Testosterone replacement therapy in people with HIV

It is estimated that as many as 40% of HIV-positive men who are ill because of HIV have low levels of testosterone (hypogonadism). Low testosterone can result in decreased appetite, depression, poor metabolism of food, and sexual problems, including the inability to obtain and maintain an erection.

A blood test can show if you have low levels of testosterone and your doctor may prescribe either a short course of oral testosterone replacement therapy, testosterone patches, or testosterone gel.

Although testosterone cypionate is usually considered to be the male sexual hormone, it also occurs naturally in women. Testosterone patches have been examined as a treatment for wasting caused by HIV in women. It was found that weight and quality of life improved for some of the women, and the development of male characteristics was not reported.

Side-effects from testosterone replacement therapy are rare, but can include the shutting down of natural testosterone production, shrinking of the testicles, hair loss, increased sexual desire, and aggression. In women, male characteristics, such as the deepening of the voice, and facial hair may develop.

Steroid increases lean muscle mass in HIV-positive men, but has side-effects

Use of the steroid oxandrolone is associated with significant gains in weight and body cell mass in HIV-positive men who had experienced HIV-related wasting, according to an American study.  However, although the steroid increased muscle mass, it did not improve endurance and caused side-effects, including an increase in levels of ‘bad’ LDL cholesterol and elevations in liver enzymes.

Unintentional loss of just 3% of body weight has been associated with poorer survival in HIV-positive individuals. Although the use of antiretroviral therapy has led to a significant decrease in the prevalence of unintended weight loss, it is still common, even amongst people taking HIV treatment.

Diet and appetite stimulation can help increase weight in people affected by HIV-related wasting, but most of the gains of weight occur in the form of fat, and stores of body fat are not correlated with improved survival in HIV-positive individuals. Some small studies have shown that anabolic steroids can increase body weight and muscle mass in HIV-positive patients. To further investigate the benefits of treatment with anabolic steroid therapy, investigators designed a double blind placebo controlled trial in which men with HIV-associated wasting were randomised to receive a placebo or one of a 20mg, 40mg, or 80mg daily dose of the oral steroid oxandrolone. The investigators measured changes in the patients’ weight, body composition, endurance, and also conducted laboratory tests to assess the safety of steroid treatment. For the first twelve weeks, the men were provided with blinded treatment. At the end of this period, all the men were given the option of receiving an open-label 20mg daily dose of oxandrolone for a further twelve weeks.

The study was conducted between the autumn of 1996 and the summer of 1998. Treatment with antiretroviral drugs was not a prerequisite for entry to the study, but if an individual was taking anti-HIV treatment, they were required to have been taking a stable regimen for at least six weeks. The investigators do not state how many patients were taking anti-HIV therapy, nor do they analyse their results according to the use of antiretrovirals, making it difficult to determine the applicability of these results in patients experiencing HIV-related wasting despite antiretroviral therapy.

A total of 262 men were recruited to the study. CD4 cell count was comparable across the four arms of the study at approximately 250 cells/mm3, as was viral load at approximately 120,000 copies/ml.

Body weight increased significantly in all arms of the study, including the placebo arm during the double blind phase (p < 0.014). Body cell mass also increased in all arms of the study during this phase. However, when the investigators subjected their results to further analysis, they found that patients who took the 40mg dose of oxandrolone had significantly greater increases in body weight at weeks two, four, eight and twelve than those individuals who received a placebo (p < 0.004). Although patients receiving the 80mg dose of oxandrolone had significantly greater weight gains than patients on the placebo at weeks four and eight, this was not the case at weeks two or twelve.

In addition, the investigators found that patients treated with the 40mg (p = 0.0049) and 80mg (p = 0.0002) doses of oxandrolone experienced significant changes in body cell mass compared to patients who received the placebo.

Treatment with the steroid did not, however, lead to any improvement in endurance.

The investigators noted that levels of AST and ALT liver enzymes increased during the first four to eight weeks in patients receiving the 40mg and 80mg doses of oxandrolone. What’s more, they found a dose-related increase in the incidence of moderate-to-severe liver abnormalities in people taking the steroid. This was diagnosed by laboratory tests looking at AST, ALT, bilirubin, and uric acid levels. Analysis also showed that people treated with the 40mg and 80mg doses of the steroid were significantly more likely than those taking the placebo to experience an increase in their ‘bad’ LDL cholesterol (p < 0.017).

On completion of the twelve-week double-blind phase of the study, all the patients were offered the option of remaining on the study for a further twelve weeks and receiving an open label 20mg oxandrolone dose a day. By the end of this period, there were no differences in weight between patients and liver function ceased to be significantly different from baseline.

“Oxandrolone treatment was associated with significantly greater body weight gain above baseline than with placebo. A major portion of this weight gain occurred in the lean body compartment”, comment the investigators, who note that theirs was “the largest randomized placebo-controlled trial of an androgen in patients with HIV-associated weight loss.”

