Timothy F. Kirn

SAN FRANCISCO — The expected introduction of the integrase inhibitors will usher in the most exciting time in HIV treatment since the advent of highly active antiretroviral therapy, Dr. George Beatty predicted at a meeting on HIV management sponsored by the University of California, San Francisco.

The drug that is furthest along in trials, MK-0518, is “one of the most potent things I have ever seen,” said Dr. Beatty, commenting on recent trial results. “Clearly, MK-0518 can really kick butt.”

In the initial study in patients, MK-0518 (Merck) reduced viral loads by 2 log10 in just 10 days, a finding that was consistent with recent, double-blind trials, said Dr. Beatty, director of the HIV clinical trials group at the University of California, San Francisco, who did not participate in the trials and who said he had no conflicts of interest regarding the manufacturer.

All of the studies were presented at HIV meetings in 2006.

In the most recent of those studies, treatment-experienced patients with serious drug-resistant disease were randomly assigned to receive one of three doses of the new drug or placebo in addition to continuing their optimized background therapy. There were about 40 patients in each group.

At 16 weeks, 50% of the patients who were treated with MK-0518 had a viral load below 50 copies/mL, regardless of which dose they received, compared with only about 20% of patients on placebo.

At 24 weeks, 67% of the patients who were on active therapy had a viral load below 50 copies/mL.

The response rate was even more impressive in the subgroup whose background medications included enfuvirtide, also known as T20, an anti-HIV entry inhibitor. Overall, 90% of those patients achieved a viral load below 50 copies/mL at 24 weeks.

The patients in this trial were difficult to treat, with resistance to at least one drug in each of the three main classes of HIV medication, Dr. Beatty noted.

“It's sexy data,” he said, of all the trials of MK-0518 to date.

Integrase inhibitors prevent DNA created by the retrovirus from becoming incorporated into the host cell DNA, thereby blocking reproduction.

MK-0518 is currently available through an expanded access research program to patients whose infection was previously uncontrolled.

A second integrase inhibitor that is “close on the heels” of MK-0518 in development is GS-9137 (Gilead), Dr. Beatty said. This drug also has shown the ability to reduce viral load by 2 log10 in about 10 days.

“It appears that Merck has not cornered the market on potency, and that this degree of potency is a class effect,” he said.

One difference between the two drugs is that MK-0518 requires twice daily dosing, while GS-9137 uses once daily dosing.

Also, MK-0518 is metabolized by glucuronidation, so it does not appear to have any significant drug-drug interactions.

GS-9137, on the other hand, is metabolized by cytochrome P3A, so it may interact with other drugs.

Also, GS-9137 can be boosted with ritonavir, while MK-0518 cannot.

So far, the drugs appear to be very well tolerated. However, one patient in the MK-0518 trial developed abnormal liver enzymes that appeared to be drug related.

In vitro data suggest that when resistance does develop, it is broad resistance to all drugs in the class, Dr. Beatty added.

SAN FRANCISCO — The expected introduction of the integrase inhibitors will usher in the most exciting time in HIV treatment since the advent of highly active antiretroviral therapy, Dr. George Beatty predicted at a meeting on HIV management sponsored by the University of California, San Francisco.

The drug that is furthest along in trials, MK-0518, is “one of the most potent things I have ever seen,” said Dr. Beatty, commenting on recent trial results. “Clearly, MK-0518 can really kick butt.”

In the initial study in patients, MK-0518 (Merck) reduced viral loads by 2 log10 in just 10 days, a finding that was consistent with recent, double-blind trials, said Dr. Beatty, director of the HIV clinical trials group at the University of California, San Francisco, who did not participate in the trials and who said he had no conflicts of interest regarding the manufacturer.

All of the studies were presented at HIV meetings in 2006.

In the most recent of those studies, treatment-experienced patients with serious drug-resistant disease were randomly assigned to receive one of three doses of the new drug or placebo in addition to continuing their optimized background therapy. There were about 40 patients in each group.

At 16 weeks, 50% of the patients who were treated with MK-0518 had a viral load below 50 copies/mL, regardless of which dose they received, compared with only about 20% of patients on placebo.

At 24 weeks, 67% of the patients who were on active therapy had a viral load below 50 copies/mL.

The response rate was even more impressive in the subgroup whose background medications included enfuvirtide, also known as T20, an anti-HIV entry inhibitor. Overall, 90% of those patients achieved a viral load below 50 copies/mL at 24 weeks.

The patients in this trial were difficult to treat, with resistance to at least one drug in each of the three main classes of HIV medication, Dr. Beatty noted.

“It's sexy data,” he said, of all the trials of MK-0518 to date.

Integrase inhibitors prevent DNA created by the retrovirus from becoming incorporated into the host cell DNA, thereby blocking reproduction.

MK-0518 is currently available through an expanded access research program to patients whose infection was previously uncontrolled.

A second integrase inhibitor that is “close on the heels” of MK-0518 in development is GS-9137 (Gilead), Dr. Beatty said. This drug also has shown the ability to reduce viral load by 2 log10 in about 10 days.

“It appears that Merck has not cornered the market on potency, and that this degree of potency is a class effect,” he said.

One difference between the two drugs is that MK-0518 requires twice daily dosing, while GS-9137 uses once daily dosing.

Also, MK-0518 is metabolized by glucuronidation, so it does not appear to have any significant drug-drug interactions.

GS-9137, on the other hand, is metabolized by cytochrome P3A, so it may interact with other drugs.

Also, GS-9137 can be boosted with ritonavir, while MK-0518 cannot.

So far, the drugs appear to be very well tolerated. However, one patient in the MK-0518 trial developed abnormal liver enzymes that appeared to be drug related.

In vitro data suggest that when resistance does develop, it is broad resistance to all drugs in the class, Dr. Beatty added.

SAN FRANCISCO — The expected introduction of the integrase inhibitors will usher in the most exciting time in HIV treatment since the advent of highly active antiretroviral therapy, Dr. George Beatty predicted at a meeting on HIV management sponsored by the University of California, San Francisco.

The drug that is furthest along in trials, MK-0518, is “one of the most potent things I have ever seen,” said Dr. Beatty, commenting on recent trial results. “Clearly, MK-0518 can really kick butt.”

In the initial study in patients, MK-0518 (Merck) reduced viral loads by 2 log10 in just 10 days, a finding that was consistent with recent, double-blind trials, said Dr. Beatty, director of the HIV clinical trials group at the University of California, San Francisco, who did not participate in the trials and who said he had no conflicts of interest regarding the manufacturer.

All of the studies were presented at HIV meetings in 2006.

In the most recent of those studies, treatment-experienced patients with serious drug-resistant disease were randomly assigned to receive one of three doses of the new drug or placebo in addition to continuing their optimized background therapy. There were about 40 patients in each group.

At 16 weeks, 50% of the patients who were treated with MK-0518 had a viral load below 50 copies/mL, regardless of which dose they received, compared with only about 20% of patients on placebo.

At 24 weeks, 67% of the patients who were on active therapy had a viral load below 50 copies/mL.

The response rate was even more impressive in the subgroup whose background medications included enfuvirtide, also known as T20, an anti-HIV entry inhibitor. Overall, 90% of those patients achieved a viral load below 50 copies/mL at 24 weeks.

The patients in this trial were difficult to treat, with resistance to at least one drug in each of the three main classes of HIV medication, Dr. Beatty noted.

“It's sexy data,” he said, of all the trials of MK-0518 to date.

Integrase inhibitors prevent DNA created by the retrovirus from becoming incorporated into the host cell DNA, thereby blocking reproduction.

MK-0518 is currently available through an expanded access research program to patients whose infection was previously uncontrolled.

A second integrase inhibitor that is “close on the heels” of MK-0518 in development is GS-9137 (Gilead), Dr. Beatty said. This drug also has shown the ability to reduce viral load by 2 log10 in about 10 days.

“It appears that Merck has not cornered the market on potency, and that this degree of potency is a class effect,” he said.

One difference between the two drugs is that MK-0518 requires twice daily dosing, while GS-9137 uses once daily dosing.

Also, MK-0518 is metabolized by glucuronidation, so it does not appear to have any significant drug-drug interactions.

GS-9137, on the other hand, is metabolized by cytochrome P3A, so it may interact with other drugs.

Also, GS-9137 can be boosted with ritonavir, while MK-0518 cannot.

So far, the drugs appear to be very well tolerated. However, one patient in the MK-0518 trial developed abnormal liver enzymes that appeared to be drug related.

In vitro data suggest that when resistance does develop, it is broad resistance to all drugs in the class, Dr. Beatty added.

PALM DESERT, CALIF. — Performing repeated plasma skin resurfacing at low fluences improves wrinkles and results in much less patient downtime than does the use of higher fluences, Dr. Melissa Bogle reported at the annual meeting of the American Society for Dermatologic Surgery.

Many previous case series of plasma skin resurfacing have reported patients undergoing a single treatment with a fluence of 3–4 J/cm

In Dr. Bogle's series, eight patients were treated at fluences of 1.2–1.8 J/cm

The plasma device, the Portrait PSR

Each patient in the series received three full face treatments, one every 3 weeks. Sloughing lasted longer after the first treatment (average 9 days) than after the second and third treatments (4 days).

Erythema persisted for 6 days and tended to be mild. The average erythema score of the patients following a treatment was 1.8 on a 0–4 erythema scale, which Dr. Bogle described as being "between minimal and mild, closer to mild."

Dr. Bogle could not account for why sloughing lasted longer with the first procedure. Some experts now use even lower fluences than she used in her study, and a lower fluence for the first treatment than for the second and third.

The investigators rated the improvement in facial rhytids at 23% after 1 month and 37% after 3 months. Histologic samples taken from the upper lip area of six of the patients before and after treatment showed an increase in collagen thickness at the dermal-epidermal junction and less dense elastin in the collagen zone.

Dr. Bogle received a research grant from Rhytec, the maker of the Portrait device.

PALM DESERT, CALIF. — Performing repeated plasma skin resurfacing at low fluences improves wrinkles and results in much less patient downtime than does the use of higher fluences, Dr. Melissa Bogle reported at the annual meeting of the American Society for Dermatologic Surgery.

