Therapeutic effects of nandrolone and testosterone in adult male HIV patients with AIDS wasting syndrome (AWS): a randomized, double-blind, placebo-controlled trial.

PURPOSE: We aimed to compare therapeutic effects of intramuscular (IM) nandrolone decanoate and IM testosterone enanthate in male HIV patients with AIDS wasting syndrome (AWS) with placebo control. METHODS: In this randomized, double-blind, placebo-controlled, 12-week trial, 104 patients with AWS who satisfied our inclusion criteria were randomly allotted in a 2:2:1 ratio to the 3 intervention groups: nandrolone, testosterone, and placebo. We administered 150 mg nandrolone and 250 mg testosterone (both IM, biweekly). The primary outcome measure was a comparison of absolute change in weight at 12 weeks between the nandrolone decanoate, testosterone, and placebo groups. RESULTS: Intent-to-treat analysis was done. The nandrolone group recorded maximum mean increase in weight (3.20 kg; post hoc P < .01 compared to placebo). Body mass index (BMI) of subjects in the nandrolone group had a significantly greater increase (mean = 1.28) compared to both testosterone (post hoc P < .05) and placebo (post hoc P < .01). Waist circumference and triceps skinfold thickness of patients on nandrolone showed similar results. Nandrolone also ensured a better quality of life. Patients with low testosterone level (<3 ng/mL) benefited immensely from nandrolone therapy, which increased their weight and BMI significantly compared to placebo (P < .05). CONCLUSION: Our trial demonstrates the superior therapeutic effects of nandrolone in male AWS patients, including the androgen deficient.

Is HIV-2- induced AIDS different from HIV-1-associated AIDS? Data from a West African clinic.

BACKGROUND: Although AIDS is less frequent following HIV-2 than HIV-1 infection, it is unclear whether the clinical picture and clinical course of AIDS are similar in the two infections. OBJECTIVES: To compare the pattern of AIDS-defining events, CD4 cell count at the time of AIDS diagnosis, survival from time of AIDS, and CD4 cell count near time of death in HIV-1 and HIV-2-infected patients. METHODS: Adult patients with AIDS who attended the clinics of the MRC in The Gambia were enrolled. AIDS was diagnosed according to the expanded World Health Organization case definition for AIDS surveillance (1994). RESULTS: Three hundred and forty-one AIDS patients with HIV-1 and 87 with HIV-2 infection were enrolled. The most common AIDS-defining events in both infections were the wasting syndrome and pulmonary tuberculosis. The median CD4 cell count at AIDS was 109 cells/microl in HIV-1 and 176 in HIV-2 (P = 0.01) and remained significantly higher in HIV-2 after adjustment for age and sex (P = 0.03). The median time to death was 6.3 months in HIV-1 and 12.6 months in HIV-2-infected patients (P = 0.03). In a multivariable analysis adjusting for age, sex and CD4 cell count, the mortality rates of HIV-1 and HIV-2-infected patients were similar (P = 0.25). The median CD4 cell count near time of death was 62 and 120 cells/microl in HIV-1 and HIV-2-infected patients, respectively (P = 0.02). CONCLUSIONS: HIV-2 patients have a higher CD4 cell count at the time of AIDS, and a longer survival after AIDS. The mortality after an AIDS diagnosis is more influenced by CD4 cell count than HIV type.

A locally produced nutritional supplement in community-based HIV and AIDS patients.

This study examined the potential effect of a nutritional supplement on the anthropometric profiles (body measurements such as body mass index [BMI], fat percentage and waist-hip ratio) of HIV-positive/AIDS patients and the correlation between anthropometric profile, CD4+T cell count and viral load. At baseline, of the 35 patients recruited into the study, 32 (94.1%) showed a fat percentage below normal range. Twenty-four of the patients (68.6%) had a BMI within normal range, while a greater percentage of the patients had a normal waist-hip ratio. Of the 28 patients that completed the study, 26 (96.3%) reported a fat percentage of below 18.5%. The results showed that 19 (67.9%) of the 28 patients had a BMI within the normal range after nutrient intervention. There was a significant positive correlation between the BMI and fat percentage. At the end of the study the CD4+T cell count showed no correlation with any of the anthropometric indices while the viral load showed a significant negative correlation with the lean body mass and BMI. The short duration of the study probably limited the positive trend of the supplement.

RANTES, MDC and SDF-1alpha, prevent the HIVgp120-induced food and water intake decrease in rats.

