This research entry is divided into the following sub-sections:

• Key research on wasting
• Dronabinol and octreotide
• Megestrol acetate
• Testosterone and steroids
• Other treatments
• Resistance exercise
• Wasting in the age of HAART
• References

Also see Treating body fat and metabolic changes in Anti-HIV therapy: Body fat and metabolic changes whilst on treatment and Human growth hormone in Drugs used by people with HIV for related research.

Key research on wasting

Beaugerie enrolled 116 people with chronic diarrhoea and undertook a range of clinical and nutritional investigations. Diarrhoea was attributed to infections such as cryptosporidia in 55% of cases; 45% had diarrhoea of unknown cause. The study found severity of weight loss was associated with low nutrient intake, and frequent episodes of diarrhoea. There was no significant correlation between weight loss and malabsorption.

Smith reports that specific pathogens can be isolated in the majority of people with gastrointestinal problems. Grohmann detected viruses in 35% of faecal specimens from 65 HIV-positive people with diarrhoea compared with only 12% of specimens taken at the same time from 65 HIV-positive people without diarrhoea. People with diarrhoea were more likely to have astrovirus, picobirnavirus, caliciviruses and adenoviruses. However, Ullrich suggest that abnormalities of the intestinal lining can also result from HIV infection itself.

Berger (1997) retrospectively reviewed 54 patients who commenced HAART and who had valid body weight and body cell mass measurements prior to commencing HAART. Mean follow-up was 117 days (range 28-417). 41/54 developed at least one AIDS-related illness after commencing HAART. Median viral load fall after commencing HAART was -0.46log and median CD4 increase was +16 cells. 30% of those diagnosed with one or more AIDS illness lost more than 0.5kg in body cell mass, compared with none of those who remained AIDS-free. 30% of those who experienced viral load falls also experienced reductions in body cell mass of more than 0.5kg. Ritonavir and saquinavir treatment were more strongly associated with weight loss than indinavir treatment.

Sharpstone (1999) reported a study of 104 HIV-infected men conducted between 1993-1995 before the introduction of protease-inhibitor therapy. Changes in nutritional status and metabolism were not significantly associated with disease progression, although there was a trend suggesting that weight loss is an independent predictor of progression. AIDS diagnosis was associated with a decrease in urinary sugars, increased energy expenditure when resting and fat oxidation.

Dronabinol and octreotide

Dronabinol has been approved in the USA as an appetite stimulant in AIDS patients with wasting. Olson enrolled 139 AIDS patients in a double-blind placebo-controlled study dose-ranging pilot trial. All patients were at least 2.3 kg below their ideal body weights and were free from intercurrent illness. Patients were randomized to receive dronabinol (2.5 mg twice daily) or placebo for six weeks, at which time all patients received dronabinol in an open-label extension of the study. After the randomized study, 50/72 dronabinol recipients and 38/67 placebo recipients were evaluable. Appetite (measured on a visual analogue scale) was significantly improved in the dronabinol group. Mean weight change was not significantly different between the groups (0.1 kg in the dronabinol group and -0.4 kg in the placebo group). At the end of the first month of the open-label extension study, 7/18 patients who had originally received dronabinol had gained 2 kg, compared to 2/17 patients who had originally received placebo . Although central nervous system (CNS) side-effects were common in the dronabinol group, adverse reactions requiring discontinuation of therapy were equally frequent in the two groups (5 on dronabinol and 4 on placebo).

Simon enrolled 129 people with AIDS and large volume diarrhoea in a placebo-controlled study of octreotide. During 3 weeks of blinded therapy, no significant differences were observed in the proportion of people in each group who experienced a 30% reduction in stool volume.

