-----===[[[ A I D S w i r e D I G E S T 04.05.93 ]]]===----- Experts Come to Defense of AZT * Financial Times (04/05/93), P. 2 Kehoe, Louise AZT will remain the primary treatment for AIDS, even though preliminary results of a large-scale European study, published on Friday, claim that AZT should not be used early in the course of disease, said American AIDS experts. Medical experts and AIDS activists emphasized that the so-called Concorde study should not cause alarm. A spokesman for the San Francisco AIDS Foundation, which offers counseling and support to HIV-positive individuals, said the study "doesn't really change what we already knew or suspected; that AZT when administered as a single therapy is not very effective." In the United States, the current treatment for AIDS uses AZT in combination with drugs like DDI or DDC, both of which have been approved by the Food and Drug Administration. Such a therapy was developed as HIV became resistant to AZT after six to 18 months in most patients, said AIDS experts. Therefore, AIDS experts were not surprised that the European study, which followed HIV-positive people over a three-year period, demonstrated the limitations of AZT. The experts say it is still extremely important to use AZT early in infection, as studies indicate HIV is active in the lymphoid tissues, the lymph nodes, tonsils, and spleen during the latent period, which can last up to 10 years from the time of infection until symptoms appear. One observer said, "It would be a tragedy if the results of the European AZT study discouraged people from seeking early treatment." Drug Company Doubts Findings of AZT Study * Journal of Commerce (04/05/93), P. 7A A top official with the British pharmaceutical company that makes AZT questioned the results of a European study published Friday in The Lancet that showed no proof that the drug prolonged the onset of AIDS. Andrew Revell of Burroughs Wellcome, in Latvia for a two-day conference on AIDS, said AZT still has a key role to play in fighting the disease. He said many patients had withdrawn from the study and said he was not sure whether the report was representative. "I would cast doubts on the results of information, but even if the result is right I would still intervene [with medial treatment] early to help the quality of life of those living with HIV-AIDS," said Revell. Drugs on Trial * Financial Times (04/05/93), P. 11 The European researchers who conducted the "Concorde" study should be commended for executing their trial of the leading AIDS drug AZT through to its unanticipated conclusion, write the editors of the Financial Times. The researchers had bravely resisted strong pressure from colleagues, particularly in the United States, to discontinue the study. These colleagues apparently thought that they already knew AZT would benefit people infected with AZT. The study found that the modest benefits discovered after a year's treatment with AZT-- the point at which three smaller U.S. trials were stopped--had disappeared by the end of the three-year study. The drug did not delay the onset of full-blown AIDS. These findings are particularly sad for the several thousands of HIV-infected people who had hoped AZT would inhibit the development of the disease. However, the study is a powerful demonstration of the patient European approach to clinical trials, as opposed to the American inclination to rush to premature conclusions with insufficient evidence. This study will help people with HIV in the long run by exposing the inadequacies of AZT and therefore facilitating the testing of other drugs. In the world of AIDS research, activists' persistence has made it difficult for drug companies or government agencies to conduct large enough clinical trials to give worthwhile results. The Concorde study demonstrates why this must stop, the editors conclude. Around the Nation: AIDS Group Resignations * Washington Post (04/05/93), P. A7 Two senior executives of the Shanti Project in San Francisco, the nation's largest provider of housing for AIDS patients, resigned after being blamed for neglecting to account for $2.7 million in government funds. Executive director Eric Rofes and deputy director Melinda Paras presented their resignations at the board's request. Shanti makes 144 beds available for AIDS patients, as well as support services for 1,000 people. It has an annual budget of $5.4 million. The San Francisco city AIDS office had been investigating Shanti, and in March revealed that the sloppy accounting records could not show where Shanti had spent $2.7 million in public funds from mid-1991 to early 1993. Shanti must pay the money back to the city or show how the money was spent by May 1. Sexually Transmitted Diseases Abound in Ohio * United Press International (04/02/93) (Cleveland) The number of people infected with HIV and syphilis significantly increased in Ohio last year. The Cleveland Plain Dealer conducted a computer analysis that showed that more than 1,500 people died in Ohio between 1989 and 1991 from AIDS- related conditions, while dozens more died from syphilis and hepatitis. Experts said that all of the nationwide attention focusing on AIDS has overlooked the increase in the number of people with other sexually transmitted diseases (STDs). The computer analysis examined the primary cause of death for more than 300,000 people in Ohio during the three-year period. AIDS-defining illnesses, the leading killers among STDs in Ohio, affect 15 times more men than women. Such illnesses were found to be the chief cause of death of more than 1,500 people in Ohio. Syphilis caused 12 deaths, eight of them women, and 72 people died of hepatitis B virus. Authorities said no deaths resulted from gonorrhea or chlamydia, both STDs which can be quickly treated. MicroGeneSys Drops Out of NIH Trial for AIDS Vaccine * Nature (03/25/93) Vol. 362, No. 6418, P. 277 Macilwain, Colin The AIDS vaccine made by MicroGeneSys of Meriden, Conn., has been withdrawn from the main comparative trials being organized by U.S. public health agencies, a move which will exacerbate the already bitter divisions within the AIDS research community. MicroGeneSys withdrew its gp160 vaccine--the same one that is to be used in a $20 million trial program by the U.S. Army--from comparative