Human immunodeficiency virus (HIV)-wasting syndrome might be facilitated by the HIVgp120 affecting the immunological system. We studied the effect (subchronic administration: 5 days) of HIVgp120, and a few immune-response mediators: regulated upon activation normal T-cell expressed and presumably secreted (RANTES), stromal derived factor-1alpha (SDF-1alpha), macrophage-derived chemokine (MDC), and their combination, on food and water intake in rats, motor control and pain perception. Eighty male adult Wistar rats received an intracerebroventricular (icv) administration of: vehicle 5 microl/day or 0.92 nmol daily of HIVgp120IIIB, RANTES, SDF-1alpha, or MDC, and the combination of RANTES+HIVgp120IIIB, SDF-1alpha+HIVgp120IIIB, or MDC+HIVgp120IIIB. Food and water intake was measured every day during administration, and 24 and 48 h after the last administration. Rats were also weighed the first and the last day of experiment in order to detect the impact of these treatments in the body weight. HIVgp120IIIB significantly decreased food and water intake. These rats gain less weight than the control (vehicle) and chemokines-treated subjects with exception of those treated with SDF-1alpha that also gain less weight. In addition, HIVgp120 deteriorated motor control. HIVgp120IIIB effects on food and water intake, and motor control were prevented by these chemokines. HIVgp120+RANTES, HIVgp120+SDF-1alpha, and SDF-1alpha alone induced hyperalgesia. Results suggest an interaction between HIVgp120 and the chemokine system to generate the HIV-wasting syndrome, the motor abnormalities and changes in pain perception.

HIV-associated wasting in the era of highly active antiretroviral therapy: a syndrome of residual HIV infection in monocytes and macrophages?

Human immunodeficiency virus (HIV) infection in peripheral blood mononuclear cells (PBMCs) might be influencing the development of wasting in the era of potent antiretroviral therapy. In a retrospective study of 57 subjects, HIV proviral DNA levels in PBMCs were higher in subjects whose body weight decreased by >5% one year after initiation of highly active antiretroviral therapy, compared with subjects whose body weight was stable or increased (median HIV proviral DNA load, 8.9 vs. 0.9 copies/10(6) PBMCs; P = .006).

Effect of indinavir on HIV-related wasting.

OBJECTIVE: To study the effect of the protease inhibitor indinavir on body weight and body composition of subjects with HIV-related wasting. DESIGN: Prospective measurement of body weight in patients who had wasting and were treated with indinavir. A subgroup of 16 representative patients also underwent a metabolic study that included measurements of body composition (skinfolds and bioelectrical impedance) and food intake. Seven from this subgroup who did not have chronic diarrhoea also underwent indirect calorimetry for measurement of resting energy expenditure; the nine patients with wasting and chronic diarrhoea had measurements of faecal losses and intestinal permeability using the lactulose-mannitol test. SETTING: A tertiary care university hospital. PATIENTS: Two hundred and fourteen HIV-infected patients with wasting (less than 95% of usual body weight) had their body weight measured at day 0; 186 patients had a second body weight measurement within the first 100 days of treatment, and 160 patients were weighed a third time, at a median of 176 days. RESULTS: Body weight increased significantly (P < 0.0001) during treatment, whatever the degree of weight loss at baseline. After a median of 176 days on treatment, body weight had increased in 119 out of the 160 patients followed (74.4%; mean weight gain, 6.3+/-SD 3.8 kg; range, 1-18 kg), had not changed in 13 (8.1%) and had fallen in 28 (17.5%; mean weight loss, 4.2+/-3.0 kg; range, 1-12 kg), relative to baseline. Overall, 119 out of the 214 patients (55.6%) from the initial population gained weight. Fat mass, fat-free mass and body cell mass increased significantly in the 16 patients who underwent metabolic studies, together with energy, protein and lipid intake. In the patients with chronic diarrhoea, intestinal permeability improved but there was no change in intestinal losses. In patients who had wasting but not chronic diarrhoea, resting energy expenditure did not change significantly. Body weight changes correlated with changes in the CD4+ cell count (r = 0.882; P = 0.00001) and, to a lesser extent, with changes in the viral load (r = -0.466; P = 0.047). CONCLUSION: Indinavir significantly improved the nutritional status of these patients with HIV-related wasting.

Nutritional status of HIV-1 seropositive patients in the Free State Province of South Africa--laboratory parameters.

