Human Immunodeficiency Virus Infection and Male Hypogonadism: A Review.

Hypogonadism is a common complication among HIV infected patients. The prevalence of hypogonadism is 30 to 50% in HIV infected men with wasting syndrome and 20 to 25% in those without wasting syndrome. HIV infection affects the entire hypothalamus-pituitary-gonadal axis via both direct and indirect effects, which are defined in four categories, 1) direct effect of HIV particles, 2) opportunistic infections, 3) HIV-related malignancy and its treatment, and 4) medications that are used for HIV infection or its opportunistic infection. The association between HIV infection, hypogonadism, and cardiovascular diseases has yet to be determined; however, there are data that HIV infection and its treatment, particularly protease inhibitors, worsened the metabolic profiles, which were surrogate markers of cardiovascular diseases. Considerably more attention should be paid to the diagnosis of hypogonadism in this group particularly because HIV infection increases both sex hormone-binding globulin and total testosterone level. Testosterone replacement shows benefits on mood, body composition, and seems to benefit the metabolic profile in HIV infected men with low body mass index.

A Case of Hypercalcemia and Overexpression of CYP27B1 in Skeletal Muscle Lesions in a Patient with HIV Infection After Cosmetic Injections with Polymethylmethacrylate (PMMA) for Wasting.

Foreign body-induced granuloma is an uncommon yet clinically significant cause of hypercalcemia. The molecular mechanisms are uncertain, although extrarenal calcitriol production has been proposed. We describe severe hypercalcemia associated with increased levels of plasma calcitriol in a patient with HIV and local granulomatous reaction 5 years after injection of polymethylmethacrylate (PMMA) as dermal filler for cosmetic body sculpting. Extensive evaluation revealed no identifiable cause of increased calcitriol levels. Nuclear imaging was remarkable for diffuse uptake in the subcutaneous tissues of the buttocks. Subsequent muscle biopsy and immunohistochemical staining showed strong local expression of CYP27B1 within histiocytes surrounding globules of PMMA. This case highlights an unfortunate complication of dermal fillers and shows that inflammatory cells can express high levels of CYP27B1 even without frank granulomas. The growing trend of body contour enhancement using injectable fillers should raise suspicion for this cause of hypercalcemia in clinical practice. Patients with HIV who receive this treatment for lipodystrophy or other cosmetic purposes may have increased susceptibility to hypercalcemia in the setting of underlying chronic inflammation. This may be a concern when changing anti-retroviral therapy, since alterations in levels of HIV viremia may initiate or contribute to worsening hypercalcemia.

The effects of an ActRIIb receptor Fc fusion protein ligand trap in juvenile simian immunodeficiency virus-infected rhesus macaques.

There are no approved therapies for muscle wasting in children infected with human immunodeficiency virus (HIV), which portends poor disease outcomes. To determine whether a soluble ActRIIb receptor Fc fusion protein (ActRIIB.Fc), a ligand trap for TGF-ß/activin family members including myostatin, can prevent or restore loss of lean body mass and body weight in simian immunodeficiency virus (SIV)-infected juvenile rhesus macaques (Macaca mulatta). Fourteen pair-housed, juvenile male rhesus macaques were inoculated with SIVmac239 and, 4 wk postinoculation (WPI) treated with intramuscular injections of 10 mg ⋅ kg(-1) ⋅ wk(-1) ActRIIB.Fc or saline placebo. Body weight, lean body mass, SIV titers, and somatometric measurements were assessed monthly for 16 wk. Age-matched SIV-infected rhesus macaques were injected with saline. Intervention groups did not differ at baseline. Gains in lean mass were significantly greater in the ActRIIB.Fc group than in the placebo group (P < 0.001). Administration of ActRIIB.Fc was associated with greater gains in body weight (P = 0.01) and upper arm circumference than placebo. Serum CD4(+) T-lymphocyte counts and SIV copy numbers did not differ between groups. Administration of ActRIIB.Fc was associated with higher muscle expression of myostatin than placebo. ActRIIB.Fc effectively blocked and reversed loss of body weight, lean mass, and fat mass in juvenile SIV-infected rhesus macaques.

