Timothy F. Kirn

LOS ANGELES — Two novel HIV medications produced striking improvement in AIDS patients otherwise failing standard therapy, according to four separate studies presented at a conference on retroviruses and opportunistic infections.

“The results here are as exciting as the development of HAART [highly active antiretroviral therapy] for treatment-experienced patients,” said Dr. John W. Mellors, chief of infectious diseases at the University of Pittsburgh, commenting on the studies at a press briefing.

Each drug reduced viral loads to fewer than 400 copies/mL in 60%–80% of study patients, who already had resistance to currently available drugs.

“This is really a remarkable development in the field,” added Dr. Mellors, who is also codirector of the center for viral diseases at the University of Pittsburgh.

One of the drugs, Pfizer Inc.'s maraviroc, is an antagonist to the CCR5 coreceptor used by HIV to enter CD4-positive T cells. The other drug, Merck & Co.'s raltegravir, is an integrase inhibitor, which blocks viral genes from being incorporated into the host cell genome where they can be activated.

In one trial of maraviroc conducted in Europe, Australia, and North America, the drug reduced HIV RNA levels to below 400 copies/mL at 24 weeks in 55% of 182 triple-class-experienced patients who took the drug (150 or 300 mg) once daily in addition to their optimized, standard therapy. The drug reduced viral loads below that level in 61% of 191 patients who took the drug twice daily, reported Dr. Howard Mayer, executive director for global research and development at Pfizer.

That compared with only 23% of 91 placebo-treated patients whose viral loads dropped below that level, he said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

The dosage that the patients received in the trial—either 150 mg or 300 mg—depended on what drugs were in their optimized background therapy during the trial. Patients whose background treatment regimen included a protease inhibitor or delavirdine received the lower dose.

In a second trial conducted only in the United States and Canada, the results were almost the same. Of the 232 patients who took the drug once daily, 55% had viral levels that dropped below 400 copies/mL, as did those of 60% of 235 patients who took the drug twice daily. That compared with 31% of 118 placebo-treated patients.

Raltegravir (400 mg twice daily) decreased the HIV RNA level to less than 400 copies/mL in 77% of 232 patients with triple-class-resistant virus on optimized therapy, versus 41% of 118 placebo-treated patients, at 16 weeks, reported Dr. David Cooper, head of the immunology, HIV, and infectious diseases clinical services unit at St. Vincent's Hospital, Sydney.

In a second study, those percentages were 77% and 43%, respectively.

Maraviroc produced viral RNA loads of fewer than 50 copies/mL—considered an undetectable viral load—in 40%–48% of treated patients in its two studies, compared with 21% and 24% of placebo-treated patients.

Raltegravir produced viral loads of fewer than 50 copies/mL in 61% and 62% of treated patients, versus 33% and 36% of placebo patients.

Mean CD4 T-cell levels increased to a greater degree in treated patients for both drugs, and both drugs had low discontinuation rates that were comparable with discontinuations in placebo patients.

According to Pfizer, maraviroc is receiving accelerated review by the U.S. Food and Drug Administration and in Europe.

Merck is providing expanded access to raltegravir for patients unable to participate in a clinical trial.

If approved, the drugs should find ready use. It is estimated that 5%–15% of new infections are infections with virus that already has some resistance to available drugs, said Dr. Mellors, who called the results a “milestone” in HIV therapy.

For treatment of patients with drug-resistant HIV, 'this is really a remarkable development in the field.' DR. MELLORS

LOS ANGELES — Two novel HIV medications produced striking improvement in AIDS patients otherwise failing standard therapy, according to four separate studies presented at a conference on retroviruses and opportunistic infections.

“The results here are as exciting as the development of HAART [highly active antiretroviral therapy] for treatment-experienced patients,” said Dr. John W. Mellors, chief of infectious diseases at the University of Pittsburgh, commenting on the studies at a press briefing.

Each drug reduced viral loads to fewer than 400 copies/mL in 60%–80% of study patients, who already had resistance to currently available drugs.

“This is really a remarkable development in the field,” added Dr. Mellors, who is also codirector of the center for viral diseases at the University of Pittsburgh.

One of the drugs, Pfizer Inc.'s maraviroc, is an antagonist to the CCR5 coreceptor used by HIV to enter CD4-positive T cells. The other drug, Merck & Co.'s raltegravir, is an integrase inhibitor, which blocks viral genes from being incorporated into the host cell genome where they can be activated.

In one trial of maraviroc conducted in Europe, Australia, and North America, the drug reduced HIV RNA levels to below 400 copies/mL at 24 weeks in 55% of 182 triple-class-experienced patients who took the drug (150 or 300 mg) once daily in addition to their optimized, standard therapy. The drug reduced viral loads below that level in 61% of 191 patients who took the drug twice daily, reported Dr. Howard Mayer, executive director for global research and development at Pfizer.

That compared with only 23% of 91 placebo-treated patients whose viral loads dropped below that level, he said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

The dosage that the patients received in the trial—either 150 mg or 300 mg—depended on what drugs were in their optimized background therapy during the trial. Patients whose background treatment regimen included a protease inhibitor or delavirdine received the lower dose.

In a second trial conducted only in the United States and Canada, the results were almost the same. Of the 232 patients who took the drug once daily, 55% had viral levels that dropped below 400 copies/mL, as did those of 60% of 235 patients who took the drug twice daily. That compared with 31% of 118 placebo-treated patients.

Raltegravir (400 mg twice daily) decreased the HIV RNA level to less than 400 copies/mL in 77% of 232 patients with triple-class-resistant virus on optimized therapy, versus 41% of 118 placebo-treated patients, at 16 weeks, reported Dr. David Cooper, head of the immunology, HIV, and infectious diseases clinical services unit at St. Vincent's Hospital, Sydney.

In a second study, those percentages were 77% and 43%, respectively.

Maraviroc produced viral RNA loads of fewer than 50 copies/mL—considered an undetectable viral load—in 40%–48% of treated patients in its two studies, compared with 21% and 24% of placebo-treated patients.

Raltegravir produced viral loads of fewer than 50 copies/mL in 61% and 62% of treated patients, versus 33% and 36% of placebo patients.

Mean CD4 T-cell levels increased to a greater degree in treated patients for both drugs, and both drugs had low discontinuation rates that were comparable with discontinuations in placebo patients.

According to Pfizer, maraviroc is receiving accelerated review by the U.S. Food and Drug Administration and in Europe.

Merck is providing expanded access to raltegravir for patients unable to participate in a clinical trial.

If approved, the drugs should find ready use. It is estimated that 5%–15% of new infections are infections with virus that already has some resistance to available drugs, said Dr. Mellors, who called the results a “milestone” in HIV therapy.

For treatment of patients with drug-resistant HIV, 'this is really a remarkable development in the field.' DR. MELLORS

LOS ANGELES — Two novel HIV medications produced striking improvement in AIDS patients otherwise failing standard therapy, according to four separate studies presented at a conference on retroviruses and opportunistic infections.

“The results here are as exciting as the development of HAART [highly active antiretroviral therapy] for treatment-experienced patients,” said Dr. John W. Mellors, chief of infectious diseases at the University of Pittsburgh, commenting on the studies at a press briefing.

Each drug reduced viral loads to fewer than 400 copies/mL in 60%–80% of study patients, who already had resistance to currently available drugs.

“This is really a remarkable development in the field,” added Dr. Mellors, who is also codirector of the center for viral diseases at the University of Pittsburgh.

One of the drugs, Pfizer Inc.'s maraviroc, is an antagonist to the CCR5 coreceptor used by HIV to enter CD4-positive T cells. The other drug, Merck & Co.'s raltegravir, is an integrase inhibitor, which blocks viral genes from being incorporated into the host cell genome where they can be activated.

In one trial of maraviroc conducted in Europe, Australia, and North America, the drug reduced HIV RNA levels to below 400 copies/mL at 24 weeks in 55% of 182 triple-class-experienced patients who took the drug (150 or 300 mg) once daily in addition to their optimized, standard therapy. The drug reduced viral loads below that level in 61% of 191 patients who took the drug twice daily, reported Dr. Howard Mayer, executive director for global research and development at Pfizer.

That compared with only 23% of 91 placebo-treated patients whose viral loads dropped below that level, he said at the conference, sponsored by the Foundation for Retrovirology and Human Health.

The dosage that the patients received in the trial—either 150 mg or 300 mg—depended on what drugs were in their optimized background therapy during the trial. Patients whose background treatment regimen included a protease inhibitor or delavirdine received the lower dose.

In a second trial conducted only in the United States and Canada, the results were almost the same. Of the 232 patients who took the drug once daily, 55% had viral levels that dropped below 400 copies/mL, as did those of 60% of 235 patients who took the drug twice daily. That compared with 31% of 118 placebo-treated patients.

Raltegravir (400 mg twice daily) decreased the HIV RNA level to less than 400 copies/mL in 77% of 232 patients with triple-class-resistant virus on optimized therapy, versus 41% of 118 placebo-treated patients, at 16 weeks, reported Dr. David Cooper, head of the immunology, HIV, and infectious diseases clinical services unit at St. Vincent's Hospital, Sydney.

In a second study, those percentages were 77% and 43%, respectively.

Maraviroc produced viral RNA loads of fewer than 50 copies/mL—considered an undetectable viral load—in 40%–48% of treated patients in its two studies, compared with 21% and 24% of placebo-treated patients.

Raltegravir produced viral loads of fewer than 50 copies/mL in 61% and 62% of treated patients, versus 33% and 36% of placebo patients.

