Conference Highlights

• Heart Attack Debate Continues
• Not-so-Rosy Glitazone
• Treatment Interruption Dangers
• Racial Differences in Sustiva Effectiveness?
• Possible Benefits of Drug-Resistant Virus
• Life-Threatening Events Becoming More Common Than AIDS
• Switching Stavudine
• Vitamin B Belly Buster?
• Anti-HIV Therapy Not Helping Some Immune Cells
• Amprenavir and Delavirdine Interaction
• New Drugs and Therapies

The Annual Retrovirus Conference is the major HIV research meeting in the US. Each year, several thousand healthcare providers, researchers, and community activists meet for 5 days to review the latest developments in the field of HIV. Information at the conference covers new anti-HIV drugs, drug interactions, side effects, vaccine research, and more. You can learn about the conference, read many of the research posters, and even hear some of the science presentations by visiting the conference Web site: www.retroconference.org. The following are some reports from this year's 9th Annual Retrovirus Conference.

Heart Attack Debate Continues

The debate rages on about whether or not elevated blood fats put HIV-infected individuals at increased risk of heart attack or stroke. One study (from multiple locations in the US) found that 13 out of 3,013 patients taking protease inhibitors had heart attacks compared to only 2 out of 2,663 patients not taking protease inhibitors. The number of heart attacks was small overall, and the heart attacks usually happened in people with other risk factors. However, protease inhibitor use was still "strongly associated" with the occurrence of heart attacks. A second study by researchers with the Kaiser Permanente Medical Care Program found no association between types of anti-HIV drugs and risk of heart attack after 5.5 years of follow-up. The study did find a greater rate of heart attacks in HIV-positive versus HIV-negative men and emphasized that longer follow-up is needed. Finally, a study of 36,766 patients treated in US Veterans Health Administration facilities over 8.5 years found no relationship between use of anti-HIV drugs and risk of heart attack or stroke. In fact, when combination anti-HIV therapy was begun, the actual numbers of heart attacks and strokes dropped slightly. The study also found that patients on anti-HIV drugs for 12 months had lower risk of heart attack or stroke than patients who had never been on anti-HIV drugs. Obviously the verdict is still out on this issue, but efforts to lower blood fat levels and reduce the risk of heart attack in HIV-infected people through diet and exercise couldn't hurt.

Not-so-Rosy Glitazone

A drug called "rosiglitazone" that is used for treating people with diabetes does not seem to have an effect on body fat changes commonly experienced by people taking anti-HIV drugs. The drug did seem to improve insulin resistance (a sign of diabetes), but also significantly increased blood fat levels. In addition, liver fat was decreased with rosiglitazone. However, the waist-to-hip ratio and amount of fat in the gut were not improved. The researchers conclude that rosiglitazone treatment cannot reverse body fat changes in HIV-infected patients.

Treatment Interruption Dangers

A study from Europe presented at the conference suggests that treatment interruption increases the risk of AIDS-defining illnesses and death, especially in patients with T-cell counts below 200. The risk of death was greatly increased when T cells were less than 50. The safest range for treatment interruption included T-cell counts above 200. Always consult your health care provider before attempting to interrupt treatment. For more information on treatment interruption, see the CFA fact sheet at: www.centerforaids.org/rita/facts/STI.pdf.

Racial Differences in Sustiva Effectiveness?

A study of HIV-infected patients in a US Department of Defense health care program has found that African Americans may become resistant to efavirenz (Sustiva) therapy faster than Caucasian Americans. Half of the African American patients became resistant to efavirenz after little more than a year (422 days). However, half the Caucasians were still not resistant to efavirenz at almost 4 years (1,400 days). Such differences were not seen in patients taking the protease inhibitors indinavir (Crixivan) or nelfinavir (Viracept) instead of efavirenz as part of their drug regimens. Age, T-cell counts, anti-HIV treatment history, and health care access were similar between African Americans and Caucasians. The researchers have planned more studies to find out the cause for such differences.

Possible Benefits of Drug-Resistant Virus

Continuing their study of "viral fitness" (how well HIV reproduces and infects cells), researchers in California have found more evidence that drug-resistant virus may be weaker than wild-type (natural) virus. The researchers looked at 170 patients divided into 3 groups: those with undetectable viral loads (90), those with detectable viral loads and drug-resistant virus while on anti-HIV treatment (52), and untreated patients (28). The study found that the group with drug-resistant virus had greater HIV-specific immune responses (82%) than either the group with undetectable viral load (14%) or the untreated group (36%). The best responses were seen when viral load levels were 1000 to 10,000. This supports the idea that drug-resistant virus may not be as fit as wild-type virus, so people without many drug options left may still benefit from staying on a "failing" drug regimen.