Tuberculosis: características epidemiológicas en un hospital tipo IV / Tuberculosis: epidemiological characteristics in a type IV hospital

La tuberculosis (TB) es un problema de salud pública. Analizar la epidemiologia de la tuberculosis en los últimos 10 años. Se diseñó un estudio de casos, descriptivo y analítico, observacional, transversal y retrospectivo en una muestra no probabilística, que incluye 100% de las historias de pacientes mayores de 14 años de edad, de cualquier sexo, con diagnóstico de TB en cualquiera de sus formas clínicas, atendidos en el Hospital General del Oeste, Dr. José Gregorio Hernández, de Caracas, durante el periodo comprendido entre enero de 2004 y diciembre 2013, divididos en dos grupos de 5 años consecutivos denominados A y B. Se analizaron 475 historias médicas, correspondientes a 241 pacientes del grupo A y 234 del B. La edad promedio del grupo total fue 38,97 ± 15,97 con un predominio del género masculino en 60.6%. La mayor parte de la muestra fueron personas que provienen de Caracas en ambos grupos. El estrato socioeconómico fue predominantemente IV de la clasificación de Graffar y representó el 41% en el grupo A y a 73,9% en el B con diferencia estadísticamente significativa. Se identificaron14, 1% y 19,7% de pacientes con enfermedad relacionada con el VIH en los Grupos A y B. Pocos sujetos tenían enfermedades debilitantes crónicas predisponentes y la más importante fue la desnutrición que duplicó la frecuencia en el grupo B (26,5%) vs (12%) en el A , estadísticamente significativa. La radiología de tórax fue el método más utilizado. En el Grupo A recibieron Prueba Terapéutica 52 pacientes mientras que en grupo B, 70. El grupo representó tuberculosis pulmonar en 71,78% para el grupo A y 68,37% para el B: el resto fue en diversas localizaciones extra pulmonares donde predominaron la pleura y los ganglios. Se cumplió la meta terapéutica en 77,1% de grupo A y 80.36% del grupo B y los restantes en ambos grupos correspondieron al abandono de tratamiento o fallecimiento. La desnutrición fue muy importante en el grupo de estudio reciente y el VIH se mantuvo...

Tuberculosis is a public health problem. To analyze the epidemiology of tuberculosis in the last 10 years. A case study, descriptive and analytical, observational, cross-sectional and retrospective in a non random sample, which includes 100% of the records of patients over 14 years of age, of any gender, diagnosed with TB in any one of its clinical forms, treated in the Hospital Dr. José Gregorio Hernández, Caracas, during the period between January 2004 and December 2013 divided in two groups of 4 consecutive years called A and B. 475 medical records were analyzed corresponding to 241 patients in group A and 234 in B. The average age of the total group was 38.97 ± 15.97 with a predominance of the male gender in 60.6%. The majority of the sample belonged to people coming from Caracas in both groups. Socioeconomic level classification Graffar IV was predominant and accounted for 41% in group A and 73.9% in group B with significant statistical difference. 14.1% and 19.7% of patients were identified with HIV-related in Groups A and B. Few patients had chronic debilitating diseases and malnutrition was the most important and it doubled its frequency in group B (26.5%) vs (12%) with a statistically significant difference. The chest x-ray was the most used method. In Group A, 52 patients received therapeutic test while in group B were 70. The group accounted for pulmonary tuberculosis in 71.78% in group A and 68.37% for the B: the rest were in various extrapulmonary sites where it dominated in pleura and ganglia. The therapeutic goal was fulfilled in 77, 1% of group A and 80, 36% in group B and the rest in both groups corresponded to treatment abandonment or death. Malnutrition was very important in the second study group and HIV remained with similar frequency in both groups

Wasting among Uganda men with pulmonary tuberculosis is associated with linear regain in lean tissue mass during and after treatment in contrast to women with wasting who regain fat tissue mass: prospective cohort study.