Compean enrolled 20 men with AIDS and large-volume refractory diarrhoea in a study comparing octreotide (100, 200 and 300 µg subcutaneously every 8 hours) with a control arm of standard anti-diarrhoea medication (high doses of loperamide and diphenyloxylate) plus placebo. Compared with the control group, after 10 days octreotide recipients experienced a significant reduction in mean bowel movements per day (2.1 versus 7) and mean stool volume (ml) per day (485 versus 1080). Complete response (stool volume less than 250 ml/day) was observed in 2 people in the octreotide group and none in the control arm; partial responses (greater than 50% reduction in stool volume) occurred in 4 and 2 respectively, and no response in 4 and 8 respectively. Side-effects occurred in /10 octreotide recipients and 3/10 controls, but the only side-effect that was more common in octreotide recipients was pain at the injection site, and none required discontinuation of treatment.

Cello enrolled 51 patients with HIV-related wasting in an open-label dose-escalating study of octreotide (50, 100, 250, 500 µg subcutaneously three times daily). 21/51 patients (41.2%) had a complete response (reduction in daily stool volume by 50% or reduction to below 250 ml per day). 14/21 responders (67%) had no identifiable pathogens at initial screening compared to 9/30 (30%) nonresponders. Reduction in stool volume from baseline was associated with doses higher than 50 µg. Side-effects included burning at injection site, nausea and vomiting.

Montaner treated 32 people with refractory AIDS-related diarrhoea with octreotide (100 µg subcutaneously three times daily, increasing to 250 µg after 7 days in non-responders). People who did not respond by 14 days were withdrawn. responders continued on the same dose for 21 days. Of 30 evaluable participants, 17 responded to treatment. A complete response was seen in 5 participants. Withdrawal of treatment in responders led to a significant increase in frequency and volume of bowel movements. Body weight remained stable during therapy.

Romeu treated 25 patients with chronic diarrhoea with octreotide (150 µg/day increased progressively at 48 hour intervals to 300, 750 and 1500 µg/day according to response). 10 patients (4 with Cryptosporidium enteritis, 5 without an identifiable pathogen and 1 with I.belli enteritis) achieved a complete response (40%) and 9 cases (all with cryptosporidial enteritis) had a partial response (36%). Patients with higher weight and Karnofsky status and non-cryptosporidial enteritis had a better response to treatment. 16/19 responders (84%) received doses of octreotide between 100 and 250 µg every 8 hours. Only 3 patients (15%) required 1500 µg/day to reach response (1 complete, 2 partial responses).

Human growth hormone

Koster randomized 60 people with AIDS wasting (median weight loss 17% from baseline, median CD4 count 21) into 4 groups: recombinant human growth hormone (rHGH) 1.4 mg/day subcutaneously; recombinant human Insulin-like Growth Factor type 1 (rhIGF) 5 mg twice daily subcutaneously; both hormones; or placebo for 12 weeks. After 6 weeks lean body mass had increased by 0.8 kg compared to placebo in each of the monotherapy treatment arms, and by 2.0 kg in the combination arm. Increase in lean body mass was accompanied by a decrease in body fat among participants receiving rhIGF, and was associated with significant improvement in health status on 7 of the 14 domains. No effects on muscle strength or immunological or virological parameters were seen. All hormone recipients experienced oedema.

Schambelan enrolled 178 people who had lost over 10% of their body weight, or whose weight was less than 90% of the ideal, in a placebo-controlled trial of human growth hormone (HGH) at a dose of 0.1 mg/kg/day for three months. The treated group experienced a significant and sustained average increase in weight (+3.0 kg), a greater average increase in lean body mass (+3 kg) and a significant average decrease in fat mass (-1.7 kg). The treatment also significantly improved participants' ability to exercise. No effects on CD4 counts, HIV p24 antigen levels, plasma HIV RNA levels, disease progression or survival were observed. Mild side-effects included abnormalities in blood tests and oedema.

