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Issue #222: March 26, 1999
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 articles in this issue include AIDS, Annals of Internal Medicine, East Brunswick Home News Tribune, Reuters
In This Issue:
NJ regs hamper anonymous HIV testing for teens
More study on medical marijuana urged
St. John's wort may be toxic to PWAs
Sustiva found effective in combo
TB still leading killer of PWAs
Nevirapine may prevent HIV during labor
FDA approves Epivir for children
Epivir may cause fat redistribution in women
Pro-2000 promising as microbicide
Frisco gays want bathhouses reopened
New Jersey's classification of HIV as a communicable rather than a sexually transmitted disease -- thus requiring parental consent -- is hampering anonymous testing among minors at New Jersey's largest AIDS service provider, the Hyacinth AIDS Foundation according to the East Brunswick Home News Tribune.
The problem may be unique to New Jersey, according to Dr. Robert Johnson of University of Medicine and Dentistry of New Jersey Medical School.
Johnson said the classification can be traced back to a decision made by state regulators in the 1980s, when "conventional wisdom ... was that if HIV was classified as an STD, the state would be obligated to pay for treatment." The problem for the Hyacinth AIDS Foundation is that testing a minor for a non-STD requires parental permission, and state Attorney General Peter Verniero's (R) office has warned that "testing for the disease without parental permission could expose clinicians to risk."
Hyacinth Executive Director Riki Jacobs said that until the situation is resolved, the foundation will not offer anonymous testing to teens without parental consent. She said that "clinic workers who merely are testing for a disease do not have the same protections as physicians who are under a legal obligation to do whatever is medically necessary for their patients."
She said, "As an AIDS service organization ... I think our position on things is dissected a little more differently that a health care institution." She added, "The problem is that there has not been a concerted effort on anyone's part to test large numbers of teenagers. We're the only group doing it. If we don't (test adolescents), we will fail to recognize a group that could benefit from treatment and continue to spread the illness."
[This article is reprinted with permission from the Kaiser Daily HIV/AIDS Report. The Daily Report is published for The Henry J. Kaiser Family Foundation by National Journal Group Inc. Copyright 1999 by National Journal Group Inc., 1501 M St., N.W., Washington, DC 20005. All rights reserved. The Daily Report is available in its entirety free on the Kaiser Family Foundation's Web site, www.kff.org. You may also register for free e-mail delivery at www.kff.org/register.]
More study on medical marijuana urged
The medical value of marijuana has been overlooked and its abuse potential exaggerated, according to an Institute of Medicine (IOM) panel, which has recommended that studies of the medical uses of marijuana be undertaken as soon as possible.
The panel's report concludes that the psychoactive ingredient in marijuana -- THC -- and related compounds called cannabinoids, have many important biological effects, including roles in pain control and in the treatment of wasting associated with AIDS.
Asked in January 1997 to look into the issue by the White House's Office of National Drug Control Policy, the IOM panel assessed clinical trials, heard from advocates and experts, and made visits to marijuana "Buyer's Clubs."
Published data shows that cannabinoids have therapeutic value for pain relief, control of nausea and vomiting, and appetite stimulation, said the panel. But it advised against medical use of the substance, except in the terminally ill, and even then, under restricted conditions. Marijuana is generally not as effective as other drugs, said the IOM, but it may be a good last resort for some patients.
"Marijuana has potential as medicine, but it is undermined by the fact that patients must inhale harmful smoke," said Stanley Watson, co-principal investigator of the IOM study. "Until researchers develop a safe and effective delivery system, caregivers must consider the health problems that can result from smoking when deciding whether to recommend marijuana to patients," added Watson, who is a researcher at the University of Michigan.
The panel urged trials to find a new, rapid-onset delivery mechanisms so that the dangers of smoking could be avoided.
There is no evidence that legal use of marijuana as a medical substance will lead to widespread abuse either in patients or in the population at-large, said the Institute. Dependence among marijuana users is relatively rare, said the panel, adding that abuse potential would be highest among those predisposed to substance abuse. This of special concern in AIDS care because of the high number of active and former drug users diagnosed with the disease.
The panel also found no conclusive evidence that marijuana is a "gateway" drug that leads to use of "harder" drugs. Most drug users begin with alcohol and nicotine, and it is unlikely that medical users -- who are likely to be older -- will progress to using other illicit drugs.
