|
 |
|
|
|
Issue #172: April 12, 1998
fastfax is available by fax in the 215 and 610 area codes at no cost, or by mail anywhere for $20.00 per year, by calling 215-545-6868, and by E-mail by contacting and type the message SUBSCRIBE in the message section. Sources for some information in this issue include Boston Globe, Nature Medicine and Reuters.Study: treatment best for addicts
Cancer drug boosts effects of some HIV drugs
Mature antibody response linked to immunity
CMV prophylaxis may be discontinued in some
Surgeon general confronted by exchange advocates
Study: treatment best for addicts
Drug and alcohol abuse are medical problems that respond to medical treatment just as well as diabetes and other chronic diseases do--and treatment is cheaper and more effective than jail, says new research.Yet the nation spends only 20 percent of its $17 billion drug-control budget to treat addicts, and the public believes that jailing addicts is best, a bipartisan group of public health experts said Tuesday.
"We've been telling people to 'just say no' when addiction is a biological event," said Dr. June Osborn, who chairs the new Physician Leadership on National Drug Policy.
"There must be a bridge between what the public believes and the science," added Dr. Lonnie Bristow of the American Medical Association.
The group of prominent physicians and public health leaders from the Clinton, Bush and Reagan administrations commissioned the research. They are using it to urge doctors to play a greater role in diagnosing and treating addiction--and are providing it to politicians who control drug-treatment money. Many of the 14 million American alcoholics and 6.7 million drug addicts relapse after drug treatment, but the scientists concluded that:
Jailing a drug addict costs $25,900 per year. A year of traditional outpatient drug treatment costs $1,800, intensive outpatient care costs $2,500, methadone treatment for heroin users costs $3,900 and residential drug-treatment programs range from $4,400 to $6,800 a year. Drug treatment can cut crime by 80 percent, said Brown University addiction director Norman Hoffman. Brown researcher Craig Love studied female substance abusers who were in jail, and found that 25 percent who underwent treatment were later re-arrested, vs. 62 percent released without substance abuse treatment. A California study of 1,600 drug abusers found their involvement in drug sales, drug-related prostitution and theft decreased threefold after treatment.Every dollar invested in drug treatment can save $7 in societal and medical costs, said former Assistant Health Secretary Philip Lee.Long-term drug treatment is as effective as long-term treatment for chronic diseases, said Dr. Thomas McLellan of the University of Pennsylvania. One-year relapse rates for the diseases and for addicts all are about 50 percent, he said. Compliance with therapy is similar, too: Fewer than half of diabetics comply with their therapy, as do fewer than 30 percent of asthma and hypertension patients and fewer than 40 percent of alcohol or drug abusers. Drug treatment also helps society's health, McLellan said.
Heroin users, for example, are at huge risk of catching and spreading the AIDS virus or hepatitis. A seven-year study of heroin addicts found 51 percent who never entered drug treatment caught HIV during that period, vs. 21 percent of treated addicts.
Yet, there is a severe shortage of drug-treatment programs, the doctors said.
About 15 percent of people who need treatment get it. Seven states don't offer any methadone clinics for heroin addicts, and every U.S. methadone clinic has a waiting list. Only 5 percent to 20 percent of pregnant drug abusers can get drug treatment because of too few programs, inability to pay or too few inpatient programs that will accept the woman's other children, said Pennsylvania's Dr. Jeffrey Merrill.
The findings conflict with public opinion.
An analysis of surveys being published today in the Journal of the American Medical Association finds support for increased spending on drug treatment has dropped from 65 percent in 1990 to 53 percent in 1996.
In contrast, 84 percent of Americans say the solution is tougher criminal penalties. Next on the list are anti-drug education, more police and mandatory drug testing.
The survey also found Americans believe drug abusers are predominantly poor, uneducated and minorities. In fact, the majority are like Dr. Richard Corlin's son, once a cocaine addict: white, from well-educated families and initially employed.
Dispelling those myths is vital to public commitment for drug treatment, said Corlin, a Los Angeles medical professor. "People think it is someone else's problem. It is not."