Although the investigators note that treatment with the steroid was generally “well tolerated” they note that over 5% of patients had moderate or severe increases in levels of liver enzymes and that “LDL levels decreased and HDL levels increased.”

They recommend “further studies…to determine the efficacy of oxandrolone in improving muscle strength, physical function, and health-related quality of life in HIV-infected patients with weight loss.

Human Growth Hormone Being Used in AIDS patients

Serostim, a form of recombinant HGH  is being used to reverse the pernicious form of weight loss seen in later stage AIDS, called "wasting."

Wasting is different than the loss of weight and fat that comes from under eating, this wasting also occurs in later stages of cancer. Wasting is the unintentional loss of weight in which the lean muscle, the body mass, the bones and the body organs are all withering away. Many experts believe this loss of lean body mass contributes to immune dysfunction and makes it harder for AIDS patients to fight off life-threatening infections. The wasting process itself, if it goes beyond about 33% of ideal body weight, is incompatible with life, as was seen in concentration camp victims of World War II.

A number of medical centers took part in a study of 178 patients with AIDS-associated wasting, which is defined as having lost at least 10% of body weight. The patients who received growth hormone therapy gained an average of 6.6 pounds of lean body mass while losing an average of three pounds of fat after three months of treatment. The therapy also resulted in an improvement of their endurance and quality of life.

Dr. Schambelan, of UCSF says "At the moment there isn't another therapy in the late stages of AIDS that has had this kind of effect on the lean body mass." "There are therapies that can increase weight, such as an appetite stimulant called megestroacetate, but that weight gain tends to be primarily fat. The advantage of growth hormone is that it causes lean body mass to increase." Dr. Schambelan says that some of the patients are still coming in, even though the original study ended three years ago. "Obviously these are the people who are still alive and doing well and the people who didn't do well are no longer there, so you can't talk about the average effect. I think that the anecdotal experience is that for the people who continue to take the drug, who continue to eat, and don't get serious opportunistic infections, they have had a very robust response. The medication has increased the benefits. The gain in lean body mass they had in their three months of the study has doubled or tripled over the next year or two."

 Although human growth hormone does not cure AIDS, there is some evidence that it may lengthen the life of AIDS patients. The increase in lean body mass may make the AIDS patient less vulnerable to infections. When given with antiviral agents such as AZT, human growth hormone did not cause any increase in the amount of HIV. In fact, human growth hormone has been shown to stimulate the formation of new red blood cells, which are depleted by AZT.

Even more exciting, human growth hormone also appears to reduce the incidence of AIDS associated infections, such as polycystic pneumonia and Kaposi's sarcoma. It can rejuvenate the immune system; if it can actually strengthen the ability of HIV+ patients to resist infectious diseases it may improve both the quality and the quantity of their lives.

HIV causes structural heart disease

Researchers from Spain have shown that HIV causes structural heart disease. These findings support the introduction of cardiovascular screening for all HIV patients, particularly those who have a positive viral load.

"It is well known that patients with HIV have a high incidence of structural heart disease (mainly diastolic dysfunction and pulmonary hypertension) as measured by echocardiography but the reason is not clear. We decided to conduct a study to evaluate whether the stage of HIV or the detectable blood viral load were related to the degree of heart disease."

The Centers for Disease Control and Prevention (CDC) estimates that there are 1,144,500 people aged over 13 living with HIV in the US.

For the study, researchers analyzed data from 65 HIV patients, with an average age of 48. All the participants reported shortness of breath - dyspnea - which was graded as greater than class II on the New York Heart Association (NYHA) scale.

According to the Heart Failure Society of America, the NYHA scale is used by physicians to determine the stage of heart failure in patients and focuses on the patient's symptoms in relation to their daily activities and quality of life.

It ranges from class I with mild symptoms through to IV, where symptoms are severe and patients are unable to perform any physical activity without discomfort. This study focuses on classes III and IV, where patients display moderate to severe symptoms.

Participants' HIV stage was determined by the CD4 (T-cells) count, their susceptibility to opportunistic diseases and their viral blood load, tested by determining the number of virus particles, or copies, within a milliliter of blood.
AIDs.gov explains that while there is no "normal" viral load, as people who are not infected have no viral load, it is considered "undetectable" if the test measures are less than 40-75 copies in 1 milliliter of blood.

Patients were also given a transthoracic echocardiogram to see if they had structural heart disease (ventricular hypertrophy, systolic or diastolic dysfunction or pulmonary hypertension). Cardiovascular risk factors, such as diabetes, hypertension, smoking status and renal failure, were also assessed.

The researchers found that almost half of the patients (47%) had some type of structural heart disease, usually left ventricular hypertrophy, left ventricular dysfunction, pulmonary hypertension and signs of right ventricle failure.