BACKGROUND: Nutritional changes during and after tuberculosis treatment have not been well described. We therefore determined the effect of wasting on rate of mean change in lean tissue and fat mass as measured by bioelectrical impedance analysis (BIA), and mean change in body mass index (BMI) during and after tuberculosis treatment. METHODS: In a prospective cohort study of 717 adult patients, BMI and height-normalized indices of lean tissue (LMI) and fat mass (FMI) as measured by BIA were assessed at baseline, 3, 12, and 24 months. RESULTS: Men with wasting at baseline regained LMI at a greater rate than FMI (4.55 kg/m2 (95% confidence interval (CI): 1.26, 7.83 versus 3.16 (95% CI: 0.80, 5.52)) per month, respectively during initial tuberculosis therapy. In contrast, women with wasting regained FMI at greater rate than LMI (3.55 kg/m2 (95% CI: 0.40, 6.70) versus 2.07 (95% CI: -0.74, 4.88)), respectively. Men with wasting regained BMI at a rate of 6.45 kg/m2 (95% CI: 3.02, 9.87) in the first three months whereas women, had a rate of 3.30 kg/m2 (95% CI: -0.11, 6.72). There were minimal changes in body composition after month 3 and during months 12 to 24. CONCLUSION: Wasted tuberculosis patients regain weight with treatment but the type of gain differs by gender and patients may remain underweight after the initial phase of treatment.

The CD4:CD8 ratio is associated with markers of age-associated disease in virally suppressed HIV-infected patients with immunological recovery.

OBJECTIVES: Inversion of the CD4:CD8 ratio (< 1) has been identified as a hallmark of inmmunosenescence and an independent predictor of mortality in the general population. We aimed to assess the association between the CD4:CD8 ratio and markers of age-associated disease in treated HIV-infected patients with good immunovirological response. METHODS: A cross-sectional analysis was conducted in 132 HIV-infected adults on antiretroviral therapy (ART), with plasma HIV RNA < 50 HIV-1 RNA copies/mL for at least 1 year, CD4 count > 350 cells/µL and age < 65 years. We analysed the associations between the CD4:CD8 ratio and subclinical atherosclerosis [assessed using carotid intima-media thickness (IMT)], arterial stiffness [assessed using the augmentation index (AIx)], the estimated glomerular filtration rate (eGFR), muscle wasting and sarcopenia [assessed using appendicular lean mass/height(2) (ALM) measured by dual-energy X-ray absorptiometry (DEXA)]. RESULTS: CD4:CD8 ratio inversion was associated with higher IMT, lower eGFR and lower ALM (all values P < 0.05), but not with AIx. In multivariate analyses adjusted for age, sex, hypertriglyceridaemia, tobacco use and cumulative ART exposure, inversion of the CD4:CD8 ratio was independently associated with higher IMT [odds ratio (OR) 2.9; 95% confidence interval (CI) 1.2-7.1], arterial stiffness (OR 4.8; 95% CI 1.0-23.5) and lower eGFR (OR 5.2; 95% CI 1.0-64.4), but not sarcopenia (OR 0.7; 95% CI 0.2-2.7). These associations persisted when models were applied to subjects with nadir CD4 counts > 200 cells/µL and those with CD4 counts > 500 cells/µL. CONCLUSIONS: The CD4:CD8 ratio in treated HIV-infected subjects with good immunovirological response is independently associated with markers of age-associated disease. Hence, it might be a clinically useful predictor of non-AIDS-defining conditions.

Prevalencia de Encephalitozoon intestinalis y Enterocytozoon bieneusi en pacientes VIH positivos de Maracaibo, Venezuela / Prevalence of Encephalitozoon intestinalis and Enterocytozoon bieneusi in HIV positive patients to Maracaibo, Venezuela

Los microsporidios pueden provocar infecciones emergentes y oportunistas en individuos inmunocomprometidos de todo el mundo. Se realizó éste estudio para identificar las especies de microsporidios intestinales presentes en pacientes con VIH-SIDA del Servicio Autónomo Hospital Universitario de Maracaibo (SAHUM). Se recolectaron 50 muestras fecales de individuos con diagnóstico confirmado de VIH durante los años 2007-2008; se obtuvieron las cifras de CD4 de solo 42 pacientes. Las muestras se analizaron mediante PCR separadas para la identificación de Encephalitozoon intestinalis y Enterocytozoon bieneusi. Las especies de microsporidios presentaron un 36% de prevalencia, 10 pacientes presentaron Encephalitozoon intestinalis, 4 Enterocytozoon bieneusi y 4 ambas especies. Se determinó una relación inversamente proporcional y estadísticamente significativa entre el contaje de CD4 y la presencia de microsporidios en la muestra fecal. Es destacable la elevada prevalencia de especies de microsporidios observada en los pacientes VIH estudiados, donde predominó E. intestinalis.