Cancer drug boosts effects of some HIV drugs
Hydroxyurea is a cheap, licensed drug used in the treatment of some forms of leukaemia. A few years ago, researchers found that it can also boost the antiviral effects of ddI in test-tube studies. The Fifth Conference on Retroviruses and Opportunistic Infections held in Chicago in February heard the results of several treatment studies looking at its risks and benefits.Swiss researchers tested hydroxyurea in a placebo-controlled trial, comparing a group of 72 people taking d4T/ddI/hydroxyurea with a control group of 72 people taking just d4T/ddI. Their average viral load at baseline was about 30,000. After 12 weeks, 54% of people receiving hydroxyurea had achieved viral load below 200, compared with only 28% of those not receiving hydroxyurea. The proportions achieving viral load below 20, measured with an ultra-sensitive viral load test, were 19% and 8%.
In another study, 31 people with higher viral load (average 100,000) were treated with d4T/ddI/hydroxyurea. There was an average 1.3 log reduction in viral load and about 50 CD4 cell increase after 12 weeks of therapy, and after 16 weeks eight out of eleven participants had achieved viral load below 500.
A number of cases have also been reported in which hydroxyurea treatment appears to be associated with disappearance of detectable HIV, even in latently infected cells containing HIV proviral DNA (the most stubbornly persistent form of HIV's genetic material). Dr Franco Lori presented data on 24 patients treated with ddI/indinavir/hydroxyurea, of whom 10 started treatment just weeks after infection. After 11 months, the average CD4 count increase was 168 and all participants had viral load below 500. Seven out of eight people who underwent lymph node biopsy had no detectable viral RNA in their lymph nodes, while two out of six had no detectable proviral DNA either.
One patient in the study was investigated even more closely. Even after increasing the sensitivity of the tests for proviral DNA and HIV RNA up to 60-fold, it was only possible to detect one cell in ten million that was able to produce infectious HIV particles. This result is even more dramatic than those achieved after 2.5 years of triple therapy in David Ho's laboratory. This individual has now been off treatment for 13 months without any viral load rebound. However, it has been suggested that these impressive findings may be a consequence of the very early stage at which treatment was started, rather than of the specific drugs used.
These intriguing results are still very preliminary, and need to be confirmed in much larger studies with proper control groups for comparison.
Some doctors are also using hydroxyurea as part of salvage therapy regimens for people who have developed resistance to many or all of the licensed anti-HIV drugs. One test-tube study found that even ddI-resistant strains of HIV remained susceptible to ddI when it was given in combination with hydroxyurea. Since hydroxyurea works by affecting the human cell rather than HIV (see box opposite), HIV resistance mutations are unlikely to have any effect on hydroxyurea's action.
Most studies testing hydroxyurea are using it in combination with ddI, since this combination seemed to be the most effective in the test-tube. A report at the Retroviruses conference two years suggested that hydroxyurea did not boost the anti-HIV effects of AZT in laboratory tests. Other test-tube studies suggest that the only anti-HIV drugs whose effects are likely to be enhanced by hydroxyurea are ddI, abacavir (1592U89) and adefovir dipivoxil.
A much lower dose of hydroxyurea (often 500mg twice daily) is used when treating people with HIV, compared with the dose used for treating leukaemia. Nevertheless, the downside of hydroxyurea is that it can be quite toxic, suppressing the bone marrow and causing problems such as neutropenia, mouth ulcers and hair loss.
People adding hydroxyurea to their ddI-containing regimen may experience a greater reduction in viral load because of the increased antiviral effects, but any CD4 count rise may be smaller because of hydroxyurea's toxic effects on blood cells.
Mature antibody response linked to immunity
The answer to a single question may hold the key to an AIDS vaccine: why does it take six to 10 months for monkeys inoculated with attenuated live simian immunodeficiency virus (SIV) vaccines to develop protective immunity?Comparison of the immune responses of various mammals and humans to lentivirus infection reveals that the maturation of antibody responses is a common theme in protection against disease. Immature antibody responses are associated with disease progression.
The findings come with a promise and a warning. The promise is that there may be a way to elicit mature anti-HIV immunity. The warning is that suboptimal HIV vaccines may actually do harm.
"A vaccine may not just fail to protect, but may also make disease worse when a person is infected with HIV," warned Ronald C. Montelaro of the University of Pittsburgh, Pennsylvania.
