Many institutions conducting AIDS clinical trials have been unable to find and keep study participants. A study of 28 institutions participating in U.S. government-sponsored clinical trials showed that 18 of the sites (64 percent) failed to meet their patient accrual goals.
One of the nations leading AIDS caretakers is gone. Recognized as an outstanding physician during his life, John Carey of Case Western Reserve University, Cleveland, Ohio, posthumously received the Young Investigator Award of the AIDS Clinical Trials Group.
Can the main clinical trials group in the U.S. shed its image as a dinosaur too large and slow-moving to respond to new developments in AIDS therapies? According to the chair of the group's Adult Executive Committee - University of Colorado researcher Robert "Chip" Schooley - recent reorganization has accomplished this objective.
What some call the new wave in passive immunity - human monoclonal antibodies (MAbs) - will be tested for their ability to protect children born to women with HIV infection. Unlike natural polyclonal antibodies produced by humans or animals inoculated with antigens, MAbs are tailored to recognize only highly specific epitopes.
The Chiron/Biocine SF-2 recombinant gp120 vaccine appears more immunogenic than the Genentech MN recombinant gp120 vaccine in infants born to women with HIV infection. The SF-2 rgp120 vaccine was most effective at the lowest dose tested in a clinical trial comparing the HIV envelope-based vaccines developed separately by Chiron/Biocine and by Genentech.
Tantalizing evidence suggests that giving an experimental HIV vaccine to pregnant women might help their children fight off HIV infection. The evidence, from an ongoing Phase I clinical trial, is extremely preliminary. Indeed, the study was designed to explore vaccine safety and immunogenicity and cannot prove efficacy.
Researchers suggested recently that congenital HIV infection may be uniquely suited to a genetic engineering based therapy. The birth of a child provides the once in a lifetime opportunity to collect autologous cord blood. If the child is born to an HIV infected mother, and is a victim of congenital transmission of this disease, a unique opportunity presents itself to treat the child with a protocol being developed by researchers.
A live attenuated AIDS vaccine is a recipe for disaster, a Harvard researcher warns. Hopes for a live AIDS vaccine were recently bolstered by the discovery of a cluster of Australian blood recipients who remain healthy up to 14 years after infection with the same defective strain of HIV.
Disseminated infection with Mycobacterium avium complex (MAC) remains a major threat to people with AIDS, but aggressive state-of-the-art treatment and prevention are reducing MAC-associated morbidity and mortality. The U.S. Centers for Disease Control and Prevention (CDC) recently published guidelines for MAC prophylaxis established by the U.S. Public Health Service (USPHS) and the Infectious Disease Society of America (IDSA).
French researchers are currently exploring three gene therapy modalities for treating HIV infection. As HIV predominantly infects cells of the hematopoietic system, stem cells are good potential targets for the introduction of foreign anti-HIV genes.
A retroviral vector encoding env/rev could potentially augment cytotoxic T lymphocytes in HIV infected patients. Numerous strategies have been developed to try to diminish the impact of HIV infection on the host's immune system. With the recent development of retroviral vectors containing HIV genes, intracellular immunization has become a feasible approach to stimulate HIV specific cytotoxic T lymphocytes (CTLs).
As HIV predominantly infects cells of the hematopoietic system, stem cells are good potential targets for the introduction of foreign anti-HIV genes. Ex vivo transduction, and then reimplantation of the genetically modified stem cells into HIV infected patients could allow the repopulation of the host with mature CD4(+) cell populations expressing novel molecules that interfere with viral replication and slow progression into AIDS.
A retroviral vector encoding env/rev could potentially augment cytotoxic T lymphocytes in HIV infected patients. Numerous strategies have been developed to try to diminish the impact of HIV infection on the host's immune system. With the recent development of retroviral vectors containing HIV genes, intracellular immunization has become a feasible approach to stimulate HIV specific cytotoxic T lymphocytes (CTLs).
