In this issue:
Teens may respond better to HAART
Europe restricts Viramune after incidents
TB outbreak seen among transgenders
Russians to open prison for PWAs
Needle exchange participants more likely to quit sharing
Exercise better than hormone for increased muscle strength
Panel issues plan to close ethnic health gap
IMF, World Bank commit more AIDS funding
Adolescents infected with HIV have a surprisingly robust immune response and may benefit particularly well from aggressive early treatment with anti-HIV medications, according to a research team led by an immunologist at The Children's Hospital of Philadelphia.
The study is reported in the April issue of the Archives of Pediatric and Adolescent Medicine.
Studying 270 HIV-infected and uninfected teenagers, the researchers measured the levels of T lymphocytes, cells that originate in the thymus gland and play important roles in the immune system. Among those cells, they found an unexpectedly higher number of CD8 naive T lymphocytes in adolescents who had been infected with HIV, compared to uninfected adolescents. Naive T lymphocytes are cells that have not been previously exposed to invading microorganisms, including HIV.
"The high levels of naive CD8 cells that we found suggests that these cells may be capable of mounting an immune response," said the study's lead author, Steven D. Douglas, M.D., Chief of Immunology at Children's Hospital, who added, "CD8 cells are major players in killing the virus."
The naive T lymphocytes are produced by the thymus gland, which gradually shrinks after puberty, becoming less active in immune function during adulthood. "If the thymus continues to produce immune system cells in HIV- infected adolescents, the adolescent immune system may be stronger than previously thought," said Dr. Douglas. "With aggressive use of current medications, we may be able to rebuild immune systems in HIV-infected adolescents."
Adolescents represent the fastest growing segment of the U.S. population newly infected with HIV; a 1996 White House report estimated that a new infection occurs every hour of every day. However, because of the long incubation period before symptoms appear, relatively small numbers of HIV- infected teenagers are aware of their infection and receiving medical care for it. Another complicating factor is the social situation of many infected adolescents, which may leave them with inadequate access to the health care system.
"Although HIV infection has been moving into adolescents, relatively little is known about the specifics of how adolescents' immune system respond to the virus," says Bret Rudy, M.D., medical director of the Adolescent AIDS Initiative at Children's Hospital, and a co-author of the study. The current study builds on earlier work by Drs. Douglas and Rudy, who recently published the first reference measurements for cells that act as immune system markers for both HIV-infected and healthy adolescents.
The current standard of treatment for controlling HIV infection is called highly active antiretroviral therapy (HAART), a combination of drugs that interfere with the virus' ability to replicate. "Because of their robust immune systems, HIV-infected adolescents may be the best candidates to benefit from aggressive drugs such as HAART," says Dr. Rudy. "However, it's imperative for individuals to become aware of their infections before they actually become sick, because early treatment may give their immune systems the best opportunity for a strong response." Dr. Rudy is co-chair of Project ACCESS, a social marketing campaign aimed at educating at-risk youth about the importance of HIV counseling and testing.
The current study was co-sponsored by the National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Drug Abuse, the National Institute of Mental Health, and the Health Resources and Services Administration. Blood samples were drawn from adolescents at 16 clinical sites throughout the United States participating in the Adolescent Medicine HIV/AIDS Research Network, established by the National Institutes of Health and the Health Resources and Services Administration. Further studies will be conducted on how the immune system of adolescents responds to HIV infection over a period of time. (PR Newswire)
An urgent safety restriction has been issued by the European Agency for the Evaluation of Medicinal Products (EMEA) following additional reports of sometimes fatal cutaneous and hepatic reactions associated with the AIDS drug Viramune (nevirapine).
In a statement, the agency said, "The first 8 weeks of nevirapine therapy are a critical period which therefore require close monitoring of the patients to disclose the potential appearance of severe and life threatening skin reactions or serious hepatitis/hepatic failure.
