Drug for reduction of abdominal fat in HIV patients may also reduce fatty liver disease

The only drug to receive FDA approval for reduction of the abdominal fat deposits that develop in some patients receiving antiviral therapy for HIV infection may also reduce the incidence of fatty liver disease in such patients. The International AIDS Conference - Massachusetts General Hospital (MGH) investigators report that daily injections of Tesamorelin significantly reduced fat in the liver without affecting glucose metabolism.

"Tesamorelin's ability to reduce liver fat in conjunction with the reduction of abdominal fat may be clinically important for patients with HIV infection who have fatty liver disease along with increased abdominal fat," says Steven Grinspoon of the MGH Neuroendocrine Unit and Program in Nutrition Metabolism, the study's senior author. "While some patients with nonalcoholic fatty liver disease have a benign course, others may develop a more serious condition involving liver inflammation, cellular damage and fibrosis, which can progress to cirrhosis and end-stage liver disease or to liver cancer."

Between 30 and 40 percent of HIV-infected patients develop nonalcoholic fatty liver disease (NAFLD), often but not always in conjunction with lipodystrophy, the abnormal abdominal fat accumulation that develops in 20 to 30 percent of patients receiving antiretroviral drugs. Tesamorelin stimulates the body's release of growth hormone, which is reduced in HIV lipodystrophy and several studies by Grinspoon's team and others led to the 2010 approval of the drug to treat the lipodystrophy.

In designing the current study, the MGH team originally planned to further investigate tesamorelin's effects on abdominal fat with a secondary focus on fat in the liver and muscle, and on markers of inflammation and cardiovascular risk. But since several studies suggested a significant incidence of NAFLD in HIV-infected patients, the study's goals were broadened to focus on Tesamorelin's ability to reduce fatty deposits in the liver as well as abdominal fat in general. The study enrolled 48 adult patients who were receiving antiretroviral treatment for HIV and had developed excessive abdominal fat deposits. Participants were first randomized to receive daily injections of either Tesamorelin or a placebo. In addition, since growth hormone treatment can lead to increased blood sugar levels and reduced insulin sensitivity, half of those in each group also had a procedure that analyzes insulin secretion and resistance at the study's outset and at assessment sessions conducted at three months and at the end of the six-month study. The assessments also included comprehensive measures of factors related to HIV infection, lipid and glucose metabolism, along with analysis of abdominal fat by CT scan and of liver fat by MR spectroscopy.

At the end of the study period, participants receiving Tesamorelin had a significant, modestly sized decrease in liver fat along with the expected reduction in overall abdominal fat. Those receiving placebo treatment had increases in both measures. Although Tesamorelin treatment did appear to have reduced insulin sensitivity and raised blood sugar levels at the three-month assessment, by six months both measures had returned to levels observed at the study's outset, implying that the drug's impact on glucose metabolism was only temporary.

"Tesamorelin's neutral long-term effects on insulin sensitivity and glucose are important, since HIV patients with abdominal fat accumulation may have underlying insulin resistance, so it's important to know that won't be worsened by this treatment," says Grinspoon, a professor of Medicine at Harvard Medical School. "Since we know that liver fat is associated with inflammation in the liver, reducing it may result in less inflammation. Indeed levels of AST, a marker of liver inflammation, were reduced in response to tesamorelin in our study.

One of Favorites Anabolic Steroids and immune system

Primobolan is generally advised in case of men suffering from the deficiency of a hormone known as androgen in men. In some rare instances this drug has also been advised to treat a condition known as aplastic anaemia which is mainly characterised by the deficiency of blood cells. In some other instances it has been advised to counter the abnormal weight loss associated with certain disorders or following major trauma. It is illegal to obtain and use Primobolan without being prescribed by the doctor.
Primobolan has been advised for women suffering with breast cancer in some instances as it has been believed to aid in the reduction of the tumor size. The anabolic steroids such as Primobolan reduce the excretion of nitrogen from the tissue. This retention of nitrogen within the muscle tissues aids in the building of muscle mass to a certain extent. The muscle building effect may be present to a certain extent while no clear evidence about enhancement in athletic performance has been observed with the use of Primobolan.

Primobolan supposedly burns fat thereby reducing its amount in the body. This effect of Primobolan has increased its popularity among athletes who look at building a lean mass with less fat in their body. Further it has been stated that Primobolan prevents wasting of muscles and reverses the effects of anaemia. Anabolic steroids may enhance the formation of blood cells in some instances. In case of individuals suffering from chronic immune disorders such as AIDS, Primobolan has been advised as immune booster drug.