Mean CD4 T-cell levels increased to a greater degree in treated patients for both drugs, and both drugs had low discontinuation rates that were comparable with discontinuations in placebo patients.

According to Pfizer, maraviroc is receiving accelerated review by the U.S. Food and Drug Administration and in Europe.

Merck is providing expanded access to raltegravir for patients unable to participate in a clinical trial.

If approved, the drugs should find ready use. It is estimated that 5%–15% of new infections are infections with virus that already has some resistance to available drugs, said Dr. Mellors, who called the results a “milestone” in HIV therapy.

For treatment of patients with drug-resistant HIV, 'this is really a remarkable development in the field.' DR. MELLORS

SAN DIEGO — Physicians who treat children must have plans for identifying families with violence problems and then dealing with it, Betsy McAlister Groves, a licensed social worker, said at a conference sponsored by the Chadwick Center for Children and Families at Children's Hospital and Health Center, San Diego.

In 40%–60% of families in which there is domestic abuse, there also is child abuse, the social worker said.

Many physicians are uncomfortable tackling family violence issues. But guidelines published in 2004 give specific recommendations for what primary care physicians ought to do in their practices, said Ms. McAlister Groves, the founding director of the Child Witness to Violence Project at the Boston Medical Center.

The consensus guidelines were put together by experts from 15 states and had the support of the Family Violence Prevention Fund, and are available at www.endabuse.org/programs/display.php3?DocID=206

The recommendations suggest that physicians implement three steps:

▸ They should provide screening by asking the parent if there is violence in the home.

▸ They should have resources available so that patients and/or parents can be educated and exposed to the message that family violence is extremely destructive.

▸ They should know where to send families for help and/or reporting.

In her talk, Ms. McAlister Groves told the story of a woman who came to this country as a mail-order bride—who initially spoke no English—whose husband turned out to be abusive. The impetus, eventually, for her to seek help was a poster in the waiting area of her pediatrician's office that stated simply that no one deserves to be hit.

She told another story about a 13-month-old girl who was being held by her mother when the woman was hit by her boyfriend. For the next 3 weeks, that child had such intense separation anxiety that the mother could not even go to the bathroom by herself.

This story illustrates that even very young children are profoundly affected by violence, Ms. McAlister Groves said.

According to her figures, 85% of children who witness an incidence of violence against their mother experience symptoms of posttraumatic stress disorder, and the latest figures indicate that perhaps one-third of children are exposed to some domestic violence.

“If a parent is vulnerable, a child is also vulnerable,” she said.

There is a role for the pediatric health provider to help parents and children talk about this, she added.

Among other recommendations in these guidelines:

▸ Who and when to ask. New patients should be asked about violence in the home, and regular patients should be queried at least once a year at routine appointments, such as well-child visit, or if there is reason to be concerned. The parent should be asked, not the child, until the child is perhaps 12 years old.

Direct questions are best, such as “Have you ever been hurt or threatened by your partner?” and “Has your child witnessed a violent or frightening event in your neighborhood or home?” But the physician should use his or her own style, and often, indirect questions will suffice, such as “What happens when there is a disagreement in your home?” and “Do you feel safe in your home?”

You can preface your questions by explaining that you are asking because the problem of domestic violence is so common that these questions have become routine.

“The majority of women I have talked to are not offended by questioning,” Ms. McAlister Groves said.

▸ Should the child be in the room? There is debate over whether the child should be in the room when the questions are asked, Ms. McAlister Groves said. It is better to ask indirect questions with the child in the room than to miss asking patients.

▸ Who should ask these questions? Written questions should not take the place of verbal questioning, and the inquiry can be made by anyone in the office who has had the proper training.

▸ Know how to respond to answers to your questions. If you are going to ask, then you need to know what to do with this information. All but 10 states require reporting of specific injurious incidents, and some require reporting when you hear about domestic violence. Physicians and other practitioners should familiarize themselves with their state's reporting laws and should know where to refer the parent for help; it is a good idea to have information on hand about domestic violence and its impact on children.

When you hear about violence, ask if the mother and child are safe currently. If you plan to report an incident, inform the parent that you are going to make a report.

At her center, the staff tries to make the reporting call with the parent present, Ms. McAlister Groves said.

▸ What to do when the child tells about violence in the home. When a child tells his doctor about violence in the home, the recommendation is that the physician gets as much information as possible and then tells the nonabusing parent that she knows. Since the child could get in trouble, the physician needs to explain to the parent that the child simply is doing what he thinks is right.

▸ Know when to refer. The definitive time to refer a patient for more expert help is when the child has symptoms from the violence that have persisted more than 3 months (1 month in young children), when the trauma was particularly violent or injurious, when the caretaker is unable to be empathic and attuned to the child's needs, or when the nonabusive caretaker is in danger.

SAN DIEGO — Physicians who treat children must have plans for identifying families with violence problems and then dealing with it, Betsy McAlister Groves, a licensed social worker, said at a conference sponsored by the Chadwick Center for Children and Families at Children's Hospital and Health Center, San Diego.

In 40%–60% of families in which there is domestic abuse, there also is child abuse, the social worker said.

Many physicians are uncomfortable tackling family violence issues. But guidelines published in 2004 give specific recommendations for what primary care physicians ought to do in their practices, said Ms. McAlister Groves, the founding director of the Child Witness to Violence Project at the Boston Medical Center.

The consensus guidelines were put together by experts from 15 states and had the support of the Family Violence Prevention Fund, and are available at www.endabuse.org/programs/display.php3?DocID=206

The recommendations suggest that physicians implement three steps:

▸ They should provide screening by asking the parent if there is violence in the home.

▸ They should have resources available so that patients and/or parents can be educated and exposed to the message that family violence is extremely destructive.

▸ They should know where to send families for help and/or reporting.

In her talk, Ms. McAlister Groves told the story of a woman who came to this country as a mail-order bride—who initially spoke no English—whose husband turned out to be abusive. The impetus, eventually, for her to seek help was a poster in the waiting area of her pediatrician's office that stated simply that no one deserves to be hit.

She told another story about a 13-month-old girl who was being held by her mother when the woman was hit by her boyfriend. For the next 3 weeks, that child had such intense separation anxiety that the mother could not even go to the bathroom by herself.

This story illustrates that even very young children are profoundly affected by violence, Ms. McAlister Groves said.

According to her figures, 85% of children who witness an incidence of violence against their mother experience symptoms of posttraumatic stress disorder, and the latest figures indicate that perhaps one-third of children are exposed to some domestic violence.

“If a parent is vulnerable, a child is also vulnerable,” she said.

There is a role for the pediatric health provider to help parents and children talk about this, she added.

Among other recommendations in these guidelines:

▸ Who and when to ask. New patients should be asked about violence in the home, and regular patients should be queried at least once a year at routine appointments, such as well-child visit, or if there is reason to be concerned. The parent should be asked, not the child, until the child is perhaps 12 years old.

Direct questions are best, such as “Have you ever been hurt or threatened by your partner?” and “Has your child witnessed a violent or frightening event in your neighborhood or home?” But the physician should use his or her own style, and often, indirect questions will suffice, such as “What happens when there is a disagreement in your home?” and “Do you feel safe in your home?”

You can preface your questions by explaining that you are asking because the problem of domestic violence is so common that these questions have become routine.

“The majority of women I have talked to are not offended by questioning,” Ms. McAlister Groves said.

▸ Should the child be in the room? There is debate over whether the child should be in the room when the questions are asked, Ms. McAlister Groves said. It is better to ask indirect questions with the child in the room than to miss asking patients.

▸ Who should ask these questions? Written questions should not take the place of verbal questioning, and the inquiry can be made by anyone in the office who has had the proper training.

▸ Know how to respond to answers to your questions. If you are going to ask, then you need to know what to do with this information. All but 10 states require reporting of specific injurious incidents, and some require reporting when you hear about domestic violence. Physicians and other practitioners should familiarize themselves with their state's reporting laws and should know where to refer the parent for help; it is a good idea to have information on hand about domestic violence and its impact on children.

When you hear about violence, ask if the mother and child are safe currently. If you plan to report an incident, inform the parent that you are going to make a report.

At her center, the staff tries to make the reporting call with the parent present, Ms. McAlister Groves said.

▸ What to do when the child tells about violence in the home. When a child tells his doctor about violence in the home, the recommendation is that the physician gets as much information as possible and then tells the nonabusing parent that she knows. Since the child could get in trouble, the physician needs to explain to the parent that the child simply is doing what he thinks is right.

▸ Know when to refer. The definitive time to refer a patient for more expert help is when the child has symptoms from the violence that have persisted more than 3 months (1 month in young children), when the trauma was particularly violent or injurious, when the caretaker is unable to be empathic and attuned to the child's needs, or when the nonabusive caretaker is in danger.

SAN DIEGO — Physicians who treat children must have plans for identifying families with violence problems and then dealing with it, Betsy McAlister Groves, a licensed social worker, said at a conference sponsored by the Chadwick Center for Children and Families at Children's Hospital and Health Center, San Diego.

In 40%–60% of families in which there is domestic abuse, there also is child abuse, the social worker said.

Many physicians are uncomfortable tackling family violence issues. But guidelines published in 2004 give specific recommendations for what primary care physicians ought to do in their practices, said Ms. McAlister Groves, the founding director of the Child Witness to Violence Project at the Boston Medical Center.