Interestingly, the panel found no evidence to support smoking marijuana as a treatment for glaucoma. When smoked, the drug does reduce intraocular pressure. But, "the effect is too short-lived, requires too high doses, and there are too many side effects to recommend lifelong use in the treatment of glaucoma," said the report.
The study was funded by the Office of the National Drug Control Policy, Executive Office of the President. The Institute of Medicine is a private, non-profit organization that provides health policy advice to the federal government.
St. John's wort may be toxic to PWAs
Hypericin, the active ingredient in St. John's wort, may trigger severe skin reactions in AIDS patients, researchers conclude.
And in contrast to previous reports, the study found that hypericin had no activity against HIV in patients tested.
"These findings raise concerns about the safety of hypericin, which is available as an herbal preparation and is commonly used by HIV-infected patients," conclude a team of AIDS researchers led by Dr. Roy Gulick, of the Cornell Clinical Trials Unit in New York City. Their report is published in the March 16th issue of the Annals of Internal Medicine.
According to Gulick's team, laboratory trials in mice have suggested that hypericin might "interfere with steps in the replicative cycle" of HIV - inhibiting proliferation of the virus. Many HIV-positive individuals currently use St. John's wort in the belief that it can help fight the virus.
To test the efficacy of the compound in fighting HIV in humans, the researchers attempted to administer hypericin orally or intravenously to 30 AIDS patients with impaired immune systems over a period of 6 months.
They report that more than half (53%) of patients "discontinued treatment before completing 8 weeks of therapy because of... moderate or severe phototoxicity." Phototoxicity involves a red, itchy rash that occurs whenever skin is exposed to sunlight. Overall, just 2 of the 30 patients were able to tolerate a full 6 months of hypericin therapy.
This high incidence of side effects meant that most patients never received planned, higher doses of hypericin. In any case, the therapy "lacked demonstrable antiretroviral (anti-HIV) activity at the doses tested in our study," according to the authors. They observed no significant change in either blood HIV load or CD4 counts associated with hypericin treatment.
Gulick's team notes that St. John's wort and other "preparations containing hypericin are largely unregulated and contain varying amounts of (the) drug." They advise that individuals consuming these types of products be made aware of the danger of side effects.
Although St. John's wort/hypericin may be too toxic for most AIDS patients, the researchers speculate that other compounds related to the drug "may have antiretroviral activity and could be investigated" in future trials.
Sustiva found effective in combo
DuPont Co. has announced that its AIDS drug Sustiva, taken in combination with two other non-protease inhibitors, Zerit and Epivir, reduced viral load to below quantifiable levels in 100 percent of patients studied after 24 weeks.
Sustiva is DuPont's once-daily non-nucleoside reverse transcriptase inhibitor, which was approved by the U.S. Food and Drug Administration last September, after fast-track review.
The medication can be used with or without protease inhibitors, which have been a component of most anti-HIV drug "cocktails."
DuPont said that three of the 42 patients in the ongoing 48-week study dropped out, but that discontinuation was not related to adverse events.
The company said in a press release that data were presented at the 9th European Conference of Clinical Microbiology and Infectious Diseases in Berlin.
"These data show that non-protease combinations including Sustiva continue to provide effective treatment options for people with HIV that are relatively simple to take," said Cal Cohen, Director, Community Research Initiative of New England, in the statement.
Zerit and Epivir are nucleoside analogues.
Reverse transcriptase inhibitors, which include both the non-nucleoside variety, such as Sustiva, and the nucleoside variety, interfere with an enzyme vital for replication of the HIV virus.
Protease inhibitors also target an enzyme vital for HIV virus replication, but interfere at a different site.
TB still leading killer of PWAs
Tuberculosis (TB) remains one of the most important health issues worldwide, according to Dr. Peter Piot, Executive Director of UNAIDS. And TB has "especially drastic implications for countries with high AIDS/HIV prevalence," he says.
"Coinfection with TB and HIV is the leading killer of people with AIDS in sub-Saharan Africa, where the majority of AIDS-related deaths are now occurring," Dr. Piot pointed out.
In a statement coinciding with World Tuberculosis Day, Dr. Piot added that "TB can be cured, even in HIV-infected individuals, if it is diagnosed in time and treated properly." This highlights the importance of early identification and treatment of active TB through community health programs in areas with a high HIV prevalence.
"Successful TB control has been demonstrated when community health programs, which serve large numbers of HIV-infected people, integrate active TB diagnosis and treatment into their services," he continued. Access to voluntary HIV testing and counseling to identify individuals who should receive TB prophylaxis can further reduce the spread of TB.