Microsporidioses are considered emerging and opportunistic infections in immunocompromised individuals worldwide. The purpose of this study was to identify the species of intestinal microsporidia in patients with HIV-AIDS from the Servicio Autónomo Hospital Universitario de Maracaibo, Venezuela (SAHUM). Fecal samples were collected from 50 patients with confirmed diagnosis of HIV, during the years 2007 and 2008; the CD4 values were obtained from 42 patients. The samples were analyzed by separate PCRs to identify Encephalitozoon intestinalis and Enterocytozoon bieneusi. Microsporidia species showed a 36% prevalence: ten patients had Encephalitozoon intestinalis, four Enterocytozoon bieneusi and four both species. An inverse and statistically significant relationship between the CD4 count and the presence of microsporidia in the fecal sample was also found. It is remarkable the high prevalence of microsporidia species observed in the HIV patients studied, with a predominance of E. intestinalis.

Declining incidence of AIDS-defining opportunistic illnesses: results from 16 years of population-based AIDS surveillance.

OBJECTIVE: To measure the incidence and risk factors of AIDS-defining opportunistic illnesses (AOIs) in the pre-highly active antiretroviral therapy (HAART) (1993-1995), early-HAART (1996-2000), and late-HAART (2001-2008) periods. DESIGN: Prospective cohort analysis of AIDS surveillance data. METHODS: Individuals living with, or diagnosed with AIDS from 1993 through 2008 were included. Poisson regression models were used to estimate annual incidence rates of the eight most frequently occurring AOIs, and to compare these rates in the pre-HAART (1993-1995), early-HAART (1996-2000), and late-HAART (2001-2008) periods. RESULTS: There were 18 733 individuals with AIDS included; 5788 were diagnosed prior to 1993 and 12 945 were diagnosed between 1 January 1993 and 31 December 2008. The incidence rates of Pneumocystis jiroveci pneumonia, wasting syndrome, Kaposi's sarcoma, HIV encephalopathy, cytomegalovirus retinitis, cytomegalovirus, and esophageal candidiasis decreased during the study period, with the largest declines observed between the pre-HAART and early-HAART periods. Incidence rates also decreased between the early-HAART and late-HAART periods, though not as sharply. Incidence rate reductions between the earliest and latest period ranged from 84 to 99%. CONCLUSIONS: Steep declines in incidence of AOIs were found following the introduction of HAART and continued into the late-HAART era. These declines reflect the impact of HIV diagnosis and treatment on a population level.

Genital microsporidiosis in women with AIDS: a post-mortem study.

BACKGROUND: Microsporidiosis is a life threatening opportunistic infection of AIDS patients. The infection is usually restricted to specific anatomical areas, but could become systemic depending on the involved species. Genital microsporidiosis in female patients is rare. OBJECTIVE: To report genital microsporidiosis in female AIDS patients. METHODS: Tissues samples from the genital tract (ovary, fallopian tubes and uterus) of eight deceased women who died of wasting syndrome associated to AIDS and disseminated microsporidiosis at the Institute of Tropical Medicine Pedro Kourí were collected between 1997 and 2005. Using an indirect immunohistochemistry assay the microsporidia species involved in those cases were identified. RESULTS: We report several cases of microsporidial infection of the female genital tract. Six out of eight women with the disseminated form of the disease showed the presence of microsporidia in the genital tract. Encephalitozoon cuniculi and Encephalitozoon hellem were identified in the internal lining epithelium of the fallopian tubes and endometrium. CONCLUSIONS: Microsporidia species could disseminate to other organs and become systemic in severe immunocompromised cases. To our knowledge this is the greatest number of female genital tract microsporidiosis cases so far reported in humans.

Global nutrition policy review: What does it take to scale up nutrition action?