The consensus guidelines were put together by experts from 15 states and had the support of the Family Violence Prevention Fund, and are available at www.endabuse.org/programs/display.php3?DocID=206

The recommendations suggest that physicians implement three steps:

▸ They should provide screening by asking the parent if there is violence in the home.

▸ They should have resources available so that patients and/or parents can be educated and exposed to the message that family violence is extremely destructive.

▸ They should know where to send families for help and/or reporting.

In her talk, Ms. McAlister Groves told the story of a woman who came to this country as a mail-order bride—who initially spoke no English—whose husband turned out to be abusive. The impetus, eventually, for her to seek help was a poster in the waiting area of her pediatrician's office that stated simply that no one deserves to be hit.

She told another story about a 13-month-old girl who was being held by her mother when the woman was hit by her boyfriend. For the next 3 weeks, that child had such intense separation anxiety that the mother could not even go to the bathroom by herself.

This story illustrates that even very young children are profoundly affected by violence, Ms. McAlister Groves said.

According to her figures, 85% of children who witness an incidence of violence against their mother experience symptoms of posttraumatic stress disorder, and the latest figures indicate that perhaps one-third of children are exposed to some domestic violence.

“If a parent is vulnerable, a child is also vulnerable,” she said.

There is a role for the pediatric health provider to help parents and children talk about this, she added.

Among other recommendations in these guidelines:

▸ Who and when to ask. New patients should be asked about violence in the home, and regular patients should be queried at least once a year at routine appointments, such as well-child visit, or if there is reason to be concerned. The parent should be asked, not the child, until the child is perhaps 12 years old.

Direct questions are best, such as “Have you ever been hurt or threatened by your partner?” and “Has your child witnessed a violent or frightening event in your neighborhood or home?” But the physician should use his or her own style, and often, indirect questions will suffice, such as “What happens when there is a disagreement in your home?” and “Do you feel safe in your home?”

You can preface your questions by explaining that you are asking because the problem of domestic violence is so common that these questions have become routine.

“The majority of women I have talked to are not offended by questioning,” Ms. McAlister Groves said.

▸ Should the child be in the room? There is debate over whether the child should be in the room when the questions are asked, Ms. McAlister Groves said. It is better to ask indirect questions with the child in the room than to miss asking patients.

▸ Who should ask these questions? Written questions should not take the place of verbal questioning, and the inquiry can be made by anyone in the office who has had the proper training.

▸ Know how to respond to answers to your questions. If you are going to ask, then you need to know what to do with this information. All but 10 states require reporting of specific injurious incidents, and some require reporting when you hear about domestic violence. Physicians and other practitioners should familiarize themselves with their state's reporting laws and should know where to refer the parent for help; it is a good idea to have information on hand about domestic violence and its impact on children.

When you hear about violence, ask if the mother and child are safe currently. If you plan to report an incident, inform the parent that you are going to make a report.

At her center, the staff tries to make the reporting call with the parent present, Ms. McAlister Groves said.

▸ What to do when the child tells about violence in the home. When a child tells his doctor about violence in the home, the recommendation is that the physician gets as much information as possible and then tells the nonabusing parent that she knows. Since the child could get in trouble, the physician needs to explain to the parent that the child simply is doing what he thinks is right.

▸ Know when to refer. The definitive time to refer a patient for more expert help is when the child has symptoms from the violence that have persisted more than 3 months (1 month in young children), when the trauma was particularly violent or injurious, when the caretaker is unable to be empathic and attuned to the child's needs, or when the nonabusive caretaker is in danger.

LOS ANGELES — Two novel HIV medications produced striking improvement in AIDS patients otherwise failing standard therapy, according to four separate studies presented at a conference on retroviruses and opportunistic infections.

“The results here are as exciting as the development of HAART [highly active antiretroviral therapy] for treatment-experienced patients,” said Dr. John W. Mellors, chief of infectious diseases at the University of Pittsburgh, commenting on the studies at a press briefing.

Each drug reduced viral loads to fewer than 400 copies/mL in 60%–80% of study patients, who already had resistance to currently available drugs, said Dr. Mellors, who is also codirector of the center for viral diseases at the University of Pittsburgh.

One of the drugs, Pfizer Inc.'s maraviroc, is an antagonist to the CCR5 coreceptor used by HIV to enter CD4-positive T cells. The other drug, Merck & Co.'s raltegravir, is an integrase inhibitor, which blocks viral genes from being incorporated into the host cell genome where they can be activated.

In a trial of maraviroc conducted in Europe, Australia, and North America, the drug reduced HIV RNA levels to below 400 copies/mL at 24 weeks in 55% of 182 triple-class-experienced patients who took the drug (150 or 300 mg) once daily in addition to their optimized, standard therapy. The drug reduced viral loads below that level in 61% of 191 patients who took the drug twice daily, said Dr. Howard Mayer, executive director for global research and development at Pfizer.

That compared with only 23% of 91 placebo-treated patients whose viral loads dropped below that level, he said at the conference, which was sponsored by the Foundation for Retrovirology and Human Health.

In a second trial conducted only in the United States and Canada, the results were almost the same. Of the 232 patients who took the drug once daily, 55% had viral levels that dropped below 400 copies/mL, as did those of 60% of 235 patients who took the drug twice daily. That compared with 31% of 118 placebo-treated patients.

Raltegravir (400 mg twice daily) decreased the HIV RNA level to less than 400 copies/mL in 77% of 232 patients with triple-class-resistant virus on optimized therapy, versus 41% of 118 placebo-treated patients, at 16 weeks, reported Dr. David Cooper, head of the immunology, HIV, and infectious diseases clinical services unit at St. Vincent's Hospital, Sydney.

In a second study, those percentages were 77% and 43%, respectively.

Maraviroc produced viral RNA loads of fewer than 50 copies/mL—considered an undetectable viral load—in 40%–48% of treated patients in its two studies, compared with 21% and 24% of placebo-treated patients.

Raltegravir produced viral loads of fewer than 50 copies/mL in 61% and 62% of treated patients, versus 33% and 36% of placebo patients.

According to Pfizer, maraviroc is receiving accelerated review by the U.S. Food and Drug Administration and in Europe. Merck is providing expanded access to raltegravir for patients unable to participate in a clinical trial.

If approved, the drugs, should find ready use. It is currently estimated that 5%–15% of new infections are infections with virus that already has some resistance to currently available drugs, said Dr. Mellors, who called the results a “milestone” in HIV therapy.

The results are as exciting as the development of HAART for treatment-experienced patients. DR. MELLORS

LOS ANGELES — Two novel HIV medications produced striking improvement in AIDS patients otherwise failing standard therapy, according to four separate studies presented at a conference on retroviruses and opportunistic infections.

“The results here are as exciting as the development of HAART [highly active antiretroviral therapy] for treatment-experienced patients,” said Dr. John W. Mellors, chief of infectious diseases at the University of Pittsburgh, commenting on the studies at a press briefing.

Each drug reduced viral loads to fewer than 400 copies/mL in 60%–80% of study patients, who already had resistance to currently available drugs, said Dr. Mellors, who is also codirector of the center for viral diseases at the University of Pittsburgh.

One of the drugs, Pfizer Inc.'s maraviroc, is an antagonist to the CCR5 coreceptor used by HIV to enter CD4-positive T cells. The other drug, Merck & Co.'s raltegravir, is an integrase inhibitor, which blocks viral genes from being incorporated into the host cell genome where they can be activated.

In a trial of maraviroc conducted in Europe, Australia, and North America, the drug reduced HIV RNA levels to below 400 copies/mL at 24 weeks in 55% of 182 triple-class-experienced patients who took the drug (150 or 300 mg) once daily in addition to their optimized, standard therapy. The drug reduced viral loads below that level in 61% of 191 patients who took the drug twice daily, said Dr. Howard Mayer, executive director for global research and development at Pfizer.

That compared with only 23% of 91 placebo-treated patients whose viral loads dropped below that level, he said at the conference, which was sponsored by the Foundation for Retrovirology and Human Health.

In a second trial conducted only in the United States and Canada, the results were almost the same. Of the 232 patients who took the drug once daily, 55% had viral levels that dropped below 400 copies/mL, as did those of 60% of 235 patients who took the drug twice daily. That compared with 31% of 118 placebo-treated patients.

Raltegravir (400 mg twice daily) decreased the HIV RNA level to less than 400 copies/mL in 77% of 232 patients with triple-class-resistant virus on optimized therapy, versus 41% of 118 placebo-treated patients, at 16 weeks, reported Dr. David Cooper, head of the immunology, HIV, and infectious diseases clinical services unit at St. Vincent's Hospital, Sydney.

In a second study, those percentages were 77% and 43%, respectively.

Maraviroc produced viral RNA loads of fewer than 50 copies/mL—considered an undetectable viral load—in 40%–48% of treated patients in its two studies, compared with 21% and 24% of placebo-treated patients.

Raltegravir produced viral loads of fewer than 50 copies/mL in 61% and 62% of treated patients, versus 33% and 36% of placebo patients.

According to Pfizer, maraviroc is receiving accelerated review by the U.S. Food and Drug Administration and in Europe. Merck is providing expanded access to raltegravir for patients unable to participate in a clinical trial.

If approved, the drugs, should find ready use. It is currently estimated that 5%–15% of new infections are infections with virus that already has some resistance to currently available drugs, said Dr. Mellors, who called the results a “milestone” in HIV therapy.

The results are as exciting as the development of HAART for treatment-experienced patients. DR. MELLORS

LOS ANGELES — Two novel HIV medications produced striking improvement in AIDS patients otherwise failing standard therapy, according to four separate studies presented at a conference on retroviruses and opportunistic infections.