Berger enrolled 115 people who had lost over 10% of their body weight, or whose weight was less than 90% of the ideal, in a placebo-controlled trial of human growth hormone (HGH) at a dose of 6 mg/day for 12 weeks. The treated group experienced a significant average increase in weight (+2.6 kg), although this was no longer statistically significantly greater than the placebo group by week 12. Pooled data from this and the above trial showed significant weight gain at both 6 and 12 weeks in the treated groups.

Krentz enrolled 10 patients in a double-blind randomized prospective trial of human recombinant growth hormone (2.5 or 5.0 mg subcutaneously every other day). Weight loss was reversed in 4/4 patients who completed the study. Weight gain was associated with increases in total body water, lean body mass and urinary nitrogen secretion/kg). Muscle strength and endurance also improved. All 4 patients lost weight again 6 weeks after completion of the study and termination of treatment.

Mulligan treated six men with HIV-related weight loss (mean loss of 19%) with a constant metabolic diet and rHGH (0.1 mg/kg/day for seven days). The men were hospitalized, as were six HIV-negative volunteers who served as controls. A mean body weight increase of 2.0 (+0.3 kg) was observed in the HIV-positive men compared with 1.6 +0.2 kg increase in the control group. Increases in protein anabolism and lipid oxidation were observed.

Lee randomised patients AIDS wasting to either low dose subcutaneous HGH (0.34mg twice a day for 21 weeks) plus insulin-like growth factor I or placebo. No significant increase in weight or strength occurred.

Waters also combined HGH (1.4 kg daily) with insulin-like growth factor 1 (5mg twice daily. Mean weight increase was 3.2kg in lean body mass but there was no overall weight or quality of life improvement.

Paton randomised 20 patients diagnosed with an acute opportunistic infection to rHGH or placebo. The rHGH group experienced significant increases in lean body mass during the 14 day course of treatment, suggesting that rHGH may exert a lean muscle sparing effect during acute infection and thus prevent weight loss during episodes of acute illness.

Schmitt-Rau reported successful maintenance of lean body mass gain up to two months after rHGH treatment ceased in 15 patients with >5% weight loss despite HAART. Participants gained an average 2kg over 12 weeks of treatment.

Torres reported total resolution of buffalo hump after 12 weeks of treatment in one patient, and 50% reduction in size of the hump in another patient. No significant alterations in LBM were seen.

For the effects of rHGH on body fat changes associated with anti-HIV therapies, see Treating body fat and metabolic changes in Anti-HIV therapy: Body fat and metabolic changes whilst on treatment and Human growth hormone in Drugs used by people with HIV: Anti-wasting treatments.

Megestrol acetate

Von Roenn enrolled 271 patients in a phase III randomized dose-ranging placebo-controlled trial of megestrol acetate (100 mg, 400 mg or 800 mg every day for 12 weeks). 270 and 195 were evaluable for safety and efficacy, respectively. Of those receiving 800 mg/day, 62.3% gained 5 pounds or more, compared with 25% of the placebo group. Recipients of 800 mg/day reported improvement in overall well-being and had an increase in mean weight gain, lean body mass, appetite grade and calorific intake compared with placebo recipients.

Oster enrolled 100 patients in a double-blind placebo-controlled trial of megestrol acetate (MA) (800 mg/day). MA recipients increased their daily calorific intake by 608 calories, versus an increase of 134 in the placebo group. People treated with MA had a mean body weight increase of 3.86 kg, compared with 0.46 kg decrease in the placebo group, and gained 3.68 kg in fat compared with a 0.28 kg loss. No statistically significant differences in body water, lean mass or survival were observed between the groups.

Johnston enrolled 89 people with CD4 counts below 200 and a weight loss of greater than 5% in a placebo-controlled study of megestrol acetate (320 mg/day for two weeks each month). After 6 months, treated people had a significant increase in tricipital skinfold thickness and quality of life, but other changes in nutritional parameters were not significant.