Este informe presenta los actuales desafíos globales de nutrición, sobre la base de datos de diversas fuentes, incluyendo bases de datos existentes de nutrición mundiales de la OMS está administrado por el Departamento de Nutrición para la Salud y el Desarrollo, los métodos y los principales resultados de la Revisión de la Política Global de Nutrición, mostrando el alcance de la política y la ejecución de los programas y la gestión nutricional en 119 Estados Miembros de la OMS y 4 territorios que proporciona respuestas , las conclusiones sumarias y el camino a seguir. Aunque los países tienen diferentes preocupaciones nutricionales, algunas intervenciones son relevantes a nivel mundial; por ejemplo, los que se ocupan de la "ventana de oportunidad" desde el embarazo hasta los 2 años de edad, como la lactancia materna óptima y las prácticas adecuadas de alimentación complementaria. Debido a que muchos países de una región tienen problemas de nutrición similares, los datos están desglosados por regiones en la mayoría de las partes del informe. El informe también incluye una evaluación de lo bien actual políticas y programas relacionados con la nutrición se encuentran los problemas de nutrición que se enfrentan los países, y de la política y la gobernanza para la ampliación de las actividades de nutrición. La comunidad internacional debe comprender los desafíos en la implementación de la nutrición políticas y programas con el fin de prestar apoyo a las áreas de mayor necesidad y las áreas donde serán más efectivos. Entender "el paisaje de nutrición" y su "arquitectura" en los países, y la identificación de las formas de superar los desafíos, se asegurará el uso eficaz de los recursos. Este informe está dirigido a las partes interesadas que están trabajando con los países para aplicar políticas y programas de nutrición; incluidos los organismos internacionales y bilaterales, organizaciones no gubernamentales (ONG), la sociedad civil y el sector privado.

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.

Medical marijuana in HIV-positive patients: what do we know?

On November 4, 2008, our state passed the Michigan Medical Marijuana Act (MMMA), which allows the medical use of marijuana for certain conditions and/or constellation of symptoms. This article will (1) review the current evidence that medical marijuana is useful for certain chronic conditions, particularly pain and wasting syndromes experienced by HIV-positive people; (2) discuss the adverse effects of marijuana; (3) summarize the new Michigan law and the challenges it poses for physicians, and (4) review the experience in California where medical marijuana has been legal since 1996.

Causes of death in the era of highly active antiretroviral therapy: a retrospective analysis of a hybrid hematology-oncology and HIV practice and the Seattle/King county adult/adolescent spectrum of HIV-related diseases project.

BACKGROUND: HIV-infected patients continue to die in the era of highly active antiretroviral therapy (HAART). OBJECTIVE: To describe the cause of mortality in the HAART era between 2 cohorts by conducting a comparative retrospective analysis. METHODS: The Virginia Mason Medical Center (VMMC) cohort was composed of 60 died HIV-infected patients from 600 patients. The second cohort was comprised of 351 died patients from the Seattle portion of the Adult and Adolescent Spectrum of Diseases Project (Seattle-ASD) of 4721 patients. Among the abstracted data were the conditions present at death, defined as any major cause of morbidity present at death for both cohorts. RESULTS: Non-AIDS defining illnesses (non-ADI) were a major source of mortality in 60% and 45% for the VMMC and Seattle-ASD cohorts, respectively. The most common fatal non-ADI in both cohorts were cancer (7% and 19%), bacterial infections (15%), and liver failure (9% and 14%). Cancer (10%) and wasting (7%) were prominent fatal ADI in both cohorts. In each cohort, patients died despite a nondetectable HIV viral load and a CD4 lymphocyte count >200 cells/microL. This included 11 of 60 (18%) VMMC patients (all of whom died of non-ADI) and 35 of 351 (10%) Seattle-ASD patients (81% died with non-ADI). CONCLUSIONS: In 2 well-characterized urban HIV cohorts, non-ADI were a major cause of mortality in the HAART era. A substantial number of these patients died despite nondetectable HIV viral loads and reasonably well-preserved immune function measured by CD4 cell counts.

O papel do hormônio de crescimento no tratamento dos distúrbios endócrino-metabólicos do paciente com a síndrome da imunodeficiência adquirida (Aids): [revisão] / The use of growth hormone to treat endocrine-metabolic disturbances in acquired immunodeficiency syndrome (Aids) patients: [review]

As primeiras descrições da síndrome da imunodeficiência adquirida (Aids) associavam-se à síndrome de emaciamento, e os distúrbios metabólicos às alterações na composição corporal. Após a introdução da terapia anti-retroviral altamente ativa (HAART), houve declínio na desnutrição, e surge a lipodistrofia como importante distúrbio metabólico. A Aids também se caracteriza por distúrbios hormonais, principalmente no eixo hormônio de crescimento/fator de crescimento insulina-like tipo 1 (GH/IGF-1). O uso do GH recombinante humano (hrGH) foi inicialmente indicado na síndrome de emaciamento, a fim de aumentar a massa muscular. Embora também não existam dúvidas quanto aos efeitos do hrGH na lipodistrofia, a diminuição na sensibilidade à insulina limita o seu uso, o qual ainda não está oficialmente aprovado. A diversidade nos esquemas de tratamento é outro limitante do uso dessa medicação em pacientes com Aids. Esta revisão apresenta os principais distúrbios endócrino-metabólicos associados à Aids e ao uso do hrGH nessas condições.