“The results here are as exciting as the development of HAART [highly active antiretroviral therapy] for treatment-experienced patients,” said Dr. John W. Mellors, chief of infectious diseases at the University of Pittsburgh, commenting on the studies at a press briefing.

Each drug reduced viral loads to fewer than 400 copies/mL in 60%–80% of study patients, who already had resistance to currently available drugs, said Dr. Mellors, who is also codirector of the center for viral diseases at the University of Pittsburgh.

One of the drugs, Pfizer Inc.'s maraviroc, is an antagonist to the CCR5 coreceptor used by HIV to enter CD4-positive T cells. The other drug, Merck & Co.'s raltegravir, is an integrase inhibitor, which blocks viral genes from being incorporated into the host cell genome where they can be activated.

In a trial of maraviroc conducted in Europe, Australia, and North America, the drug reduced HIV RNA levels to below 400 copies/mL at 24 weeks in 55% of 182 triple-class-experienced patients who took the drug (150 or 300 mg) once daily in addition to their optimized, standard therapy. The drug reduced viral loads below that level in 61% of 191 patients who took the drug twice daily, said Dr. Howard Mayer, executive director for global research and development at Pfizer.

That compared with only 23% of 91 placebo-treated patients whose viral loads dropped below that level, he said at the conference, which was sponsored by the Foundation for Retrovirology and Human Health.

In a second trial conducted only in the United States and Canada, the results were almost the same. Of the 232 patients who took the drug once daily, 55% had viral levels that dropped below 400 copies/mL, as did those of 60% of 235 patients who took the drug twice daily. That compared with 31% of 118 placebo-treated patients.

Raltegravir (400 mg twice daily) decreased the HIV RNA level to less than 400 copies/mL in 77% of 232 patients with triple-class-resistant virus on optimized therapy, versus 41% of 118 placebo-treated patients, at 16 weeks, reported Dr. David Cooper, head of the immunology, HIV, and infectious diseases clinical services unit at St. Vincent's Hospital, Sydney.

In a second study, those percentages were 77% and 43%, respectively.

Maraviroc produced viral RNA loads of fewer than 50 copies/mL—considered an undetectable viral load—in 40%–48% of treated patients in its two studies, compared with 21% and 24% of placebo-treated patients.

Raltegravir produced viral loads of fewer than 50 copies/mL in 61% and 62% of treated patients, versus 33% and 36% of placebo patients.

According to Pfizer, maraviroc is receiving accelerated review by the U.S. Food and Drug Administration and in Europe. Merck is providing expanded access to raltegravir for patients unable to participate in a clinical trial.

If approved, the drugs, should find ready use. It is currently estimated that 5%–15% of new infections are infections with virus that already has some resistance to currently available drugs, said Dr. Mellors, who called the results a “milestone” in HIV therapy.

The results are as exciting as the development of HAART for treatment-experienced patients. DR. MELLORS

SAN DIEGO — In its second year, the National Screening Program for Venous Disease conducted free clinics in 40 states, and more than half the persons screened were found to be at risk of a venous thromboembolism if put in a conducive situation, Dr. Robert B. McLafferty said at the annual meeting of the American Venous Forum.

“There has been extreme and rapid growth,” said Dr. McLafferty, professor of vascular surgery at Southern Illinois University, Springfield. In the second year, 149 centers conducted free screening clinics versus 17 centers in the first year.

As with the first year's screening, data from the 56 clinics that have reported their results so far showed a high rate of risk and disease among those screened, with 57% deemed to be at high or very high risk of a venous thromboembolism if placed in a risky situation, defined as a surgical procedure, major injury or hospitalization, malignancy, or prolonged immobility.

This is not surprising given that the mean age of participants was 60 years, 40% were overweight, and the second most common reason participants came to the clinics was varicose veins (30%), Dr. McLafferty said.

In all, 17% had a quality of life that was very limited by venous symptoms, or had probable disease. Participants were mostly white and female (both about 80%).

Differences from the first year were that a slightly higher percentage of participants were considered CEAP (clinical, etiologic, anatomic, pathophysiologic) class 0 (29% versus 20%), and fewer were overweight (40% had a body mass index over 25, versus 67%), Dr. McLafferty said. Otherwise, there were few differences, “even though we have tripled the number of people screened,” he added. One in 20 participants had segments of obstruction in the veins examined by ultrasound, and almost 40% had one or more segments of reflux.

The results of the first year's screening program were recently published (J. Vasc. Surg. 2007;45:142–8).

Participants filled out a demographic questionnaire and a quality of life form. They had a venous thromboembolism risk assessment using a standardized tool, and an abbreviated ultrasound examination that looked at the common femoral vein, the saphenofemoral junction, and the popliteal vein above the knee. Lastly, the participants were examined by trained professionals or physicians to classify their lower extremities using the CEAP classification system, and were given an exit interview detailing the findings of their exams.

The screening program is the brainchild of the American Venous Forum, with assistance from the American Vascular Association.

The two annual screening programs have taken place during a week in early November.

Of those screened, 57% were at high or very high risk of a venous thromboembolism if placed in a risky situation. DR. MCLAFFERTY

SAN DIEGO — In its second year, the National Screening Program for Venous Disease conducted free clinics in 40 states, and more than half the persons screened were found to be at risk of a venous thromboembolism if put in a conducive situation, Dr. Robert B. McLafferty said at the annual meeting of the American Venous Forum.

“There has been extreme and rapid growth,” said Dr. McLafferty, professor of vascular surgery at Southern Illinois University, Springfield. In the second year, 149 centers conducted free screening clinics versus 17 centers in the first year.

As with the first year's screening, data from the 56 clinics that have reported their results so far showed a high rate of risk and disease among those screened, with 57% deemed to be at high or very high risk of a venous thromboembolism if placed in a risky situation, defined as a surgical procedure, major injury or hospitalization, malignancy, or prolonged immobility.

This is not surprising given that the mean age of participants was 60 years, 40% were overweight, and the second most common reason participants came to the clinics was varicose veins (30%), Dr. McLafferty said.

In all, 17% had a quality of life that was very limited by venous symptoms, or had probable disease. Participants were mostly white and female (both about 80%).

Differences from the first year were that a slightly higher percentage of participants were considered CEAP (clinical, etiologic, anatomic, pathophysiologic) class 0 (29% versus 20%), and fewer were overweight (40% had a body mass index over 25, versus 67%), Dr. McLafferty said. Otherwise, there were few differences, “even though we have tripled the number of people screened,” he added. One in 20 participants had segments of obstruction in the veins examined by ultrasound, and almost 40% had one or more segments of reflux.

The results of the first year's screening program were recently published (J. Vasc. Surg. 2007;45:142–8).

Participants filled out a demographic questionnaire and a quality of life form. They had a venous thromboembolism risk assessment using a standardized tool, and an abbreviated ultrasound examination that looked at the common femoral vein, the saphenofemoral junction, and the popliteal vein above the knee. Lastly, the participants were examined by trained professionals or physicians to classify their lower extremities using the CEAP classification system, and were given an exit interview detailing the findings of their exams.

The screening program is the brainchild of the American Venous Forum, with assistance from the American Vascular Association.

The two annual screening programs have taken place during a week in early November.

Of those screened, 57% were at high or very high risk of a venous thromboembolism if placed in a risky situation. DR. MCLAFFERTY

SAN DIEGO — In its second year, the National Screening Program for Venous Disease conducted free clinics in 40 states, and more than half the persons screened were found to be at risk of a venous thromboembolism if put in a conducive situation, Dr. Robert B. McLafferty said at the annual meeting of the American Venous Forum.

“There has been extreme and rapid growth,” said Dr. McLafferty, professor of vascular surgery at Southern Illinois University, Springfield. In the second year, 149 centers conducted free screening clinics versus 17 centers in the first year.

As with the first year's screening, data from the 56 clinics that have reported their results so far showed a high rate of risk and disease among those screened, with 57% deemed to be at high or very high risk of a venous thromboembolism if placed in a risky situation, defined as a surgical procedure, major injury or hospitalization, malignancy, or prolonged immobility.

This is not surprising given that the mean age of participants was 60 years, 40% were overweight, and the second most common reason participants came to the clinics was varicose veins (30%), Dr. McLafferty said.

In all, 17% had a quality of life that was very limited by venous symptoms, or had probable disease. Participants were mostly white and female (both about 80%).

Differences from the first year were that a slightly higher percentage of participants were considered CEAP (clinical, etiologic, anatomic, pathophysiologic) class 0 (29% versus 20%), and fewer were overweight (40% had a body mass index over 25, versus 67%), Dr. McLafferty said. Otherwise, there were few differences, “even though we have tripled the number of people screened,” he added. One in 20 participants had segments of obstruction in the veins examined by ultrasound, and almost 40% had one or more segments of reflux.

The results of the first year's screening program were recently published (J. Vasc. Surg. 2007;45:142–8).

Participants filled out a demographic questionnaire and a quality of life form. They had a venous thromboembolism risk assessment using a standardized tool, and an abbreviated ultrasound examination that looked at the common femoral vein, the saphenofemoral junction, and the popliteal vein above the knee. Lastly, the participants were examined by trained professionals or physicians to classify their lower extremities using the CEAP classification system, and were given an exit interview detailing the findings of their exams.

The screening program is the brainchild of the American Venous Forum, with assistance from the American Vascular Association.