trials scheduled by the AIDS Clinical Trials Group (ACTG) of the U.S. National Institutes of Health (NIH). The drug company and its development partner, Wyeth-Ayerst Research, opposed the proposed dosing schedule, the duration of the study, and the criteria being used to assess the vaccine. The company said the withdrawal was "driven primarily by the needs of our development program." The vaccine, also known as VaxSyn, consists of the outer envelope protein of HIV and is designed to strengthen the immune systems of people already infected with HIV. One researcher at NIH said, "This was the only study giving direct comparability between rival vaccines. But put yourself in their shoes: why would they want to help generate data showing that their vaccine offers less immunogenicity than others." However, the president of MicroGeneSys, Franklin Volvovitz, says that the mention that his company fears the results of the proposed trials is "preposterous." He said, "It's bizarre for them to say these things. We disagreed with the primary and secondary end-points set for protocol 214. As the firm with the largest database, our views should be considered." Volvovitz added that MicroGeneSys has been repeatedly excluded from another NIH competitive study that observes the effect of vaccines on patients' response to AZT. HIV Infection is Active and Progressive in Lymphoid Tissue During the Clinically Latent Stage of Disease * Nature (03/25/93) Vol. 362, No. 6418, P. 355 Pantaleo, Giuseppe et al. HIV disease is active and progressive even when there is little evidence of disease activity and by readily measured viral parameters in the peripheral blood, and the patient is experiencing asymptomatic HIV infection, write Giuseppe Pantaleo et al. of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Md. Primary infection with HIV is typically followed by a burst of viremia with or without clinical symptoms. This is usually followed by a prolonged period of clinical latency. During the latency period there is little, if any, detectable viremia, the numbers of infected cells in the blood are very low, and it is extremely difficult to demonstrate virus expression in these cells. The researchers evaluated viral burden and levels of virus replication simultaneously in the blood and lymphoid organs of the same individuals at various stages of HIV disease. They found that during clinical latency, HIV accumulates in the lymphoid organs and replicates actively despite a low viral burden and low-to-absent viral replication in peripheral blood mononuclear cells (PBMC). Hence, a state of true microbiological latency does not exist during the course of HIV infection. The peripheral blood does not accurately reflect the actual state of HIV disease, particularly early in the clinical course of HIV infection, conclude the authors. Massive Covert Infection of Helper T Lymphocytes and Macrophages by HIV During the Incubation Period of AIDS * Nature (03/15/93) Vol. 362, No. 6418, P. 359 Embretson, Janet et al. Latently infected lymphocytes and macrophages comprise an intracellular reservoir large enough ultimately to contribute to much of the immune depletion in AIDS, write Janet Embretson et al. of the University of Minnesota in Minneapolis, Minnesota. The researchers used polymerase chain reaction (PCR) in situ double-label methods to determine how many CD4 lymphocytes are latently infected by HIV in patient lymph nodes and whether the pool of infected cells is large enough to account for immune depletion through continual activation of viral gene expression and attrition of cells responding to antigens. The researchers found an extraordinarily large number of latently infected CD4 lymphocytes and macrophages throughout the lymphoid system from early to late stages of infection, and confirmed the extracellular association of HIV with follicular dentritic cells. Follicular dentritic cells may transmit infection to cells as they migrate through lymphoid follicles. The extent of infection in the CD4 lymphocyte population in lymphoid organs where 98 percent of these cells reside is sufficient to account for a substantial portion of the immune depletion in AIDS by a mechanism of slow elimination of small fractions of cells in which productive infection is continually activated concomitantly with the immune response to a particular antigen or pathogen. Because the end result of so many CD4 lymphocytes is determined relatively early in the course of infection emphasizes the difficulties in developing treatment programs that can be initiated in time to affect the outcome favorably, the researchers conclude. Endocrine Effects of HIV Infection * New England Journal of Medicine (03/25/93) Vol. 328, No. 12, P. 889 Martinez, Esteban et al. Aerosolized pentamidine can affect pancreatic function, write Esteban Martinez et al. of the Hospital de la Santa Creu in Barcelona, Spain. Grinspoon and Bilezikian write in the Nov. 5 issue of the New England Journal of Medicine that "there is no evidence that pentamidine administered by aerosol alters pancreatic function." However, there have been at least three cases of pancreatitis, one of hypoglycemia, and two of diabetes mellitus reported after treatment with aerosolized pentamidine. The drug can be absorbed systemically after being inhaled in aerosol form, despite typically low plasma levels. Possible predisposing conditions include previous subclinical pancreatic damage, therapy with other drugs associated with acute pancreatitis (such as trimethoprim-sulfamethoxazole and didanosine), and overdosing of pentamidine administered by aerosol as a result of difficulties with nebulizer use, conclude Martinez et al. AIDS Study Casts Doubt on Value of Hastened Drug Approval in U.S. * New York Times (04/06/93), P. C3 Altman, Lawrence K. The recent summary of a European study that revealed no benefit from early treatment with AZT in HIV infection has also raised questions about the validity of certain tests that the U.S. government has used to hasten the drug approval process. The tests are known as surrogate markers, and are designed to be quick substitutes for the standard, time-consuming approaches traditionally used in predicting the benefit of a treatment. The "Concorde" study challenged the efficacy of using the