(RITA!) HIV Treatment Alerts - May 2003

The Annual Retrovirus Conference is the major HIV research meeting in the US. Each winter, the conference brings together several thousand healthcare providers, researchers, and community activists to review the latest developments in the field of HIV. Over 5 days, the conference covers research on experimental anti-HIV drugs, drug interactions, side effects, potential vaccines, and more. Information about the conference, many of the research posters, and recorded presentations are available at the conference website: www.retroconference.org. The following are some reports from this year's 10^th Annual Retrovirus Conference, which was held in Boston.

Reversing fat loss?
Several presentations at the conference focused on treatments for lipodystrophy, which happens to many people with HIV. One symptom is fat loss in the face. Two French studies looked at the effects of injections of polylactic acid (New-fill) in the face. New-fill is a substance that stimulates production of collagen, a natural protein found in skin. New-fill is not yet approved for use in the US, but efforts are underway to apply for approval. In the studies, patients experienced increased skin thickness after a series of injections, roughly 2 weeks apart. Massaging the skin after injection seemed to help improve the New-fill distribution. In one study, skin thickening in areas of fat wasting was seen out to 72 and 96 weeks. Some side effects were reported including mild to moderate pain and swelling after injections. Twenty-two patients (44%) in one study experienced the formation of small bumps in the skin (they could be felt but not seen at a distance); these disappeared in some patients by 96 weeks after the injections began. Most patients in these studies reported satisfaction with the effects of this therapy. However, more research is needed.

Liposuction for lipodystrophy
Another aspect of lipodystrophy involves fat accumulation at the back and sides of the neck. This fat gives the appearance of a hump and is commonly called "buffalo hump." Patients suffering from buffalo hump usually experience pain and limited range of head motion, depending on the severity of fat accumulation. Also, this fat is usually tougher than subcutaneous fat, making surgical removal more difficult. Several presentations at the conference reported on the use of liposuction (specifically "ultrasound-assisted" liposuction) to remove accumulated fat around the head and neck. Although most patients experienced improvement, buffalo hump returned (at least partially) in as many as a third of patients (in one study of 23 patients) by 6 months or later after surgery. In 2 studies, some patients experienced complications such as anemia, infection, and minor facial nerve damage. In contrast, another study reported very few complications and return of buffalo hump in only 1 patient (out of 18).

Battling bone loss
Bone loss and thinning bones are a problem in many people with HIV/AIDS that may be caused by anti-HIV drugs or HIV itself. A small study of 31 patients on HIV therapy showed that bone loss can be improved using a combination of a drug called Fosamax plus Vitamin D and calcium. The patients who took all 3 showed an increase in bone mineral density compared to patients who only took vitamin D and calcium. This increase was seen in the lower (lumbar) spine, but not as much in other areas such as the hip and neck. However, this study does show that this 3-pronged approach to bone loss in HIV+ people may be as effective as in HIV-negative people. Larger studies are needed to verify the results of this small study.

Weakness Warning
Over the past couple of years, there have been reports of progressive neuromuscular weakness in patients with HIV who are taking nucleoside reverse transcriptase inhibitors ("nukes"). These drugs include Videx, Zerit, Hivid, Retrovir, Epivir, and Ziagen. One report at the conference looked at 55 HIV+ patients with neuromuscular weakness. This problem can sometimes be caused by lactic acidosis (a build-up of lactic acid in the body). Lactic acidosis can cause many problems such as vomiting, abdominal pain, muscle pain or weakness, breathing problems, and even death. The researchers found that 58% of these patients had vomiting/nausea and abdominal pain, 44% had liver or pancreas inflammation, and 59% had increased levels of lactic acid in their blood. Of the 55 patients, 47 were taking Zerit, 27 were taking Epivir, and 23 were taking Videx as part of their drug regimens. Also, 36 of these patients had follow-up records indicating that 14 recovered, 13 had severe continued weakness, and 9 died. This is clearly a life-threatening situation that patients and doctors must watch out for and react quickly to if such symptoms appear.

