The once-daily regimen of Emtriva, Videx EC, and Sustiva was shown to be effective and safe in 40 HIV+ patients who had never before taken HIV medication. Patients were required to have T cell counts greater than 100 and a viral load greater than 5,000. At bedtime, patients took a total of 5 pills. Three years later, 75% of the patients had maintained a viral load of less than 400. Drug-resistance mutations developed in 5 patients. Treatment was well tolerated with only 3 patients stopping treatment because of side effects. Common side effects included high triglycerides (a type of fat that travels in the blood), changes in liver enzymes (which indicate stress on the liver), and body shape changes (lipodystrophy).
Rosiglitazone (brand name: Avandia), is a drug used to treat diabetes. This drug is being tested for the treatment of lipodystrophy and the related problems in body metabolism, such as with fats and sugars. One study compared rosiglitazone (4 mg) with a placebo. This study was a "double-blind" study, meaning that both patients and health care workers did not know which treatment each patient was receiving. After 3 months, patients and healthcare workers knew which treatment each patient was receiving, and all patients were given the choice of taking rosiglitazone at a slightly higher dose (8 mg) for 3 additional months. During the first 3 months, rosiglitazone improved sensitivity to insulin (allowing better control of blood sugars). The drug also increased total body fat, subcutaneous fat, and adiponectin (a hormone secreted by fat cells that affects the body's response to insulin and may have other important effects), compared to patients in the placebo group. Unfortunately, levels of cholesterol increased in patients taking rosiglitazone. Over the next 3 months, rosiglitazone continued to improve insulin sensitivity and to increase subcutaneous fat. The researchers admit that larger studies are needed to figure out the best dose and length of time for treatment, as well as which patients will most likely benefit from this drug.
In related news, a recent double-blind study published in the journal Antiviral Therapy (8:3, p. 199, 2003) also reported that after 24 weeks of rosiglitazone, triglyceride and cholesterol levels were significantly increased compared to patients who took a placebo. In contrast to the first study (described above), this study found that rosiglitazone had no positive effects on total body fat, including fat in the gut and subcutaneous fat. On a positive note, rosiglitazone did improve insulin resistance and tests of liver function.
While no one wants to talk about diarrhea, it is a common side effect of several HIV medications, especially the protease inhibitor Viracept. A small study of 18 patients focused on developing a step-wise plan to treat diarrhea. The strategy was adjusted every 2 weeks and additional treatments were added if the diarrhea persisted. Initial steps included 1) dietary counseling by a nutritionist to see if eating habits were contributing to the problem, 2) taking lactase if the patient had problems digesting dairy products, and 3) taking psyllium (pronounced "silly-um"), a source of dietary fiber. If the diarrhea persisted, calcium carbonate was added to their treatment. Two weeks later, if any patients were still experiencing diarrhea, they were also treated with loperamide (found in over-the-counter diarrhea medications such as Imodium). After completing the 9-week study, patients had fewer bowel movements per day and firmer stools. Incontinence and urgency (a strong desire to go to the bathroom usually caused by some abnormal stress) were also reduced. Patients reported that they felt better both physically and emotionally, and they worried less about the side effects of their HIV treatment.
The nucleotide reverse transcriptase inhibitor Viread has been linked to problems such as increased levels of a substance in the body called creatinine (pronounced "kree-at-n-neen"). Elevations of creatinine in the blood can signal kidney damage. With the help of a large collection of patient records, researchers gathered information on 476 HIV+ patients who took Viread. Compared to patients using a Ziagen-containing regimen without Viread, patients taking Viread were more likely to have increased creatinine levels and signs of kidney damage. Patients with advanced HIV disease and low T cell counts were more likely to have kidney problems. In addition, more patients on Viread stopped it because of these problems. The researchers recommend keeping a close watch on patients who are taking Viread, especially if they have advanced HIV disease, even if they showed no signs of kidney problems before starting Viread.