Many previous case series of plasma skin resurfacing have reported patients undergoing a single treatment with a fluence of 3–4 J/cm

In Dr. Bogle's series, eight patients were treated at fluences of 1.2–1.8 J/cm

The plasma device, the Portrait PSR

Each patient in the series received three full face treatments, one every 3 weeks. Sloughing lasted longer after the first treatment (average 9 days) than after the second and third treatments (4 days).

Erythema persisted for 6 days and tended to be mild. The average erythema score of the patients following a treatment was 1.8 on a 0–4 erythema scale, which Dr. Bogle described as being "between minimal and mild, closer to mild."

Dr. Bogle could not account for why sloughing lasted longer with the first procedure. Some experts now use even lower fluences than she used in her study, and a lower fluence for the first treatment than for the second and third.

The investigators rated the improvement in facial rhytids at 23% after 1 month and 37% after 3 months. Histologic samples taken from the upper lip area of six of the patients before and after treatment showed an increase in collagen thickness at the dermal-epidermal junction and less dense elastin in the collagen zone.

Dr. Bogle received a research grant from Rhytec, the maker of the Portrait device.

PALM DESERT, CALIF. — Performing repeated plasma skin resurfacing at low fluences improves wrinkles and results in much less patient downtime than does the use of higher fluences, Dr. Melissa Bogle reported at the annual meeting of the American Society for Dermatologic Surgery.

Many previous case series of plasma skin resurfacing have reported patients undergoing a single treatment with a fluence of 3–4 J/cm

In Dr. Bogle's series, eight patients were treated at fluences of 1.2–1.8 J/cm

The plasma device, the Portrait PSR

Each patient in the series received three full face treatments, one every 3 weeks. Sloughing lasted longer after the first treatment (average 9 days) than after the second and third treatments (4 days).

Erythema persisted for 6 days and tended to be mild. The average erythema score of the patients following a treatment was 1.8 on a 0–4 erythema scale, which Dr. Bogle described as being "between minimal and mild, closer to mild."

Dr. Bogle could not account for why sloughing lasted longer with the first procedure. Some experts now use even lower fluences than she used in her study, and a lower fluence for the first treatment than for the second and third.

The investigators rated the improvement in facial rhytids at 23% after 1 month and 37% after 3 months. Histologic samples taken from the upper lip area of six of the patients before and after treatment showed an increase in collagen thickness at the dermal-epidermal junction and less dense elastin in the collagen zone.

Dr. Bogle received a research grant from Rhytec, the maker of the Portrait device.

PALM DESERT, CALIF. — The 755-nm alexandrite laser was highly effective in improving lentigines in 18 volunteers treated at Naval Hospital Camp Pendleton, Lt. Cmdr. John Paul Trafeli, USN, said at the annual meeting of the American Society for Dermatologic Surgery.

Independent reviewers judged that the patients had a 60% average improvement in their lentigines after a single treatment with one or two passes of the alexandrite laser, which is more commonly used for hair removal.

Dr. Trafeli said that 18 patients were also treated for facial telangiectasis in the same study, but the results were not quite as good. Those patients had a 30% average improvement.

"For telangiectasis, the alexandrite laser is a ground ball, but for lentigo, it is a definite home run," he said.

After experimenting with several parameters on test areas, the investigators generally settled on a 3-millisecond pulse duration at 34 J/cm

Increasing the pulse duration improved the background epidermal tolerance and did not work as well.

The 755-nm alexandrite laser is an "interesting" wavelength because it appears to be optimal for absorption in areas of dyspigmentation, Dr. Trafeli said.

It has a high absorption by melanin relative to hemoglobin, compared with the 532-nm and 595-nm lasers, and it has three times the melanin absorption of the 1064-nm laser.

"The nicest thing about this alexandrite is that it is very fast and simple," he added.

"I liken it to a lawn mower. You don't need much skill. You just kind of go over the whole face."

PALM DESERT, CALIF. — The 755-nm alexandrite laser was highly effective in improving lentigines in 18 volunteers treated at Naval Hospital Camp Pendleton, Lt. Cmdr. John Paul Trafeli, USN, said at the annual meeting of the American Society for Dermatologic Surgery.

Independent reviewers judged that the patients had a 60% average improvement in their lentigines after a single treatment with one or two passes of the alexandrite laser, which is more commonly used for hair removal.

Dr. Trafeli said that 18 patients were also treated for facial telangiectasis in the same study, but the results were not quite as good. Those patients had a 30% average improvement.

"For telangiectasis, the alexandrite laser is a ground ball, but for lentigo, it is a definite home run," he said.

After experimenting with several parameters on test areas, the investigators generally settled on a 3-millisecond pulse duration at 34 J/cm

Increasing the pulse duration improved the background epidermal tolerance and did not work as well.

The 755-nm alexandrite laser is an "interesting" wavelength because it appears to be optimal for absorption in areas of dyspigmentation, Dr. Trafeli said.

It has a high absorption by melanin relative to hemoglobin, compared with the 532-nm and 595-nm lasers, and it has three times the melanin absorption of the 1064-nm laser.

"The nicest thing about this alexandrite is that it is very fast and simple," he added.

"I liken it to a lawn mower. You don't need much skill. You just kind of go over the whole face."

PALM DESERT, CALIF. — The 755-nm alexandrite laser was highly effective in improving lentigines in 18 volunteers treated at Naval Hospital Camp Pendleton, Lt. Cmdr. John Paul Trafeli, USN, said at the annual meeting of the American Society for Dermatologic Surgery.

Independent reviewers judged that the patients had a 60% average improvement in their lentigines after a single treatment with one or two passes of the alexandrite laser, which is more commonly used for hair removal.

Dr. Trafeli said that 18 patients were also treated for facial telangiectasis in the same study, but the results were not quite as good. Those patients had a 30% average improvement.

"For telangiectasis, the alexandrite laser is a ground ball, but for lentigo, it is a definite home run," he said.

After experimenting with several parameters on test areas, the investigators generally settled on a 3-millisecond pulse duration at 34 J/cm

Increasing the pulse duration improved the background epidermal tolerance and did not work as well.

The 755-nm alexandrite laser is an "interesting" wavelength because it appears to be optimal for absorption in areas of dyspigmentation, Dr. Trafeli said.

It has a high absorption by melanin relative to hemoglobin, compared with the 532-nm and 595-nm lasers, and it has three times the melanin absorption of the 1064-nm laser.

"The nicest thing about this alexandrite is that it is very fast and simple," he added.

"I liken it to a lawn mower. You don't need much skill. You just kind of go over the whole face."

PALM DESERT, CALIF. — The one-two punch of a combination pulsed dye/Nd:YAG laser system can enhance the treatment of hypertrophic port wine stains, Dr. Elizabeth Tanzi said at the annual meeting of the American Society for Dermatologic Surgery.

Dr. Tanzi presented data on 25 patients with recalcitrant and hypertrophic port wine stains that she treated using the Cynergy laser workstation. All of the patients had at least 10 previous treatments that had not yielded a satisfactory result.

With the combined laser system, which was introduced in the United States last year by Cynosure Inc., all of the patients had "continued" improvement with four to six treatments, as judged by two independent reviewers 3 months after the last treatment, said Dr. Tanzi, a dermatologist in practice in Washington.

"This is a double whammy, so to speak. We really get a double hit on the vasculature," she said.

Pulsed dye laser treatment works well for many port wine stains, but not those that are thick and hypertrophic. The combination system appears to be better because treatment first with the pulsed dye laser heats hemoglobin and damages the vasculature but also creates a new chromophore susceptible to the Nd:YAG treatment that follows, she said.

One patient who had improvement with the Cynergy laser had received 16 previous treatments.

The Cynergy system allows the operator to fire both lasers through the same handpiece, so there is no need to change between treatments, which allows for quick firing between lasers, Dr. Tanzi said.

The patients were each treated at 6-month intervals. The spot size was 1 mm. The fluence used for the pulsed dye laser (595 nm) was 77.5 J with a pulse duration of 100 milliseconds; the fluence for the Nd:YAG laser was 30–50 J, with a pulse duration of 15 milliseconds. The delay between the two lasers' pulses was 0.5–1 millisecond.

Patients had some edema afterward that lasted for 1–4 days, but there was no vesicle formation, no dyspigmentation, and no scarring, she reported.

Dr. Tanzi said that the Cynergy workstation was provided to her clinic for the investigation by Cynosure.

PALM DESERT, CALIF. — The one-two punch of a combination pulsed dye/Nd:YAG laser system can enhance the treatment of hypertrophic port wine stains, Dr. Elizabeth Tanzi said at the annual meeting of the American Society for Dermatologic Surgery.

Dr. Tanzi presented data on 25 patients with recalcitrant and hypertrophic port wine stains that she treated using the Cynergy laser workstation. All of the patients had at least 10 previous treatments that had not yielded a satisfactory result.

With the combined laser system, which was introduced in the United States last year by Cynosure Inc., all of the patients had "continued" improvement with four to six treatments, as judged by two independent reviewers 3 months after the last treatment, said Dr. Tanzi, a dermatologist in practice in Washington.

"This is a double whammy, so to speak. We really get a double hit on the vasculature," she said.

Pulsed dye laser treatment works well for many port wine stains, but not those that are thick and hypertrophic. The combination system appears to be better because treatment first with the pulsed dye laser heats hemoglobin and damages the vasculature but also creates a new chromophore susceptible to the Nd:YAG treatment that follows, she said.

One patient who had improvement with the Cynergy laser had received 16 previous treatments.

The Cynergy system allows the operator to fire both lasers through the same handpiece, so there is no need to change between treatments, which allows for quick firing between lasers, Dr. Tanzi said.

The patients were each treated at 6-month intervals. The spot size was 1 mm. The fluence used for the pulsed dye laser (595 nm) was 77.5 J with a pulse duration of 100 milliseconds; the fluence for the Nd:YAG laser was 30–50 J, with a pulse duration of 15 milliseconds. The delay between the two lasers' pulses was 0.5–1 millisecond.

Patients had some edema afterward that lasted for 1–4 days, but there was no vesicle formation, no dyspigmentation, and no scarring, she reported.

Dr. Tanzi said that the Cynergy workstation was provided to her clinic for the investigation by Cynosure.