CD-4 count as a surrogate marker for AZT among asymptomatic HIV- positive people. The Food and Drug Administration relied heavily on studies that found an improvement in CD-4 counts when it licensed AZT for early treatment of HIV. It also used the same markers in approving DDI and DDC, two other anti-AIDS drugs. However, the British government rejected applications to approve DDI based on a decline in CD-4 cell counts that the United States observed. Tim Peto, an AIDS expert at Oxford University, said the primary reason it was rejected in England was widespread doubts among European experts, including himself, about the validity of CD-4 counts as a surrogate marker for the clinical benefit of an AIDS drug. Dr. David A. Kessler, Commissioner of the FDA, revealed his faith in the validity of the CD-4 count. "It is a reliable predictor," he said, adding that his agency would examine the complete data from the Concorde study when it is published in a few months. The researchers in the Concorde study said CD-4 failed as a surrogate marker because although the CD-4 count increased by 30 cells among the asymptomatic HIV-positive patients who were given AZT, the rise did not indicate any medical benefit. Major Study of People With HIV, TB is Set * Philadelphia Inquirer (04/06/93), P. A8 Dixon, Jennifer The federal government yesterday revealed that it will launch the first major American study of drug treatment approaches for people infected with tuberculosis and HIV. Nearly 650 HIV- infected people with active TB will be involved in the clinical trials. Dr. Anthony S. Fauci, director of the National Institute of Allergy and Infectious Diseases, said a substantial proportion of the subjects would probably be from New York City, where TB, particularly drug-resistant TB, is an increasing problem. In addition, the U.S. Department of Health and Human Services announced plans for a $2.1-million, five- year grant to Johns Hopkins University to examine the efficacy and appropriate use of AZT, DDI, and other anti-AIDS drugs. This move is a result of preliminary findings of the European Concorde study, which found that AZT is not effective when used in the early course of HIV infection. HHS Secretary Donna Shalala said, "While drugs have been reviewed for basic safety and effectiveness before they go on the market, these further studies should help physicians make the best treatment choices." The government will evaluate the clinical drug trials involving HIV-positive patients with TB for the benefit of adding a new drug for TB treatment, levofloxacin, to the usual four-drug therapy used in areas where TB organisms are commonly resistant to one or more anti-TB drugs. People who live in areas where drug-resistant TB is rare can also enroll in the trial and will receive the four-drug regimen without levofloxacin. Around the Nation: HIV-Infected Haitians Arrive * Washington Post (04/06/93), P. A10 A total of 16 HIV-positive Haitian refugees and four non- infected children previously held in Guantanamo Bay, Cuba, arrived in Miami, Fla., yesterday as a result of a recent federal court order. This was the first group of Haitian refugees with HIV that have been sent to the United States. Justice Department authorities determined last week that 36 HIV-infected refugees would be admitted into the country after a court order ruled that they were receiving inadequate medical care at the base. A Justice Department spokesman said 12 of the Haitians would stay in the Miami area while eight will be taken to New York. He added that refugees will arrive in Miami this week. The Haitian refugees at the Guantanamo Bay naval base were either repatriated or allowed to enter the United States to pursue political asylum claims. Those infected with HIV who remained at the base were believed to have plausible claims of asylum, but their HIV-related conditions prevented them from being admitted into the United States. Britain Announces New Guidelines for Health Workers With AIDS" * United Press International (04/05/93) (London) The British government issued new guidelines for HIV- positive health-care workers Monday, but decided against mandatory HIV testing for National Health Service employees. The new guidelines simply encourage physicians, dentists, nurses, and other health-care workers who believe they may have been exposed to HIV to seek medical advice and undergo HIV testing where appropriate. The government has called for health officials to inform every patient who may have been put at risk by a health-care worker found to have AIDS. The revised guidelines require that HIV-positive health-care workers be taken off high-risk duties, such as invasive surgery, where there may be a possibility of transmitting the disease. Dr. Kenneth Calman, the government's chief medical officer, opposes mandatory HIV tests and says that public safety will be ensured if health workers promise to voluntarily seek medical advice and undergo HIV testing where appropriate. The review of the guidelines was prompted by an influx of recent cases in which thousands of patients were tested for HIV after they learned they had been treated by HIV-positive physicians. Thai Firms Face Up to Threat of AIDS * Toronto Globe and Mail (04/05/93), P. B7 Stier, Ken The World Health Organization estimates that by the year 2000, Asia will have more new AIDS cases each year than Africa, which is currently the continent hardest hit by the AIDS epidemic. That means that more than one million Asian adults will contract HIV each year--about 40 percent of the new cases expected globally. But in Thailand, where prostitution runs rampant, businesses are working to fight the spread of HIV. Fearing the loss of millions of young and middle-aged adults in their most productive years, the Thai business community is beginning to take steps to thwart the disease's spread. Escalating health-care costs will be dwarfed only by lost income. The indirect and direct costs of AIDS are estimated to increase to about $9 billion by the end of the decade, says a study conducted by Thai researchers along with Harvard University. Every year, about 7 percent of those HIV-positive Thais will develop AIDS, and more than 500,000 Thais are expected to die before the year 2000. Chookiat Pratoetong, human resources