The two annual screening programs have taken place during a week in early November.

Of those screened, 57% were at high or very high risk of a venous thromboembolism if placed in a risky situation. DR. MCLAFFERTY

SAN FRANCISCO — Some HIV-infected patients who are well managed on highly active antiretroviral therapy are developing Kaposi's sarcoma, Dr. Toby A. Maurer said at a meeting on HIV management sponsored by the University of California, San Francisco.

In this trend, which has been identified in San Francisco by Dr. Maurer and her associates, patients often have CD4 counts of 300 and even 600 cells/mcL and low viral loads. Yet they have the telltale purple blotches of Kaposi's, said Dr. Maurer, chief of dermatology at San Francisco General Hospital.

Dr. Maurer said that these are not flares of Kaposi's, which can sometimes happen at the start of highly active antiretroviral therapy (HAART). Rather, these are occurrences in patients who are fairly well maintained on the therapy.

The main question is whether these patients have developed abnormal T-cell function over time on HAART, despite high CD4 cell counts, thus causing the loss of immunologic control of their Kaposi's sarcoma; or, alternatively, whether their systemic disease was not detected and treated.

“We're really trying to understand these patients and, more importantly, clinically we are trying to decide what to do with these patients because antiretrovirals don't seem to do it,” Dr. Maurer said. “And, [the patients] are not sick enough nor do they have evidence of systemic KS to warrant chemotherapy.”

Although she said there is still no good, reliable method of detecting Kaposi's that has spread and is systemic, Dr. Maurer offered a suggestion to those checking Kaposi's lesions on the legs: Look for edema in the appendage because that is a sign of systemic disease. Systemic disease has a high mortality rate, about 25%; those patients need more than just antiretrovirals.

Physicians who've seen patients on HAART who have had a recurrence of Kaposi's sarcoma should contact Dr. Maurer by e-mail at maurert@derm.ucsf.edu

SAN FRANCISCO — Some HIV-infected patients who are well managed on highly active antiretroviral therapy are developing Kaposi's sarcoma, Dr. Toby A. Maurer said at a meeting on HIV management sponsored by the University of California, San Francisco.

In this trend, which has been identified in San Francisco by Dr. Maurer and her associates, patients often have CD4 counts of 300 and even 600 cells/mcL and low viral loads. Yet they have the telltale purple blotches of Kaposi's, said Dr. Maurer, chief of dermatology at San Francisco General Hospital.

Dr. Maurer said that these are not flares of Kaposi's, which can sometimes happen at the start of highly active antiretroviral therapy (HAART). Rather, these are occurrences in patients who are fairly well maintained on the therapy.

The main question is whether these patients have developed abnormal T-cell function over time on HAART, despite high CD4 cell counts, thus causing the loss of immunologic control of their Kaposi's sarcoma; or, alternatively, whether their systemic disease was not detected and treated.

“We're really trying to understand these patients and, more importantly, clinically we are trying to decide what to do with these patients because antiretrovirals don't seem to do it,” Dr. Maurer said. “And, [the patients] are not sick enough nor do they have evidence of systemic KS to warrant chemotherapy.”

Although she said there is still no good, reliable method of detecting Kaposi's that has spread and is systemic, Dr. Maurer offered a suggestion to those checking Kaposi's lesions on the legs: Look for edema in the appendage because that is a sign of systemic disease. Systemic disease has a high mortality rate, about 25%; those patients need more than just antiretrovirals.

Physicians who've seen patients on HAART who have had a recurrence of Kaposi's sarcoma should contact Dr. Maurer by e-mail at maurert@derm.ucsf.edu

SAN FRANCISCO — Some HIV-infected patients who are well managed on highly active antiretroviral therapy are developing Kaposi's sarcoma, Dr. Toby A. Maurer said at a meeting on HIV management sponsored by the University of California, San Francisco.

In this trend, which has been identified in San Francisco by Dr. Maurer and her associates, patients often have CD4 counts of 300 and even 600 cells/mcL and low viral loads. Yet they have the telltale purple blotches of Kaposi's, said Dr. Maurer, chief of dermatology at San Francisco General Hospital.

Dr. Maurer said that these are not flares of Kaposi's, which can sometimes happen at the start of highly active antiretroviral therapy (HAART). Rather, these are occurrences in patients who are fairly well maintained on the therapy.

The main question is whether these patients have developed abnormal T-cell function over time on HAART, despite high CD4 cell counts, thus causing the loss of immunologic control of their Kaposi's sarcoma; or, alternatively, whether their systemic disease was not detected and treated.

“We're really trying to understand these patients and, more importantly, clinically we are trying to decide what to do with these patients because antiretrovirals don't seem to do it,” Dr. Maurer said. “And, [the patients] are not sick enough nor do they have evidence of systemic KS to warrant chemotherapy.”

Although she said there is still no good, reliable method of detecting Kaposi's that has spread and is systemic, Dr. Maurer offered a suggestion to those checking Kaposi's lesions on the legs: Look for edema in the appendage because that is a sign of systemic disease. Systemic disease has a high mortality rate, about 25%; those patients need more than just antiretrovirals.

Physicians who've seen patients on HAART who have had a recurrence of Kaposi's sarcoma should contact Dr. Maurer by e-mail at maurert@derm.ucsf.edu

SAN FRANCISCO — As the incidence of gonorrhea continues to increase, physicians need to be doing more testing for the venereal disease in the anus and the throat, particularly in gay men, said the chief of the sexually transmitted diseases control branch for the state of California.

Gonorrhea incidence in the United States as a whole and in California specifically had been declining for 3 decades before starting to climb in about the year 2000, Dr. Gail Bolan said at a meeting on HIV management sponsored by the University of California, San Francisco.

A recent study in San Francisco of men who have sex with men reported that if only urine and urethral screening were performed in those men, about 65% of gonorrhea cases would be missed, Dr. Bolan said.

The study found that 85% of the rectal infections were asymptomatic, indicating the possibility that these infections may be an important factor fueling the incidence increase (Clin. Infect. Dis. 2005;41:67–74).

Additionally, the study reported that 53% of chlamydial infections were at nonurethral sites, Dr. Bolan noted.

In part because of these concerns, the Centers for Disease Control and Prevention recently updated its sexually transmitted diseases guidelines to include what to ask when taking a sexual history to screen for disease. According to the new guidelines, the sexual history taking must include specific questions regarding what is known as the “5 P's”: partners, pregnancy protection, protection from sexually transmitted diseases, practices, and past history of sexually transmitted diseases.

Because testing for gonorrhea at the rectal and pharyngeal sites requires culturing, physicians need to make sure they have culturing available, she noted.

Dr. Bolan also said that fluoroquinolone-resistant gonorrhea continues to be a problem. The CDC guidelines recommend that fluoroquinolones not be used in men who have sex with men or in areas where fluoroquinolone resistance is high.

SAN FRANCISCO — As the incidence of gonorrhea continues to increase, physicians need to be doing more testing for the venereal disease in the anus and the throat, particularly in gay men, said the chief of the sexually transmitted diseases control branch for the state of California.

Gonorrhea incidence in the United States as a whole and in California specifically had been declining for 3 decades before starting to climb in about the year 2000, Dr. Gail Bolan said at a meeting on HIV management sponsored by the University of California, San Francisco.

A recent study in San Francisco of men who have sex with men reported that if only urine and urethral screening were performed in those men, about 65% of gonorrhea cases would be missed, Dr. Bolan said.

The study found that 85% of the rectal infections were asymptomatic, indicating the possibility that these infections may be an important factor fueling the incidence increase (Clin. Infect. Dis. 2005;41:67–74).

Additionally, the study reported that 53% of chlamydial infections were at nonurethral sites, Dr. Bolan noted.

In part because of these concerns, the Centers for Disease Control and Prevention recently updated its sexually transmitted diseases guidelines to include what to ask when taking a sexual history to screen for disease. According to the new guidelines, the sexual history taking must include specific questions regarding what is known as the “5 P's”: partners, pregnancy protection, protection from sexually transmitted diseases, practices, and past history of sexually transmitted diseases.

Because testing for gonorrhea at the rectal and pharyngeal sites requires culturing, physicians need to make sure they have culturing available, she noted.

Dr. Bolan also said that fluoroquinolone-resistant gonorrhea continues to be a problem. The CDC guidelines recommend that fluoroquinolones not be used in men who have sex with men or in areas where fluoroquinolone resistance is high.

SAN FRANCISCO — As the incidence of gonorrhea continues to increase, physicians need to be doing more testing for the venereal disease in the anus and the throat, particularly in gay men, said the chief of the sexually transmitted diseases control branch for the state of California.

Gonorrhea incidence in the United States as a whole and in California specifically had been declining for 3 decades before starting to climb in about the year 2000, Dr. Gail Bolan said at a meeting on HIV management sponsored by the University of California, San Francisco.

A recent study in San Francisco of men who have sex with men reported that if only urine and urethral screening were performed in those men, about 65% of gonorrhea cases would be missed, Dr. Bolan said.

The study found that 85% of the rectal infections were asymptomatic, indicating the possibility that these infections may be an important factor fueling the incidence increase (Clin. Infect. Dis. 2005;41:67–74).

Additionally, the study reported that 53% of chlamydial infections were at nonurethral sites, Dr. Bolan noted.

In part because of these concerns, the Centers for Disease Control and Prevention recently updated its sexually transmitted diseases guidelines to include what to ask when taking a sexual history to screen for disease. According to the new guidelines, the sexual history taking must include specific questions regarding what is known as the “5 P's”: partners, pregnancy protection, protection from sexually transmitted diseases, practices, and past history of sexually transmitted diseases.