PALM DESERT, CALIF. — The one-two punch of a combination pulsed dye/Nd:YAG laser system can enhance the treatment of hypertrophic port wine stains, Dr. Elizabeth Tanzi said at the annual meeting of the American Society for Dermatologic Surgery.

Dr. Tanzi presented data on 25 patients with recalcitrant and hypertrophic port wine stains that she treated using the Cynergy laser workstation. All of the patients had at least 10 previous treatments that had not yielded a satisfactory result.

With the combined laser system, which was introduced in the United States last year by Cynosure Inc., all of the patients had "continued" improvement with four to six treatments, as judged by two independent reviewers 3 months after the last treatment, said Dr. Tanzi, a dermatologist in practice in Washington.

"This is a double whammy, so to speak. We really get a double hit on the vasculature," she said.

Pulsed dye laser treatment works well for many port wine stains, but not those that are thick and hypertrophic. The combination system appears to be better because treatment first with the pulsed dye laser heats hemoglobin and damages the vasculature but also creates a new chromophore susceptible to the Nd:YAG treatment that follows, she said.

One patient who had improvement with the Cynergy laser had received 16 previous treatments.

The Cynergy system allows the operator to fire both lasers through the same handpiece, so there is no need to change between treatments, which allows for quick firing between lasers, Dr. Tanzi said.

The patients were each treated at 6-month intervals. The spot size was 1 mm. The fluence used for the pulsed dye laser (595 nm) was 77.5 J with a pulse duration of 100 milliseconds; the fluence for the Nd:YAG laser was 30–50 J, with a pulse duration of 15 milliseconds. The delay between the two lasers' pulses was 0.5–1 millisecond.

Patients had some edema afterward that lasted for 1–4 days, but there was no vesicle formation, no dyspigmentation, and no scarring, she reported.

Dr. Tanzi said that the Cynergy workstation was provided to her clinic for the investigation by Cynosure.

SAN DIEGO — The use of the Mohs technique for melanoma is probably limited to those with a Breslow thickness of 1 mm, because in melanomas thicker than that, sentinel node biopsy takes precedence, Dr. Kenneth Gross said at a meeting sponsored by the American Society for Mohs Surgery.

Much of the important work establishing the safety of the Mohs approach in melanoma has been done by Dr. John Zitelli of Pittsburgh, said Dr. Gross, who practices surgical dermatology in San Diego.

In studies with 5-year follow-up on patients, Dr. Zitelli has shown that recurrence rates and mortality using a Mohs technique are equivalent to, or better than, those of historical controls treated with conventional surgery using recommended margins.

However, for those melanomas with a Breslow thickness of between 1 mm and 3.5 mm, surgical oncologists like to know the results of a sentinel node biopsy, Dr. Gross noted. The reason they do is that the Multicenter Selective Lymphadenectomy Trial showed that this could be very important in intermediate thickness lesions. Five-year survival among those individuals in the trial who were found to have positive nodes was 72% when patients had immediate lymphadenectomy, but only 52% when the lymphadenectomy was delayed (N. Engl. J. Med. 2006;355:1307–17).

Dr. Gross said when he performs Mohs on a patient with melanoma he is careful to obtain a detailed consent from the patient. He also uses a Wood's lamp and magnification before and during the procedure to be sure he is seeing all it is possible to see.

When removing and sectioning a melanoma, Dr. Zitelli often takes the tumor plus about a 3-mm margin in the first stage, and he takes the specimen all the way down to the fat, Dr. Gross said.

Dr. Gross said he takes sections slightly larger than standard, and once he believes he has a clear margin, he removes another 4–5 mm which is sent for permanent sectioning. He also has a pathologist reading his slides with him.

What constitutes a clear margin has been defined by Dr. Zitelli as a margin that does not have three or more unusual melanocytes or melanocytes above the dermal-epidermal junction.

Dr. Gross said that he often uses Mohs zinc chloride paste, applying the escharotic agent to the lesion the night before the surgery is to be performed, and that he also often uses the MART-1 (melanoma antigen recognized by T-cells 1 staining) immunostain.

Because he takes a fairly large margin around the melanoma lesion when he makes his first Mohs excision, 90% of his melanoma cases are cleared on the first stage, Dr. Gross said.

SAN DIEGO — The use of the Mohs technique for melanoma is probably limited to those with a Breslow thickness of 1 mm, because in melanomas thicker than that, sentinel node biopsy takes precedence, Dr. Kenneth Gross said at a meeting sponsored by the American Society for Mohs Surgery.

Much of the important work establishing the safety of the Mohs approach in melanoma has been done by Dr. John Zitelli of Pittsburgh, said Dr. Gross, who practices surgical dermatology in San Diego.

In studies with 5-year follow-up on patients, Dr. Zitelli has shown that recurrence rates and mortality using a Mohs technique are equivalent to, or better than, those of historical controls treated with conventional surgery using recommended margins.

However, for those melanomas with a Breslow thickness of between 1 mm and 3.5 mm, surgical oncologists like to know the results of a sentinel node biopsy, Dr. Gross noted. The reason they do is that the Multicenter Selective Lymphadenectomy Trial showed that this could be very important in intermediate thickness lesions. Five-year survival among those individuals in the trial who were found to have positive nodes was 72% when patients had immediate lymphadenectomy, but only 52% when the lymphadenectomy was delayed (N. Engl. J. Med. 2006;355:1307–17).

Dr. Gross said when he performs Mohs on a patient with melanoma he is careful to obtain a detailed consent from the patient. He also uses a Wood's lamp and magnification before and during the procedure to be sure he is seeing all it is possible to see.

When removing and sectioning a melanoma, Dr. Zitelli often takes the tumor plus about a 3-mm margin in the first stage, and he takes the specimen all the way down to the fat, Dr. Gross said.

Dr. Gross said he takes sections slightly larger than standard, and once he believes he has a clear margin, he removes another 4–5 mm which is sent for permanent sectioning. He also has a pathologist reading his slides with him.

What constitutes a clear margin has been defined by Dr. Zitelli as a margin that does not have three or more unusual melanocytes or melanocytes above the dermal-epidermal junction.

Dr. Gross said that he often uses Mohs zinc chloride paste, applying the escharotic agent to the lesion the night before the surgery is to be performed, and that he also often uses the MART-1 (melanoma antigen recognized by T-cells 1 staining) immunostain.

Because he takes a fairly large margin around the melanoma lesion when he makes his first Mohs excision, 90% of his melanoma cases are cleared on the first stage, Dr. Gross said.

SAN DIEGO — The use of the Mohs technique for melanoma is probably limited to those with a Breslow thickness of 1 mm, because in melanomas thicker than that, sentinel node biopsy takes precedence, Dr. Kenneth Gross said at a meeting sponsored by the American Society for Mohs Surgery.

Much of the important work establishing the safety of the Mohs approach in melanoma has been done by Dr. John Zitelli of Pittsburgh, said Dr. Gross, who practices surgical dermatology in San Diego.

In studies with 5-year follow-up on patients, Dr. Zitelli has shown that recurrence rates and mortality using a Mohs technique are equivalent to, or better than, those of historical controls treated with conventional surgery using recommended margins.

However, for those melanomas with a Breslow thickness of between 1 mm and 3.5 mm, surgical oncologists like to know the results of a sentinel node biopsy, Dr. Gross noted. The reason they do is that the Multicenter Selective Lymphadenectomy Trial showed that this could be very important in intermediate thickness lesions. Five-year survival among those individuals in the trial who were found to have positive nodes was 72% when patients had immediate lymphadenectomy, but only 52% when the lymphadenectomy was delayed (N. Engl. J. Med. 2006;355:1307–17).

Dr. Gross said when he performs Mohs on a patient with melanoma he is careful to obtain a detailed consent from the patient. He also uses a Wood's lamp and magnification before and during the procedure to be sure he is seeing all it is possible to see.

When removing and sectioning a melanoma, Dr. Zitelli often takes the tumor plus about a 3-mm margin in the first stage, and he takes the specimen all the way down to the fat, Dr. Gross said.

Dr. Gross said he takes sections slightly larger than standard, and once he believes he has a clear margin, he removes another 4–5 mm which is sent for permanent sectioning. He also has a pathologist reading his slides with him.

What constitutes a clear margin has been defined by Dr. Zitelli as a margin that does not have three or more unusual melanocytes or melanocytes above the dermal-epidermal junction.

Dr. Gross said that he often uses Mohs zinc chloride paste, applying the escharotic agent to the lesion the night before the surgery is to be performed, and that he also often uses the MART-1 (melanoma antigen recognized by T-cells 1 staining) immunostain.

Because he takes a fairly large margin around the melanoma lesion when he makes his first Mohs excision, 90% of his melanoma cases are cleared on the first stage, Dr. Gross said.

SACRAMENTO — Another medical school has joined what could be a growing movement to ban faculty and residents from accepting any gifts whatsoever from drug company representatives.

The University of California, Davis, Health System decided late last year to forbid its medical staff to accept any gifts from drug salesmen, including drug samples, pens, mugs, and meals, however small they might be. Earlier, the school had banned drug company representatives from walking into the clinical areas on a preceptorship.

By taking this action, the school joins a cadre of institutions that includes Yale University, which implemented its policy in 2005, the University of Pennsylvania, which did so in July 2006, and Stanford University, which implemented its policy in October 2006. At UC Davis, the policy goes into effect in July 2007.

The new prohibition “picks off the low-lying fruit” in an attempt by the institution to create a greater distance between its clinical practice and the pharmaceutical industry, said Dr. Timothy E. Albertson, the university system's executive director of clinical care.

The school has plans to look at the issue of conflict of interest in further detail, particularly in regard to relationships with and practices of other vendors, he said. “We're certainly not trying to change capitalism, but we are trying to redefine the ethics of this type of involvement,” he said.

The efforts at UC Davis and the other academic medical centers were spurred in part by an article in the Journal of the American Medical Association (2006;295:429–33).

The article noted that many authoritative bodies, including the Pharmaceutical Research and Manufacturers of America and government agencies, have made attempts to curtail practices that constitute a conflict of interest for physicians. But the article also said those actions have largely failed to change the current climate. Thus, the 11 authors of the paper urged academic medical centers to take the lead by, among other things, banning the acceptance of gifts, samples, and payment for time spent at meetings.