The unique advantages of nucleic acid vaccines will make it possible to vaccinate more people against more diseases than would ever be possible with traditional vaccines. According to researcher Heather L. Davis of the Loeb Medical Research Institute, Ottawa, Ontario, Canada, nucleic acid vaccine technology will not only overcome many of the problems associated with current vaccine approaches, but will also be relatively inexpensive to produce.
There will soon be vaccines able to prevent - or even cure - many diseases that have plagued mankind for centuries, an expert vaccinologist predicted. Recent technological breakthroughs have revolutionized the field of vaccinology, said Stanley Plotkin, a research scientist at the venerable laboratories of Pasteur Merieux, Marnes-la-Coquette, France.
Derivatives of a type of plant compound with medicinal properties have anti-HIV-1 properties. The new drugs inhibit HIV-1 but not HIV-2 reverse transcriptase and are therefore new members of the class of compounds known as non-nucleoside reverse transcriptase inhibitors (NNRTIs), report researchers Toshiaki Fujihashi of Jefferson Medical College, Philadelphia, Pennsylvania, and colleagues.
Japanese researchers have identified a new family of non-nucleoside reverse transcriptase inhibitors (NNRTIs). Like other NNRTIs, the new compounds inhibit HIV-1 but not HIV-2 reverse transcriptase. The most potent of the compounds has a selectivity index (ratio of 50 percent effective to 50 percent toxic concentrations) of 2,280, reported Katsushi Ijichi of Rational Drug Design Laboratories, Fukushima, Japan, and colleagues.
AIDS clinical trials will fail if they do not take into account the dynamic interactions between experimental drugs, HIV, and virus-infected cells in individual patients, a pharmacologist warned. Confusion about how best to use currently approved anti-HIV drugs is a direct result of a focus on the dosage, rather than the dynamics, of experimental drugs, early in the clinical trial process, according to Michael N. Dudley of Roger Williams Medical Center, Providence, Rhode Island.
Intermittent infusions of the cytokine interleukin 2 (IL-2) increase CD4 counts to normal levels in patients with HIV infection who have CD4 counts of more than 200 cells/(micro)L. These findings, based on a study that enrolled 60 volunteers, confirm earlier reports that 13 years of studying IL-2 have at last borne fruit (see AIDS Weekly, March 13, 1995).
Anti-HIV drugs cannot eliminate the virus, but well chosen combinations could force it to become less deadly. People infected with HIV-1 don't harbor just one virus. Because of HIV's vast replicative capacity and its inherent tendency to mutate, HIV infection is characterized by the presence of a swarm of genetic variants that researchers call quasispecies.
As researchers begin to unravel the complex web of interactions between HIV and the immune system, they hope to develop new strategies for delaying - or even preventing - the onset of AIDS. University of Colorado AIDS researcher Robert T. "Chip" Schooley noted that early laboratory studies of HIV gave an incomplete model of how the virus acts to cause AIDS.
Saquinavir - one of the long-awaited protease inhibitors - only marginally improves standard combination anti-HIV therapy. But the first major clinical trial to test one of the new protease inhibitors with two currently approved anti-HIV drugs validates the concept of simultaneously attacking the virus at different target areas.
In a finding that has implications for all gene therapies, data from an AIDS clinical trial show that normal immune responses may eradicate genetically modified cells. In the trial, patients' own CD8(+) cytotoxic lymphocytes (CTLs) are genetically altered so that the express - and are thereby sensitized to - HIV proteins.
A new study suggests that AIDS survival can be prolonged by the aggressive use of currently available drugs. The findings are based on a retrospective study of survival trends, not on clinical trials designed to provide proof of drug efficacy. But the data, from the Adult/Adolescent Spectrum of Disease Project conducted by the U.S. Centers for Disease Control and Prevention (CDC), provide tantalizing insights into factors associated with AIDS survival.
An antisense molecule targeted against HIV failed to show signs of efficacy in an early clinical trial. Although the trial was not designed to test the efficacy of the drug, the lack of evidence of antiviral effect was discouraging. The drug, code named GEM 91, is the first antisense oligodeoxynucleoside (ODN) to reach clinical trials. The drug is manufactured by Hybridon Inc., Worcester, Massachusetts.