Because testing for gonorrhea at the rectal and pharyngeal sites requires culturing, physicians need to make sure they have culturing available, she noted.

Dr. Bolan also said that fluoroquinolone-resistant gonorrhea continues to be a problem. The CDC guidelines recommend that fluoroquinolones not be used in men who have sex with men or in areas where fluoroquinolone resistance is high.

SAN FRANCISCO — The HIV epidemic has brought to light evidence that men who have sex with men now have a rate of anal cancer as high as the incidence rate of cervical cancer in women prior to Pap smear.

The incidence rate in women also has risen, Dr. Joel Palefsky said at a meeting on HIV management sponsored by the University of California, San Francisco.

The incidence rate of cervical cancer prior to Pap smear screening was 40–50 cases per 100,000 females. The present rate of anal cancer in HIV-negative men who have sex with men is 35 per 100,000, and the rate for HIV-positive men is probably twice as high, said Dr. Palefsky, a professor of medicine and the director of the Anal Dysplasia Clinic at the UCSF Cancer Center.

Both anal dysplasia and cervical cancer are related to human papillomavirus (HPV) infection. The incidence rate in HIV-positive men appears to be rising for a few reasons. Highly active antiretroviral therapy (HAART) is prolonging the life of HIV-infected individuals long enough for cancer to develop. HIV infection itself accelerates the process, said Dr. Palefsky, who is part of group urging anal Pap smear screening for at-risk individuals. “If you are HIV positive, you have anal HPV infection,” he said.

Studies he conducted in the pre-HAART era found abnormal anal cytology in 80% of HIV-infected men with CD4 T-cell levels less than 200 cells/mcL, Dr. Palefsky said. Since then, studies have shown that HPV-infected persons develop intraepithelial neoplasia regularly and rapidly, and that HAART may not lower the incidence (Clin. Infect. Dis. 2002;35:1127–34).

Women too have high rates of anal HPV infection, and it is not just HIV-positive women, he said. In the Women's Interagency HIV Study, they found a high prevalence of HPV infection. In fact, anal HPV was more common than cervical infection in both 251 HIV-positive women (79% vs. 53%) and in 68 HIV-negative women (43% vs. 24%) (J. Infect. Dis. 2001;183:383–91).

Surveys he did in Planned Parenthood clinics and a cervical dysplasia clinic also suggest that anal HPV infection is as least as common as cervical HPV in women.

Evidence that anal cancer is becoming more common is less certain, Dr. Palefsky said. Data from the Surveillance, Epidemiology, and End Results survey suggest that squamous cell carcinoma of the anus has increased perhaps 96% in men and 39% in women over the past 40 years.

Much of anal HPV infection results from receptive anal intercourse, but not all. It has been found to be common in HIV-positive men who are injection drug users.

Data suggest that half of women in this country engage in anal intercourse at least once in their lifetime, and, “as we know from the cervix, it doesn't take too many exposures to get HPV,” he noted.

Dr. Palefsky said he examines for anal dysplasia the same way one does for cervical dysplasia. He inserts a water-moistened Dacron swab into the anus and rubs the swab around the wall of the canal. The material obtained is graded according to the Bethesda System like a cervical sample.

A digital rectal exam, done after the swabbing, requires lubricant. “You will feel things with your finger that you'll not see either on a Pap smear or through the anoscope because a lot of the cancers are subcutaneous at that point,” he said.

Patients with a positive Pap smear undergo examination with a cervical colposcope. A gauze pad is soaked in a vinegar solution (2:1 vinegar to water), then wrapped around a swab and inserted through an anoscope. The anoscope is then removed, and the gauze is left in place for 1 minute. Once the gauze is removed, the anoscope is reinserted and examination is done with the colposcope.

The same signs used for the cervix have been validated in the anal canal, he said.

Small lesions can be treated with trichlor-oacetic acid, and larger lesions can be treated with infrared coagulation, which is being shown to be successful, he added.

Squamous cell carcinoma of the anus has increased perhaps 96% in men and 39% in women over the past 40 years. DR. PALEFSKY

SAN FRANCISCO — The HIV epidemic has brought to light evidence that men who have sex with men now have a rate of anal cancer as high as the incidence rate of cervical cancer in women prior to Pap smear.

The incidence rate in women also has risen, Dr. Joel Palefsky said at a meeting on HIV management sponsored by the University of California, San Francisco.

The incidence rate of cervical cancer prior to Pap smear screening was 40–50 cases per 100,000 females. The present rate of anal cancer in HIV-negative men who have sex with men is 35 per 100,000, and the rate for HIV-positive men is probably twice as high, said Dr. Palefsky, a professor of medicine and the director of the Anal Dysplasia Clinic at the UCSF Cancer Center.

Both anal dysplasia and cervical cancer are related to human papillomavirus (HPV) infection. The incidence rate in HIV-positive men appears to be rising for a few reasons. Highly active antiretroviral therapy (HAART) is prolonging the life of HIV-infected individuals long enough for cancer to develop. HIV infection itself accelerates the process, said Dr. Palefsky, who is part of group urging anal Pap smear screening for at-risk individuals. “If you are HIV positive, you have anal HPV infection,” he said.

Studies he conducted in the pre-HAART era found abnormal anal cytology in 80% of HIV-infected men with CD4 T-cell levels less than 200 cells/mcL, Dr. Palefsky said. Since then, studies have shown that HPV-infected persons develop intraepithelial neoplasia regularly and rapidly, and that HAART may not lower the incidence (Clin. Infect. Dis. 2002;35:1127–34).

Women too have high rates of anal HPV infection, and it is not just HIV-positive women, he said. In the Women's Interagency HIV Study, they found a high prevalence of HPV infection. In fact, anal HPV was more common than cervical infection in both 251 HIV-positive women (79% vs. 53%) and in 68 HIV-negative women (43% vs. 24%) (J. Infect. Dis. 2001;183:383–91).

Surveys he did in Planned Parenthood clinics and a cervical dysplasia clinic also suggest that anal HPV infection is as least as common as cervical HPV in women.

Evidence that anal cancer is becoming more common is less certain, Dr. Palefsky said. Data from the Surveillance, Epidemiology, and End Results survey suggest that squamous cell carcinoma of the anus has increased perhaps 96% in men and 39% in women over the past 40 years.

Much of anal HPV infection results from receptive anal intercourse, but not all. It has been found to be common in HIV-positive men who are injection drug users.

Data suggest that half of women in this country engage in anal intercourse at least once in their lifetime, and, “as we know from the cervix, it doesn't take too many exposures to get HPV,” he noted.

Dr. Palefsky said he examines for anal dysplasia the same way one does for cervical dysplasia. He inserts a water-moistened Dacron swab into the anus and rubs the swab around the wall of the canal. The material obtained is graded according to the Bethesda System like a cervical sample.

A digital rectal exam, done after the swabbing, requires lubricant. “You will feel things with your finger that you'll not see either on a Pap smear or through the anoscope because a lot of the cancers are subcutaneous at that point,” he said.

Patients with a positive Pap smear undergo examination with a cervical colposcope. A gauze pad is soaked in a vinegar solution (2:1 vinegar to water), then wrapped around a swab and inserted through an anoscope. The anoscope is then removed, and the gauze is left in place for 1 minute. Once the gauze is removed, the anoscope is reinserted and examination is done with the colposcope.

The same signs used for the cervix have been validated in the anal canal, he said.

Small lesions can be treated with trichlor-oacetic acid, and larger lesions can be treated with infrared coagulation, which is being shown to be successful, he added.

Squamous cell carcinoma of the anus has increased perhaps 96% in men and 39% in women over the past 40 years. DR. PALEFSKY

SAN FRANCISCO — The HIV epidemic has brought to light evidence that men who have sex with men now have a rate of anal cancer as high as the incidence rate of cervical cancer in women prior to Pap smear.

The incidence rate in women also has risen, Dr. Joel Palefsky said at a meeting on HIV management sponsored by the University of California, San Francisco.

The incidence rate of cervical cancer prior to Pap smear screening was 40–50 cases per 100,000 females. The present rate of anal cancer in HIV-negative men who have sex with men is 35 per 100,000, and the rate for HIV-positive men is probably twice as high, said Dr. Palefsky, a professor of medicine and the director of the Anal Dysplasia Clinic at the UCSF Cancer Center.

Both anal dysplasia and cervical cancer are related to human papillomavirus (HPV) infection. The incidence rate in HIV-positive men appears to be rising for a few reasons. Highly active antiretroviral therapy (HAART) is prolonging the life of HIV-infected individuals long enough for cancer to develop. HIV infection itself accelerates the process, said Dr. Palefsky, who is part of group urging anal Pap smear screening for at-risk individuals. “If you are HIV positive, you have anal HPV infection,” he said.

Studies he conducted in the pre-HAART era found abnormal anal cytology in 80% of HIV-infected men with CD4 T-cell levels less than 200 cells/mcL, Dr. Palefsky said. Since then, studies have shown that HPV-infected persons develop intraepithelial neoplasia regularly and rapidly, and that HAART may not lower the incidence (Clin. Infect. Dis. 2002;35:1127–34).

Women too have high rates of anal HPV infection, and it is not just HIV-positive women, he said. In the Women's Interagency HIV Study, they found a high prevalence of HPV infection. In fact, anal HPV was more common than cervical infection in both 251 HIV-positive women (79% vs. 53%) and in 68 HIV-negative women (43% vs. 24%) (J. Infect. Dis. 2001;183:383–91).