Montelaro discussed maturation of antibody responses to persistent lentivirus infection in an invited address to the 1998 Palm Springs Symposium on HIV/AIDS, "Towards an HIV Vaccine: Immunopathogenesis of HIV Infection," held March 5-8, 1998, in Palm Springs, California.
Montelaro et al. began by studying antibody responses in monkeys protected against challenge by live, attenuated vaccines. They investigated the conformational dependence of antibodies, antibody avidity (as opposed to affinity), and virus neutralization. These responses had several distinct characteristics:
Antibody avidity increased slowly over time.
There was a six- to eight-month period of immature immunity wherein dynamic, complex antibody properties evolved and changed over time.
Final mature immunity was stable and characterized by increased antibody titer, decreased neutralizing activity against the vaccine strain, increased breadth of neutralization activity, and a decreased conformation ratio.
The study of antibody maturation in successfully immunized monkeys yielded a number of findings with applications for vaccine development:
Only minimal levels of SIV expression were needed to drive antibody responses.
Severely attenuated SIV vaccine strains failed to produce mature antibody responses.
Env sequence variation is not required for maturation of antibody responses.
"The serologic parameters identified in the study are necessary but not sufficient correlates of protection," Montelaro said. "The study raised more questions than it answered."
To answer these questions, Montelaro and colleagues performed a series of serological analyses - "serology ad nauseam," the researcher joked - to explore the development of envelope-specific antibody responses in several lentivirus/host systems.
The researchers examined monkeys infected with pathogenic strains of SIV or chimeric simian/human SHIV, humans infected with HIV, and horses infected with equine infectious anemia virus (EIAV).
These studies provided some answers:
Is the maturation of antibody responses in vaccinated monkeys applicable to disease progression? Montelaro and colleagues showed that monkeys that do not progress to disease have similar antibody- maturation parameters to vaccine-protected animals.
Is this maturation process unique to SIV envelope proteins?
Monkeys infected with pathogenic SHIV - which bears the HIV envelope - showed the same type of antibody responses as SIV infected animals, except that maturation of antibody avidity took longer to mature in SHIV infection.
Does antibody maturation occur in people with HIV? Human antibody responses to HIV Env evolved differently than those in the monkeys in terms of conformational requirements, but the avidity data was generally comparable. "This means that these parameters are not necessarily linked to one another," Montelaro said.
Does antibody maturation occur in other lentivirus hosts?
The horse/EIAV model yielded data comparable to that seen in the monkey/SIV model.
"I think this slow maturation of immunity is one more trick of lentiviruses," Montelaro said. "These viruses have evolved to be immune slippery."
He concluded that lentivirus infection is associated with a common maturation of antibody responses, and although there may be some interspecies differences in the nature of this maturation the process takes six to eight months.
"It appears that the development of immune responses to lentivirus infections involve a complex and lengthy maturation of antibody responses to viral antigens," he said. "This initial negotiation between virus and host may be critical for determining viral set points and disease progression."
Protection can only occur after the maturation process is complete. Completion of the process apparently required prolonged presentation of small amounts of antigen.
"The design of attenuated vaccines must minimize safety problems but maximize the ability to elicit mature protective immunity," Montelaro said. "This may not be as hard as many think."
CMV prophylaxis may be discontinued in some
A report published in the April Issue of the Journal of Infectious Diseases indicates that AIDS patients who respond to highly active antiretroviral therapy (HAART) may not need continuous cytomegalovirus (CMV) suppressive therapy after the successful treatment of CMV retinitis.Dr. B. Clotet of Hospital Universitari 'Germans Trias i Pujol' in Badalona, Spain, and colleagues report on seven AIDS patients undergoing secondary prophylaxis for CMV retinitis. Following three months of taking HAART, the subjects ceased treatment for secondary CMV retinitis if they had CD4 cell counts greater than 150/ microliter, an HIV RNA load lower than 200 copies/mL, and undetectable CMV.
All seven of the patients tested negative for CMV after a median of nine months, and they maintained CD4 cell counts greater than 150/microliter and HIV RNA counts less than 200 copies/mL.