One of the great difficulties facing people with AIDS is the enormous number of antimicrobial drugs they have to take every day. The toxicity, expense, and inconvenience of this shotgun approach to preventing life-threatening opportunistic infections (OIs) could be reduced by more rational prophylaxis strategies, an infectious disease expert suggests.
The novel herpesvirus associated with Kaposi's sarcoma (KS) can be detected in the nuclei of the cells associated with the tumor. In 1994, Columbia University researchers Yuan Chang and colleagues reported finding DNA from a new herpesvirus in KS tumors from both AIDS and non-AIDS KS patients (Science, 1994;266:1885-9).
The powerful anti-HIV effects of the Merck protease inhibitor indinavir sulfate are sustained when it is administered in combination with zidovudine (AZT). Indinavir sulfate (MK-639, formerly L-735,524 or L-524, trade name Crixivan), is one of several members of this new class of anti-HIV agents in the advanced stages of clinical development.
The promising new HIV protease inhibitor AG1343 is effective and well tolerated at all doses studied in Phase II clinical trials. The drug, developed by Agouron Pharmaceuticals and Japan Tobacco Inc. under the trade name Viracept, has been the subject of intense interest since the 1994 2nd National Conference on Human Retroviruses.
Both HIV-1 and HIV-2 jumped the species barrier from monkeys to humans - and it could happen again. These monkey-to-human transmissions of what would become the AIDS viruses occurred not once but at least twice in the case of HIV-1 and at least several times in the case of HIV-2.
No matter how effective an anti-HIV drug may be, it can never prevent the appearance of drug-resistant mutants - because such mutants already exist. According to retrovirologist John Coffin of Tufts University School of Medicine, Boston, Massachusetts, the enormous number of HIV virions produced during infection guarantees a highly diverse and evolutionarily robust population.
AIDS is the result of extensive HIV replication and is not caused by antigenic exhaustion or self-destruction of the immune system, clinical data suggest. The loss of CD4(+) T lymphocytes that characterizes AIDS is a phenomenon that researchers have struggled to explain since the dawn of the AIDS epidemic.
The raging fire of HIV infection burns up a person's CD4(+) T cells and causes AIDS, according to David D. Ho, director of New York's Aaron Diamond AIDS Research Center. As a consequence, Ho strongly favors very early antiretroviral therapy - using a combination of agents - for people with HIV infection.
Very high doses of the HIV protease inhibitor saquinavir (manufactured by Hoffmann-La Roche, Nutley, New Jersey) have a profound antiviral effect in people with intermediate-stage HIV disease. Saquinavir, also known as Ro 31-8959 or Invirase, was the first of the new class of anti-HIV drugs known as protease inhibitors to reach advanced clinical trials.
The HIV protease inhibitor ritonavir (ABT-538) nearly obliterated HIV in some patients who took the drug in combination with two standard AIDS therapies. Moreover, animal studies show that ritonavir in combination with another protease inhibitor, saquinavir, overcomes pharmacologic barriers to that drug and packs an intense one-two punch against HIV.
The newly-released results of a major AIDS clinical trial support changing the first-line therapy for people with HIV infection. Instead of monotherapy with zidovudine (AZT), the study shows that patients benefit more from combination therapy with AZT and either didanosine (ddI) or zalcitabine (ddC).
The drug discovery program at the U.S. National Cancer Institute has found a new class of distamycin analogs that potently inhibit a wide array of HIV isolates. The most active of the compounds acts against strains of both HIV-1 and HIV-2, including a clinical isolate, an AZT-resistant isolate, and an isolate that preferentially infects monocytes rather than T lymphocytes.
Two compounds isolated from a common Chinese medicinal herb selectively inhibit HIV-1 reverse transcriptase. The herb, Phyllanthus myrtifolius Moon, is a member of the Euphorbiaceae family grown in southern China and widely used as a component of traditional Chinese medicine.