Academic medical centers need to adopt such policies because the medical profession looks to them for leadership, and because academic medical centers shape the ethics of the profession, the proposal said.

The article notes that 90% of the marketing dollars spent by the pharmaceutical industry were directed at doctors, despite the increase in money spent on direct-to-consumer marketing in recent years.

According to IMS Health, a pharmaceutical information and consulting company, drug companies spent $27 billion on product promotion in 2004, of which $16 billion was for free drug samples and $7.3 billion, including gifts and meals, went to sales representative contacts.

The pharmaceutical industry, which adopted strict guidelines on gift giving in 2002, says limiting the practices and access of their sales representatives will deprive physicians of the best expertise on their medicines.

But gifts, however insignificant, establish an unspoken quid pro quo between physicians and pharmaceutical companies If gifts did not serve this purpose, companies would not give them, the JAMA authors say. They note that the research bears this out.

According to a 2003 survey of more than 1,000 third-year medical students, an average third-year student receives one gift or attends one company-sponsored activity a week (JAMA 2005;294:1034–42). That is precisely the point of the no-gift policies proposed by the JAMA article, said one of its authors, Dr. Jerome P. Kassirer, former editor-in-chief of the New England Journal of Medicine.

“These meals and gifts give residents and trainees the idea that pharmaceutical largesse is all right and the way things work, but it taints the profession,” Dr. Kassirer said in an interview. “They wouldn't pass out these gifts if it didn't matter. “I think the academic medical centers needed a little nudge,” he added, noting the impact the article appears to be having. “It's a beginning.”

At the academic medical centers, free meals appear to be the biggest issue impeding acceptance of the policies among staff. The free meals allow physicians to attend midday meetings they otherwise would not have time to attend, and they are a big ticket item.

At the UC Davis Cancer Center alone, it is estimated that companies spend about $70,000 on free lunches a year. The center will now pick up those costs, and other departments may have to do the same.

At the University of Pennsylvania Health System, the adoption of its policy caused some grumbling at first, along with the loss of some legitimate educational programs that were sponsored. For the most part, however, physicians and other staff members have adjusted, said Dr. Patrick J. Brennan, the chief medical officer of the university health system.

He said there is “much less evidence” of sales representatives around the clinics and school. At one suburban clinic run by the university, sales reps turned in their identification badges in protest; but, he believes, the sales force may have adjusted. He has lately seen an increasing number of medical education programs offered to faculty and staff sponsored by a third party hired by a drug company.

At UC Davis and some of the other institutions, efforts are being made to help patients who previously might have benefitted from receiving free drug samples or devices; these items have been very helpful, especially for lower-income patients, Dr. Albertson noted. The university is going to try to purchase some of the equipment that has been donated in the past, such as training inhalers for asthma patients and supplies for those with diabetes. “We're going to make every effort to buy them” for use by lower-income patients, he added.

SACRAMENTO — Another medical school has joined what could be a growing movement to ban faculty and residents from accepting any gifts whatsoever from drug company representatives.

The University of California, Davis, Health System decided late last year to forbid its medical staff to accept any gifts from drug salesmen, including drug samples, pens, mugs, and meals, however small they might be. Earlier, the school had banned drug company representatives from walking into the clinical areas on a preceptorship.

By taking this action, the school joins a cadre of institutions that includes Yale University, which implemented its policy in 2005, the University of Pennsylvania, which did so in July 2006, and Stanford University, which implemented its policy in October 2006. At UC Davis, the policy goes into effect in July 2007.

The new prohibition “picks off the low-lying fruit” in an attempt by the institution to create a greater distance between its clinical practice and the pharmaceutical industry, said Dr. Timothy E. Albertson, the university system's executive director of clinical care.

The school has plans to look at the issue of conflict of interest in further detail, particularly in regard to relationships with and practices of other vendors, he said. “We're certainly not trying to change capitalism, but we are trying to redefine the ethics of this type of involvement,” he said.

The efforts at UC Davis and the other academic medical centers were spurred in part by an article in the Journal of the American Medical Association (2006;295:429–33).

The article noted that many authoritative bodies, including the Pharmaceutical Research and Manufacturers of America and government agencies, have made attempts to curtail practices that constitute a conflict of interest for physicians. But the article also said those actions have largely failed to change the current climate. Thus, the 11 authors of the paper urged academic medical centers to take the lead by, among other things, banning the acceptance of gifts, samples, and payment for time spent at meetings.

Academic medical centers need to adopt such policies because the medical profession looks to them for leadership, and because academic medical centers shape the ethics of the profession, the proposal said.

The article notes that 90% of the marketing dollars spent by the pharmaceutical industry were directed at doctors, despite the increase in money spent on direct-to-consumer marketing in recent years.

According to IMS Health, a pharmaceutical information and consulting company, drug companies spent $27 billion on product promotion in 2004, of which $16 billion was for free drug samples and $7.3 billion, including gifts and meals, went to sales representative contacts.

The pharmaceutical industry, which adopted strict guidelines on gift giving in 2002, says limiting the practices and access of their sales representatives will deprive physicians of the best expertise on their medicines.

But gifts, however insignificant, establish an unspoken quid pro quo between physicians and pharmaceutical companies If gifts did not serve this purpose, companies would not give them, the JAMA authors say. They note that the research bears this out.

According to a 2003 survey of more than 1,000 third-year medical students, an average third-year student receives one gift or attends one company-sponsored activity a week (JAMA 2005;294:1034–42). That is precisely the point of the no-gift policies proposed by the JAMA article, said one of its authors, Dr. Jerome P. Kassirer, former editor-in-chief of the New England Journal of Medicine.

“These meals and gifts give residents and trainees the idea that pharmaceutical largesse is all right and the way things work, but it taints the profession,” Dr. Kassirer said in an interview. “They wouldn't pass out these gifts if it didn't matter. “I think the academic medical centers needed a little nudge,” he added, noting the impact the article appears to be having. “It's a beginning.”

At the academic medical centers, free meals appear to be the biggest issue impeding acceptance of the policies among staff. The free meals allow physicians to attend midday meetings they otherwise would not have time to attend, and they are a big ticket item.

At the UC Davis Cancer Center alone, it is estimated that companies spend about $70,000 on free lunches a year. The center will now pick up those costs, and other departments may have to do the same.

At the University of Pennsylvania Health System, the adoption of its policy caused some grumbling at first, along with the loss of some legitimate educational programs that were sponsored. For the most part, however, physicians and other staff members have adjusted, said Dr. Patrick J. Brennan, the chief medical officer of the university health system.

He said there is “much less evidence” of sales representatives around the clinics and school. At one suburban clinic run by the university, sales reps turned in their identification badges in protest; but, he believes, the sales force may have adjusted. He has lately seen an increasing number of medical education programs offered to faculty and staff sponsored by a third party hired by a drug company.

At UC Davis and some of the other institutions, efforts are being made to help patients who previously might have benefitted from receiving free drug samples or devices; these items have been very helpful, especially for lower-income patients, Dr. Albertson noted. The university is going to try to purchase some of the equipment that has been donated in the past, such as training inhalers for asthma patients and supplies for those with diabetes. “We're going to make every effort to buy them” for use by lower-income patients, he added.

SACRAMENTO — Another medical school has joined what could be a growing movement to ban faculty and residents from accepting any gifts whatsoever from drug company representatives.

The University of California, Davis, Health System decided late last year to forbid its medical staff to accept any gifts from drug salesmen, including drug samples, pens, mugs, and meals, however small they might be. Earlier, the school had banned drug company representatives from walking into the clinical areas on a preceptorship.

By taking this action, the school joins a cadre of institutions that includes Yale University, which implemented its policy in 2005, the University of Pennsylvania, which did so in July 2006, and Stanford University, which implemented its policy in October 2006. At UC Davis, the policy goes into effect in July 2007.

The new prohibition “picks off the low-lying fruit” in an attempt by the institution to create a greater distance between its clinical practice and the pharmaceutical industry, said Dr. Timothy E. Albertson, the university system's executive director of clinical care.

The school has plans to look at the issue of conflict of interest in further detail, particularly in regard to relationships with and practices of other vendors, he said. “We're certainly not trying to change capitalism, but we are trying to redefine the ethics of this type of involvement,” he said.

The efforts at UC Davis and the other academic medical centers were spurred in part by an article in the Journal of the American Medical Association (2006;295:429–33).

The article noted that many authoritative bodies, including the Pharmaceutical Research and Manufacturers of America and government agencies, have made attempts to curtail practices that constitute a conflict of interest for physicians. But the article also said those actions have largely failed to change the current climate. Thus, the 11 authors of the paper urged academic medical centers to take the lead by, among other things, banning the acceptance of gifts, samples, and payment for time spent at meetings.

Academic medical centers need to adopt such policies because the medical profession looks to them for leadership, and because academic medical centers shape the ethics of the profession, the proposal said.

The article notes that 90% of the marketing dollars spent by the pharmaceutical industry were directed at doctors, despite the increase in money spent on direct-to-consumer marketing in recent years.

According to IMS Health, a pharmaceutical information and consulting company, drug companies spent $27 billion on product promotion in 2004, of which $16 billion was for free drug samples and $7.3 billion, including gifts and meals, went to sales representative contacts.

The pharmaceutical industry, which adopted strict guidelines on gift giving in 2002, says limiting the practices and access of their sales representatives will deprive physicians of the best expertise on their medicines.

But gifts, however insignificant, establish an unspoken quid pro quo between physicians and pharmaceutical companies If gifts did not serve this purpose, companies would not give them, the JAMA authors say. They note that the research bears this out.

According to a 2003 survey of more than 1,000 third-year medical students, an average third-year student receives one gift or attends one company-sponsored activity a week (JAMA 2005;294:1034–42). That is precisely the point of the no-gift policies proposed by the JAMA article, said one of its authors, Dr. Jerome P. Kassirer, former editor-in-chief of the New England Journal of Medicine.

“These meals and gifts give residents and trainees the idea that pharmaceutical largesse is all right and the way things work, but it taints the profession,” Dr. Kassirer said in an interview. “They wouldn't pass out these gifts if it didn't matter. “I think the academic medical centers needed a little nudge,” he added, noting the impact the article appears to be having. “It's a beginning.”