Being described as Arnold Schwarzenegger’s favorite steroid, Primobolan is widely abused in sports and bodybuilding. It is considered that it Primobolan builds strength with adding bulk to the muscles. Primobolan is generally more favoured by athletes as it helps them to maintain a lean body mass while improving the ability of the muscles to contract. Also it has been proposed that it is not associated with the common side-effects of other steroids such as acne, water retention, infertility and others. In case of body builders, it is used during the bulking or cutting cycles.

Chronic abuse of Primobolan is associated with a number of adverse effects. Providing a constant supply of synthetic steroids to the body can have a multitude of side-effects on the normal functioning of various organs in the body. The body regularly requires steroids at a controlled level and is generally produced within our body. Loading up the body with steroids though may provide benefit to a certain extent, the harmful effects always have an upper hand. Some of the major effects have been discussed below.
Effect on heart

Prolonged use of Primobolan has been associated with a wide number of effects both directly and indirectly on the heart. An increase in the blood pressure is commonly noted. Other effects such as abnormal changes in the cells and tissues of the heart and premature onset of heart related disorders are also noted in chronic abusers of anabolic steroids. Occurrence of stroke has been reported in anabolic steroid abusers. Other neurological symptoms such as mania, hallucinations, mood swings and depression have also been associated with the abuse of Primobolan.

Ingestion of high doses of Primobolan within short interval periods can result in vomiting and gastric irritation. Primobolan can alter the normal functioning of the liver resulting in the elevation of certain enzyme levels that can often be harmful. At times, it results in the increased incidence of jaundice in chronic abusers. Excessive use of anabolic steroids such as Primobolan can result in a condition called peliosis hepatitis. This abnormal condition of the liver is generally characterized by the formation of cysts (fluid filled cavities) in the liver. These cysts affect the liver function and at times result in liver failure which may lead to life threatening situations. The incidence of liver tumors is also noted to be increased in individuals who abuse Primobolan. Increased occurrence of cancer of the prostate gland has been noticed in anabolic steroid abusers. Prolonged use of Primobolan is associated with increased proliferation of the cells and tissues of the prostate gland, a condition commonly referred to as prostate hypertrophy.

HIV-1 and immune system

Of the two major types of HIV, only one, HIV-1, typically causes AIDS in infected people who don't receive treatment. A study published by Cell Press November 21st in the journal Immunity reveals how HIV-1 escapes detection by essentially becoming invisible to a patient's immune system, whereas HIV-2 triggers protective immune responses in patients. This understanding of how HIV-1's "invisibility cloak" works could lead to the development of effective vaccines against HIV-1.

"Our study shows for the first time exactly how immune cells sense the virus and how the virus uses one of its proteins to tune its stealthiness and infectivity," says senior study author Nicolas Manel of the Institut Curie. "We also show how to modify the virus so that it is properly recognized and leads to a beneficial immune response."

Individuals who are infected with both HIV-1 and HIV-2 do better than those infected with HIV-1 alone, suggesting that the immune response against HIV-2 protects against the effects of HIV-1 infection. While searching for an explanation in previous studies, Manel and his collaborators found that HIV-2, but not HIV-1, naturally infects and activates dendritic cells, which play a major role in triggering protective immune responses. But until now, it was not known how HIV is detected in dendritic cells.

In the new study, Manel and his team focused on the capsid—the protein shell of a virus that encloses its genetic material. By mutating HIV-1 and HIV-2 capsids, they discovered that these viral proteins control the ability of dendritic cells to sense the viruses and activate immune responses.

The researchers found that the HIV-1 capsid allows the virus to escape detection by dendritic cells under normal conditions. But when they mutated the HIV-1 and HIV-2 capsids, the dendritic cells produced immune responses without getting infected by the viruses. These cells relied on a protein called cyclic GMP-AMP synthase (cGAS) to sense the viral DNA in the cytosol before the foreign DNA became integrated into the host genome.

These findings open new avenues for the development of effective treatments against HIV-1. "By modifying the capsid of a virus, we could engineer a virus that is both better recognized by the immune system and that has also lost its ability to infect cells," Manel says. "Beyond capsid-mutated viruses, our results suggest that activating the cGAS pathway in dendritic cells could induce immunity against HIV-1.