The AIDS clinical trial behemoth moves at a glacial pace that is far too slow for people who now have symptomatic HIV disease or AIDS. Efficacy trials for experimental AIDS therapies currently determine whether the proposed treatment either improves survival or delays the appearance of AIDS-defining opportunistic infections.
A monkey virus engineered to carry HIV-1 reverse transcriptase (RT) provides a much-needed animal model for testing anti-HIV drugs. Current primate models for HIV infection use simian immunodeficiency virus (SIV) or a chimeric SIV/HIV strain carrying the HIV envelope glycoprotein.
NCI researchers say they have solved the riddle of why the cancer drug hydroxyurea enhances some anti-HIV drugs more than others. Several teams of researchers have found that hydroxyurea increases the potency of antiretroviral nucleoside analogs (Lori et al., Science, 1994;266:801-5; Malley et al., PNAS, 1994;91:11017-21; and Gao et al., Mol Pharmacol, 1994;46:767-72).
A dramatic increase in CD4 counts and a drop in HIV burden occurred in subjects who received combination therapy with didanosine (ddI) and hydroxyurea in a small French clinical trial. All of the 12 asymptomatic, HIV(+) trial participants had a substantial reduction in the amount of virus in their peripheral blood as measured by a highly sensitive quantitative RNA PCR assay . . . .
More than a decade into the AIDS epidemic, most physicians are still unable to provide adequate primary care to patients with HIV infection. AIDS is the leading cause of death among U.S. men aged 15 to 44 years and the fourth leading cause of death among 15-to-44-year-old women, noted researchers J. Randall Curtis, Paul G. Ramsey, and colleagues of the University of Washington
Monkey experiments bolster hopes that a naked DNA HIV vaccine might one day give people with HIV infection the upper hand in their battle with HIV. The vaccine is being developed by a research team led by David B. Weiner of the University of Pennsylvania, Philadelphia, in collaboration with Apollon Inc., Malvern, Pennsylvania.
The ugly secret about AIDS in America is that the epidemic is spreading most quickly in racial and ethnic populations victimized by the U.S. healthcare system. A recent study by the U.S. Centers for Disease Control and Prevention (see AIDS Weekly, September 9, 1995) found that racial and ethnic disparities in HIV prevalence are becoming greater among both heterosexuals and homosexuals.
HIV's lack of a gene present in feline immunodeficiency virus (FIV) may be the key to the its extraordinary ability to generate mutations that confound the immune system and give rise to drug-resistant viral strains. Both HIV and FIV are members of the lentivirus family. These viruses share numerous properties; however, the primate lentiviruses differ from those that infect other mammals in that they produce three and not four enzymes.
An Australian research team has put a powerful new tool into the hands of researchers developing gene therapies and DNA vaccines for AIDS. The new tool provides a rapid means of growing cultures of gene-transfected primary human peripheral blood lymphocytes (PBLs).
The face of the U.S. HIV epidemic is becoming increasingly African American. Analysis of anonymous blood samples from people attending sexually transmitted disease (STD) clinics shows that while HIV prevalence has decreased among white men and women - including white homosexual men - it has remained stable among black Americans.
HIV-1 that develops resistance to one protease inhibitor may be cross-resistant to other protease inhibitors, new studies show. The studies offer hope, however, that combination therapy with two protease inhibitors can significantly delay the emergence of resistant mutants. Currently approved anti-HIV drugs attack the viral reverse transcriptase enzyme.
The new antiretroviral drug lamivudine (3TC) restores zidovudine (AZT) sensitivity to AZT-resistant HIV mutants. A major problem with AZT therapy is that drug-resistant strains of HIV appear within six to 12 months of treatment. The virus develops resistance to 3TC even more quickly.
In a deadly game of tag, HIV infected cells cause uninfected CD4(+) T cells to self-destruct. One of the great unanswered questions about AIDS pathogenesis is how HIV can cause the elimination all CD4(+) T lymphocytes when 1) the virus infects only a minority of these cells at any given time and 2) CD4(+) T cells are constantly being replenished.
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