At the academic medical centers, free meals appear to be the biggest issue impeding acceptance of the policies among staff. The free meals allow physicians to attend midday meetings they otherwise would not have time to attend, and they are a big ticket item.

At the UC Davis Cancer Center alone, it is estimated that companies spend about $70,000 on free lunches a year. The center will now pick up those costs, and other departments may have to do the same.

At the University of Pennsylvania Health System, the adoption of its policy caused some grumbling at first, along with the loss of some legitimate educational programs that were sponsored. For the most part, however, physicians and other staff members have adjusted, said Dr. Patrick J. Brennan, the chief medical officer of the university health system.

He said there is “much less evidence” of sales representatives around the clinics and school. At one suburban clinic run by the university, sales reps turned in their identification badges in protest; but, he believes, the sales force may have adjusted. He has lately seen an increasing number of medical education programs offered to faculty and staff sponsored by a third party hired by a drug company.

At UC Davis and some of the other institutions, efforts are being made to help patients who previously might have benefitted from receiving free drug samples or devices; these items have been very helpful, especially for lower-income patients, Dr. Albertson noted. The university is going to try to purchase some of the equipment that has been donated in the past, such as training inhalers for asthma patients and supplies for those with diabetes. “We're going to make every effort to buy them” for use by lower-income patients, he added.

VAIL, COLO. — Many providers have begun to treat molluscum contagiosum with cantharidin, a blistering agent produced by a beetle, instead of with liquid nitrogen.

The reason is that cantharidin is less painful and very well tolerated compared with curettage or liquid nitrogen, Dr. Lawrence F. Eichenfield said at a meeting sponsored by the American Academy of Pediatrics.

“It has been shown in a variety of studies [to be] a highly effective agent,” said Dr. Eichenfield, a pediatric dermatologist at the University of California, San Diego, and Rady Children's Hospital, also in San Diego. The majority of the time, he said, one to three 4-hour applications are sufficient to treat the lesions.

Dr. Eichenfield uses the method made popular by a report in 2000 from investigators at Northwestern University, Chicago. In their report, the investigators treated 300 patients with cantharidin and later interviewed their parents. The researchers said that, with an average of about two treatments, 90% of the patients were cleared of their lesions. Another 8% had improvement but were not cleared by the treatment, although their lesions resolved afterward (J. Am. Acad. Dermatol. 2000;43:503–7).

Ninety-two percent of the patients experienced blistering, and 37% reported erythema at the site after treatment, which lasted for up to 3 weeks. Fourteen percent reported mild to moderate pain after treatment and 10% reported a transient burning sensation. Other adverse events—including pruritus (6%) and bleeding (1%)—occurred less frequently. There were no serious events.

Ninety-five percent of parents said they would have their child treated the same way again. Of the 14 who would not, 3 gave their child's blistering as the reason and 1 mentioned pain. The others found multiple visits inconvenient or did not give a reason.

In the Northwestern method used by Dr. Eichenfield, the cantharidin (0.7% concentration) is daubed on the lesions with the wooden end of a cotton-swab, sparing the surrounding skin. He treats no more than 20 lesions at a time; he does not treat facial lesions with this method.

The sites are not occluded afterward, and the agent is washed off with soap and water 4–6 hours later, Dr. Eichenfield said.

Although the treatment is relatively safe, he said he would recommend physicians receive training before using cantharidin to avoid severe blisters.

Cantharidin is less painful and very well tolerated compared with curettage or liquid nitrogen. DR. EICHENFIELD

VAIL, COLO. — Many providers have begun to treat molluscum contagiosum with cantharidin, a blistering agent produced by a beetle, instead of with liquid nitrogen.

The reason is that cantharidin is less painful and very well tolerated compared with curettage or liquid nitrogen, Dr. Lawrence F. Eichenfield said at a meeting sponsored by the American Academy of Pediatrics.

“It has been shown in a variety of studies [to be] a highly effective agent,” said Dr. Eichenfield, a pediatric dermatologist at the University of California, San Diego, and Rady Children's Hospital, also in San Diego. The majority of the time, he said, one to three 4-hour applications are sufficient to treat the lesions.

Dr. Eichenfield uses the method made popular by a report in 2000 from investigators at Northwestern University, Chicago. In their report, the investigators treated 300 patients with cantharidin and later interviewed their parents. The researchers said that, with an average of about two treatments, 90% of the patients were cleared of their lesions. Another 8% had improvement but were not cleared by the treatment, although their lesions resolved afterward (J. Am. Acad. Dermatol. 2000;43:503–7).

Ninety-two percent of the patients experienced blistering, and 37% reported erythema at the site after treatment, which lasted for up to 3 weeks. Fourteen percent reported mild to moderate pain after treatment and 10% reported a transient burning sensation. Other adverse events—including pruritus (6%) and bleeding (1%)—occurred less frequently. There were no serious events.

Ninety-five percent of parents said they would have their child treated the same way again. Of the 14 who would not, 3 gave their child's blistering as the reason and 1 mentioned pain. The others found multiple visits inconvenient or did not give a reason.

In the Northwestern method used by Dr. Eichenfield, the cantharidin (0.7% concentration) is daubed on the lesions with the wooden end of a cotton-swab, sparing the surrounding skin. He treats no more than 20 lesions at a time; he does not treat facial lesions with this method.

The sites are not occluded afterward, and the agent is washed off with soap and water 4–6 hours later, Dr. Eichenfield said.

Although the treatment is relatively safe, he said he would recommend physicians receive training before using cantharidin to avoid severe blisters.

Cantharidin is less painful and very well tolerated compared with curettage or liquid nitrogen. DR. EICHENFIELD

VAIL, COLO. — Many providers have begun to treat molluscum contagiosum with cantharidin, a blistering agent produced by a beetle, instead of with liquid nitrogen.

The reason is that cantharidin is less painful and very well tolerated compared with curettage or liquid nitrogen, Dr. Lawrence F. Eichenfield said at a meeting sponsored by the American Academy of Pediatrics.

“It has been shown in a variety of studies [to be] a highly effective agent,” said Dr. Eichenfield, a pediatric dermatologist at the University of California, San Diego, and Rady Children's Hospital, also in San Diego. The majority of the time, he said, one to three 4-hour applications are sufficient to treat the lesions.

Dr. Eichenfield uses the method made popular by a report in 2000 from investigators at Northwestern University, Chicago. In their report, the investigators treated 300 patients with cantharidin and later interviewed their parents. The researchers said that, with an average of about two treatments, 90% of the patients were cleared of their lesions. Another 8% had improvement but were not cleared by the treatment, although their lesions resolved afterward (J. Am. Acad. Dermatol. 2000;43:503–7).

Ninety-two percent of the patients experienced blistering, and 37% reported erythema at the site after treatment, which lasted for up to 3 weeks. Fourteen percent reported mild to moderate pain after treatment and 10% reported a transient burning sensation. Other adverse events—including pruritus (6%) and bleeding (1%)—occurred less frequently. There were no serious events.

Ninety-five percent of parents said they would have their child treated the same way again. Of the 14 who would not, 3 gave their child's blistering as the reason and 1 mentioned pain. The others found multiple visits inconvenient or did not give a reason.

In the Northwestern method used by Dr. Eichenfield, the cantharidin (0.7% concentration) is daubed on the lesions with the wooden end of a cotton-swab, sparing the surrounding skin. He treats no more than 20 lesions at a time; he does not treat facial lesions with this method.

The sites are not occluded afterward, and the agent is washed off with soap and water 4–6 hours later, Dr. Eichenfield said.

Although the treatment is relatively safe, he said he would recommend physicians receive training before using cantharidin to avoid severe blisters.

Cantharidin is less painful and very well tolerated compared with curettage or liquid nitrogen. DR. EICHENFIELD

SAN FRANCISCO — The use of complementary and alternative medicines is common, but often overlooked, among patients infected with HIV, Dr. Jason Tokumoto said at a meeting on HIV management sponsored by the University of California, San Francisco.

Studies have indicated that 70% of HIV-infected patients use some form of complementary or alternative medicine (CAM). A survey of 1,675 HIV-infected patients found that the most commonly used CAM products included multivitamins (54% of patients), garlic (53%), massage (49%), and acupuncture (45%) (AIDS Care 2001;13:197–208).

Physicians are often unaware of the use of CAM products. “This can be a problem because in some cases these [complementary or alternative medicines] can actually be harmful,” said Dr. Tokumoto of the department of family and community medicine at UCSF.

In one study, 25% of the surveyed HIV-positive patients were using a CAM product that was potentially harmful, and one-third of these patients did not tell their clinicians about their CAM use (J. Aquir. Immune Defic. Syndr. 2003;33:157–65).

For example, St. John's wort, which may have some efficacy for depression, interacts with the cytochrome P-450 enzyme system and can thereby decrease indinavir trough blood levels by 81% and nevirapine levels by 21%.

St. John's wort should not be used with any protease inhibitor or nonnucleoside reverse transcriptase inhibitor, Dr. Tokumoto said.

Garlic, which many HIV patients use to improve lipid levels, should not be used with saquinavir. Garlic can reduce saquinavir blood levels by 51%, probably because it, too, is an inducer of the cytochrome P-450 system, he said.

The profile of HIV-infected patients who often use CAM products is similar to that of CAM users in the general patient population, Dr. Tokumoto said.

These patients tend to be women, be involved in medical decisions, have a negative attitude toward antiretroviral therapy, have been infected for a relatively long time, and have high income and education levels.

“If you have a patient who fits this profile, you want to be asking about CAM,” he said.

Dr. Tokumoto offered these comments about what is known about specific CAM uses and HIV:

▸ Herbals. Nothing known in herbal medicine or Chinese medicine has been shown to be effective in suppressing HIV or stimulating the immune system. A Cochrane review recently looked at nine randomized, placebo-controlled trials of eight herbal products in HIV patients. “What the authors concluded was that none of these herbs really worked,” Dr. Tokumoto said.

There has been some debate over whether HIV patients should take echinacea, which is sometimes used to treat colds, because of concerns that long-term use could lead to immunosuppression.

