and central obesity; no men had breast enlargement and no women had a dorsocervical fat pad. Some improvement has been seen. However, one subject has lost virologic control.

HIV-Related Wasting-New Problems, New Solutions

Several reports concerning body composition changes and wasting related to HIV were presented. Mary Romeyn, MD, and Julia Ireland, D.O. (Doctor of Osteopathy), reported on bone wasting in HIV positive men with CD4 cell count nadirs (lowest levels) less than or equal to 100 cells/mm3. Osteoporosis (bone wasting) was found in 40% and osteopenia (a reduction in bone volume) in an additional 45%, with normal bone density seen in only 3/20. In eight additional subjects with CD4 cell count nadirs greater than 100 cells/mm3, no normal subjects were found; 87% had osteopenia and 13% osteoporosis. Loss of bone mineral density did not appear related to protease inhibitor therapy or current use of anabolic therapies. The authors recommend bone density evaluations for all men with HIV who have had a documented episode of wasting or a CD4 cell count nadir of 100 cells/mm3 or less.

Janet Forrester of the Nutrition for Healthy Living Study at Tufts University looked at body composition changes during weight loss. In most of her cohort, fat and lean mass were lost proportionately, as reported by Dr. Mulligan and others in the era of HAART. Those with less than 15% body fat, however, lost lean mass preferentially. This suggests that a certain cushion of fat may be protective of lean working tissue. According to Forrester, "If you're going to be in the normal range, be in the top half," i.e., the normal range of body composition (fat-to-lean body mass ratio). She also recommends "saving 15% of body fat for a rainy day."

M. Keiserman of UCSF presented on a cohort of people with HIV who reported using marijuana for symptomatic relief. Self-prescribed marijuana use correlated more with gastrointestinal symptoms than with reduced appetite. No increase in body weight was seen in users over nonusers. Subjects used the drug especially when experiencing nausea and vomiting. People with more severe side effects were more likely to resort to treatment.

With regard to treatment for wasting, Cade Fields-Gardner, MS, RD, of NYU Medical Center reported on 136 male and female subjects treated with anabolic steroids, including testosterone, oxymetholone (Anadrol-50), and HGH. On serial measurements, these subjects demonstrated improved weight, more lean body mass, less fat, and a better symptom profile than those not receiving anabolics.

Dr. Romeyn and Nathan Gunn evaluated oxandrolone (Oxandrin) and progressive resistance exercise (PRE) for their relative contribution to the reversal of HIV-associated weight loss. In this pilot study oxandrolone alone was tested against oxandrolone and PRE, measuring increases in weight, body cell mass, and phase angle (an indicator of cell membrane integrity found to be a powerful prognostic indicator in HIV) at one and three months in stable HIV positive subjects. Weight, phase angle, and body cell mass increased in the oxandrolone-PRE arm, in keeping with the Strawford paper published in the April 14, 1999 issue of the Journal of the American Medical Association, which tested exercise alone against exercise and oxandrolone together. Unlike the Strawford protocol, this study had an oxandrolone-only arm as well as an oxandrolone-PRE arm. Subjects in the oxandrolone-only arm improved weight, BCM, and phase angle in the absence of PRE. This is a hopeful finding for those who can not use, and therefore benefit from, PRE.

Julian Gold, MD, of the Albion Street Centre in Sydney, Australia, reported on the use of nandrolone decanoate (Deca Durabolin) to treat HIV wasting. He sought to determine if anabolic effects might alleviate FRS and the fat and glucose metabolic abnormalities associated with the syndrome. (In addition, anabolic steroids are used in osteoporosis, as well as in muscle catabolism [building].) First, Dr. Gold gave nandrolone decanoate to the sickest people in his Australian practice. Lean body mass increased, total body weight increased, and capacity to function improved. Then Dr. Gold attempted a randomized, placebo-controlled study, but could not enroll the study because subjects were unwilling to risk a placebo arm. So they designed a study with HIV positive subjects experiencing 5-15% weight loss who were unable to gain weight by diet. All subjects received nandrolone at 50, 100, or 150 mg every two weeks for 24 weeks. Two hundred and twenty subjects were enrolled with a median weight loss of 9.8%. Eighty-seven percent and 53% completed 12 and 24 weeks, respectively. Subjects gained weight and increased body mass index. Depression and anxiety, self-reported in 40% at the onset of treatment, was not exacerbated. Short-term data show no exacerbation of lipid or glucose metabolic changes. While gains in the lower-dose groups were not significant, people taking the l50 mg dose showed highly significant gains in lean body mass and fat free mass.

Dr. Wahnke showed proportional increases in body cell mass and fat in subjects treated with both oxandrolone, an anabolic steroid, and medroxyprogesterone (Megace), an appetite enhancer which replaces primarily fat when used alone.

Oxymetholone, an anabolic steroid approved in the 1970s for critical anemia, was tested by U.R. Hengge of Germany for 14 months on subjects with HIV-associated wasting. Seventeen percent of subjects showed rises in liver function tests. Body mass index (not a reliable indicator of nutritional status) improved; changes in body cell mass were not reported.