Tierney randomized people with AIDS with a greater than or equal to 10% weight loss to receive a daily dose of 100, 400 or 800 mg of megestrol acetate or placebo during a three month double-blind trial. 19/21 evaluable treated subjects gained weight (1.5 - 29 lbs), while those randomized to receive placebo continued to lose weight. The 2 treated subjects who lost weight had developed an oesophageal ulcer and histoplasmosis, respectively. Megestrol acetate was associated with significant weight gain with a linear dose response relationship. An increase in both lean body mass and body fat was detected using bioelectrical impedance analysis. Weight gain was associated with an increase in appetite and food intake. No improvements in CD3, CD4, CD8 counts or skin reactivity was seen. While Karnofsky scores did not change, improvement in perceived quality of life was associated with weight gain.

Graham enrolled 10 patients with HIV-related wasting in a pharmacokinetic evaluation study of a new suspension formulation of megestrol acetate 40 mg/ml. All patients received a single oral dose of 800 mg/day for 21 days. All patients reported an increase in appetite and 8/10 patients gained weight at three weeks.

Testosterone and steroids

Research into testosterone plus exercise are summarised under the sub-heading Resistance exercise below.

Grinspoon randomised 51 HIV-positive men with low testosterone levels to either 300mg of intramuscular testosterone enanthate injected every 3 weeks for 6 months, or placebo. The testosterone group gained fat-free mass (-0.6kg and 2.0kg), lean body mass (no change to 1.9kg) and muscle mass (-0.8 ad 2.4kg). There was no significant change in fat mass, weight, water content or exercise capacity between the groups. The men on testosterone reported feeling better, improved quality of life and improved appearance. A further 6 months of open label follow-up resulted in an 8% gain in LBM in the treatment group. Grinspoon (1999) updated results. At 12 months, the mean increase in lean body mass was 3.7 kg. Hemocrit also increased by 3.5%.

Gold treated 24 men with AIDS wasting who had not gained weight after standard strategies were tried. 17 men completed 16 weeks of treatment with nandrolone decanoate (100mg/ml) intramuscular injection every 2 weeks. Mean weight gain was 0.14kg per week and mean lean body mass gain was 3 kg. Quality of life improved and no side-effects were reported.

Fisher found that men with wasting gained an average of 1.8kg after 14 weeks treatment with 15mg oxandrolone per day. Men on placebo gained 0.7kg. Low dose oxandrolone (5mg per day) did not produce an increase in weight.

Berger (1996) conducted an open label study of oxandrolone (12mg per day) in men with HIV-related weight loss. After 12 months, mean weight increase was 5.2 kg and body cell mass increase was 3.5kg.

Miller conducted a pilot study of transdermal testosterone in women (150 or 300ug per day). The lower dose produced normalised testosterone levels, a mean weight gain of 1.9kg and improved quality of life. Weight gain in the placebo group was 0.6kg. The higher dose did not produce significant results. No masculinisation was seen in the women on testosterone.

Coodley randomised 39 patients with weight loss of more than 5% to receive oxandrolone and prednisone or oxandrolone alone or placebo. After 60 days the oxandrolone and prednisone group had gained 7.4lbs, compared to weight gain of 3.2lbs in the oxandrolone group and weight loss of 1.6lbs in the placebo group. The difference between oxandrolone and oxandrolone/prednisone groups was not significant.

Coodley demonstrated markedly lower testosterone levels in people with AIDS who had wasting syndrome as compared with people who had similar CD4 counts but no wasting. Testosterone replacement may be a potential treatment for people with HIV-associated wasting. Jekot suggested that anabolic steroids may have a role in the treatment of AIDS-related weight loss.

Romeyn reported on the additive effect of progressive resistance exercise (PRE) in a group of HIV-positive individuals with wasting syndrome who were receiving oxandrolone. They were randomised to receive oxandrolone alone or to engage in a programme of PRE (3 x 1hr per week). Those randomised to PRE gained an average of 8.7lbs after three months, compared to 6.1 lbs in the oxandrolone alone group.

