|
STANDARDS OF CARE
|
Methods: We studied 403 adult male patients enrolled in a staff-model health maintenance organisation in whom first AIDS-defining illnesses were diagnosed from 1984 through mid-1994; we determined that these illnesses met the 1987 case definition of the Centers for Disease Control. We defined three levels of experience for the patients 125 primary care physicians according to their experience with AIDS during residency training and the cumulative number of patients with AIDS they had cared for in their practices.
Results: The median survival of the patients of physicians with the least experience in the management of AIDS was 14 months, as compared with 26 months for the patients of physicians with the most experience (P<0.001). Controlling for the severity of illness and the year of diagnosis, we found that the patients cared for by physicians with the most experience had a 31 percent lower risk of death than the patients cared for by physicians with the least experience (P<0.02). Among 244 patients with an AIDS-defining illness diagnosed from 1989 through 1994, after adjustment for the CD4+ cell count and the severity of illness, the risk of death was 43 percent lower for patients of the most experienced physicians than for patients of the least experienced (P<0.02).
Conclusions: The experience of primary care physicians in the management of AIDS is
significantly associated with survival among their patients.
(N Engl J Med 1996;334:701-706)
Mari M. Kitahata et al, University of Washington, Center for AIDS and STD, 1001 Broadway,
Suite 215, Seattle, WA 98122.
|
ANTIRETROVIRALS
|
Abbott Laboratories has received approval
for marketing itsHIV protease inhibitor Norvir in Europe. The drug was cleared for use in HIV-infected
adults with advanced or progressive disease, in combination with antiretroviral nucleoside analogues. Final authorisation is
awaiting approval by the European Commission in Brussels.
Source: Reuters (05/28/96)
******SEE TREATMENT ALERT AT END OF DOCUMENT****** |
Agouron Pharmaceuticals, Inc., (Nasdaq-NNM: AGPH) today provided updated information concerning the anti-viral activity of its anti-HIV drug VIRACEPTô (nelfinavir mesylate, formerly AG1343) from two pilot Phase II trials. The report on VIRACEPT, an inhibitor of the HIV protease enzyme, was presented today at the Ninth International Conference on Antiviral Research in Fukushima, Japan.
Agouron senior medical research scientist Joanna Peterkin, M.D., reported results from a 60-day study of 36 HIV-infected patients who received one of three doses of VIRACEPT in combination with the approved drug ZERIT (stavudine or d4T) or ZERIT alone. In subjects receiving standard doses of ZERIT plus 500mg, 750mg or 1000mg VIRACEPT three times daily, mean reductions in HIV were greater than 98% in each dose group, while HIV was reduced by a mean of 82% in patients receiving ZERIT alone. During the 60-day study, mean CD4+ T cell counts increased by 105 to 130 cells per ml in the blood of patients receiving the three doses of VIRACEPT plus ZERIT, and by 72 CD4+ T cells in those receiving ZERIT monotherapy.
Dr. Peterkin also reported updated results from an earlier phase II study of VIRACEPT administered as monotherapy to 30 HIV-infected individuals. After an initial four-week period of treatment, patients receiving either 500mg, 750mg or 1000mg VIRACEPT three times daily experienced mean reductions in HIV between 95% and 99%, while mean CD4+ T cell counts increased by 35 to 100 cells. In more than 20 patients who continued to receive treatment for a total of 16 weeks, mean reductions in HIV were between 81% and 99% for the three dose groups; and mean CD4+ T cells increased from pre-treatment levels by 115 to 170 cells.
In both the monotherapy and combination studies, VIRACEPT was safe and generally well tolerated. More than 700 patients are currently receiving VIRACEPT in pivotal phase II/III clinical trials throughout the United States. The drug is being developed by Agouron in collaboration with the pharmaceutical division of Japan Tobacco Inc. of Tokyo, Japan.
Source: PR Newswire, 810 Seventh Avenue, New York, NY 10019
|
Nelfinavir is only currently available in the U.K. as the placebo controlled arm of
the AVANTI III trial in combination with AZT and 3TC at the Royal Free and Chelsea & Westminster Hospitals. |
|
VIRAL LOAD TESTING
|
Viral load, the amount of human immunodeficiency virus (HIV) RNA in the plasma of infected individuals, can accurately predict how quickly people with HIV infection will progress to AIDS and, ultimately, their survival, according to a study published in the May 24, 1996 issue of Science.