Life-Threatening Events Becoming More Common Than AIDS

With the widespread use of combination anti-HIV therapy, life-threatening "grade 4" events may now be more common in HIV-infected patients than AIDS-defining illnesses. A report presented at the conference looked back at over 3,000 patients enrolled in 5 large clinical trials during December 1996 to August 2001. Of these patients, 38% had a prior AIDS diagnosis and 45% had never taken anti-HIV therapy. A total of 642 patients had been studied for at least 2.5 years and in this group 27% had a grade 4 event, 13.4% had an AIDS-defining illness, and 10.6% died. The grade 4 events included liver problems (6.1%), low white blood cell counts (3.9%), heart-related or cardiovascular problems (3.2%), pancreatitis (2.2%), low red blood cell counts (2.1%), psychiatric problems (2.1%), kidney problems (1.5%), low blood platelets (1.2%), and internal bleeding or hemorrhage (0.9%). The risk of death associated with a grade 4 event and the risk of death associated with an AIDS-defining illness were both high. This study shows a changing profile of how people with HIV get sick. More studies are needed to look at the overall rates of such events and to better establish the risks and benefits of anti-HIV therapy.

Switching Stavudine

The anti-HIV drug d4T or stavudine (Zerit) has been associated with body fat changes in HIV-infected patients. Although other drugs also have this risk, d4T seems to be most associated with loss of peripheral body fat (fat in the arms, legs, face, and buttocks). Several studies presented at the conference switched d4T for another drug to see if fat loss would improve in people with HIV. One study looked at switching d4T or AZT (Retrovir) for abacavir (Ziagen) in 111 patients. Of this group, 93 were taking d4T and only 18 were taking AZT. After 6 months, special body scans showed significant increases in peripheral body fat in the group that switched to Ziagen compared to the group that stayed on d4T or AZT. However, the patients didn't report any noticeable changes. Two other studies sponsored by the pharmaceutical company that makes Ziagen and AZT looked at switching d4T and found improvements in peripheral fat 6 months and 1 year after the switch. The recovery of peripheral fat is likely to be slow and incomplete (meaning all the fat may not return).

Vitamin B Belly Buster?

A small study by researchers in San Francisco looked at whether or not daily doses of "immediate release" niacin could help boost HDL (good cholesterol) levels and decrease fat in the abdomens of HIV patients experiencing body fat changes. Niacin is an essential B vitamin. The middle dose of niacin taken by the patients was 3,000 mg. Of 16 HIV-infected patients, 13 experienced a decrease in abdominal fat (average decrease of 27%) after taking niacin for 6 months or longer. HDL levels rose and total cholesterol dropped. The longer niacin was used, the greater the amount of fat reduction. It is important to note that this study looked at a small number of patients. However, other research has shown that high-potency B vitamin supplements help HIV-infected people stay healthier in general.

Anti-HIV Therapy Not Helping Some Immune Cells

Combination anti-HIV therapy can help increase T-cell counts and improve the health status of most HIV-infected patients. However, less is known about how anti-HIV treatment affects "B cells," the cousins of the T cells. B cells are an important part of the immune system and help organize antibody responses. (Antibodies are special proteins that are made when an infection happens so that the infection can be quickly stopped if it ever comes back again.) Researchers in San Francisco found abnormal B cell function in patients taking anti-HIV therapy for more than 2 years. Even though T cells were restored, B cells were not. Such incomplete immune restoration may leave HIV-infected patients at increased risk of non-Hodgkin's lymphoma (a B cell cancer) and other immune diseases.

Amprenavir and Delavirdine Interaction

Researchers in Denmark report that the protease inhibitor amprenavir (Agenerase) lowers the levels of delavirdine (Rescriptor). The study was done to see if the combination of the two drugs would help reduce the number of Agenerase pills required per day (16 large pills). The researchers reduced the Agenerase in half. The dose of each drug was 600 mg twice a day. Even though Agenerase levels in the blood were increased, Rescriptor levels dropped dramatically. Until more information is available, caution should be used when prescribing these drugs in combination.

New Drugs and Therapies

Several potentially helpful drugs and therapies are making their way through clinical studies and may eventually become options for people with HIV. However, none of these is a cure.

• Tipranavir is a new protease inhibitor that seems to be effective against resistant virus from heavily treatment-experienced patients.

• Atazanavir is also a new, once-a-day protease inhibitor that does not affect blood fat and cholesterol levels as much as other protease inhibitors. Despite this "superior" fat profile, the drug can cause other side effects like increased bilirubin, a substance in the body that can cause yellow skin if levels are too high.

• T-20 is continuing to show effectiveness in clinical trials, although one study paired T-20 with efavirenz (Sustiva) in patients who had never taken either class of drug. If the patients just switched to Sustiva, they would have likely experienced the same degree of success. Still, T-20 is a member of a new class of drug called "fusion inhibitors" that may be important for patients with few or no options left. One drawback is that the drug requires two injections per day.

• Interleukin-2 (IL-2) has been studied for several years. This therapy is not an anti-HIV drug but an immune therapy designed to boost T-cell counts. IL-2 is injected in cycles that cover several weeks. There are many flu-like side effects associated with IL-2, but lower doses seem better tolerated. Studies presented at the conference indicate that IL-2 may increase the overall survival time of T cells in some patients and may also expand the numbers of naive T cells (which are important because they can learn new "tricks" and aren't just copies of T cells already in the body).

Other new drugs and new classes of drugs are in development, but still need much more study before they can be evaluated. Look for updates in future issues of HIV Treatment ALERTS!

Back to the HIV Treatment ALERTS! April 2002 contents page.