Surgeon general confronted by exchange advocates
Protesters advocating needle-exchange programs confronted Surgeon General David Satcher Tuesday as he spoke on unrelated subjects in the Charlestown Navy Yard in Boston. Satcher had come to Massachusetts to commemorate the U.S. Public Health Service's bicentennial at the site of the nation's first permanent marine hospital.Demonstrator and spokesman for the AIDS Action Committee Larry Kessler said that the needle-exchange programs are effective in reducing the spread of HIV and getting people into treatment. He also said that AIDS Action Council members met with Satcher in an effort to get the surgeon general to urge the Clinton administration to use federal funds for local needle-exchange programs. Satcher did not comment on the programs during his speech.
ACT UP seeks volunteers to DC lobby day
ACT UP Philadelphia is serving as state-wide coordinating group for AIDS Watch, the annual Spring lobby day on HIV/AIDS issues in Washington, DC.This year, AIDS Watch happens on Sunday, May 3 to Tuesday, May 5. ACT UP Philadelphia is sponsoring a day trip on Tuesday, May 5 and providing transportation from Center City, Philadelphia.
The group can also help arrange transportation for people in other parts of the state.
"We will spend the day talking to our elected officials about the need for continued funding for HIV/AIDS prevention, research and care; lifting the Federal funding ban on syringe exchange; and making research on microbicides and other novel prevention methods a NIH priority," according to Julie Davids, a spokesperson for the group.
To reserve a space, call 731-1844, box 9.
Davids said that for people interested in attending all the days of AIDS Watch, community housing may be available and national organizers have information on hotels. Sunday is a training day, and volunteers will have the opportunity for more lobbying and issue updates on Monday and Tuesday. If interested, call Jean-Michelle Brevelle at (202) 898-0414 x 103 or email "thewonks@aol.com," and say that ACT UP Philadelphia made the referral.
Information on AIDSWATCH '98
If you believe that federal government can and must do more to end the HIV epidemic...
If you believe that people living with or at risk for HIV need full access to quality prevention, care, housing, and research...
If you believe that your voice and your vision can make a difference...
You Belong at AIDSWatch '98!
May 3 - 5, 1998
Washington, DC
What is AIDSWatch '98?
AIDSWatch is the largest annual constituent-based federal HIV/AIDS education and lobbying event in the United States. Every year, hundreds of people living with HIV, their supporters and advocates, come to Washington, DC to educate Congress on the need for increased funding and a strong commitment to federal HIV/AIDS programs for prevention, care and treatment, research, and housing.
AIDSWatch is in its seventh year of providing meaningful opportunities for constituents to meet in person with their federal elected officials to discuss the impact of the HIV epidemic on the lives of real people. Every participant receives a half-day briefing on key issues and training on effective lobbying strategies by experts in the field. The following two days are spent on Capitol Hill meeting with Representatives and Senators and their staff. These face-to-face meetings are one of the most effective ways of influencing our elected officials and are crucial in obtaining increased funding.
Participants at AIDSWatch increase their knowledge of HIV/AIDS issues, and create links with other advocates from across the country to continue their involvement in the policy process in their home congressional districts.
AIDSWatch is a powerful personal experience for all those who participate.
What Does it Cost to Participate?
There is no registration fee or charge for materials. The only costs are those for your travel (airfare, train, bus, etc.), hotel accommodations, food, and ground transportation. In general, and depending upon what region of the country you are traveling from, costs range between $700 - $1,000. A sample budget might look like this: Airfare = $350.00; Hotel (3 nights) = $300.00; Food (3 meals/day) = $ 90.00 ; Ground transportation (includes shuttle to/from airport and Metro around town) = $ 45.00: Total: = $785.00.
A limited number of scholarships will be made available to assist constituents from key congressional districts to attend this important three-day lobbying event. Efforts to make community (no-cost) housing available are also under way.
What Happens After I Register?
You will receive a phone call from the Regional Coordinator for your area, or from the National Coordinator if your area does not have a Regional Coordinator, to discuss your participation and answer any questions you may have. All of your appointments will be scheduled for you, and a trained facilitator will be at each meeting to assist and support you. You will also receive at least one future mailing containing information about hotel accommodations, ground transportation, discounted airfare if available, and a schedule for the event.
To obtain a weekly email version of fastfax, contact with the message: "subscribe" or fill in the box on the fastfax index page.