On October 26, 2001, the Food and Drug Administration (FDA) approved a new drug for the treatment of HIV disease. Tenofovir (brand name Viread), the first in a new class of HIV medications called the nucleotide reverse transcriptase inhibitors, has the benefit of once-daily dosing as well as a unique mutation pattern which makes it effective in medication-experienced patients with resistant viral strains. While an effective and exciting new drug, tenofovir is not without its side effects. Commonly reported adverse events include gastrointestinal events (nausea, vomiting, diarrhea, and flatulence), weakness, and abdominal pain; and, precautions include renal impairment, lactic acidosis and severe hepatomegaly with steatosis (enlarged liver with fat accumulation) and bone toxicity or impairment.
This last precaution, bone toxicity or impairment, is most likely associated with a phosphorus deficiency induced or caused by tenofovir. Because phosphorus deficiencies are associated with tenofovir, physicians should check a patient's phosphorus levels before prescribing tenofovir, as well as regularly monitor phosphorus levels during therapy with tenofovir. Fortunately, healthy phosphorus levels can be maintained through nutrient-rich foods, thus avoiding a long-term deficiency that may result in more severe conditions.
Phosphorus is an essential mineral that is crucial for almost every cell in the body. First, it is critical for bone structure. In the kidneys, phosphorus plays an important role in converting vitamin D to its biologically active form, which is required in order for the body to absorb calcium, needed for development and maintenance of bone. Phosphorus is also a component of hydroxyapatite, the structural component of bone. Second, phosphorus is found in phospholipids, which make up the structure of cellular and plasma membranes in the body, as well as in many enzymes required for proper metabolism. Third, all energy production and storage in the body is dependent upon phosphorus to form adenosine triphosphate (ATP), the molecule responsible for carrying energy. Fourth, phosphorus is important in hormonal function and in regulating the acid-base (pH) balance in the body. Of total body phosphorus, roughly 80 percent is found in bone, and 9 percent is found in skeletal muscle.
When the body becomes deficient in phosphorus (a condition known as hypophosphatemia), several processes are affected. In the early stages of hypophosphatemia the body experiences shifts in electrolytes. There is typically an increase in sodium, chloride, calcium, and water, while there is a marked decrease in potassium, magnesium, and nitrogen. If the deficiency persists, the body will try to compensate for the phosphorus deficiency by pulling calcium from the bones. Therefore, with chronic hypophosphatemia, adults tend to develop osteomalacia, which is a softening of the bones, along with muscle weakness and bone pain. Children often experience impaired growth as a result of hypophosphatemia. The potential for hypophosphatemia resulting from a tenofovir-induced deficiency is probably why possible bone toxicity or impairment is listed with other precautions in tenofovir's full prescribing information (see package insert (PDF)).
Many other disorders can also be associated with phosphorus deficiency. Proximal myopathy consists of muscle atrophy and weakness, and is often accompanied by osteomalacia. Rhabdomyolysis is characterized by severe muscle pain, weakness, tenderness, stiffness, and swelling, although this usually occurs only in hospitalization situations. Low energy (ATP) levels are common, resulting in fatigue. Cardiomyopathy (weakening of the heart) and/or arrhythmias occur in about 20 percent of patients with hypophosphatemia. Several other events are possible, although rare: respiratory problems, platelet disorders (impaired blood clotting), metabolic acidosis, and nervous system disorders.
The key to success lies in prevention of phosphorus deficiency. Fortunately, many foods high in phosphorus are also high in protein -- another nutrient that is crucial for people living with HIV. Meats, dried beans, milk, and eggs are all excellent sources of phosphorus. Grains and cereals are also good sources. Carbonated beverages or sodas do contain a fair amount of phosphorus, but they may be contraindicated because of other medical conditions.
Here are some tips to help you maintain your phosphorus levels while taking tenofovir:
Another diet-related issue with tenofovir is taking the medication with food. Tenofovir should be taken with food to enhance its bioavailability. In clinical studies, the best types of meals contained 700 to 1000 calories with 40 percent to 50 percent of the calories coming from fat because they maximized bioavailability of the active drug; however, it is best to discuss such diet recommendations with a dietitian before implementing such a high fat diet as it may be contraindicated because of other medical or health considerations.
Remember, it is extremely important for all HIV-positive individuals to consult with a registered dietitian (R.D.). In addition to helping you maintain adequate phosphorus levels, a dietitian can help you maintain or accomplish a healthy weight, prevent or fight wasting, and manage side effects associated with HIV and HIV medications.