▸ Micronutrients or vitamins. Studies suggest that most HIV-infected patients are not micronutrient deficient and not clinically vitamin deficient, although it has been reported that HIV-infected persons have low serum levels of vitamins A, E, B₆, and B₁₂.

But in one trial, researchers gave micronutrients or placebo to 40 HIV patients for 12 weeks, and found an increase in the mean number of CD4 cells in the micronutrient group and a decrease in the placebo group. There was no difference in viral load (J. Aquir. Immune Defic. Syndr. 2006;42:523–8).

“However, although these results look promising, this is a small study,” Dr. Tokumoto commented.

Some vitamins and antioxidants such as riboflavin, thiamine, and vitamins C, E, and K may theoretically prevent lactacidemia caused by mitochondrial toxicity from nucleoside analogues. But there have been no trials in HIV patients, and these substances have had only limited value in patients with congenital mitochondrial disease.

“There are scattered anecdotal reports of patients responding to some of these vitamins,” Dr. Tokumoto said.

▸ L-carnitine. In an uncontrolled study of 21 HIV patients, administration of L-carnitine 1,500 mg twice daily for 6 months, appeared to reduce nucleoside analogue-related neuropathy.

Overall, 76% of the patients showed improvement (HIV Clin. Trials 2005;6:344–50).

▸ Lipodystrophy. No CAM is currently being investigated for lipodystrophy; however, in one 74-patient survey, 25% used vitamins, 23% used resistance exercise, 21% used specific diets, and some used meditation in an effort to reduce lipodystrophy. Only 37% told their physician they were using these modalities (J. Altern. Complement. Med. 2006;12:475–82).

▸ Hyperlipidemia. The supporting studies of garlic to lower lipid levels are compromised by their short duration and the different preparations used, according to Dr. Tokumoto.

Cholestin, which is produced by red yeast fermented on rice, contains natural statins. This substance has been shown to reduce LDL cholesterol and triglyceride levels by 20%–30%. But there are no studies in HIV patients, and no studies of the interactions with protease inhibitors.

Fish oil has also been shown to decrease triglyceride levels.

▸ Milk thistle. Milk thistle could be attractive to HIV patients who are on antiretrovirals and/or coinfected with hepatitis B or C because its active ingredient, silymarin, may be hepatorestorative.

At the dosages used, it probably does not interfere with the efficacy of protease inhibitors.

Although the data are inconclusive, “I do know some hepatologists who are prescribing milk thistle for their hepatitis C patients,” he said.

▸ Acupuncture. Acupuncture is widely used by HIV patients for pain and neuropathy. One study of 215 patients reported that neither acupuncture nor amitriptyline was more effective than placebo (JAMA 1998;280:1590–5). But most acupuncturists say that the procedure is difficult to study rigorously because treatment is highly individualized, Dr. Tokumoto said.

▸ Marijuana. Anywhere from 14% to 43% of HIV patients may use marijuana medicinally or recreationally. Because of the political climate, marijuana use has not been studied in clinical trials.

But smoking marijuana over a short period of time has been shown not to affect CD4 cell counts, viral load, or antiretroviral levels, he said.

SAN FRANCISCO — The use of complementary and alternative medicines is common, but often overlooked, among patients infected with HIV, Dr. Jason Tokumoto said at a meeting on HIV management sponsored by the University of California, San Francisco.

Studies have indicated that 70% of HIV-infected patients use some form of complementary or alternative medicine (CAM). A survey of 1,675 HIV-infected patients found that the most commonly used CAM products included multivitamins (54% of patients), garlic (53%), massage (49%), and acupuncture (45%) (AIDS Care 2001;13:197–208).

Physicians are often unaware of the use of CAM products. “This can be a problem because in some cases these [complementary or alternative medicines] can actually be harmful,” said Dr. Tokumoto of the department of family and community medicine at UCSF.

In one study, 25% of the surveyed HIV-positive patients were using a CAM product that was potentially harmful, and one-third of these patients did not tell their clinicians about their CAM use (J. Aquir. Immune Defic. Syndr. 2003;33:157–65).

For example, St. John's wort, which may have some efficacy for depression, interacts with the cytochrome P-450 enzyme system and can thereby decrease indinavir trough blood levels by 81% and nevirapine levels by 21%.

St. John's wort should not be used with any protease inhibitor or nonnucleoside reverse transcriptase inhibitor, Dr. Tokumoto said.

Garlic, which many HIV patients use to improve lipid levels, should not be used with saquinavir. Garlic can reduce saquinavir blood levels by 51%, probably because it, too, is an inducer of the cytochrome P-450 system, he said.

The profile of HIV-infected patients who often use CAM products is similar to that of CAM users in the general patient population, Dr. Tokumoto said.

These patients tend to be women, be involved in medical decisions, have a negative attitude toward antiretroviral therapy, have been infected for a relatively long time, and have high income and education levels.

“If you have a patient who fits this profile, you want to be asking about CAM,” he said.

Dr. Tokumoto offered these comments about what is known about specific CAM uses and HIV:

▸ Herbals. Nothing known in herbal medicine or Chinese medicine has been shown to be effective in suppressing HIV or stimulating the immune system. A Cochrane review recently looked at nine randomized, placebo-controlled trials of eight herbal products in HIV patients. “What the authors concluded was that none of these herbs really worked,” Dr. Tokumoto said.

There has been some debate over whether HIV patients should take echinacea, which is sometimes used to treat colds, because of concerns that long-term use could lead to immunosuppression.

▸ Micronutrients or vitamins. Studies suggest that most HIV-infected patients are not micronutrient deficient and not clinically vitamin deficient, although it has been reported that HIV-infected persons have low serum levels of vitamins A, E, B₆, and B₁₂.

But in one trial, researchers gave micronutrients or placebo to 40 HIV patients for 12 weeks, and found an increase in the mean number of CD4 cells in the micronutrient group and a decrease in the placebo group. There was no difference in viral load (J. Aquir. Immune Defic. Syndr. 2006;42:523–8).

“However, although these results look promising, this is a small study,” Dr. Tokumoto commented.

Some vitamins and antioxidants such as riboflavin, thiamine, and vitamins C, E, and K may theoretically prevent lactacidemia caused by mitochondrial toxicity from nucleoside analogues. But there have been no trials in HIV patients, and these substances have had only limited value in patients with congenital mitochondrial disease.

“There are scattered anecdotal reports of patients responding to some of these vitamins,” Dr. Tokumoto said.

▸ L-carnitine. In an uncontrolled study of 21 HIV patients, administration of L-carnitine 1,500 mg twice daily for 6 months, appeared to reduce nucleoside analogue-related neuropathy.

Overall, 76% of the patients showed improvement (HIV Clin. Trials 2005;6:344–50).

▸ Lipodystrophy. No CAM is currently being investigated for lipodystrophy; however, in one 74-patient survey, 25% used vitamins, 23% used resistance exercise, 21% used specific diets, and some used meditation in an effort to reduce lipodystrophy. Only 37% told their physician they were using these modalities (J. Altern. Complement. Med. 2006;12:475–82).

▸ Hyperlipidemia. The supporting studies of garlic to lower lipid levels are compromised by their short duration and the different preparations used, according to Dr. Tokumoto.

Cholestin, which is produced by red yeast fermented on rice, contains natural statins. This substance has been shown to reduce LDL cholesterol and triglyceride levels by 20%–30%. But there are no studies in HIV patients, and no studies of the interactions with protease inhibitors.

Fish oil has also been shown to decrease triglyceride levels.

▸ Milk thistle. Milk thistle could be attractive to HIV patients who are on antiretrovirals and/or coinfected with hepatitis B or C because its active ingredient, silymarin, may be hepatorestorative.

At the dosages used, it probably does not interfere with the efficacy of protease inhibitors.

Although the data are inconclusive, “I do know some hepatologists who are prescribing milk thistle for their hepatitis C patients,” he said.

▸ Acupuncture. Acupuncture is widely used by HIV patients for pain and neuropathy. One study of 215 patients reported that neither acupuncture nor amitriptyline was more effective than placebo (JAMA 1998;280:1590–5). But most acupuncturists say that the procedure is difficult to study rigorously because treatment is highly individualized, Dr. Tokumoto said.

▸ Marijuana. Anywhere from 14% to 43% of HIV patients may use marijuana medicinally or recreationally. Because of the political climate, marijuana use has not been studied in clinical trials.

But smoking marijuana over a short period of time has been shown not to affect CD4 cell counts, viral load, or antiretroviral levels, he said.

SAN FRANCISCO — The use of complementary and alternative medicines is common, but often overlooked, among patients infected with HIV, Dr. Jason Tokumoto said at a meeting on HIV management sponsored by the University of California, San Francisco.

Studies have indicated that 70% of HIV-infected patients use some form of complementary or alternative medicine (CAM). A survey of 1,675 HIV-infected patients found that the most commonly used CAM products included multivitamins (54% of patients), garlic (53%), massage (49%), and acupuncture (45%) (AIDS Care 2001;13:197–208).

Physicians are often unaware of the use of CAM products. “This can be a problem because in some cases these [complementary or alternative medicines] can actually be harmful,” said Dr. Tokumoto of the department of family and community medicine at UCSF.

In one study, 25% of the surveyed HIV-positive patients were using a CAM product that was potentially harmful, and one-third of these patients did not tell their clinicians about their CAM use (J. Aquir. Immune Defic. Syndr. 2003;33:157–65).

For example, St. John's wort, which may have some efficacy for depression, interacts with the cytochrome P-450 enzyme system and can thereby decrease indinavir trough blood levels by 81% and nevirapine levels by 21%.

St. John's wort should not be used with any protease inhibitor or nonnucleoside reverse transcriptase inhibitor, Dr. Tokumoto said.

Garlic, which many HIV patients use to improve lipid levels, should not be used with saquinavir. Garlic can reduce saquinavir blood levels by 51%, probably because it, too, is an inducer of the cytochrome P-450 system, he said.

The profile of HIV-infected patients who often use CAM products is similar to that of CAM users in the general patient population, Dr. Tokumoto said.

These patients tend to be women, be involved in medical decisions, have a negative attitude toward antiretroviral therapy, have been infected for a relatively long time, and have high income and education levels.

“If you have a patient who fits this profile, you want to be asking about CAM,” he said.