OBJECTIVE: To evaluate the nutritional status of HIV-1 seropositive patients with regards to laboratory parameters; the correlation between nutrient intake and actual values of nutrients, as well as the relationship between malnutrition and disease progression. DESIGN: A cross sectional study. SETTING: The Immunology Clinic at the Pelonomi Hospital in Bloemfontein, South Africa. SUBJECTS: 90 HIV/AIDS patients in different stages of disease were recruited consecutively from January to May 1995. Sixteen patients were followed up in 1997. MAIN OUTCOME MEASURES: The patients were divided into three groups according to their CD4+ T-cell counts, and blood levels of protein, albumin, cholesterol, ferritin, vitamin B12, magnesium, and phosphorus, as well as several micronutrients including vitamin E, vitamin C, beta-carotene and retinol which were determined using standard methods. These values were compared with the normal reference values used in the laboratory, and we tried to correlate these parameters with disease stage, as well as recorded nutrient intake in a subgroup of 35 patients. RESULTS: Abnormal values for several parameters, including plasma-retinol and serum-protein were found, but no correlation between more advanced disease and micronutrient deficiencies could be demonstrated. CONCLUSIONS: HIV/AIDS patients from this population are deficient in several micronutrients, and for some patients this is mirrored by a low intake. Multivitamin/anti-oxidant supplementation of HIV/AIDS patients should be considered, as this could lead to improved immune function in these patients.

Skeletal muscle involvement in human immunodeficiency virus (HIV)-infected patients in the era of highly active antiretroviral therapy (HAART).

Skeletal muscle involvement can occur at all stages of human immunodeficiency virus (HIV) infection, and may represent the first manifestation of the disease. Myopathies in HIV-infected patients are classified as follows: (1) HIV-associated myopathies and related conditions, including HIV polymyositis, inclusion-body myositis, nemaline myopathy, diffuse infiltrative lymphocytosis syndrome (DILS), HIV-wasting syndrome, vasculitic processes, myasthenic syndromes, and chronic fatigue; (2) muscle complications of antiretroviral therapy, including zidovudine and toxic mitochondrial myopathies related to other nucleoside-analogue reverse-transcriptase inhibitors (NRTIs), HIV-associated lipodystrophy syndrome, and immune restoration syndrome related to highly active antiretroviral therapy (HAART); (3) opportunistic infections and tumor infiltrations of skeletal muscle; and (4) rhabdomyolysis. Introduction of HAART has dramatically modified the natural history of HIV disease by controlling viral replication, but, in turn, lengthening of the survival of HIV-infected individuals has been associated with an increasing prevalence of iatrogenic conditions.

Levels of HIV RNA are quantitatively related to prior weight loss in HIV-associated wasting.

Thirty-three patients referred to a wasting clinic were evaluated to assess whether levels of HIV RNA were related to the magnitude of prior weight loss. Their median RNA level was 46,887 gene copies/ml (range, <200-510,070 gene copies/ml) at the time of referral. Patients had lost 10.5 +/- 6.4 kg over 461 +/- 304 days. RNA levels were correlated with the absolute amount and percentage of weight lost as well as the difference in body mass index (BMI) at the prior maximal and minimal recorded weights (r = 0.7, 0.67, 0.69; p = .0001 for the comparisons). The magnitude of these changes increased across strata of HIV RNA levels (p < or = .004), previously defined as associated with increasing risk for disease progression. The other parameter that could be associated with weight loss was the CD4 lymphocyte count (r = -0.43; p = .01). Low levels of testosterone and measures of body cell mass, fat free mass, or fat mass within 6 weeks of the RNA level could not be related to weight loss, change in BMI, or RNA levels. Thirty-two of the patients had chronic, relentless weight loss; in 15 of these subjects, no apparent secondary opportunistic complications were associated with weight loss or gastrointestinal symptoms to impair energy intake. Levels of HIV replication appear to be causally related to the magnitude of weight loss in some patients with wasting.

Myopathy and spontaneous Pasteurella pneumotropica-induced abscess formation in an HIV-1 transgenic mouse model.

In an effort to augment human immunodeficiency virus type 1 (HIV-1) gene expression in transgenic mice, an infectious proviral DNA clone was modified by deleting the two NF kappa B binding sites and some adjacent upstream LTR sequences and replacing them with the core enhancer of Moloney murine leukemia virus (MLV). Two independent lines of MLV/HIV transgenic mice were established that expressed HIV-1-specific RNA in lymphoid tissue, striated skeletal muscle, and the eye lens. Heterozygous animals from each transgenic line spontaneously developed an inflammatory disease of the eye associated with the production of copious amounts of purulent lacrimal secretions beginning at 2 weeks of age. Periorbital abscess formation became grossly apparent by 2 months of age and Pasteurella pneumotropica was cultured from the harderian glands and conjunctival surfaces of many of the MLV/HIV animals but not their nontransgenic, cohabiting littermates. This gram-negative commensal bacterium has been previously associated with a similar disease phenotype in immunocompromised (e.g., nude mice) rodent colonies. MLV/HIV mice developed normally until 15 weeks of age, when weight loss and wasting occurred, culminating in premature death (as earlier as 6 months of age). The cachexia was associated with an initially focal and subsequently progressive myopathy, coinciding with age-related increases of HIV gene expression in muscle.