manager for a Thai department store chain, said, "In AIDS prevention, a businessman is more useful than a hospital. A business can prevent, say, 100 deaths, which a hospital cannot do." Thai companies have been known to distribute condoms along with products or services, and one bank's automatic teller machines flash an AIDS hotline number. The government is currently spending about $48 million a year on AIDS education, while the private sector contributes a similar amount. White House Says Health Plan on Track, Changes for Insurers * Reuters (04/02/93) Frank, Jacqueline (Washington) A leading White House aide announced Friday that insurance companies will be drastically changed by health reform and claimed that the administration's proposal will be released in May. Administration officials have revealed they have no estimate yet on the cost to bring health care coverage to the nation's 37 million uninsured and to expand coverage for other Americans. But regarding costly care for those with diseases such as AIDS, the task force is opting for a requirement that all health plans pay into a national reinsurance program to absorb the risk of these expensive illnesses, said Ira Magaziner, director of the White House health care task force. ACT UP Schedules Emergency Meeting to Keep Betak Open * PR Newswire (04/02/93) AIDS advocacy group ACT-UP/Philadelphia was expected to conduct an "emergency meeting to keep Betak House open" yesterday at the offices of We the People Living With AIDS of the Delaware Valley in Philadelphia. Betak House is a nursing home for 43 AIDS patients located in the city's Mount Airy section. It was initially opened after much pressure from ACT-UP on Gov. Robert Casey's administration. Norman L. Baker, a member of ACT-UP, said, "We have invited Health Secretary Dr. Allen. S. Noonan, Welfare Secretary Karen Snider, Mayor Ed Rendell, all of the City Council members, and members of the Philadelphia delegation to the Pennsylvania General Assembly to attend this very critical meeting to once and for all settle the financial difficulties so that Betak House will stay open." He added, "It is our hope that with all the leaders of the city and state government assembled, we will solve this problem. However, based on the track record of Governor Casey and his administration on this matter, we are very dubious of the outcome. Bearing that in mind, we will take any and all actions necessary to keep Betak open." Hysteria Over Doctors With HIV * Lancet (03/20/93) Vol. 341, No. 8847, P. 764 Ellis, Simon J. HIV-related policies among health-care workers should be based on medical facts of transmission and not media-induced hysteria, writes Simon J. Ellis of Green College in Oxford, U.K. The media reaction in the United Kingdom to the discovery of health-care workers infected with HIV has been spurred by response from the Department of Health or the health officials concerned. The risk of HIV infection to patients is infinitesimal and theoretical since there have been no reported cases of surgeons infecting patients and only one case of a dentist who allegedly infected a patient. The latest commotion involved the media naming the unfortunate gynecologist and reporting his lifestyle and sexual orientation. This is a severe invasion of privacy. There is no legal basis for informing the patients treated by this person other than political expediency. Physicians are much more likely to contract HIV from patients than vice versa. In the United States, some surgical personnel may be facing a 2 percent per year risk of contracting HIV. Over a professional lifetime of 35 years, more than half such surgeons would become infected with HIV. The U.K. General Medical Council's recommendations that doctors who discover that a colleague is HIV-positive should report the result to the authorities violates patient confidentiality. Therefore, doctors' civil liberties are jeopardized, concludes Ellis. HIV Blood Test Counseling * American Medical News (03/22/93-03/29/93) Vol. 36, No. 12, (special insert) The American Medical Association (AMA) has developed its second edition of physician guidelines for HIV blood test counseling. The guidelines urge physicians to educate the public and provide patients with specific counseling on the HIV antibody blood test. The AMA says that the ELISA (enzyme-linked immunosorbent assay) is the most widely used HIV test. But for someone to be considered to be HIV-positive, results of three tests conducted on the same serum specimen must be reactive. These confirmatory tests include the Western Blot, the radioimmuno precipitation assay (RIPA), and the indirect immunofluorescence assay (IFA). The AMA states that HIV tests should be readily available for anyone requesting testing. Also, doctors should encourage voluntary HIV testing for anyone whose history or clinical status suggests risk for HIV infection. Pretest procedures include providing HIV education; providing information about the test; conducting risk assessment, including sex and drug history; and counseling about risk reduction. The pretest counseling should be conducted face-to-face and should involve the discussion of the medical, psychological, and social implications of HIV testing. Adolescents and women have special considerations regarding HIV that should be addressed, such as women's more ambiguous manifestations of HIV infection. The AMA supports routine HIV testing, which is the testing of all patients regardless of their risk. But such testing should involve consent that can be provided as part of the general consent for treatment. Every patient should subsequently be informed of his or her test results, according to the AMA. The New Faces of the Epidemic * American Nurse (03/93) Vol. 25, No. 3, P. 16 Cassetta, Robin A. The AIDS epidemic is no longer primarily concentrated among the white male homosexual population, and now the fastest growing groups of HIV-positive individuals are women, children, young adults, African-Americans, and Hispanics. Nearly every 13 minutes another American contracts HIV infection, and every 17 minutes someone dies of AIDS. About one in 800 adult females is HIV-positive, and AIDS is the sixth leading cause of death in women between the ages of 25 and 44. This high rate of HIV is partly