Treatment interruptions: no verdict yet
Two back-to-back presentations at the conference show the ongoing problems with studying anti-HIV treatment interruptions. The first presentation, on a study called CPCRA 064, looked at whether it was better to take a 4-month treatment interruption before switching anti-HIV treatments or to just switch treatment right away. After only 20 months, the study was stopped because the group that interrupted treatment had almost twice as many opportunistic infections and much lower T cell counts. The second presentation, however, used 2-month treatment interruptions before starting a new treatment using 8 to 9 drugs. The group with the treatment interruption responded better in viral load and T cells than the group that immediately switched therapy. There is no sure explanation for these different results, but one possibility may be that shorter interruptions work better.

Playing with protease inhibitors
In highly treatment-experienced patients, there are very few, if any, anti-HIV medications to take because of drug-resistant HIV. The real challenge becomes staying alive until new drugs or treatments are approved. Some researchers, such as Dr. Steven Deeks from the University of California at San Francisco, have concentrated on innovative ways to keep these "salvage" patients alive. Out of such research has come the idea that drug-resistant (or mutated) viruses may not be as deadly as the natural virus that exists when drugs are not in the body. For example, keeping patients on drugs that don't work seems to preserve T cells longer. In his presentation at the conference, Dr. Deeks showed some very early research on what he called "partial treatment interruptions." Rather than stopping all anti-HIV therapy, patients stopped just their nukes or just their protease inhibitors—mainly to reduce toxicity. The researchers found that the patients who stopped protease inhibitors but continued taking nukes were able to maintain stable viral loads. However, the 15 patients who stopped their nukes but continued taking protease inhibitors experienced a rapid increase in their viral loads. More patients must be studied for longer periods of time to see if partial treatment interruptions of protease inhibitors can help highly treatment-experienced patients stay alive longer.

New drugs and therapies
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.

• GW433908 or "fos-amprenavir" is a new form of the approved protease inhibitor, Agenerase. The reason this drug is important is that the current version of Agenerase requires taking 16 large capsules a day. The new form would cut that down to about 2 regular-size pills twice a day, or once a day if taken with a small amount of Norvir, another protease inhibitor. Agenerase has a different resistance pattern from several other protease inhibitors and therefore may be another option after treatment failure.
  
• TNX-355 is an experimental antibody that binds to the CD4 receptor on T cells. Early study results in humans indicate that a single injection of TNX-355 in treatment-experienced patients reduces viral load significantly for out to 14 days or longer, depending on the dose. These are early results and more studies are planned. This potential therapy is being developed by Tanox, Inc., a company in Houston.
  
• Amdoxovir or DAPD is an experimental nuke that has been studied for several years. In a study of 18 treatment-experienced patients, the drug showed T cell increases and viral load decreases after 3 months However, 2 patients could not achieve viral load decreases, 3 patients were considered "noncompliant" (which means they did not or could not follow the study's instructions for taking the drug), and 5 patients stopped taking the drug because of changes in their vision. This drug needs longer study in more patients, with special attention paid to side effects involving the eyes.
  
• TMC114 is an experimental protease inhibitor that may be active against HIV that is resistant to other protease inhibitors. Early research in treatment-experienced patients showed that TMC114 reduced viral load after 14 days. However, several side effects were seen. More study is needed to determine the safety and long-term effectiveness of this potential drug.

20030510
RI030502

Copyright © 2003 - Research Initiative Treatment Action (RITA!). Reproduced with permission. RITA! is published by The Center for AIDS. Contact Thomas Gegeny, MS, ELS, Editor, RITA! for permission to reproduce RITA!. tom@centerforaids.org. http://www.centerforaids.org

ÆGiS is made possible through unrestricted grants from Boehringer Ingelheim, iMetrikus, Inc., the National Library of Medicine, and donations from users like you. Always watch for outdated information. This article first appeared in 2003. This material is designed to support, not replace, the relationship that exists between you and your doctor.

ÆGiS presents published material, reprinted with permission and neither endorses nor opposes any material. All information contained on this website, including information relating to health conditions, products, and treatments, is for informational purposes only. It is often presented in summary or aggregate form. It is not meant to be a substitute for the advice provided by your own physician or other medical professionals. Always discuss treatment options with a doctor who specializes in treating HIV.

Copyright ©1985, 2003. ÆGiS . All materials appearing on ÆGiS are protected by copyright as a collective work or compilation under U.S. copyright and other laws and are the property of ÆGIS , or the party credited as the provider of the content.