"Some of the severe cutaneous reactions were associated with risk factors such as not following the dose escalation regimen or delaying seeking medical attention when the symptoms appeared.
"Furthermore, most of the cases of hepatitis were reported to be within the first 8 weeks of treatment, some of them associated with hypersensitivity reactions such as fever, rash, arthralgia, myalgia, hypereosinophilia or acute renal failure."
An EMEA spokesman was not immediately available to say how many severe reactions and deaths had occurred.
In its public statement, the EMEA said that the initial dosing of nevirapine of 200 mg daily, or 4mg/kg once daily for patients aged 2 months up to 8 years, during the 14-day lead-in period, must be strictly followed.
Patients should also be intensively monitored during the first 8 weeks of treatment. Nevirapine must be permanently withdrawn in patients developing a serious cutaneous reaction. From the point of view of hepatic reactions, close liver monitoring of patients must be performed especially during the first 8 weeks of therapy.
Nevirapine should be stopped and never readministered in patients with ASAT or ALAT greater than 2x ULN associated with hypersensitivity reactions or hepatitis, the statement said.
Viramune is a non-nucleoside reverse transcriptase inhibitor, which is indicated for HIV-infected patients with advanced or progressive immunodeficiency. European marketing authorization for the 200 mg tablets was granted on February 5, 1998 and the product is available in all European Union countries.
A strain of AIDS-related tuberculosis identified in Baltimore and New York City may be spreading among transgendered people, federal health officials said on April 20th.
The Centers for Disease Control and Prevention said experts have identified 26 cases of active tuberculosis and 37 cases of dormant or latent infection since 1998 in the two cities' communities of people who present themselves as members of the opposite sex.
The CDC said 62 percent of the TB patients they have identified as part of this outbreak had HIV. But anyone can become infected as the bacteria that causes TB spreads through airborne particles.
The cases identified in the outbreak were among men and women who were members of a social network known as a "house," or who had contact with "house" members. "Each 'house' represents a local social club of gay and bisexual individuals, some of whom are transgender," the CDC said.
Researchers said that because members frequently travel to take part in fashion and dance competitions, there is concern that the tuberculosis strain may be spreading to other cities.
TB control staff in Atlanta, Boston, Philadelphia and Washington, D.C. are exploring whether there are linked TB cases in their cities.
"Frequently, young transgender persons are reluctant to identify themselves. Many of them desire to maintain their anonymity because they are fearful because of the way society treats them," CDC epidemiologist Peter McElroy said.
Because infection with HIV weakens the immune system, people infected with tuberculosis and HIV are at a very high risk of developing tuberculosis disease, the CDC said.
Tuberculosis is a potentially fatal lung disease caused by bacteria that are spread through the air from one person to another. There were 18,361 cases of active TB in the United States in 1998.
Tuberculosis is easily cured in most cases with a course of drugs, but can be fatal if it is not diagnosed or treated. McElroy said the tuberculosis strain seen in the outbreak is vulnerable to the therapies generally tried first to treat tuberculosis sufferers. (Reuters)
Russians to open prison for PWAs
Authorities in a Siberian region plan to open a separate prison for inmates infected with HIV, a news report said on April 20th.
About 600 HIV-positive convicts are serving time in prisons of the Irkutsk region, and another 300 infected people are held in pre-trial detention, said Boris Gronik, chief of the regional Justice Ministry branch in charge of prison administration.
Gronik said afflicted inmates present a danger to other prisoners, and need to be removed, the ITAR-Tass news agency reported.
"Unless they are all gathered in one place, the situation may get out of control," Gronik was quoted as saying.
Russia already has one special prison for HIV-positive convicts, ITAR-Tass said. The jail is located in the Baltic Sea enclave of Kaliningrad, which has one of the highest concentrations of AIDS cases in Russia.
In a separate development, authorities in the southern Siberian republic of Buryatia, next door to Irkutsk, said 101 HIV cases have been registered in the republic, up from 24 at the start of the year, ITAR-Tass reported.