due to the fact that many women were not aware of their partner's sexual practices or IV-drug use. In addition to improved research and health care for women, they must be educated on safer sexual practices and taught the skills needed to communicate with their partners. Many babies born from infected women will also contract the virus--about 25 percent. Moreover, nearly 100 percent of the new cases of HIV infection in children result from the virus being transmitted from an infected mother to her newborn. Children are possibly at the greatest disadvantage in getting AIDS care and education because they must depend on parents and a health-care system that often fails to meet their needs. But minorities are becoming infected with HIV at a much higher rate than any other group. African-Americans constitute 30 percent of the nation's reported AIDS cases and many have contracted the virus as a result of IV-drug use. Hispanics comprise 17 percent of the reported AIDS cases, and many contracted the virus through IV- drug use. A more widespread and aggressive anti-AIDS education campaign must be targeted at these new groups of HIV-positive people. Army to Test AIDS Drug Despite Objections * Washington Post (04/07/93), P. A1 Squires, Sally The Department of Defense yesterday confirmed that it expects to test a therapeutic AIDS vaccine made by MicroGeneSys of Meriden, Conn., even though federal health officials and top AIDS researchers objected to the trial. Yesterday marked the deadline for preventing the controversial $20- million trial of the vaccine from being conducted. The vaccine, gp160, is a substance made from part of the outer coating of HIV. The Defense Department has a large system of medical facilities, and plays a key role in AIDS drug research, including trials on civilians. However, the choice of which drugs to test is traditionally made by researchers at the National Institutes of Health (NIH). But in the case of gp160, Congress bypassed NIH last fall and approved both the vaccine and the funding level to be used in the trial. The trial was subsequently mandated by an amendment to the defense appropriations bill passed last fall. The amendment stated that the trial should proceed unless the NIH director, the commissioner of the Food and Drug Administration, and the secretary of defense unanimously decide not to allow it within six months of the bill's passage. Last Thursday letters were sent to Defense Secretary Les Aspin and House Appropriations Committee Chairman William H. Natcher (D- Ky.) from NIH Director Bernadine P. Healy and FDA Commissioner David A. Kessler, who recommended that the trial be conducted only if it involved testing of other therapeutic vaccines now under development. However, Army spokeswoman Sgt. Dawn Kilpatrick said yesterday that regardless of the recommendations, "the Army has decided to test only the gp160 [MicroGeneSys] vaccine." A Setback, But the Search Goes On * Financial Times (04/07/93), P. 14 Cookson, Clive Even though the recent findings from a European study claim that AZT is not effective when used early in HIV infection, research for other AIDS treatments probably will not be affected, writes columnist Clive Cookson. About 12 million people worldwide are estimated to be HIV-positive, and indirect costs of the disease are about $90 billion a year; therefore, government health agencies and the pharmaceutical industry say their research will not be thwarted. AIDS researchers have two monumental problems when it comes to the disease. First, HIV mutates more quickly than any other microbe known; there are countless different strains, and within each patient the virus changes character as the disease develops. Consequently, drug- resistant forms can emerge very quickly. The second dilemma is that although the chemistry of the virus is well understood, researchers are still confused by the extremely complex process through which HIV infects human cells and then, several years later, destroys the immune system. Some researchers even believe that nucleoside analogs like AZT, DDI, and DDC are entirely ineffective. Dr. Alan Kingsman of Oxford University said that a modest suppression of HIV might have no clinical benefit if the virus is not killing cells directly but inciting a process of cell suicide. Other AIDS researchers feel AZT can be effective when used with other drugs. In the United States, the Clinton administration is leading the fight against AIDS by establishing an Office of AIDS research with a $1 billion budget. With such a strong commitment, researchers should eventually translate the scientific understanding of HIV into more effective treatments than AZT, concludes Cookson. Laser Blood Test * Associated Press (04/05/93) (Little Rock, Ark) Because taking a blood sample can be quite risky, Russian and American researchers say they have devised a way to take a sample by substituting a laser beam for the sharp steel lancets. Charles Vestal, chairman of Venisect Inc. of Little Rock, Ark., said, "We're going to change the whole industry." The company refined a device that was once a Soviet military secret. Although lasers are currently used in surgery, the new technique allows a laser to make a minuscule opening--up to 0.5 millimeters in diameter and 0.5 millimeters deep. The hole is large enough to permit the collection of a small blood sample, and it heals exactly like other tiny punctures. The researchers claim the laser, which would not touch blood, may help allay fears about spreading disease through needles and other sharp objects. Dr. Milton Waner, clinical director of the University of Arkansas for Medical Sciences Biomedical Research Laboratory, said that if a patient is infected with a blood-borne disease like HIV, "the contaminated lancet or needle poses a serious threat to others who come in contact with it." But the laser is much safer and cheaper than steel lancets. The laser was first invented in the late 1970s by scientists at the General Physics Institute of the Russian Academy of Sciences. Last year, Vestal discovered that the technique was available for commercial development in the West. Trinity Biotech Announces Multiyear Distribution Agreement for Mexico and $4.5 Million Confirmed Order for Its AIDS test * Business Wire (04/06/93) (Dublin, Ireland) Trinity Biotech PLC, an Ireland-based diagnostics company devoted to the development of rapid on-site saliva tests for HIV, has signed a five-year distribution contract with Panamerican Enterprises S.A. de C.V. for Mexico and Central America, which will receive Trinity's rapid HIV test kits. The contract involves tests using blood or saliva as the test specimen. Clayton M. Hardman, president of Panamerican, said, "We're pleased with the association with Trinity Biotech and we feel there's a great deal of demand for Trinity's rapid HIV blood test and saliva technology." The first order specifies the Trinity test using whole blood from a finger prick as the sample. As clinical trials are completed, the contract specifies subsequent conversion to the saliva specimens. The Trinity test provides results in about seven minutes and requires no laboratory equipment or sample preparation. Trinity Vice Chairman Michael C. Hubbard said, "While Trinity is finalizing development and conducting clinical trials on its rapid, saliva-based series of tests, its current HIV blood test is generating an important stream of revenue." VitaMed Completes Reverse Takeover and Initial Financing; 'Growth Blocker' Technology Aimed at AIDS-Related Lymphoma * PR Newswire (04/06/93) (Seattle) VitaMed, a biotechnology company based in Seattle, Wash., yesterday revealed the completion of a share exchange contract and reverse takeover with Fist Ivana Technologies Ltd., a federal Canadian corporation. Charles Morgan, president and chief technical officer of VitaMed, said the funds will help support research and development of proprietary "growth blocker" drugs--a new class of non-immunosuppressive biological treatments for cancer and other life-threatening diseases identified by uncontrolled cell proliferation. "With feasibility of the therapeutic concept already demonstrated and its first growth-blocker patent filed, VitaMed can now accelerate development of its first generation of biological growth blockers that may lack the toxicity and immunosuppressive properties of chemotherapy," said Morgan, a world-renowned cancer researcher and company co-founder. The research will be designed to create growth blockers in the form of monoclonal antibodies or synthetic small molecules. The new treatments are being developed to block cell-surface receptors responsible for vitamin B12 uptake. Research has demonstrated that tumor cells die when deprived of vitamin B12, but normal cells remain alive and may be "rescued" by supplying vitamin B12. Because growth blockers lack the adverse effects of chemotherapy, they would be ideally suited for the treatment of cancers in AIDS patients and others with depressed immune systems. VitaMed's initial disease target will be treating AIDS-related lymphoma (ARL), a rapidly spreading and highly malignant cancer in AIDS patients that is expected to be the most prevalent cancer within the next ten years. Actors in Oscar Controversy Have Their Say * Reuters (04/05/93) Los Angeles--Actors Susan Sarandon and Tim Robbins, who were criticized by the Academy Awards show producer for veering from their script when presenting an award to make a plea for HIV- positive Haitian refugees in Cuba, said Monday that their actions were not inappropriate. Sarandon and Robbins wrote a letter to the Los Angeles Times and defended their protest at last Monday's televised ceremony, claiming, "Was what we did inappropriate? We think that silence in the face of cruelty is inappropriate." The ceremony's producer, Gil Cates, said last Wednesday that he would not invite Robbins and Sarandon, as well as presenter Richard Gere, who addressed Chinese oppression in Tibet, to future Oscar ceremonies for which he was responsible. In their letter, Robbins and Sarandon argued against the detainment of 266 Haitian refugees who, because they are HIV-positive, have been denied admittance into the United States. The actors said the refugees are being held at the U.S. Naval Base at Guantanamo Bay, Cuba, where they are "held behind barbed wire, with inadequate toilet facilities and no sanitation." Robbins and Sarandon said they had been attempting to emphasize the plight of the refugees for months by holding press conferences and protesting the Clinton administration's lack of action by getting arrested for civil disobedience. AIDS in Germany Stabilized--Health Department Official * Reuters (04/05/93) (Bonn, Germany) The number of HIV-positive people residing in Germany has stabilized at between 2,000 and 2,500 new infections annually, according to a senior health department official. Meinrad Koch, leader of the Berlin health office, told German radio the number of people who have developed full- blown AIDS has risen in Germany from 9,000 to 9,690 since 1992. "It appears to have stabilized. We can only estimate the number infected with HIV, but it won't have increased dramatically," said Koch. He added that homosexual men account for 60 to 70 percent of known AIDS cases, whereas drug addicts constitute 15 percent. Approximately 7 percent of those with HIV had been infected through heterosexual sex. "Experts made a huge error--we predicted (in the 1980s) completely different figures. Luckily this never happened. No doubt the prevention campaign helped," he said, referring to a government-sponsored advertising effort promoting the use of condoms as a means to prevent HIV infection. Koch said he was skeptical about whether a vaccine for the disease would be discovered in the near future. "I think it is totally unrealistic--I belong to the not so small group of scientists which is very skeptical whether it will ever be possible to develop a serum," he said. Where the AIDS Virus Hides Away * Nature (03/25/93) Vol. 362, No. 6418, P. 287 Maddox, John Because of the new findings that HIV replicates in the lymph nodes while in the so-called latent period, Professor Peter Duesberg of the University of California--Berkeley may want to change his position, writes John Maddox of Nature. Duesberg has held that drug taking is responsible for AIDS, and not HIV. Most viruses are DNA viruses, which ordinarily replicate within cells by hijacking the preexisting machinery of DNA transcription and translation. But the genomes of retroviruses, like HIV, by