Conference highlights.

The International AIDS Conference occurs every 2 years and most recently was held in Barcelona, Spain, in July 2002. The meeting draws many thousands of researchers, doctors, social and health care workers, people with HIV/AIDS, political figures, and religious leaders. The conference website is www.aids2002.com. Below are some research and treatment highlights from this year's 14th International AIDS Conference.

DOES GENDER PREDICT T CELL RESPONSE TO HAART?

Studies have shown that Blacks and Hispanics with AIDS have a greater likelihood of dying than Whites with AIDS and that women with AIDS have a 20% greater likelihood of dying than men with AIDS. A study conducted at Houston's Thomas Street Clinic by Baylor of College of Medicine researchers looked at whether the T cell response of persons who had "sustained viral suppression" differed by ethnicity or gender, and whether this difference in T cell response might account for the difference in survival. "Sustained viral suppression" was defined as 2 consecutive viral load counts less than 400, the last of which was at least 120 to 240 days from the beginning of highly active antiretroviral therapy (HAART). A total of 79 men and 24 women were included in this analysis. Even after adjusting for variables like AIDS, baseline viral load and T cell count, and use of a protease inhibitor, women were found to have a better T cell response (+66 cells) to sustained viral suppression than men. No difference was found by ethnicity. The researchers conclude that "gender-specific optimal therapy needs to be defined."

GETTING HIV TWICE

Doctors and physicians have debated the question of whether a person can be infected with HIV and then re-infected with another strain. In other words, once you have an established infection with one strain of the virus, can you get another strain? A case was presented at the Barcelona conference suggesting that indeed a person can be infected a second time with a different strain of virus. In that case, a patient was taking anti-HIV medications and undergoing a series of treatment interruptions. After controlling the virus well for some time, the patient's viral load suddenly shot up unexpectedly. At first, the researchers thought that the patient's virus might have mutated into a different, more aggressive strain. After analyzing the patient's virus, they found a different strain of HIV than the one that had originally been detected. After questioning, the patient admitted to having unprotected sex during the time of the appearance of the new strain of HIV. Despite the fact that many doctors and researchers have warned about the possibility of this type of second infection, generally referred to as "superinfection," very few actual cases have been reported.

EARLY TREATMENT TO PRESERVE IMMUNITY

Studies presented at the International AIDS Conference in Barcelona continue to suggest that early treatment to preserve defenses against HIV may work best in persons treated during the earliest time of infection and may not work as well in persons treated even a few weeks later. In one study, patients treated after infection but before testing positive for antibodies were able to maintain a viral load less than 5000 while off anti-HIV drugs for up to 3 years after a series of treatment interruptions. In contrast, patients treated after about 2 months of the initial symptoms of HIV infection (also known as acute retroviral syndrome) were not able to control their viral load when drugs were stopped, even when some of them received a vaccine to help their immune system. The bottom line seems to be that early treatment preserves the immune system's defenses against HIV only if it is started during the earliest moments of that infection, preferably during acute retroviral syndrome.

THE TIMES, THEY ARE A'CHANGING

It used to be that doctors were advised to begin anti-HIV therapy as soon as the patient's T cell count dropped below 500. After a few years it became apparent that HIV would not be eliminated with early treatment and that while anti-HIV drugs are good at suppressing the virus, they also have long-term toxicities. Soon the recommendations changed and the current guidelines for treatment recommend that patients without symptoms wait until their T cell count has dropped below 350 before starting treatment. What if you were one of the patients who started treatment under the previous guidelines? For instance, what if you started therapy when you had 450 T cells? Is it safe to stop your drugs until your T cell count drops to below 350?

A study reported at the Barcelona conference indicates that patients who started anti-HIV drugs at higher T cell counts may safely stop their drugs. In that study, patients who started anti-HIV drugs with more than 350 T cells and a viral load of less than 60,000 were divided into 2 groups. In one group, the patients continued their medications; in the other group, they stopped their drugs. The patients who stopped therapy had a rebound in their viral road, but it was still lower than the viral load they had at the beginning of treatment. Those who stopped had a small drop in their T cell count (only 14 cells at about 6 months). Given the long-term toxicities of anti-HIV drugs, it may be worthwhile stopping them until a time when they become necessary.

FIRST IN CLASS

A study known as CLASS sponsored by GlaxoSmithKline was reported at the Barcelona conference. It combined Ziagen + Epivir with one of the following:

Sustiva

Zerit

Agenerase/Norvir

A total of 297 patients who had never taken anti-HIV drugs were enrolled in the study. Half had a viral load less than 79,500, the other half had a viral load higher than 79,500 (44% of the patients had a viral load of over 100,000 copies). Half the patients had a T cell count greater than 300 and the other half had a T cell count less than 300 (35% had less 200). The combination of Sustiva/Ziagen/Epivir resulted in better viral suppression than the other combinations, even among persons with viral loads greater than 100,000. The T cell count increases were comparable among all 3 regimens.