HIV has been spreading fast in Russia and more than 30,000 registered cases were reported in March. (Associated Press)
A report in the March 31 issue of AIDS indicates that high-risk injection drug users who participate in a syringe exchange are over two times as likely to quit sharing needles than those who are not in such a program.
The four-year survey of 340 high-risk injection drug users showed that 60 percent reported at follow-up that they had stopped sharing syringes. The researchers, led by Dr. Ricky N. Blumenthal of
RAND in Santa Monica, California, asserted that despite the controversy surrounding the programs, syringe exchange programs are among the most effective ways to prevent HIV among addicts. (Reuters)
In HIV-infected men, resistance training is more effective than recombinant human growth hormone in increasing muscle strength, but it does not reduce abdominal fat.
HIV-infected patients on antiretroviral therapy often develop abdominal fat while their muscles waste away, Dr. Kevin E. Yarasheski, of Washington University Medical School in St. Louis, Missouri, pointed out in a presentation here last weekend at the Experimental Biology 2000 meeting.
To try to counter these problems, he and his colleagues treated 34 HIV-infected men with 12 weeks of recombinant growth hormone daily; supervised resistance training for 1 to 1.5 hours a day, 4 days a week; or placebo.
They found that resistance training significantly improved knee extensor muscle strength by 11% to 18%, while treatment with recombinant growth hormone slightly decreased muscle strength by 2% to 4%. Both treatments significantly increased lean muscle mass, but only treatment with growth hormone increased total body water and decreased the trunk/appendicular adipose tissue ratio.
Dr. Yarasheski also noted that compared with HIV-infected nonwasting patients or patients wasting from other diseases, patients with HIV-associated muscle wasting make lower amounts of muscle proteins and release glutamine from muscle at an increased rate and produce liver triglycerides at an increased rate. The release of glutamine may go to feed T cells that prefer glutamine at the expense of muscle cells.
"We tell this to everybody whether you're HIV-infected or not. Exercise is a good part of your normal [routine]," he said. "It's becoming even more critical, not only because of the wasting we've already seen, but now all these other metabolic complications that are starting to come out: the diabetes, the high blood fats, the strange fat distribution." (Reuters)
Claiming that the US healthcare system has failed American minorities despite a decade of "unprecedented " research funding, an advisory panel to the National Institutes of Health (NIH) has issued a set of recommended strategies to narrow disparities in healthcare and research between racial/ethnic minorities and the general population.
The approaches, developed by the Advisory Committee on Research on Minority Health, will be implemented by the Office of Research on Minority Health (ORMH), an arm of the NIH.
The plan targets realities such as higher infant mortality and premature death rates among groups including African Americans, Hispanics and American Indian/Alaska Natives, as well as the disproportionate incidence of serious illnesses including cardiovascular disease, diabetes, HIV/AIDS and certain cancers within those subpopulations.
To shape its approach to reducing minority mortality/morbidity rates, the Committee put five "strategic questions" to experts representing various therapeutic areas of minority healthcare.
The panelists were asked how to target research to identify minority risk factors, prevent and treat disease, as well as how to strengthen the ORMH/NIH partnership and increase minority presence in clinical trials. Another issue set before the experts was the need to enhance minority science education and to bolster the numbers of biomedical scientists from ethnic populations.
While each panelist brought a unique perspective to the discussion, based on the population and disease area that they represented, a few common themes pervaded the panel's solutions--concepts such as "communication," "trust," "cultural sensitivity" and "mentoring."
For example, the panelists advocated programs to make minority communities aware of clinical research grant opportunities and provide assistance to minority research funding applicants. The experts also urged minority-sensitive study procedures--such as clearly communicating to minority trial participants issues like informed consent--keeping cultural acuities and subjects' educational level at the forefront.