Viramune is commonly used to prevent HIV transmission from mother to child, but can cause a rash and inflammation of the liver, which are usually not life threatening. A study that examined 139 HIV+ pregnant women who took Viramune also observed these side effects. Unfortunately, 2 women in this study, both African-American, died from liver failure. In this study, women with serious liver inflammation tended to have higher T cell counts compared to women showing no signs of liver inflammation (524 versus 370). What is scary is that the doctors could not predict these deaths. Neither woman who died had hepatitis B or C, nor did they show any signs of liver problems during their frequent doctors' visits. Currently, Viramune is often given to mothers to prevent mother-to-baby transmission. These findings suggest that this approach may need to be changed.
Not taking all of your HIV drugs leads to drug-resistant HIV mutations, according to a large study presented at the conference. Researchers examined the relationship between medication adherence (by checking prescription refill records and by looking for actual drug levels in blood samples) and the development of drug resistance in 1,219 HIV+ people who started triple combination therapy. The doctors found that development of resistance was more likely to happen in people with a high viral load before starting treatment. In addition, patients who took their medications 60% to 90% of the time (according to prescription refill records) were most likely to develop these mutations, compared to patients who took their medications less frequently or more frequently. Low levels of these HIV drugs in blood samples were related to a higher chance for drug-resistance mutations. Low drug levels could be caused by poor adherence, problems with drug metabolism, or drug interactions.
Buffalo hump, the accumulation of fat at the back of the neck, is a body change associated with lipodystrophy, but not all people with lipodystrophy get a buffalo hump. To see which patients get this condition, a study examined 417 HIV+ patients -- all of whom had lipodystrophy, while only some had a buffalo hump. Age, gender, response to HIV treatment, and immune system strength/control of virus were not linked to the development of a buffalo hump. Instead, patients with buffalo hump tended to have a higher body mass index (larger body size), more total body fat, and more fat in their limbs and gut. Having diabetes or diabetic characteristics (such as a higher ratio of insulin to blood sugar) also increased the chance of developing buffalo hump. Patients who had taken protease inhibitors or Retrovir for longer periods of time were more likely to develop a buffalo hump as well.
The following experimental drugs are in clinical study and are not yet approved by the US Food and Drug Administration (FDA). If they become approved, they may offer new treatment options for people with HIV.
TMC114 is an experimental protease inhibitor (PI) that may work in patients who have HIV with multiple protease inhibitor mutations. Researchers examined 50 patients who had taken several PIs in the past and who were failing their current treatment. Participants received 1 of 3 doses of TMC114 boosted with Norvir or continued to take the failing regimen as a control group. When given for 14 days, TMC114 reduced viral load and was generally well tolerated. Side effects included gastrointestinal symptoms (for example, nausea or diarrhea) and elevations in liver enzymes measured in the blood (which indicate stress on the liver).
SPD754 is an experimental nucleoside reverse transcriptase inhibitor ("nuke") that may be active against HIV that is resistant to other nukes, such as Epivir or Retrovir. In a 10-day study of 63 patients who had never before received HIV treatment, patients were given 1 of 4 doses of SPD754 or a placebo. All doses of SPD754 reduced viral load and no new mutations were detected. Side effects were considered mild to moderate and were similar to side effects experienced by patients who took a placebo. These results are encouraging; however, more study is needed to examine SPD754 in treatment-experienced patients and for longer periods of time.
GW0385 is reported to be a very potent experimental PI that shows strong activity against natural forms of HIV (meaning without drug resistance mutations; this is sometimes called "wild-type" HIV). However, this drug may also be active against HIV that is resistant to other PIs. Early study results show that the effects of GW0385 are enhanced when combined with other PIs or other drug classes like the nukes or non-nukes.
GW433908 (also known as 908 or fosamprenavir) is an experimental PI that will basically be a new formulation of the PI Agenerase, which is considered difficult to take because of the size of the pills and the number required for each dose. The new formulation decreases the pill count and size. At the conference, researchers from the company that is developing 908 presented results from 2 large studies. Both studies were 48 weeks long and compared 3 groups: 1) 908 plus nukes, 2) 908 boosted (with Norvir) plus nukes, and 3) Viracept plus nukes. The researchers studied the development of drug-resistant HIV and found that no patients taking boosted GW433908 developed any drug-resistance mutations, while about 1/3 of patients taking Viracept developed mutations. Some patients taking unboosted GW433908 developed mutations, but not as many as those taking Viracept. As of press time, the FDA approved this agent, which will have the brand name "Lexiva."
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