Anabolic steroids for the treatment of weight loss in HIV-infected people

Individuals with HIV infection often lose weight during the course of their disease. Furthermore, low serum concentrations of testosterone are common in individuals with HIV infection, particularly those with weight loss. Treatment of weight loss with anabolic steroids in HIV-infected individuals may be beneficial. Randomized controlled trials that compared the use of an anabolic steroid to placebo to treat weight loss in adults with HIV were included. Randomized controlled trials that compared the use of anabolic steroids to placebo for the treatment of weight loss in adults with HIV were selected. Change from baseline in lean body mass or in body weight was reported as on outcome measure.

Two reviewers independently assessed the trials for quality of randomization, blinding, withdrawals and adequacy of allocation concealment. For continuous data, weighted mean differences (WMD) were calculated. For dichotomous outcomes, risk differences, were calculated. Because of uncertainty as to whether consistent true effects exist in such different populations and treatments, the authors decided a priori to use random effects models for all outcomes.

Thirteen trials met the inclusion criteria. Two hundred ninety-four individuals randomized to anabolic steroid therapy and 238 individuals randomized to placebo were included in the analysis of efficacy for change from baseline in lean body mass. Three hundred forty-three individuals randomized to anabolic steroid and 286 randomized to placebo were included in the analysis of efficacy for change from baseline in body weight. The mean methodological quality of the included studies was 4.1, of a maximum 5 points. Although significant heterogeneity was present for both outcomes, the average change in lean body mass was 1.3 kg (95% CI: 0.6, 2.0), while the average change in total body weight was 1.1 kg (95% CI: 0.3, 2.0). A total of eight deaths occurred during the treatment period; four in the anabolic steroid treatment groups and four in the placebo-treatment groups (risk difference 0.00, 95% CI -0.03, 0.03). The risk difference for withdrawals or discontinuations of study medication due to adverse events was 0.00 (95% CI: -0.02, 0.03).

Although the results of the trials were heterogeneous, on average, the administration of anabolic steroids appeared to result in a small increase in both lean body mass and body weight as compared with placebo. While these results suggest that anabolic steroids may be useful in the treatment of weight loss in HIV infected individuals, due to limitations, treatment recommendations cannot be made. Further information is required regarding the long-term benefit and adverse effects of anabolic steroid use, the specific populations for which anabolic steroid therapy may be most beneficial and the optimal regime. In addition, the correlation of improvement in lean body mass with more clinically relevant endpoints, such as physical functioning and survival, needs to be determined. Testosterone has been demonstrated to increase muscle mass and lean body mass in testosterone-deficient but otherwise healthy men.
Individuals with HIV infection often lose weight and have low blood levels of testosterone; thus, the use of anabolic steroids in the treatment of weight loss in individuals with HIV infection may be beneficial.

The purpose of this review was to evaluate anabolic steroids as a means of treatment of weight loss in individuals with HIV infection.
However, the results were not consistent among individual trials and the average increase was small and may not be clinically relevant.
Furthermore, the results need to be interpreted with caution as this meta-analysis was limited due to small sample sizes, short duration of treatment and of follow-up; and heterogeneity of the study populations, the anabolic interventions, and concomitant therapies.
Furthermore, low serum concentrations of testosterone are common in individuals with HIV infection, particularly those with weight loss. Our objectives were to assess the efficacy and safety of anabolic steroids for the treatment of weight loss in adults with HIV infection. Androgen deficiency is a common endocrine abnormality among men and women with human immunodeficiency virus (HIV) infection. Low testosterone concentrations are associated with lower CD4 cell count, advanced stage of illness, medication use, and weight loss. Signs and symptoms may be nonspecific. The most useful laboratory indicator is the serum bio available (free) testosterone concentration. A number of different testosterone preparations for treatment of androgen deficiency in HIV-infected men now exist. Administration of testosterone significantly increases weight and lean body mass, energy, quality of life, and depression scores in HIV-infected men with low testosterone levels. Newer trans dermal and gel preparations provide more-consistent steady-state dosing but are not as well tested, and sufficient testosterone concentrations may not be achieved with their use. Androgen deficiency is also common among HIV-infected women. Preliminary studies suggest that use of physiological testosterone administration, to achieve testosterone levels within the normal range, is of benefit in HIV-infected women, but further studies are necessary to define the therapeutic role of androgen therapy in this population.