The experts advised making study findings available to minority subjects and their families. Gary Gibbons, professor at the Moorehouse School of Medicine, Atlanta, called on ORMH to integrate disciplines like epidemiology, nutrition, molecular biology and human genomics into minority clinical trials and community "intervention."
He also urged the conducting of trials on exclusively minority subpopulations, a departure from the prevailing model, which merely compares study outcomes with the Caucasian population.
The entire panel concurred on one major concept; the ORMH's status must be raised to "center" or "institute" within NIH for the office to do its job effectively. Otherwise, the unit will be "at the mercy" of NIH, argued David Burgess, professor of biology, Boston College.
Burgess also said that centralizing the task of improving minority health through ORMH is key. "It is time to think outside the box; the period of incrementalization [in addressing minority health issues] hasn't worked." He added that a critical part of the problem could be traced to the classroom.
"Minority [science] college graduates are hitting a glass ceiling," he said, pointing to the relative dearth of minorities earning MD and PhD degrees in scientific disciplines. "We won't close the [minority] health disparity gap until we close the training gap," he stressed.
Gibbon urged a grassroots solution to the scarcity of biomedical scientists among minority ranks, advocating programs to "highlight [minority] role models' and get students "excited about science" via mentoring.
The panel's findings, to be compiled into a report in the coming weeks, will be presented to the NIH for implementation. Secretary of Health and Human Services (HHS) Donna Shalala included $4.6 billion in the 2001 budget request for minority health, a $375 million increase over 2000.
ORMH's plan augments the Clinton Administration's stated goals to eliminate, by 2010, racial/ethnic health gaps in six disease areas, including diabetes and cancer; to enhance resources for fighting HIV/AIDS in minority communities; and to convene working groups to assess minority health status and research needs. (Reuters)
The world's growing AIDS epidemic is a danger not only to the 50 million people who are infected, but to the development of many nations, the World Bank and International Monetary Fund (IMF) said on April 17th, after massive demonstrations in Washington highlighted the issue.
But World Bank President James Wolfensohn pledged that the money would be there to help, especially in Africa, which is the continent hardest hit by AIDS.
"I said to the ministers today, and I believe got their endorsement for efforts to finance AIDS, that there will be no limit on the funding we get from the bank," Wolfensohn told a news conference in Washington, where the IMF and World Bank are meeting this week.
"I have said to our African clients that if you have programs, we will fund them," he added. "We regard that with 23 million cases in Africa there is a need for a large amount of money. We're prepared to fund a very big part of this and to make sure that no sensible program is stopped for a lack of money. We'll either provide it ourselves or help them raise it," Wolfensohn said.
The Development Committee, which sets policy for the World Bank, issued a statement urging quick and coordinated action to strengthen health care in developing nations before AIDS further damages their economies. "HIV/AIDS weakens economic growth, governance, human capital, labor productivity and the investment climate," according to the statement.
"Ministers noted that the epidemic now poses not only an acute danger to the development in sub-Saharan Africa, but is a rapidly growing threat in Asia and the Caribbean, and a probable threat in many eastern European countries and elsewhere as well," the statement continued. "As HIV spreads quickly, even countries with currently low infection rates cannot afford to delay strengthening anti-HIV/AIDS programs."
One big complaint has been that the drugs that can help people infected with HIV stay alive and healthy are not available outside the richest industrialized countries.
Wolfensohn said the World Bank was working on this and discussing with pharmaceutical companies ways to make the drugs available at a cheaper price to the countries that most need them.
"The cost in this country runs about $10,000 [per person] a year and the average cost of health care in these countries is about $10 a year," he said. "I believe they are quite likely to come up with proposals at much lower cost...so that the financial constraint is going to be much less."
But even then there will be problems, he said, pointing out that HIV drugs must be given in complicated regimens, they can be toxic, and patients must be carefully monitored for treatment compliance.
"The question of delivery is going to be the biggest problem," Wolfensohn said. He repeated what experts have said for years--that a proper health care infrastructure is needed to deliver the drugs. (Reuters)