ACTG 384

The AIDS Clinical Trials Group (ACTG) presented the results of Study 384 at the Barcelona Conference. The study was designed to answer the following questions:

1. Which is better as a backbone drug combination: Retrovir + Epivir or Videx + Zerit?

2. Is Sustiva better than Viracept as an anchor drug?

3. Is a 4-drug regimen better than a 3-drug regimen?

Results in persons who had never taken anti-HIV drugs before this study showed the combination of Retrovir + Epivir to be superior to Videx + Zerit, but only when combined with Sustiva. Sustiva was superior to Viracept, but only when combined with Retrovir + Epivir. Overall, the 4-drug regimen outperformed the 3-drug regimen, but not when compared with the best 3-drug regimen, which was Sustiva + Retrovir + Epivir. Part of the problem with this study is that the twice-a-day tablets of Videx were used in the comparison. The results might have been different if the once-a-day Videx EC had been used. In the end, the results suggest that the combination of Sustiva + Retrovir + Epivir is a good first combination for persons who have never taken anti-HIV drugs.

IS VIREAD AS EFFECTIVE AS ZERIT?

Gilead Sciences reported the results of Study 903 at the Barcelona Conference. The study combined Sustiva + Epivir with one of the following:

Viread

Zerit

The study involved about 600 patients who had never taken anti-HIV drugs. Half the patients had T cell counts greater than 279 and the other half had less than 279. After 48 weeks on the anti-HIV drugs, the 2 combinations produced almost identical viral suppression and T cell increases. The study seems to prove that Zerit and Viread are equivalent when taken as part of a first regimen.

SUSTIVA FOR ADVANCED HIV

A study called EFAVIP-2 (EFAvirenz in Very Immunosuppressed Patients) compared the use of Sustiva and protease inhibitors not boosted by Norvir. The patients in the study all had T cell counts less than 100, high viral loads (half of them with greater than 250,000), and started with an initial regimen that had Sustiva or a protease inhibitor as an anchor drug. More patients quit the study because of side effects and adverse effects in the protease inhibitor group. More patients had continued viral suppression and better T cell increases in the Sustiva group. Some commentators point out that this may not be a fair comparison because almost all protease inhibitors are currently boosted by a small dose of Norvir. But the bottom line is that Sustiva produced good results in patients with very advanced HIV disease.

LOOK MA! NO NUKES!

In a study reported in the Barcelona conference, 33 patients with multiple drug failures were given a combination of only Kaletra and Fortovase (2 protease inhibitors boosted with Norvir) after resistance testing showed the patients were resistant to most nucleoside drugs. After 24 weeks, 82% of patients had a viral load less than 400 and 58% had a viral load less than 50. Half the group experienced a T cell count increase of greater than 158.

MILD LIVER ENZYME ELEVATIONS: SHOULD YOU WORRY?!

Pysicians often comment to their patients that "mild liver enzymes elevations are common among HIV-positive patients" and not a cause for concern. A study reported at the Barcelona conference seems to indicate that this attitude may be wrong. Researchers from Pittsburgh analyzed data from more than 5700 patients and found that persons with mild to moderate elevations of liver enzymes (0.5 times up to 2 times the normal levels) had an increased risk of death--almost double the risk of those with normal enzyme levels. Patients with 2 or more times the normal range had a greater than 5 times increased risk of death. Elevated enzymes are generally associated with damage to the liver that can result from the use of anti-HIV drugs, viral hepatitis, or alcohol abuse. Chronic hepatitis in particular has been known to increase substantially the risk of liver cancer and the researchers conclude that additional research is needed to ensure that anti-HIV drugs are not increasing this risk.

FUZEON

No, it's not the latest water-resistant, fuchsia-colored lipstick from Maybelline. It's a new type of experimental anti-HIV drug that keeps HIV from entering T cells and other susceptible cells. In studies reported at the Barcelona conference, this drug (also known as enfuvirtide and commonly known as T-20) was added to the "optimized" regimen of highly drug-experienced patients. How do you optimize a drug regimen? By taking into account the drug history and using resistance (genotypic and phenotypic) testing, the researchers were able to choose the drugs most likely to work in these drug-experienced patients. The patients were then divided into 2 groups. In one group, the participants were given the optimized regimen; in the other group, the participants were given the optimized regimen plus Fuzeon. Two studies using this design were reported. The first study called TORO-1 (T-20 versus Optimized Regimen Only) had the following results:

                            T-20 + Optimized    Optimized
                            Regimen             Regimen Only

Viral Load less than 400    37%                 16%
Viral Load less than 50     19%                  7%
T cell increase             +76 cells           +32 cells

The second study called TORO-2 had the following rersults:

                            T-20 + Optimized    Optimized
                            Regimen             Regimen Only

Viral Load less than 400    28%                 13%
Viral Load less than 50     12%                  5%
T cell increase

Fuzeon is given by an injection and almost all patients receiving it reported some injections site inflammation, although less than 3% discounted for this reason. Fuzeon is expected to go before the FDA sometime late this year or early next year.