The study, led by John W. Mellors, M.D., associate professor of medicine, University of Pittsburgh Medical Center (UPMC), and co-investigator of the Pittsburgh site for the Multi-center AIDS Cohort Study (MACS), demonstrates that direct quantification of HIV-1 RNA by branched DNA (bDNA) predicts HIV disease progression earlier and more accurately than CD4+ T-cell counts, the most commonly used marker, regardless of an individuals disease stage at measurement. Our findings confirm that baseline HIV RNA levels measured by bDNA can accurately predict the risk of AIDS and death, said Dr. Mellors. The data also indicate that we can predict disease progression as far as 10 years into the future.
The study results indicate that a baseline viral load measurement provides an excellent marker of both time to AIDS and time to death. Using the bDNA assay developed by Chiron Diagnostics, investigators measured baseline viral load in plasma samples from 180 HIV-infected individuals. The risk of progression to AIDS after five years was 8 percent among those whose HIV RNA measurements were in the studys lowest quartile. On the other hand, 62 percent of individuals whose viral load was in the highest quartile progressed to AIDS within five years. Estimated survival time in the lowest through highest viral load quartiles was greater than 10 years, 9.5 years, 7.4 years and 5.1 years, respectively. Conversely, among the three quartiles with the highest CD4+ T-cell counts, no differences were observed for either time to development of AIDS or time to death.
Dr. Mellors findings indicate that prognosis in HIV infection is directly related to viral load. Further, other completed studies indicate that reduction in viral load in response to therapy improves prognosis. These simple principles may help us to individualise patient therapy and provide better information to guide therapeutic research, said Dr. Mellors. Measuring HIV viral load with bDNA provides us with a prognostic tool that is similar to that of surgical staging procedures for cancer, which has important implications for both management of HIV-infected individuals and therapeutic research, Dr. Mellors continued.
Currently, a significant drop in CD4+ T-cell counts is considered an indication of disease progression and is used to gauge a patients response to anti-viral therapies. Unfortunately, changes in CD4+ T-cell counts can occur later than increases in viral load.
Measuring viral load with the bDNA assay predicts disease progression and death better
than the CD4 count because the level of HIV in plasma most likely drives the CD4 cell decline, which is a marker for the deterioration
of the immune system, said Dr. Lawrence A. Kingsley, associate professor of epidemiology and microbiology
at the University of Pittsburgh, and epidemiologist for the study.
Source: PR Newswire, 810 Seventh Avenue, New York, NY 10019
A panel of leading HIV clinicians and researchers has published interim recommendations
for how to use viral load testing, based on currently available knowledge.(1) The recommendations, which appear in the June
1996 issue of NATURE MEDICINE, answer common questions of physicians and patients about when to use the test and what the numbers
mean. The information is current; while the recommendations represent months of work by the authors, NATURE MEDICINE published
them very rapidly, about one month after receiving the manuscript.
The article summarises the recommendations in a table:
|
OPPORTUNISTIC ILLNESSES
|
New lipid preparations of the mainstay antifungal agent amphotericin B are an important contribution to the treatment of often fatal fungal infections, according to a new report published in a supplement to the May issue of Clinical Infectious Diseases. The authors say these agents should be given careful consideration, particularly for patients who cannot tolerate or fail to respond to amphotericin B, and for those with specific infections, such as invasive aspergillosis, that commonly progress despite treatment.
The three new drugs, amphotericin B lipid complex, amphotericin B colloidal dispersion, and liposomal amphotericin B, all have been cleared for commercial use in Europe.
In recent years, invasive fungal infections have become an increasingly important source of morbidity and mortality in patients whose immune systems have become suppressed, said the papers authors John Hiemenz, MD, leader of infectious disease program, H. Lee Moffitt Cancer Center, Tampa, FL; and Thomas J. Walsh, MD, head of mycology unit and immunocompromised host section of the National Cancer Institute, Bethesda, MD.
Particularly susceptible to these infections, which have mortality rates ranging from 40 percent to nearly 90 percent in the case of aspergillosis, are patients receiving cancer chemotherapy, people with AIDS, and recipients of organ and bone marrow transplants.
Amphotericin B has remained the drug of choice for many years because of its broad spectrum of activity. However, the agents effectiveness is limited by its potential to damage the kidneys. While the precise mechanism of action of the lipid preparations has yet to be described, the data analysed by Hiemenz and Walsh suggest that the new drugs provide greater safety even when significantly higher doses of the active agent are delivered.