Bucher reported on the safety of nandrolone decanoate in 70 HIV-positive volunteers in a 12 week randomised, controlled study. There were no detrimental effects on CD4 or CD8 counts or on HIV RNA levels. Haemoglobin and haematocrit levels were significantly increased in the treatment group.

Hengge tested a synthetic anabolic steroid, oxymetholone, in a thirty week unblinded, randomised study alone or in combination with ketitofen, a TNF inhibitor. Those who received oxymetholone alone gained an average 14.5% of baseline body weight, compared with 10.9% in the combination group and a loss of 1-2% in the untreated control group. Peak weight was reached after approximately 20 weeks. No adverse effects were reported.

Hengge conducted a randomised, placebo controlled phase III study of oxymetholone. A total of 89 patients (79 men and 10 women: 69 gay/bisexual men, 12 intravenous drug users, 7 heterosexual contact, one transfusion recipient) were enrolled. Patients were randomised to receive either 100mg/day twice daily (BID) or 150mg/day three times daily (TID) or placebo for 16 weeks. Patients in the placebo group gained 1.0 kg compared to 3.0kg among those receiving therapy three times daily and 3.5kg among those receiving therapy twice daily. Seventeen patients (19%) discontinued treatment during the double-blind phase of the study. Two patients in the oxymetholone TID arm discontinued due to elevated liver enzymes. 35% of patients in the TID arm, 27% of patients in the BID arm and no patients in the placebo group had a greater than five times baseline increase for alanine aminotransferase during the double-blind phase of the study.

Poles reported on twenty-one people with HIV-related weight loss who took 10 mg oxandrolone orally twice a day. Analysis showed significant increases in body cell mass, intracellular water and body fat sustained after 12 months of treatment with oxandrolone. It was used concomitantly with anti-viral therapy. For 19 people who took oxandrolone for 30 days, the mean body weight increase was 6.5lb and for the 6 people who took oxandrolone for 12 months the mean increase was 20.5lb.

Bhasin randomised 43 HIV-negative men to receive testosterone enanthate or a placebo, and further randomised the two groups to perform resistance exercise or no resistance exercise. Participants received ten weeks of treatment and were followed for a total of 30 weeks. All participants ate a high protein diet matched for body weight. The testosterone plus exercise group gained an average of 13.5 lbs compared with an average of 4 lbs in the placebo plus exercise group. The testosterone-only group gained an average of 7 lb. There were no statistically significant effects on mood.

Fraser treated eight people with low testosterone levels and weight loss of more than 10% from baseline with Sustanon, an oral form of testosterone. Patients were treated for eight weeks and showed an average weight gain of 3.6 kg in lean body mass, with a proportional decrease in total body fat. No significant adverse effects were observed. Gold reported a virtually identical average weight gain in nine patients unable to regain weight despite nutritional intervention, subsequently treated with 100 mg nandrolone decanoate intravenously for 16 weeks alongside a course of resistance exercise.

Other treatments

Tierney treated 9 HIV-positive patients with chronic diarrhoea and no enteric pathogens with mesalamine (6 g/day orally). Diarrhoeal symptoms improved in 7/9 patients, and rectal p24 content was significantly reduced over 2 months. No side-effects were reported.

Reyes-Teran enrolled 28 people who had lost at least 10% of their body weight during the last 6 months in a 12-week placebo-controlled trial of thalidomide (400 mg four times a day). Although no differences in CD4 count or viral load could be seen, 8/14 thalidomide recipients had weight gain versus 1/14 in the placebo group. Treated participants had significantly higher Karnofsky scores than placebo recipients at the end of the study. 11/14 thalidomide recipients developed mild and transient somnolence and 11/14 developed erythematosus macular lesions.

Shabert reported a 12 week study of glutamine as a treatment for AIDS wasting. 40 mg glutamine per day produced a mean body cell mass increase of 1.7 k compared with 0.4kg in the placebo group.