contrast, consist of RNA. Those of the lentiviruses, of which HIV is one, come equipped with a gene specifying a reverse transcriptase (for converting RNA into the complementary DNA). While the RNA genome may be used, as if it were one of the infected cell's own messenger molecules, to generate the proteins that would allow an intact virus particle to be regenerated, by far the more efficient means of replication is that DNA complementary to the viral RNA should be incorporated in the genome of the cell, where it will serve as a template for the production of its own genomic RNA and thus for intact viral particles. Duesberg claims that it is difficult to recover helper T lymphocytes, whose attrition for many patients indicates the onset of overt AIDS, virus particles that might plausibly infect others. The new findings show that the virus is alive and well in the lymph nodes, among other locations, of those infected with HIV. The recent revelations suggest that, nevertheless, the alternatives for AIDS patients are even less justifiable than seemed likely a few years ago. Duesberg should now admit the possibility that he has been mistaken, concludes Maddox. Where Has HIV Been Hiding? * Nature (03/25/93) Vol. 362, No. 6418, P. 292 Temin, Howard M. and Bolognesi, Dani P. The two new studies published in Nature which found that HIV replicates in the lymph nodes while in the asymptomatic period stress that HIV infection is a very complicated process and that it will require the perseverance of science to gain sufficient knowledge to control the virus, write Howard M. Temin and Dani P. Bolognesi of the University of Wisconsin-- Madison and Duke University Medical Center in Durham, North Carolina, respectively. The study conducted by Pantaleo et al. used polymerase chain reaction (PCR) to show that in asymptomatic HIV-infected patients there are many infected cells in the lymph nodes. Embretson et al. complete their earlier work combining PCR and in situ hybridization with autoradiography to demonstrate that a high fraction of cells, about a quarter, in germinal centers of lymph nodes are infected, and that these cells tend not to be expressing viral RNA. The issue of the percentage of latently infected cells notwithstanding, it can be concluded from the reports that secondary lymphoid organs are solidly infected with HIV. Both reports also point out that virus particles are carried probably passively by follicular dendritic cells but in a form that is likely to be infectious for other HIV target cells, especially T-cells, that circulate through these organs. In addition, these reports suggest that a more centralized AIDS research effort should examine cohorts of HIV-positive persons and carefully quantify, in different tissues at different times after infection, cells containing infectious provirus, cells containing defective provirus, cells containing early viral RNA, cells containing late viral RNA, and the load of free virus, conclude Temin and Bolognesi. MicroGeneSys Withdraws From Trial * Science (03/26/93) Vol. 259, No. 5103, P. 1821 Cohen, Jon Pharmaceutical company MicroGeneSys has withdrawn its therapeutic AIDS vaccine from a federally-sponsored trial, a move which has spurred criticism about the company from other AIDS researchers. Although the company would not directly respond to the accusations, its corporate partner, Wyeth-Ayerst Research, said in a letter to the organizers of the planned trial that the protocol "does not address any specific issues directly relevant to the Clinical Plan for VaxSyn [its AIDS vaccine] development and licensure." In addition, it cited "scientific considerations" as reasons for dropping out of the trial, including the timing of vaccine shots in the trial and the trial's clinical endpoints. But some AIDS researchers believe MicroGeneSys is not telling the whole story. The trial that the company pulled VaxSyn from was one that would have compared it with vaccines made by two other companies: Chiron and Genentech. The comparative trial was being planned by the National Institute of Allergy and Infectious Diseases (NIAID) to determine which vaccine is most effective. Robert Schooley, the principal investigator of the NIAID-sponsored trial, said that two events have transpired that may have caused MicroGeneSys to abandon the trial. Last fall, the company convinced Congress to allot $20 million to be used in large- scale tests of VaxSyn. Also, the company announced last month that Swedish researchers are conducting a VaxSyn trial in 1,000 HIV-positive people, which the company hopes will reveal the vaccine's clinical efficacy as early as 1995. Due to these revelations, Schooley said MicroGeneSys has "very little to gain by comparing their vaccine to the others." Wellcome's Defense Fails to Dispel Doubts About AZT * Journal of Commerce (04/08/93), P. 7A The manufacturer of AZT defended the drug Wednesday with data indicating that early use in HIV infection could enhance the chances of survival. However, Burroughs Wellcome's effort only incited controversy. Wellcome's investors, unimpressed with the company's contentions, dropped shares again as a result of fears of another round of negative publicity for the drug. Peter Cartwright, pharmaceutical analyst at stockbroker William de Broe, said, "They didn't come up with anything very new, nor did they put on a knock-out defense of their position. They handled it very badly." These incidents follow the "Concorde" study, published in The Lancet last week, which indicates that AZT has no significant effect on the development of AIDS. Paul Fiddian, Wellcome's clinical virology head, claimed that a full analysis of the Concorde study conducted in Europe would demonstrate that early treatment with AZT could improve survival rates in AIDS patients. However, industry experts said Wellcome's argument surrounds its on-going belief that the level of CD4 cells is a conclusive marker in the progression of the disease. Preliminary results of the study showed patients taking AZT before full-blown AIDS had more CD4 cells, but it found no proof that they lived longer. Concorde researchers said their discoveries raise questions on the validity of CD4 cell counts to measure benefits of AIDS treatments. Professor Richard Peto of the Clinical Trial Service