Fields-Gardner also used oxymetholone, in combination with testosterone replacement, in HIV positive men over a 12-week period. Subjects were 32 hypogonadal (low-testosterone state) HIV positive men on stable testosterone replacement treatment for over three months. One had high transaminase (liver enzyme) levels, suggesting underlying liver disease. Two had diabetes and three had lipodystrophy at the onset of the study; three were also on growth hormone. Abnormal liver function tests on one person actually improved over the 12-week period. Weight and body cell mass increased in these people, who at baseline were at 100% of desired body weight and weight percentage according to figures drawn from The Cutting Edge's 3,500 subject database. Viral loads and CD4 cell counts were unaffected. The chart review did not show alterations in lipodystrophy. Oxymetholone, viewed with concern by many due to reported liver toxicity, was well-tolerated in this brief trial.

Nicholas Paton, MD, of Tan Toc Seng Hospital, Singapore, reported on an all-male study performed in the pre-protease inhibitor era to test the effect of growth hormone administration on acute wasting during acute opportunistic infection. Many HIV positive people and their health-care providers have been anxious to see such a study, since wasting is normally episodic and associated with periods of acute infection. It has been postulated that aggressive use of anabolic therapy during this critical window of inflammatory response might prove to be a powerful and relatively cost-effective use of such therapies.

In fact, Dr. Paton did report some protective effect against wasting with this treatment regimen. However, the study excluded subjects with many of the most rapid and severe causes of wasting in HIV (Mycobacterium avium complex [MAC], tuberculosis, or cytomegalovirus [CMV] diarrhea); it did not exclude other manifestations of CMV such as oral ulcers, which could mechanically affect oral intake; and it did not control for or even address the effects of use of prednisone-another stress-associated steroid thought to oppose growth hormone anabolic action-in Pneumocystis carinii pneumonia (PCP). In addition, women were excluded from the trial. "If I had included women in my study, the data would have been meaningless," noted the author.

Thus, while the question asked was an important one, flaws in study design limited its predictive value. Dr. Schambelan pointed out that a similar study had demonstrated twice the mortality (death rate) in the growth hormone arm. Dr. Schambelan also reminded delegates that an infection-associated trial of this nature was currently enrolling people-and welcoming women-at SFGH. For more information, call 415-206-3319.

Greg Coodley, MD, of the Oregon Health Sciences University in Portland presented on a study of prednisone and oxandrolone combinations. A 60-day course of prednisone at 10 mg per day was tested with oxandrolone to enhance appetite. Results were not significantly different from oxandrolone alone, and were measured not in body cell mass but in fat-free mass, which would mask expected prednisone-associated muscle wasting. Consideration of DEXA evaluation to determine effect on bone density, concerns about the risk of suppressing subjects' own stress steroid mechanism, and the fear of anticipated prednisone-associated immunosuppression or further activation of lipid and glucose abnormalities were not addressed or discussed by the investigator, despite strong comment from delegates present.

Nutrition and Pediatric HIV Infection

Several posters demonstrated marked improvement and normalization in growth parameters in children that were associated with the use of HAART.

According to A. Plebani of the University of Milan, Italy, blood levels of insulin-like growth factor (IGF-1), a hormone that mediates the effect of growth hormone, were associated inversely with viral load and positively with age. D.C. Duiculescu of the Victor Babes Hospital for Infectious Diseases in Bucharest, Romania, reported that the degree of severity of HIV infection in children is reflected in nutritional markers such as weight, height, and cachexia (severe wasting).

Barcellandi and an Argentinean team looked at children of HIV positive mothers. Those who were later found to have HIV infection had pronounced growth retardation and height and weight differences; children who seroreverted (were not in fact infected at birth, but only antibody-positive because of the mother's antibodies) had presented a normal growth pattern since birth.

Gail Shor-Posner, MD, of the University of Miami, Florida, reported informally on a study in process with HIV positive children in the Dominican Republic. She stated that selenium supplementation was positively associated with reductions in viral load. This result may be due to effects on the stop codon, a series of three sets of nucleosides that end transcription of the HIV protein and halt viral replication. Alternatively, it may be an indirect result of immune restoration.

Finally, Fields-Gardner reported on the Paul B. Michail Project Working Group of the Andrew Ziegler Foundation. Working with pediatric thought leaders from six U.S. epicenters, the group has developed a nationwide consensus on standard of nutritional care for children with HIV. Control of HIV and other infections, support of growth and development, and a proactive stance for avoidance of wasting were stressed by all regional groups. Prevention was found to be key, and long-term growth the primary endpoint. A team approach was recommended. Consensus recommendations will be confirmed by each regional working group, and field testing of the proposed model will begin within the year.

Mary Romeyn, MD, is Medical Director of the Andrew Ziegler Foundation, Assistant Clinical Professor of Medicine at UCSF, and the author of Nutrition and HIV: A New Model for Treatment, now in its second edition. She sits on the Scientific Advisory Committee of the San Francisco AIDS Foundation.

Nathan Gunn, MS, is a fourth-year medical student. He has published in the Journal of the American Medical Association on health care for the indigent, and presented research at the Third International Conference on Nutrition and HIV Infection.

Page last updated 5 October 1999