Klausner randomised 39 people with HIV-associated wasting, with or without concomitant infection with tuberculosis, to receive 21 days treatment with thalidomide or placebo. 32 participants completed the study. In participants co-infected with HIV and TB, thalidomide was associated with a decrease in both plasma TNF-alpha levels and HIV levels. No significant reduction in TNF-alpha or HIV levels was seen among participants who had HIV only. Treated people experienced significant weight gain (mean 6.5%) compared with placebo recipients during the study period; participants co-infected with HIV and tuberculosis experienced a higher mean weight gain than those with HIV only.

Couderc treated three people with AIDS and wasting with open-label thalidomide 100 mg daily. The three patients all gained weight (mean gain of 5 kg within three weeks) and had reduced constitutional symptoms. No changes in CD4 counts or serum TNF-alpha levels were observed. No adverse reactions were noted.

Landman treated five people with AIDS-related wasting with pentoxifylline (400 mg three times daily). The rationale for the treatment was based on pentoxifylline's anti-TNF-alpha activity; TNF-alpha may a role in the pathogenesis of AIDS wasting. 3/5 patients had elevated serum TNF-alpha levels. No significant weight gain was observed in any of the patients. In the two patients without elevated TNF-alpha, continued to lose weight and also developed bacterial pneumonia within 3 weeks of starting therapy.

Melchior enrolled 31 malnourished and severely immunosuppressed individuals in a two-month study comparing total parenteral nutrition versus dietary counselling. TPN recipients gained 8 kg, compared with a 3 kg weight loss in the control group. Lean body mass increased 9% and decreased 5% in the two groups respectively.

Resistance exercise

Corcoran randomised 54 eugonadal men with AIDS wasting to testosterone (200 mg/week) or placebo and to resistance training (3 times a week for 12 weeks) or no resistance training. Lean body mass (LBM), arm muscle area (AMA) and leg muscle area (LMA) increased significantly in all treatment arms, while weight increased and fat decreased in the testosterone groups. The combined exercise/testosterone arm was superior in terms of LBM increase, AMA and LMA where the increases were +4.6 kg, +15 mm² %, +9.9mm² % compared with +4.2 kg, +9.6 mm² and +8.4 mm² in the testosterone alone group and +2.3 kg, +7.8mm² and +5.9mm² in the exercise alone group.

Bhasin studied 61 HIV-positive men whose body weight had declined by more than 5% in the previous 6 months, and who had low serum testosterone levels (< 12.1 nmol/L (349 ng/dL). The men were randomly assigned to receive either 100mg testosterone enanthate weekly as an intramuscular injection or a placebo injection. They were also randomly assigned to a programme of resistance exercise or to maintain their normal activity levels. Daily food intake was standardised for all four groups at 1.5g of protein per kg of body weight and 40kcal per kg of body weight, a diet very high in protein and carbohydrates. After 16 weeks, muscle strength had improved by 20-30% in all groups apart from the placebo group, and this improvement was statistically significant. Weight and muscle changes in each group were: placebo/no exercise -0.5kg (not significant) and +0.9 (ns); exercise alone +2.2kg and +2.1kg; testosterone alone +2.6kg and +2.3kg; testosterone and exercise +0.7kg (ns) and +2.6kg. The authors could not explain why the testosterone and exercise group failed to perform better than the exercise alone or testosterone alone group, despite the expected additive effect of combining the two interventions.

Roubenoff enrolled 25 HIV-infected adults into a study of highly intensive progressive resistance training (PRT) for 8 weeks. Lean body mass increased by an average of 1.75kg. Fat declined by an average of 0.92kg. Strength also increased. These changes were statistically significant. Two months after completion of the study, those who continued training had a mean lean mass increase of 1.1kg compared with an increase of 0.28kg among those who did not continue to exercise.