Unit in Oxford said it would probably take several more years and more extensive trials to reach final conclusions about the net effects of early use of AZT. Related Story: Investor's Business Daily (04/08) P. 3 Woman With AIDS Virus Assails Accused in Court * Toronto Globe and Mail (04/07/93), P. A6 An HIV-positive woman who claims she contracted the virus from a former storekeeper testified in court in London, Ontario, on Tuesday, claiming that being infected has "irreversibly" made her life a tragedy. The woman said, "I'm 25 years old, and this should be the prime of my life, and what do I have to face? Death." The accused is Charles Ssenyonga, a 35-year-old who came to Canada from Uganda in 1983. He is believed to have infected three women with HIV. Previously in the proceedings, Ssenyonga pleaded not guilty to three counts each of aggravated assault and criminal negligence causing bodily harm. Crown attorney Bruce Long said he hopes to show that Ssenyonga had deliberately transmitted HIV to his sexual partners. Long said, "They trusted him and, in some cases, they were in awe of him." Unforeseen Cost of AIDS Care * Washington Times (04/08/93), P. B1 Barras, Jonetta Rose One Washington, D.C.-area woman lost her job because of a conflict with an AIDS peer counseling workshop. Jackie Mitchell decided to adopt an HIV-positive child, unaware that caring for the 9-year-old she would cause the loss of her job. Mitchell was fired last week as a counselor at the Greater Washington Boys and Girls Club after she continued to attend the workshop, against her employer's objections. Archie Avedisian, the club's executive vice president, who confirmed Mitchell's firing, said, "The bottom line is, her supervisor told her she cannot go and she went. That's insubordination." However, what appears as insubordination to some is the story of a woman's effort to help children affected by HIV. Last year, Mitchell took the HIV-positive child into her home, after the child's mother died of AIDS. While Mitchell knew some things about HIV, she said she didn't know enough. Therefore, she began her search for education on the topic. She found the Inner City AIDS Network (ICAN), which conducts 10-week workshops in peer counseling for persons with the virus. Mitchell said the workshop provided her with an opportunity not just to improve care for her own child, but also to help similarly affected children she met on the job. But five weeks ago, her boss fired her. Although she worked Tuesdays through Saturday and the workshop was held for only three hours every Tuesday, supervisor Edwin Washington refused to work out an agreement. Avedisian said that the club allows employees to attend only those sessions approved by a supervisor. He said the sessions cannot interfere when the employee may be needed at work. In this case, Mitchell's supervisor felt he needed her during the hours of the workshop. WHO Warns of AIDS Catastrophe in Eastern Europe * Reuters (04/07/93) (Berlin) A leading World Health Organization authority told a news conference Wednesday that eastern Europe may experience an influx of AIDS cases because of rampant prostitution and drug use. "All the factors that have fueled this epidemic in Africa and South East Asia are now in central and eastern Europe," said Michael Merson, director of the WHO's AIDS program. He added, "I am very worried about central and eastern Europe. They must act now to avoid catastrophe." Merson indicated that Berlin was selected to host the five-day International AIDS Conference in June to express the impending crisis to those countries. "We do not have a cure for AIDS or a vaccine. But we know everything we need to know to prevent the disease and slow down the epidemic. It is important that we get this message across," said Merson. Since 1990 when the Berlin wall was torn down, prostitution and drug abuse have escalated. Merson said, "The situation is very ripe there." Cameroon--AIDS * Associated Press (04/07/93) (Korup, Cameroon) A chemical that inhibits the reproduction of HIV in the test tube has been found in the rain forests of Camaroon, according to researchers. Duncan Thomas, the British botanist who discovered the vine containing the promising chemical in Cameroon's remote Korup National Park, said, "Our hope is that it [the research] will go straight through to an AIDS cure." However, all researchers involved are aware that any cure or treatment derived from the chemical would be years away. An alkaloid called Michellamine B was yielded from the leaves of the vine through laboratory tests at the National Cancer Institute in Frederick, Md. The NCI researchers claim Michellamine B blocks replication of HIV. Gordon Cragg, chief of the U.S. National Cancer Institute's natural products branch, said limited testing is being conducted on mice and dogs. The vine, tentatively named ancistrocladus korupensis after the park where it was discovered, is one of the NCI's best leads from a comprehensive plant collecting program. Since 1986, only two other plants, from Samoa and Sarawak in Malaysia, have shown some activity against HIV. Cragg said both are in earlier stages of research than korupensis. But what alarms the researchers is where to get the vine, because they still do not know how much of the vine exists, over how big of an area it grows, or how best to cultivate it. The vine has only been found in a small area of the 740,000-acre rain forest, located on Cameroon's northern border with Nigeria. Thomas first found the vine in 1987 and gave it to the NCI; it was during one of the routine tests in late 1990 that scientists discovered Michellamine B and its effect on HIV. Gov. Casey Pledges Assistance to Keep AIDS Hospice Open * PR Newswire (04/06/93) (Harrisburg, PA) On Tuesday, Pennsylvania Gov. Robert P. Casey ordered the state departments of Health and Public Welfare to provide technical assistance and, if necessary, additional funding to the Betak AIDS hospice in Philadelphia to assist it in staying open after June 1. Casey said, "I'm committed to ensuring that people with AIDS have access to desperately needed nursing services. I will do everything within my power to make sure that the Betak facility remains open." In -----===[[[ A I D S w i r e D I G E S T 04.05.93 ]]]===----- .