This message was echoed by Dr. George Alleyne, Director of the Pan American Health Organization. In the Americas, more than 400,000 individuals develop TB and 50,000 die from this infection each year, Dr. Alleyne pointed out in a PAHO statement. And this threat to public health "has not diminished in the 1990s."
Dr. Alleyne warns that TB may increase in some countries if control efforts are not accelerated. "New economic uncertainties, social and economic disruption due to recent devastating natural disasters, the HIV/AIDS epidemic, as well as failure to control the spread of drug-resistant TB, all loom as threats."
Nonetheless, for the fifth straight year, tuberculosis cases declined last year in the United States. There were 18,371 cases of TB reported in the United States in 1998, a 7.5 decrease from 1997 levels, according to the Centers for Disease Control and Prevention. Still, the World Health Organization believes that tuberculosis will cause an estimated 3.1 million deaths worldwide this year.
Nevirapine may prevent HIV during labor
A single dose of nevirapine, administered to HIV-infected women during labor, and to their infants during the first week of life, appears to be safe and well-tolerated, according to a multinational team of investigators who believe this drug has the potential to be an effective prophylactic treatment for vertical HIV transmission.
The non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine has potent antiretroviral effects, rapid oral absorption, good bioavailability and can cross the placenta, Dr. Philippa Musoke of the Makerere University in Kampala, Uganda and colleagues explain in the March 11th issue of AIDS. This makes nevirapine an "excellent candidate for a single-dose antiretroviral intervention administered during labor."
Dr. Musoke's group conducted a phase I/II trial with 21 HIV-1-infected women attending a tertiary care hospital in Kampala, Uganda. The women were given a single dose of 200 mg nevirapine during labor. In addition, 13 infants also received a single dose of nevirapine (2 mg/kg) 72 hours after birth. The other 8 infants were not treated.
The investigators followed the mothers and infants for up to 6 weeks after delivery, monitoring adverse events, nevirapine concentrations in breast milk, and maternal viral load.
Both the women and the infants tolerated the drug well, and they observed "...no serious adverse events that were related to nevirapine." Specifically, there were "...no serious skin rashes, abnormal complete blood counts, or elevations of liver function tests or creatinine associated with the use of nevirapine in this study."
One hour after dosing, nevirapine appeared to be rapidly transferred across the placenta. When nevirapine was administered to the women at least 1 hour prior to delivery, nevirapine plasma concentrations above the targeted 100 ng/mL were maintained for 7 days in both the mother and the infant. The infants who received an additional dose of nevirapine after birth maintained nevirapine levels of 170 ng/mL for 7 days.
"Nevirapine elimination was prolonged in the study mothers and infants, with considerable interpatient variability," the investigators continue. In addition, they found that drug levels in breast milk were above 100 ng/mL for 7 days after birth.
"The antiviral activity of nevirapine appeared to be quite strong, resulting in a relatively consistent median 1.3 log reduction in maternal plasma HIV-1 RNA at 1 week after a single 200 mg dose in all mothers," they report.
"Because the majority of HIV-1 vertical transmission is thought to occur around the time of delivery," Dr. Musoke's group believes that "...this simple regimen could be very effective in substantially reducing the vertical transmission rate in this population." Along with intrapartum prophylaxis, they also point out the potential usefulness of nevirapine in preventing HIV-1 transmission through breast milk.
"This phase I/II study shows that nevirapine is a non-toxic, well-tolerated medication when used in these pregnant women in Uganda," Dr. Amal Murarka, one of the study co-investigators at Johns Hopkins University, said.
The findings also show that nevirapine levels were quite high in breast milk, he continued. "One of the theories, although not yet substantiated, is that most of the breast milk transmission [of HIV-1] occurs during a fixed period of time right after birth."
In this study, the level of nevirapine in the breast milk is high enough that the child may get some effect from nevirapine after birth, thereby preventing further transmission from the breast milk, he continued.
Although this study is preliminary, Dr. Murarka believes the findings are a "very important step" in bringing simple, cost-effective therapies to prevent vertical transmission in the African and Asian populations, which have the majority of the HIV-1 burden.
FDA approves Epivir for children
The US Food and Drug Administration has approved the use of lamivudine (Epivir, 3TC) in HIV-infected infants, children and adolescents, according to a statement from Glaxo Wellcome.