Acquired Immunodeficiency Syndrome (Aids) was initially related to HIV-associated wasting syndrome, and its metabolic disturbances to altered body composition. After Highly Active Antiretroviral Therapy (HAART) was started, malnutrition has declined and HIV-associated lipodystrophy syndrome has emerged as an important metabolic disorder. Aids is also characterized by hormonal disturbances, principally in growth hormone/insulin-like growth factor 1 (GH/IGF-1) axis. The use of recombinant human GH (hrGH) was formerly indicated to treat wasting syndrome, in order to increase lean body mass. Even though the use of hrGH in lipodystrophy syndrome has been considered, the decrease in insulin sensitivity is a limitation for its use, which has not been officially approved yet. Diversity in therapeutic regimen is another limitation to its use in Aids patients. The present study has reviewed the main HIV-related endocrine-metabolic disorders as well as the use of hrGH in such conditions.

Novel approaches to the treatment of cachexia.

Cachexia is a complex syndrome. The main components of this pathological state are anorexia and metabolic abnormalities, such as glucose intolerance, fat depletion and muscle protein catabolism among others. The aim of the present article is to review the recent therapeutic approaches that have been designed to fight and counteract muscle wasting in different pathological states such as cancer, AIDS and chronic heart failure.

Role of recombinant human growth hormone in HIV-associated wasting and cachexia: pathophysiology and rationale for treatment.

BACKGROUND: Wasting, or cachexia, is a significant, debilitating, and potentially life-threatening complication of HIV infection. It is associated with reduced strength and functional ability, reduced ability to withstand opportunistic infections, and increased risk of mortality. Although the incidence of HIV-associated wasting may have declined since the introduction of highly active antiretroviral therapy (HAART), it continues to be a concern in this patient population. OBJECTIVE: This paper reviews available data on the etiology and clinical impact of HIV-associated wasting, the role of the growth hormone/insulin-like growth factor-I axis in the pathophysiology of this condition, and the rationale for its treatment with recombinant human growth hormone (rhGH). METHODS: MEDLINE was searched for articles published in English through August 2007 using the terms HIV, wasting (and related terms), and growth hormone. Preference was given to clinical studies (including randomized clinical studies), meta-analyses, and guidelines. Review articles were evaluated and the bibliographies examined for additional relevant articles. The analysis was restricted to studies conducted in developed countries. RESULTS: Alterations in the growth hormone/insulin like growth factor-I axis have been observed in patients with HIV-associated wasting, including elevated levels of the former and reduced levels of insulin-like growth factor I. In randomized, placebo-controlled studies, rhGH significantly improved lean body mass by approximately 3 kg compared with placebo (P < 0.001) and total body weight by approximately 3 kg (P < 0.001), and was associated with significant improvements in physical endurance and quality of life (P < 0.001). Common adverse events with rhGH therapy include blood glucose elevations, arthralgia (36.4%), myalgia (30.4%), and peripheral edema (26.1%), but these usually respond to dose reduction or drug discontinuation. CONCLUSIONS: Physicians should be alert to the possibility of wasting in HIV-infected patients receiving HAART and should consider treatment to improve patients' stamina and quality of life. The evidence supports a role for rhGH in the treatment of patients with HIV-associated wasting. Regular blood glucose monitoring is advised when treating wasting with rhGH.

Changes in facial fat in HIV-related lipoatrophy, wasting, and weight gain measured by magnetic resonance imaging.