Dr. Tokumoto offered these comments about what is known about specific CAM uses and HIV:

▸ Herbals. Nothing known in herbal medicine or Chinese medicine has been shown to be effective in suppressing HIV or stimulating the immune system. A Cochrane review recently looked at nine randomized, placebo-controlled trials of eight herbal products in HIV patients. “What the authors concluded was that none of these herbs really worked,” Dr. Tokumoto said.

There has been some debate over whether HIV patients should take echinacea, which is sometimes used to treat colds, because of concerns that long-term use could lead to immunosuppression.

▸ Micronutrients or vitamins. Studies suggest that most HIV-infected patients are not micronutrient deficient and not clinically vitamin deficient, although it has been reported that HIV-infected persons have low serum levels of vitamins A, E, B₆, and B₁₂.

But in one trial, researchers gave micronutrients or placebo to 40 HIV patients for 12 weeks, and found an increase in the mean number of CD4 cells in the micronutrient group and a decrease in the placebo group. There was no difference in viral load (J. Aquir. Immune Defic. Syndr. 2006;42:523–8).

“However, although these results look promising, this is a small study,” Dr. Tokumoto commented.

Some vitamins and antioxidants such as riboflavin, thiamine, and vitamins C, E, and K may theoretically prevent lactacidemia caused by mitochondrial toxicity from nucleoside analogues. But there have been no trials in HIV patients, and these substances have had only limited value in patients with congenital mitochondrial disease.

“There are scattered anecdotal reports of patients responding to some of these vitamins,” Dr. Tokumoto said.

▸ L-carnitine. In an uncontrolled study of 21 HIV patients, administration of L-carnitine 1,500 mg twice daily for 6 months, appeared to reduce nucleoside analogue-related neuropathy.

Overall, 76% of the patients showed improvement (HIV Clin. Trials 2005;6:344–50).

▸ Lipodystrophy. No CAM is currently being investigated for lipodystrophy; however, in one 74-patient survey, 25% used vitamins, 23% used resistance exercise, 21% used specific diets, and some used meditation in an effort to reduce lipodystrophy. Only 37% told their physician they were using these modalities (J. Altern. Complement. Med. 2006;12:475–82).

▸ Hyperlipidemia. The supporting studies of garlic to lower lipid levels are compromised by their short duration and the different preparations used, according to Dr. Tokumoto.

Cholestin, which is produced by red yeast fermented on rice, contains natural statins. This substance has been shown to reduce LDL cholesterol and triglyceride levels by 20%–30%. But there are no studies in HIV patients, and no studies of the interactions with protease inhibitors.

Fish oil has also been shown to decrease triglyceride levels.

▸ Milk thistle. Milk thistle could be attractive to HIV patients who are on antiretrovirals and/or coinfected with hepatitis B or C because its active ingredient, silymarin, may be hepatorestorative.

At the dosages used, it probably does not interfere with the efficacy of protease inhibitors.

Although the data are inconclusive, “I do know some hepatologists who are prescribing milk thistle for their hepatitis C patients,” he said.

▸ Acupuncture. Acupuncture is widely used by HIV patients for pain and neuropathy. One study of 215 patients reported that neither acupuncture nor amitriptyline was more effective than placebo (JAMA 1998;280:1590–5). But most acupuncturists say that the procedure is difficult to study rigorously because treatment is highly individualized, Dr. Tokumoto said.

▸ Marijuana. Anywhere from 14% to 43% of HIV patients may use marijuana medicinally or recreationally. Because of the political climate, marijuana use has not been studied in clinical trials.

But smoking marijuana over a short period of time has been shown not to affect CD4 cell counts, viral load, or antiretroviral levels, he said.

SAN FRANCISCO — Depression and stress appear to be important considerations in the treatment of HIV-infected patients, Dr. Frederick Hecht said at a meeting on HIV management sponsored by the University of California, San Francisco.

Although research on the topic is not conclusive, available evidence suggests that a patient's ability to experience positive emotions may be somewhat protective against CD4 cell count loss, he said.

And, in a small pilot study of yoga practice, he obtained intriguing, but not definitive, evidence that there might be ways to mitigate depression and response to stress without writing a prescription.

The first studies that found an association between depression and CD4 cell loss were published in 1993, but they were not entirely convincing, said Dr. Hecht, research director of the UCSF Osher Center for Integrative Medicine.

Subsequent studies have suggested that it is not depression per se that is associated with rapid HIV disease progression, and that negative affective symptoms have little or no impact on HIV progression.

Instead, these studies have shown that positive affect—in other words, the ability to experience positive thoughts and emotions, and to enjoy some aspects of life despite also feeling sadness—can have a large effect, Dr. Hecht said.

One study, the San Francisco Men's Health Study, included 407 HIV-positive men who were followed over a period of 10 years. The relative risk of AIDS mortality was 0.89 in those who had high scores on positive affect measures. Negative affect, however, had little relationship to mortality (Psychosom. Med. 2003;65:620–66).

In another study, of 82 HIV-positive men followed for an average of 5 years, the presence of stress was associated with risk of progression. One major stressful event in a 6-month period, such as the dissolution of an intimate relationship or loss of a loved one, doubled the risk of disease progression.

Studies done by researchers at the University of California, Los Angeles, have hinted at how mood and affect might be tied to the immune system in the setting of HIV infection. That research has suggested that the connection might be through the CCR5 receptor, the major coreceptor of HIV on CD4 cells. Persons who have rapidly progressing disease may have more CCR5 receptors, and the researchers have shown that neurotransmitters such as norepinephrine can increase receptor expression in vitro.

In an intriguing study, those researchers found that a high level of autonomic nervous system activity, as would be seen in times of stress, impairs response to highly active antiretroviral therapy and increases virus levels (Proc. Natl. Acad. Sci. U.S.A. 2001; 98:12695–700).

In his unpublished study of yoga practice, Dr. Hecht assigned 23 HIV-infected patients to a group that practiced yoga three times a week, and 25 others to a control group.

At the end of 3 months, both groups had improvement in their positive and negative affect scores on a test known as the Positive and Negative Affect Schedule, but the mean improvement for the group that practiced yoga was eight times greater on positive affect and twice as great on negative affect.

The yoga group had an increase in average CD4 cell level, while the control group had a decrease, but the difference was not statistically significant, Dr. Hecht said.

“There's at least a little bit of preliminary evidence that interventions like this yoga intervention might have some effect on CD4 cell counts,” he said.

Dr. Hecht said that he uses this information when treating his own HIV patients. He advises them that withdrawing from life in order to avoid stressors is not advisable, but that chronic stress or depression do need to be addressed.

He does not mislead them into thinking that by developing positive affect they can prevent progression. “The issue here is really rate of progression, not whether you progress or not,” he said.

Antidepressant treatment probably does not have a benefit, Dr. Hecht added. In a study of HIV patients put on a selective serotonin reuptake inhibitor, there was no significant effect on T-cell levels (J. Clin. Psychiatry 1994;55:92–7).

That study may not have been large enough to detect an improvement. But it may also indicate that antidepressants have no appreciable impact on positive affect, he said.

SAN FRANCISCO — Depression and stress appear to be important considerations in the treatment of HIV-infected patients, Dr. Frederick Hecht said at a meeting on HIV management sponsored by the University of California, San Francisco.

Although research on the topic is not conclusive, available evidence suggests that a patient's ability to experience positive emotions may be somewhat protective against CD4 cell count loss, he said.

And, in a small pilot study of yoga practice, he obtained intriguing, but not definitive, evidence that there might be ways to mitigate depression and response to stress without writing a prescription.

The first studies that found an association between depression and CD4 cell loss were published in 1993, but they were not entirely convincing, said Dr. Hecht, research director of the UCSF Osher Center for Integrative Medicine.

Subsequent studies have suggested that it is not depression per se that is associated with rapid HIV disease progression, and that negative affective symptoms have little or no impact on HIV progression.

Instead, these studies have shown that positive affect—in other words, the ability to experience positive thoughts and emotions, and to enjoy some aspects of life despite also feeling sadness—can have a large effect, Dr. Hecht said.

One study, the San Francisco Men's Health Study, included 407 HIV-positive men who were followed over a period of 10 years. The relative risk of AIDS mortality was 0.89 in those who had high scores on positive affect measures. Negative affect, however, had little relationship to mortality (Psychosom. Med. 2003;65:620–66).

In another study, of 82 HIV-positive men followed for an average of 5 years, the presence of stress was associated with risk of progression. One major stressful event in a 6-month period, such as the dissolution of an intimate relationship or loss of a loved one, doubled the risk of disease progression.

Studies done by researchers at the University of California, Los Angeles, have hinted at how mood and affect might be tied to the immune system in the setting of HIV infection. That research has suggested that the connection might be through the CCR5 receptor, the major coreceptor of HIV on CD4 cells. Persons who have rapidly progressing disease may have more CCR5 receptors, and the researchers have shown that neurotransmitters such as norepinephrine can increase receptor expression in vitro.

In an intriguing study, those researchers found that a high level of autonomic nervous system activity, as would be seen in times of stress, impairs response to highly active antiretroviral therapy and increases virus levels (Proc. Natl. Acad. Sci. U.S.A. 2001; 98:12695–700).

In his unpublished study of yoga practice, Dr. Hecht assigned 23 HIV-infected patients to a group that practiced yoga three times a week, and 25 others to a control group.

At the end of 3 months, both groups had improvement in their positive and negative affect scores on a test known as the Positive and Negative Affect Schedule, but the mean improvement for the group that practiced yoga was eight times greater on positive affect and twice as great on negative affect.

The yoga group had an increase in average CD4 cell level, while the control group had a decrease, but the difference was not statistically significant, Dr. Hecht said.

“There's at least a little bit of preliminary evidence that interventions like this yoga intervention might have some effect on CD4 cell counts,” he said.

Dr. Hecht said that he uses this information when treating his own HIV patients. He advises them that withdrawing from life in order to avoid stressors is not advisable, but that chronic stress or depression do need to be addressed.

He does not mislead them into thinking that by developing positive affect they can prevent progression. “The issue here is really rate of progression, not whether you progress or not,” he said.