FDA approval broadens the indications for lamivudine use, in combination with other antiretroviral drugs, in HIV-infected patients, officials at the Company's Research Triangle Park, North Carolina facility said. The Agency granted accelerated approval for lamivudine use in combination regimens for HIV-infected adults in November 1995.
Epivir may cause fat redistribution in women
About 10% of women treated with HIV drug 'cocktails' experience a redistribution of body fat, researchers report.
This redistribution is "characterized by a progressive enlargement of breast and abdominal girth associated with a wasting of the lower limbs," explain Dr. Cristina Gervasoni and colleagues at the L. Sacco Hospital in Milan, Italy. Their findings are published in the March issue of the journal
AIDS.
The researchers studied the body composition of 306 HIV-infected women treated as outpatients at a Milan hospital between December 1997 and February 1998. All of these patients were taking at least two antiretroviral drugs.
The study authors observed significant fat redistribution in 32 subjects (10.5%). This phenomenon was not associated with any weight gain, and its exact cause remains unclear. The authors say they found "no significant differences in laboratory tests" conducted in patients with or without the syndrome. Fat redistribution was not associated with an excessive amount of lipids (fats) in the blood, altered blood-sugar metabolism, or hormonal disorders, according to the investigators.
All of the women who experienced fat redistribution were receiving the drug lamivudine (Epivir, 3TC) over a long period of time (about 3 years) as part of their anti-HIV drug regimen. Only 20 of these subjects were also receiving one of the protease inhibitor family of HIV-suppressing medications, indicating that these medications may not play a role in fat redistribution.
Gervasoni and colleagues call the emergence of this syndrome "alarming," noting that "aesthetic alterations (in body shape) are beginning to arouse serious psychological problems in young women that may significantly reduce their compliance with (HIV) therapies."
Pro-2000 promising as microbicide
The results of a preliminary trial indicate that the topical PRO 2000 Gel exhibits protective effects in a monkey model of vaginal HIV transmission, according to a press release from Procept, Inc., based in Cambridge, Massachusetts.
The study, which was conducted by the British Medical Research Council, involved the intravaginal application of PRO 200 Gel, a 5-kD naphthalene sulfonate polymer, in female rhesus monkeys. The investigators found the rate of infection was reduced after the animals were subsequently exposed to a high dose of a simian/human immunodeficiency virus.
The current findings extend those of previous laboratory studies that have found PRO 2000 to be active against HIV-1, HIV-2, herpes simplex virus type 2 and Chlamydia. Encouraged by the results, Dr. John F. Dee, Procept CEO, believes this "...'proof of concept' obtained in the monkey study represents an important milestone for the program. We now have evidence from three animal models that PRO 2000 Gel is active in vivo."
Procept officials believe these findings support phase II and III human clinical trials in which the safety and efficacy of the product would be evaluated.
Frisco gays want bathhouses reopened
Fifteen years after San Francisco cracked down on bathhouses in order to block the spread of AIDS, some gay men say its time for the city to reverse its policies.
"At this stage in the epidemic people know how to protect themselves," said Act-Up spokesman Michael Bellefountaine, in a meeting with health officials. "We need to start modifying our behavior in relation to the epidemic."
San Francisco logged an estimated 8,000 new HIV infections annually in the early 1980s, prompting the then-health director to order the bathhouses closed because of concerns they were fostering the spread of the disease.
A federal judge refused, but imposed stringent regulations aimed at preventing unsafe sex in the facilities. About 15 city bathhouses closed when owners decided they couldn't profit under the restrictions.
The number of HIV infections have plummeted since then, with about 500 new cases annually in the city. Still, unprotected sex among gay men is on the rise, said Dr. Mitchell Katz, director of San Francisco's Department of Public Health.
"If HIV were eradicated, there wouldn't be a concern about HIV transmission," he said, adding there are no plans by the department to reconsider its policies.
Critics contend no studies prove that bathhouses help spread HIV, the virus which causes AIDS, and that the current rules discriminate against homosexuals.
"It's restraint of trade, it's violation of civil liberties, it's bad science and it's homophobic," said Jonathan Klein, a gay activist.
"What it really seems to be pandering to is the anti-AIDS rhetoric of the early 80s."
Katz rejected the accusation.
"None of our rules are targeted towards individuals," he said. "They only have to do with the environment and only apply to moneymaking businesses."
Philadelphia bathhouses have never been closed due to the AIDS epidemic, although the city has funded several safer-sex campaigns aimed at bathhouse clientele and has adopted regulations governing their operation.
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