BACKGROUND: Changes in facial fat occurring over time in patients with HIV-related lipoatrophy have not been properly quantified. We aimed to define the longitudinal changes in facial fat compartments in patients with lipoatrophy and to compare these with changes accompanying wasting or weight gain. METHOD: Facial MRI scans were performed at baseline and repeated after a median of 10 months in 24 patients, of whom 12 had moderate to severe lipodystrophy continuing antiretroviral therapy, 5 lost weight, and 7 gained weight (more than 10% weight change). RESULTS: Superficial facial fat decreased by a median of 5.2 mL (p = .03) in patients with lipoatrophy, and 8 of 12 individuals showed more than 15% decrease (all of whom were taking stavudine). The decrease was mainly cheek fat. Superficial facial fat decreased by 6.0 mL in patients with weight loss (p = .04) and increased by 20.2 mL (p = .02) in patients with weight gain, and changes occurred in cheek fat, temporal fat, and masseter muscle and temporalis muscle compartments. CONCLUSION: MRI can detect substantial ongoing changes in facial fat in patients with facial lipoatrophy. A characteristic pattern of compartmental change distinguishes lipoatrophy from wasting and weight recovery. MRI should be considered for use in clinical trials of interventions to prevent or treat lipoatrophy and may be useful for documenting changes in individual patients during clinical follow-up.

Changing patterns of clinical events in perinatally HIV-1-infected children during the era of HAART.

BACKGROUND: The introduction of HAART has decreased mortality and progression to AIDS in perinatally HIV-1-infected children, but information on modification of the rate of specific clinical events is limited. METHOD: An observational population study on changes in HIV-1-related morbidity was conducted on 1402 perinatally HIV-1-infected children enrolled in the Italian Register for HIV Infection in Children and prospectively followed in the pre-HAART (1985-1995) and post-HAART periods (1996-2000, and 2001-2005). Of this group, 773 children (55.1%) were followed from birth. Median observation time was 8.58 years (interquartile range, 3.71-13.72). RESULTS: Overall, 666 (47.5%) children developed AIDS and 420 (29.9%) died. Improved survival over time was evidenced at Kaplan-Meier analysis (P < 0.0001). Poisson regression analysis indicated that Centers for Disease Control and Prevention class B and C clinical event rates and most of the HIV-1-related organ complication rates significantly decreased starting from 1996-2000. Significant reductions in rates of cancer and opportunistic infections were evidenced after 2000. Nevertheless, opportunistic infections still occurred at high rates (6.09/100 person-years) in 2001-2005, with high rate of bacterial infections (3.55/100 person-years), particularly pneumonia (1.66/100 person-years), in this period. CD4 cell percentage was > 15% in 58.5% children with pneumonia. CONCLUSIONS: Progressive reductions of both mortality and rates of class B and C clinical events, including organ complications, were evidenced in the HAART era. Nevertheless, severe bacterial infections, particularly pneumonia, still occurred at considerable high rates, even in the absence of a severe CD4 cell depletion.

Transcriptional profiling of testosterone-regulated genes in the skeletal muscle of human immunodeficiency virus-infected men experiencing weight loss.

CONTEXT: HIV-associated wasting and weight loss remain clinically significant concerns even in the era of potent antiretroviral therapy. Although androgen treatment increases muscle mass, the cell-intrinsic mechanisms engaged remain poorly understood. OBJECTIVE: This study was an unbiased approach to identify expression profiles associated with testosterone treatment using genome-wide microarray analysis of skeletal muscle biopsies. DESIGN, SETTING, AND PARTICIPANTS: Forty-four HIV-positive men with weight loss were randomized to receive either 300 mg testosterone enanthate or placebo injections im weekly for 16 wk. Muscle biopsies were obtained at baseline and on treatment d 14. A subset of specimens was chosen for microarray analysis, with changes in selected genes confirmed by real-time PCR, Western blot analysis, and in vitro culture of muscle precursor cells. RESULTS: Significantly greater gains in body mass (+2.05 and -1.07 kg, respectively; P = 0.003) and lean body mass by dual-energy x-ray absorptiometry (2.93 vs. 0.35 kg, respectively; P = 0.003) were observed in subjects treated with testosterone compared with placebo. Microarray analysis revealed up-regulation in genes involved in myogenesis and muscle protein synthesis, immune regulation, metabolic pathways, and chromatin remodeling. Representative genes were confirmed by real-time PCR and protein expression studies. In an independent analysis, gene networks that differentiate healthy young men from older men with sarcopenia had substantial overlap with those activated by testosterone treatment. CONCLUSIONS: These data provide new insights into the mechanisms of androgen action and have implications for both development of muscle biomarkers and anabolic therapies for wasting and sarcopenia.