Antidepressant treatment probably does not have a benefit, Dr. Hecht added. In a study of HIV patients put on a selective serotonin reuptake inhibitor, there was no significant effect on T-cell levels (J. Clin. Psychiatry 1994;55:92–7).

That study may not have been large enough to detect an improvement. But it may also indicate that antidepressants have no appreciable impact on positive affect, he said.

SAN FRANCISCO — Depression and stress appear to be important considerations in the treatment of HIV-infected patients, Dr. Frederick Hecht said at a meeting on HIV management sponsored by the University of California, San Francisco.

Although research on the topic is not conclusive, available evidence suggests that a patient's ability to experience positive emotions may be somewhat protective against CD4 cell count loss, he said.

And, in a small pilot study of yoga practice, he obtained intriguing, but not definitive, evidence that there might be ways to mitigate depression and response to stress without writing a prescription.

The first studies that found an association between depression and CD4 cell loss were published in 1993, but they were not entirely convincing, said Dr. Hecht, research director of the UCSF Osher Center for Integrative Medicine.

Subsequent studies have suggested that it is not depression per se that is associated with rapid HIV disease progression, and that negative affective symptoms have little or no impact on HIV progression.

Instead, these studies have shown that positive affect—in other words, the ability to experience positive thoughts and emotions, and to enjoy some aspects of life despite also feeling sadness—can have a large effect, Dr. Hecht said.

One study, the San Francisco Men's Health Study, included 407 HIV-positive men who were followed over a period of 10 years. The relative risk of AIDS mortality was 0.89 in those who had high scores on positive affect measures. Negative affect, however, had little relationship to mortality (Psychosom. Med. 2003;65:620–66).

In another study, of 82 HIV-positive men followed for an average of 5 years, the presence of stress was associated with risk of progression. One major stressful event in a 6-month period, such as the dissolution of an intimate relationship or loss of a loved one, doubled the risk of disease progression.

Studies done by researchers at the University of California, Los Angeles, have hinted at how mood and affect might be tied to the immune system in the setting of HIV infection. That research has suggested that the connection might be through the CCR5 receptor, the major coreceptor of HIV on CD4 cells. Persons who have rapidly progressing disease may have more CCR5 receptors, and the researchers have shown that neurotransmitters such as norepinephrine can increase receptor expression in vitro.

In an intriguing study, those researchers found that a high level of autonomic nervous system activity, as would be seen in times of stress, impairs response to highly active antiretroviral therapy and increases virus levels (Proc. Natl. Acad. Sci. U.S.A. 2001; 98:12695–700).

In his unpublished study of yoga practice, Dr. Hecht assigned 23 HIV-infected patients to a group that practiced yoga three times a week, and 25 others to a control group.

At the end of 3 months, both groups had improvement in their positive and negative affect scores on a test known as the Positive and Negative Affect Schedule, but the mean improvement for the group that practiced yoga was eight times greater on positive affect and twice as great on negative affect.

The yoga group had an increase in average CD4 cell level, while the control group had a decrease, but the difference was not statistically significant, Dr. Hecht said.

“There's at least a little bit of preliminary evidence that interventions like this yoga intervention might have some effect on CD4 cell counts,” he said.

Dr. Hecht said that he uses this information when treating his own HIV patients. He advises them that withdrawing from life in order to avoid stressors is not advisable, but that chronic stress or depression do need to be addressed.

He does not mislead them into thinking that by developing positive affect they can prevent progression. “The issue here is really rate of progression, not whether you progress or not,” he said.

Antidepressant treatment probably does not have a benefit, Dr. Hecht added. In a study of HIV patients put on a selective serotonin reuptake inhibitor, there was no significant effect on T-cell levels (J. Clin. Psychiatry 1994;55:92–7).

That study may not have been large enough to detect an improvement. But it may also indicate that antidepressants have no appreciable impact on positive affect, he said.

SAN FRANCISCO — New insights into HIV disease progression are emerging from a study of a group of HIV-infected patients known as “elite controllers,” so called because their viral loads remain low and their infections do not appear to progress, even without medication.

The findings suggest that chemokine (C-C-motif) receptor 5 (CCR5) expression and responses in the gut may be crucial prognostic factors.

But their long-term control of the infection probably is not that simple, Dr. Steven Deeks said at a meeting on HIV management sponsored by the University of California, San Francisco, where he is affiliated with the department of medicine.

He and his associates at Massachusetts General Hospital, Boston, have studied a cohort of approximately 110 elite controllers in an effort to learn how these patients keep the virus at bay. These individuals, defined as maintaining for many years a viral load of less than 75 copies/mL, may make up only 0.1%–1% of persons infected with HIV.

The elite controllers tend to have more of a specific type of HIV-directed CD4 and CD8 T cells, and to have a particular haplotype of the human leukocyte antigen (HLA) molecule expressed by antigen presenting cells. But these features are not universal, said Dr. Deeks.

Notably, genetic analysis has shown that these individuals tend to have polymorphisms within the CCR gene promotor region that are associated with low expression of the CCR5 receptor, which is used by HIV to enter the cell.

These patients also tend to have a lot of the ligand that binds to CCR5, competing with HIV.

In his own cohort and in the Boston cohort, every elite controller has this favorable profile, Dr. Deeks said.

What might be most important is that these individuals appear to preserve their gut mucosal integrity, he said.

In most HIV-infected patients, infection initially causes a drastic, almost complete, depletion of CD4 cells surrounding the gut, where they are most plentiful. The cell destruction causes inflammation, which compromises the gut's mucosal integrity. The loss of integrity allows persistent entry of toxins into the system, which attracts more T cells, which are then infected and destroyed.

But in a study that included four elite controllers, the elite controllers did not have such depletion (Proc. Natl. Acad. Sci. U.S.A. 2005;102:9860–5).

Nonetheless, the findings do not rule out the possibility that these persons may be infected with a compromised virus, and some evidence suggests this may be the case, Dr. Deeks added.

“It's reasonable to assume that there are several different pressures that contribute to achieving long-term innate control,” he said.

SAN FRANCISCO — New insights into HIV disease progression are emerging from a study of a group of HIV-infected patients known as “elite controllers,” so called because their viral loads remain low and their infections do not appear to progress, even without medication.

The findings suggest that chemokine (C-C-motif) receptor 5 (CCR5) expression and responses in the gut may be crucial prognostic factors.

But their long-term control of the infection probably is not that simple, Dr. Steven Deeks said at a meeting on HIV management sponsored by the University of California, San Francisco, where he is affiliated with the department of medicine.

He and his associates at Massachusetts General Hospital, Boston, have studied a cohort of approximately 110 elite controllers in an effort to learn how these patients keep the virus at bay. These individuals, defined as maintaining for many years a viral load of less than 75 copies/mL, may make up only 0.1%–1% of persons infected with HIV.

The elite controllers tend to have more of a specific type of HIV-directed CD4 and CD8 T cells, and to have a particular haplotype of the human leukocyte antigen (HLA) molecule expressed by antigen presenting cells. But these features are not universal, said Dr. Deeks.

Notably, genetic analysis has shown that these individuals tend to have polymorphisms within the CCR gene promotor region that are associated with low expression of the CCR5 receptor, which is used by HIV to enter the cell.

These patients also tend to have a lot of the ligand that binds to CCR5, competing with HIV.

In his own cohort and in the Boston cohort, every elite controller has this favorable profile, Dr. Deeks said.

What might be most important is that these individuals appear to preserve their gut mucosal integrity, he said.

In most HIV-infected patients, infection initially causes a drastic, almost complete, depletion of CD4 cells surrounding the gut, where they are most plentiful. The cell destruction causes inflammation, which compromises the gut's mucosal integrity. The loss of integrity allows persistent entry of toxins into the system, which attracts more T cells, which are then infected and destroyed.

But in a study that included four elite controllers, the elite controllers did not have such depletion (Proc. Natl. Acad. Sci. U.S.A. 2005;102:9860–5).

Nonetheless, the findings do not rule out the possibility that these persons may be infected with a compromised virus, and some evidence suggests this may be the case, Dr. Deeks added.

“It's reasonable to assume that there are several different pressures that contribute to achieving long-term innate control,” he said.

SAN FRANCISCO — New insights into HIV disease progression are emerging from a study of a group of HIV-infected patients known as “elite controllers,” so called because their viral loads remain low and their infections do not appear to progress, even without medication.

The findings suggest that chemokine (C-C-motif) receptor 5 (CCR5) expression and responses in the gut may be crucial prognostic factors.

But their long-term control of the infection probably is not that simple, Dr. Steven Deeks said at a meeting on HIV management sponsored by the University of California, San Francisco, where he is affiliated with the department of medicine.

He and his associates at Massachusetts General Hospital, Boston, have studied a cohort of approximately 110 elite controllers in an effort to learn how these patients keep the virus at bay. These individuals, defined as maintaining for many years a viral load of less than 75 copies/mL, may make up only 0.1%–1% of persons infected with HIV.

The elite controllers tend to have more of a specific type of HIV-directed CD4 and CD8 T cells, and to have a particular haplotype of the human leukocyte antigen (HLA) molecule expressed by antigen presenting cells. But these features are not universal, said Dr. Deeks.

Notably, genetic analysis has shown that these individuals tend to have polymorphisms within the CCR gene promotor region that are associated with low expression of the CCR5 receptor, which is used by HIV to enter the cell.

These patients also tend to have a lot of the ligand that binds to CCR5, competing with HIV.

In his own cohort and in the Boston cohort, every elite controller has this favorable profile, Dr. Deeks said.

What might be most important is that these individuals appear to preserve their gut mucosal integrity, he said.

In most HIV-infected patients, infection initially causes a drastic, almost complete, depletion of CD4 cells surrounding the gut, where they are most plentiful. The cell destruction causes inflammation, which compromises the gut's mucosal integrity. The loss of integrity allows persistent entry of toxins into the system, which attracts more T cells, which are then infected and destroyed.

But in a study that included four elite controllers, the elite controllers did not have such depletion (Proc. Natl. Acad. Sci. U.S.A. 2005;102:9860–5).

Nonetheless, the findings do not rule out the possibility that these persons may be infected with a compromised virus, and some evidence suggests this may be the case, Dr. Deeks added.

“It's reasonable to assume that there are several different pressures that contribute to achieving long-term innate control,” he said.