Sattler randomised 30 HIV-infected men with CD4 counts below 400 to a once-weekly injection of nandrolone decanoate or progressive resistance training. After 12 weeks, total body weight increased significantly in both groups (3.2 kg and 4 kg, respectively). Lean body mass increased significantly more in the resistance training group (3.9 vs. 5.2 kg, respectively p = 0.03). Body cell mass increased significantly in both groups. Strength increased from 10-31% in the nandrolone group and from 14-53% in the resistance training group with significantly greater gains in the resistance training group.

Strawford (1999b) randomised 24 HIV-infected men with weight loss (mean 9% body weight)and testosterone between 7.8-31.2 nmol/L. All had been on stable antiretroviral therapy for at least 3 months with 13 of 24 on PI therapy. All participants received progressive resistance exercise (PRE) plus intramuscular testosterone (100mg/week) to suppress endogenous testosterone production. Participants were randomised to either oxandrolone, 20 mg per day or placebo for 8 weeks, and followed for a further 12 weeks. Both groups had significant weight gain, with a significantly greater gain in the oxandrolone group (6.7kg vs 4.2kg). Both groups had a significant increase in lean body mass (LBM), with the oxandrolone group having a significantly greater increase (6.8kg vs 3.8kg). This study found that low dose testosterone plus anabolic steroid safe and effective at improving weight and LBM in men with HIV wasting. In the same edition of JAMA, Johansen reported that nandrolone decanoate increased LBM in people on dialysis.

Strawford (1999a) randomised 18 men with AIDS wasting syndrome and serum testosterone less than 500ng/dl to receive either placebo (n=7), 65mg/week (n = 4) or 200mg/week (n=7) of nandrolone decanoate for 21 days. Nitrogen retention was measured on an in-patient basis; both low dose and high dose nandrolone decanoate was associated with improved nitrogen retention, whilst the placebo group experienced nitrogen loss. In ten people who completed a 12 week open label phase lean body mass increased by 3.1kg(+/-0.5kg), and treadmill exercise performance improved, indicating improved muscle strength

Wasting in the age of HAART

Schwenk reviewed data on 112 people protease inhibitors from April 1996 and August 1997. Weight gain was not significant in this time but body cell mass increased by 3.3kg. The prevalence of malnutrition was significantly reduced. Other weight and mass measurements showed improvements over this period.

Raghavan analysed data on 262 men from CPCRA 036 at baseline, 4 months and 8 months. 85 men had a viral load reduction of over 1 log at eight months and their mean percentage weight change was 1.18kg.

Tang (2002) monitored a group of 552 people with HIV at six-monthly intervals between 1995 and 2000. At baseline the study population had an average CD4 count of 352 cells/mm³, and mean viral load was a little under 80,000 copies/mL. The average age was 40 and 56% of the cohort were men, 32% had experience of IV drugs and 28% were women. Two thirds of the study population had an AIDS-defining illness at baseline. HAART was being used by 44% (210) of participants when they entered the study and was started by an additional 216 people during follow-up. Excluded from the study were people with cancers (other than KS), diabetes and thyroid problems. In order to assess their value in predicting mortality, measurements to assess fat-free mass, body cell mass and fat mass were also taken. Wasting was divided into four categories: up to 3% of body weight; 3% to 4%; 5% to 9% and 10% or above of body weight (an AIDS-defining condition). Over the five years of the study, 40 people died from HIV-related conditions. Investigators found that even when HAART usage was taken into account and adjustments were made for CD4 count, social status and drug use, wasting remained a strong predictor of an increased risk of death. In particular, the investigators further found that weight loss of at least 5% over six months or 3% from baseline is significant enough to predict poor prognosis. Fat-free mass, body cell mass or fat mass was of no added prognostic value.

For discussion of body fat changes and metabolic disorders associated with anti-HIV treatments, see Treating body fat and metabolic changes in Anti-HIV therapy: Body fat and metabolic changes whilst on treatment.