Surveys he did in Planned Parenthood clinics and a cervical dysplasia clinic also suggest that anal HPV infection is as least as common as cervical HPV in women.

Evidence that anal cancer is becoming more common is less certain, Dr. Palefsky said. Data from the Surveillance, Epidemiology, and End Results survey suggest that squamous cell carcinoma of the anus has increased perhaps 96% in men and 39% in women over the past 40 years.

Much of anal HPV infection results from receptive anal intercourse, but not all. It has been found to be common in HIV-positive men who are injection drug users.

Data suggest that half of women in this country engage in anal intercourse at least once in their lifetime, and, “as we know from the cervix, it doesn't take too many exposures to get HPV,” he noted.

Dr. Palefsky said he examines for anal dysplasia the same way one does for cervical dysplasia. He inserts a water-moistened Dacron swab into the anus and rubs the swab around the wall of the canal. The material obtained is graded according to the Bethesda System like a cervical sample.

A digital rectal exam, done after the swabbing, requires lubricant. “You will feel things with your finger that you'll not see either on a Pap smear or through the anoscope because a lot of the cancers are subcutaneous at that point,” he said.

Patients with a positive Pap smear undergo examination with a cervical colposcope. A gauze pad is soaked in a vinegar solution (2:1 vinegar to water), then wrapped around a swab and inserted through an anoscope. The anoscope is then removed, and the gauze is left in place for 1 minute. Once the gauze is removed, the anoscope is reinserted and examination is done with the colposcope.

The same signs used for the cervix have been validated in the anal canal, he said.

Small lesions can be treated with trichlor-oacetic acid, and larger lesions can be treated with infrared coagulation, which is being shown to be successful, he added.

Squamous cell carcinoma of the anus has increased perhaps 96% in men and 39% in women over the past 40 years. DR. PALEFSKY

SAN FRANCISCO — As the incidence of gonorrhea continues to increase, physicians need to be doing more testing for the venereal disease in the anus and the throat, particularly in gay men, said Dr. Gail Bolan, chief of the sexually transmitted diseases control branch for California.

Gonorrhea incidence in the United States as a whole and in California specifically had been declining for 3 decades before starting to climb in about the year 2000, Dr. Bolan said at a meeting on HIV management sponsored by the University of California, San Francisco.

A recent study in San Francisco of men who have sex with men reported that if only urine and urethral screening were performed in those men, about 65% of gonorrhea cases would be missed, she noted.

The study found that 85% of the rectal infections were asymptomatic, indicating the possibility that these infections may be an important factor fueling the incidence increase (Clin. Infect. Dis. 2005;41:67–74).

In addition, the study also reported that 53% of chlamydial infections were at nonurethral sites.

Partly because of these concerns, the Centers for Disease Control and Prevention recently updated its sexually transmitted diseases guidelines to include what to ask when taking a sexual history to screen for disease.

The new guidelines suggest that the sexual history taking must include specific questions regarding what is known as the “5 P's”: partners, pregnancy protection, protection from sexually transmitted diseases, practices, and past history of sexually transmitted diseases. “You need to do appropriate sexual history, identify sites of exposure, and then, depending on those sites, do appropriate testing,” she said.

Dr. Bolan also said that fluoroquinolone-resistant gonorrhea continues to be a problem. The CDC guidelines recommend that fluoroquinolones not be used in men who have sex with men or in areas where fluoroquinolone resistance is high.

SAN FRANCISCO — As the incidence of gonorrhea continues to increase, physicians need to be doing more testing for the venereal disease in the anus and the throat, particularly in gay men, said Dr. Gail Bolan, chief of the sexually transmitted diseases control branch for California.

Gonorrhea incidence in the United States as a whole and in California specifically had been declining for 3 decades before starting to climb in about the year 2000, Dr. Bolan said at a meeting on HIV management sponsored by the University of California, San Francisco.

A recent study in San Francisco of men who have sex with men reported that if only urine and urethral screening were performed in those men, about 65% of gonorrhea cases would be missed, she noted.

The study found that 85% of the rectal infections were asymptomatic, indicating the possibility that these infections may be an important factor fueling the incidence increase (Clin. Infect. Dis. 2005;41:67–74).

In addition, the study also reported that 53% of chlamydial infections were at nonurethral sites.

Partly because of these concerns, the Centers for Disease Control and Prevention recently updated its sexually transmitted diseases guidelines to include what to ask when taking a sexual history to screen for disease.

The new guidelines suggest that the sexual history taking must include specific questions regarding what is known as the “5 P's”: partners, pregnancy protection, protection from sexually transmitted diseases, practices, and past history of sexually transmitted diseases. “You need to do appropriate sexual history, identify sites of exposure, and then, depending on those sites, do appropriate testing,” she said.

Dr. Bolan also said that fluoroquinolone-resistant gonorrhea continues to be a problem. The CDC guidelines recommend that fluoroquinolones not be used in men who have sex with men or in areas where fluoroquinolone resistance is high.

SAN FRANCISCO — As the incidence of gonorrhea continues to increase, physicians need to be doing more testing for the venereal disease in the anus and the throat, particularly in gay men, said Dr. Gail Bolan, chief of the sexually transmitted diseases control branch for California.

Gonorrhea incidence in the United States as a whole and in California specifically had been declining for 3 decades before starting to climb in about the year 2000, Dr. Bolan said at a meeting on HIV management sponsored by the University of California, San Francisco.

A recent study in San Francisco of men who have sex with men reported that if only urine and urethral screening were performed in those men, about 65% of gonorrhea cases would be missed, she noted.

The study found that 85% of the rectal infections were asymptomatic, indicating the possibility that these infections may be an important factor fueling the incidence increase (Clin. Infect. Dis. 2005;41:67–74).

In addition, the study also reported that 53% of chlamydial infections were at nonurethral sites.

Partly because of these concerns, the Centers for Disease Control and Prevention recently updated its sexually transmitted diseases guidelines to include what to ask when taking a sexual history to screen for disease.

The new guidelines suggest that the sexual history taking must include specific questions regarding what is known as the “5 P's”: partners, pregnancy protection, protection from sexually transmitted diseases, practices, and past history of sexually transmitted diseases. “You need to do appropriate sexual history, identify sites of exposure, and then, depending on those sites, do appropriate testing,” she said.

Dr. Bolan also said that fluoroquinolone-resistant gonorrhea continues to be a problem. The CDC guidelines recommend that fluoroquinolones not be used in men who have sex with men or in areas where fluoroquinolone resistance is high.

SAN FRANCISCO — Some HIV-infected patients who are well managed on highly active antiretroviral therapy are developing Kaposi's sarcoma, Dr. Toby A. Maurer said at a meeting on HIV management sponsored by the University of California, San Francisco.

In this trend, which has been identified in San Francisco by Dr. Maurer and her associates, patients often have CD4 counts of 300 and even 600 cells/mcL and low viral loads. Yet they have the telltale purple blotches of Kaposi's, said Dr. Maurer, chief of dermatology at San Francisco General Hospital.

“These patients are very perplexing to us clinically,” she said, explaining that these are not flares of Kaposi's, which can sometimes happen at the start of highly active antiretroviral therapy (HAART). Rather, these are occurrences in patients who are fairly well maintained on the therapy.

The question is whether these patients have developed abnormal T-cell function over time on HAART, despite high CD4 cell counts, thus causing the loss of immunologic control of their Kaposi's sarcoma; or whether their systemic disease was not detected and treated.

“Clinically we are trying to decide what to do with these patients because antiretrovirals don't seem to do it,” Dr. Maurer said. “And, [the patients] are not sick enough nor do they have evidence of systemic KS to warrant chemotherapy.”

Although she said there is still no good, reliable method of detecting Kaposi's that has spread and is systemic, Dr. Maurer offered a suggestion to those checking Kaposi's lesions on the legs: Look for edema in the appendage because that is a sign of systemic disease. Systemic disease has a high mortality rate, about 25%, and those patients need more than just antiretroviral treatment.

Dermatologists who have seen this phenomenon of patients on HAART who have had a recurrence of Kaposi's sarcoma may contact Dr. Maurer at maurert@derm.ucsf.edu

SAN FRANCISCO — Some HIV-infected patients who are well managed on highly active antiretroviral therapy are developing Kaposi's sarcoma, Dr. Toby A. Maurer said at a meeting on HIV management sponsored by the University of California, San Francisco.

In this trend, which has been identified in San Francisco by Dr. Maurer and her associates, patients often have CD4 counts of 300 and even 600 cells/mcL and low viral loads. Yet they have the telltale purple blotches of Kaposi's, said Dr. Maurer, chief of dermatology at San Francisco General Hospital.

“These patients are very perplexing to us clinically,” she said, explaining that these are not flares of Kaposi's, which can sometimes happen at the start of highly active antiretroviral therapy (HAART). Rather, these are occurrences in patients who are fairly well maintained on the therapy.

The question is whether these patients have developed abnormal T-cell function over time on HAART, despite high CD4 cell counts, thus causing the loss of immunologic control of their Kaposi's sarcoma; or whether their systemic disease was not detected and treated.

“Clinically we are trying to decide what to do with these patients because antiretrovirals don't seem to do it,” Dr. Maurer said. “And, [the patients] are not sick enough nor do they have evidence of systemic KS to warrant chemotherapy.”

Although she said there is still no good, reliable method of detecting Kaposi's that has spread and is systemic, Dr. Maurer offered a suggestion to those checking Kaposi's lesions on the legs: Look for edema in the appendage because that is a sign of systemic disease. Systemic disease has a high mortality rate, about 25%, and those patients need more than just antiretroviral treatment.

Dermatologists who have seen this phenomenon of patients on HAART who have had a recurrence of Kaposi's sarcoma may contact Dr. Maurer at maurert@derm.ucsf.edu

SAN FRANCISCO — Some HIV-infected patients who are well managed on highly active antiretroviral therapy are developing Kaposi's sarcoma, Dr. Toby A. Maurer said at a meeting on HIV management sponsored by the University of California, San Francisco.

In this trend, which has been identified in San Francisco by Dr. Maurer and her associates, patients often have CD4 counts of 300 and even 600 cells/mcL and low viral loads. Yet they have the telltale purple blotches of Kaposi's, said Dr. Maurer, chief of dermatology at San Francisco General Hospital.

“These patients are very perplexing to us clinically,” she said, explaining that these are not flares of Kaposi's, which can sometimes happen at the start of highly active antiretroviral therapy (HAART). Rather, these are occurrences in patients who are fairly well maintained on the therapy.

The question is whether these patients have developed abnormal T-cell function over time on HAART, despite high CD4 cell counts, thus causing the loss of immunologic control of their Kaposi's sarcoma; or whether their systemic disease was not detected and treated.

“Clinically we are trying to decide what to do with these patients because antiretrovirals don't seem to do it,” Dr. Maurer said. “And, [the patients] are not sick enough nor do they have evidence of systemic KS to warrant chemotherapy.”

Although she said there is still no good, reliable method of detecting Kaposi's that has spread and is systemic, Dr. Maurer offered a suggestion to those checking Kaposi's lesions on the legs: Look for edema in the appendage because that is a sign of systemic disease. Systemic disease has a high mortality rate, about 25%, and those patients need more than just antiretroviral treatment.

Dermatologists who have seen this phenomenon of patients on HAART who have had a recurrence of Kaposi's sarcoma may contact Dr. Maurer at maurert@derm.ucsf.edu

VAIL, COLO. — Weight loss can go a long way toward improving the effects of hyperandrogenism in the adolescent with polycystic ovary syndrome, Dr. Patricia S. Simmons said at a meeting sponsored by the American Academy of Pediatrics.

“In the obese patient, this can be all she needs,” said Dr. Simmons, a past president of the North American Society for Pediatric and Adolescent Gynecology. “If their weight normalizes, usually their insulin levels and secondary hyperandrogenism will too.”

Polycystic ovary syndrome (PCOS) can be associated with a different pathophysiology in different individuals, said Dr. Simmons, a professor of pediatrics at the Mayo Clinic, Rochester, Minn. About 2%–3% of the general female population has PCOS, and it is present in about 53% of adolescents with chronic anovulation and amenorrhea.

One of the condition's hallmarks, hyperinsulinemia, is present in about 20% of adolescents with PCOS. Those individuals are more often obese, but that is not always the case. And in those individuals, the hyperinsulinemia helps drive the hyperandrogenism, which is why weight loss and improving insulin sensitivity can help, Dr. Simmons said.

Though in overweight individuals, weight loss alone may be treatment enough, others may also require drug therapy. The first-line drug for adolescents is an estrogen/progestin oral contraceptive, she said. The progestin inhibits luteinizing hormone, which leads to decreased androgen production by the ovaries, and the inhibition of adrenal androgen production. The estrogen elevates serum hormone-binding globulin, which further inhibits the effects of androgen.

Over the long term, this therapy protects the endometrium from the dysplasia and cancer associated with PCOS.

The oral contraceptive that many experts recommend is the one with ethinyl estradiol and drospirenone, because that progestin is actually an anti-androgen structurally similar to spironolactone, which itself is used as a treatment for PCOS in conjunction with an oral contraceptive, Dr. Simmons said. Though common, this is not supported by data.

Oral contraceptive therapy also improves acne, makes menstruation more regular, and stops the progression of hirsutism.

“It's an easy thing to prescribe with great confidence,” Dr. Simmons added.

The diagnosis of PCOS in the adolescent can be difficult, especially since one would like to identify it early and begin addressing some of the long-term health impacts.

Oral contraceptives, however, do not influence insulin levels, hence the necessity for weight loss in overweight PCOS patients.

The use of oral glycemic agents in children and adolescents has not been rigorously studied and is recommended for use only in selective cases, she said, adding “We don't use them unless we have clearly defined need.”

Dr. Simmons has no conflicts of interest to report.

VAIL, COLO. — Weight loss can go a long way toward improving the effects of hyperandrogenism in the adolescent with polycystic ovary syndrome, Dr. Patricia S. Simmons said at a meeting sponsored by the American Academy of Pediatrics.

“In the obese patient, this can be all she needs,” said Dr. Simmons, a past president of the North American Society for Pediatric and Adolescent Gynecology. “If their weight normalizes, usually their insulin levels and secondary hyperandrogenism will too.”

Polycystic ovary syndrome (PCOS) can be associated with a different pathophysiology in different individuals, said Dr. Simmons, a professor of pediatrics at the Mayo Clinic, Rochester, Minn. About 2%–3% of the general female population has PCOS, and it is present in about 53% of adolescents with chronic anovulation and amenorrhea.

One of the condition's hallmarks, hyperinsulinemia, is present in about 20% of adolescents with PCOS. Those individuals are more often obese, but that is not always the case. And in those individuals, the hyperinsulinemia helps drive the hyperandrogenism, which is why weight loss and improving insulin sensitivity can help, Dr. Simmons said.

Though in overweight individuals, weight loss alone may be treatment enough, others may also require drug therapy. The first-line drug for adolescents is an estrogen/progestin oral contraceptive, she said. The progestin inhibits luteinizing hormone, which leads to decreased androgen production by the ovaries, and the inhibition of adrenal androgen production. The estrogen elevates serum hormone-binding globulin, which further inhibits the effects of androgen.

Over the long term, this therapy protects the endometrium from the dysplasia and cancer associated with PCOS.

The oral contraceptive that many experts recommend is the one with ethinyl estradiol and drospirenone, because that progestin is actually an anti-androgen structurally similar to spironolactone, which itself is used as a treatment for PCOS in conjunction with an oral contraceptive, Dr. Simmons said. Though common, this is not supported by data.

Oral contraceptive therapy also improves acne, makes menstruation more regular, and stops the progression of hirsutism.

“It's an easy thing to prescribe with great confidence,” Dr. Simmons added.

The diagnosis of PCOS in the adolescent can be difficult, especially since one would like to identify it early and begin addressing some of the long-term health impacts.

Oral contraceptives, however, do not influence insulin levels, hence the necessity for weight loss in overweight PCOS patients.

The use of oral glycemic agents in children and adolescents has not been rigorously studied and is recommended for use only in selective cases, she said, adding “We don't use them unless we have clearly defined need.”

Dr. Simmons has no conflicts of interest to report.

VAIL, COLO. — Weight loss can go a long way toward improving the effects of hyperandrogenism in the adolescent with polycystic ovary syndrome, Dr. Patricia S. Simmons said at a meeting sponsored by the American Academy of Pediatrics.

“In the obese patient, this can be all she needs,” said Dr. Simmons, a past president of the North American Society for Pediatric and Adolescent Gynecology. “If their weight normalizes, usually their insulin levels and secondary hyperandrogenism will too.”

Polycystic ovary syndrome (PCOS) can be associated with a different pathophysiology in different individuals, said Dr. Simmons, a professor of pediatrics at the Mayo Clinic, Rochester, Minn. About 2%–3% of the general female population has PCOS, and it is present in about 53% of adolescents with chronic anovulation and amenorrhea.

One of the condition's hallmarks, hyperinsulinemia, is present in about 20% of adolescents with PCOS. Those individuals are more often obese, but that is not always the case. And in those individuals, the hyperinsulinemia helps drive the hyperandrogenism, which is why weight loss and improving insulin sensitivity can help, Dr. Simmons said.

Though in overweight individuals, weight loss alone may be treatment enough, others may also require drug therapy. The first-line drug for adolescents is an estrogen/progestin oral contraceptive, she said. The progestin inhibits luteinizing hormone, which leads to decreased androgen production by the ovaries, and the inhibition of adrenal androgen production. The estrogen elevates serum hormone-binding globulin, which further inhibits the effects of androgen.

Over the long term, this therapy protects the endometrium from the dysplasia and cancer associated with PCOS.

The oral contraceptive that many experts recommend is the one with ethinyl estradiol and drospirenone, because that progestin is actually an anti-androgen structurally similar to spironolactone, which itself is used as a treatment for PCOS in conjunction with an oral contraceptive, Dr. Simmons said. Though common, this is not supported by data.

Oral contraceptive therapy also improves acne, makes menstruation more regular, and stops the progression of hirsutism.

“It's an easy thing to prescribe with great confidence,” Dr. Simmons added.

The diagnosis of PCOS in the adolescent can be difficult, especially since one would like to identify it early and begin addressing some of the long-term health impacts.

Oral contraceptives, however, do not influence insulin levels, hence the necessity for weight loss in overweight PCOS patients.

The use of oral glycemic agents in children and adolescents has not been rigorously studied and is recommended for use only in selective cases, she said, adding “We don't use them unless we have clearly defined need.”

Dr. Simmons has no conflicts of interest to report.