Source: PR Newswire, 810 Seventh Avenue, New York, NY 10019
|
Lipid preparations of amphotericin B available for prescription in the U.K. include
AmBisomeô manufactured by Vestar Inc., and Amphocilô manufactured by Sequus Pharmaceuticals Ltd. |
Thalidomide effectively and safely heals severe mouth ulcers (also called oral aphthous ulcers) in persons with HIV infection, according to an interim analysis of data from a placebo-controlled study supported by the National Institute of Allergy and Infectious Diseases (NIAID), ACTG 251.
Many patients with HIV infection suffer from these extremely painful mouth ulcers, making eating difficult and contributing to weight loss and debilitation, says Anthony S. Fauci, M.D., director of NIAID. Thalidomide is the first treatment shown in a rigorous scientific study to heal these ulcers. As the study continues, we anticipate additional valuable information about the drugs effectiveness and long-term toxicity.
As planned in the study design, an Ad Hoc Interim Review Committee looked at data from patients with mouth ulcers who had received four weeks of treatment with either placebo or 200 mg of thalidomide taken by mouth each day. The committee found that the ulcers had healed in 14 of 23 patients receiving thalidomide compared with only one out of 22 patients receiving placebo. The effectiveness of thalidomide for patients with ulcers in the oesophagus could not be evaluated because of limited patient enrolment. The committee also looked at the safety data available for the first 73 patients enrolled in either the mouth ulcer or oesophageal ulcer part of the trial and found no significant differences in severe side effects that could be attributable to either thalidomide or placebo.
According to study chair Jeffrey M. Jacobson, M.D., of the Bronx Veterans Affairs Medical Center and Mt. Sinai School of Medicine in New York, ACTG 251 is continuing to enrol HIV-infected men and women at ACTG sites across the United States. Study plans call for 164 participants. Thalidomide is known to cause malformations in infants born to women taking the drug, and women of child-bearing age who participate in ACTG 251 are fully informed about this risk. The women must agree not to become pregnant either by abstaining from sexual intercourse or by using a hormonal contraceptive as well as two barrier-type contraceptives. They also must agree to frequent tests for pregnancy.
Source: NIAID, a component of the National Institutes of Health
|
Thalidomide is available for the treatment of AIDS related mouth ulcers in the U.K.
on a named patient basis from the manufacturer - Penn Pharmaceuticals on 01495-711222.
|
May 29, 1996--NeXstar Pharmaceuticals, Inc., (NASDAQ:NXTR) announced today at its annual meeting that Portugal, Ireland, Greece and Belgium have granted final marketing authorisations for DaunoXome as a primary therapy for advanced AIDS-related Kaposis sarcoma. The four countries had previously committed to grant final approval as part of the European Community Decentralised Approval Procedure. DaunoXome is now approved in 12 European countries, as well as in Canada and the United States.
Earlier today, at the annual meeting of the European Haematology Association in Paris, Dr. Steven M. Kelsey, of the Departments of Haematology at the Royal London Hospital, presented data from a phase II study in which DaunoXome is being used to treat relapsed and resistant lymphomas. In the study, Dr. Kelsey and his colleagues treated eight patients with 120 mg/m2 of DaunoXome every 21 days and 10 patients with 40 mg/m2 of DaunoXome every 14 days.
Dr. Kelsey told his audience that of the eight patients receiving high-dose therapy, one realised a complete response, two had a partial response and one had a moderate response. One of the ten patients who received low-dose DaunoXome therapy experienced a moderate response and one patient achieved complete and rapid relief of bone pain that had been refractory to previous therapy. According to Dr. Kelsey, no patient at either dose level showed any clinical deterioration in cardiac function. He and his colleagues plan further studies with high-dose DaunoXome therapy alone as a treatment for relapsed and refractory low-grade lymphoma and in combination with other chemotherapy agents in the treatment of relapsed high-grade lymphoma
Source: BUSINESS WIRE - 44 Montgomery St, 39th Floor, San Francisco
|
Liposomal daunorubicin (DaunoXomeô) is licensed in the U.K. for the treatment of advanced Kaposis sarcoma, and is available through the distributors Chapter Ltd. Contact Mr McHutchinson,
01223-216772. |
|
IMMUNOLOGY & PATHOGENESIS
|
They reported their findings in the journal AIDS Research and Human Retroviruses (Strong Cytotoxic T Cell and Weak Neutralising Antibody Responses in a Subset of Persons with Stable Nonprogressing HIV Type 1 Infection, AIDS Res H, 1996;12(7):585-592).
All four subjects with the lowest viral loads on initial evaluation remained stable with CD4 counts greater than 500 cells/(micro)L during follow-up for 23-32 months, and maintained persistently low viral titres, Harrer et al. reported. In these individuals a relatively consistent pattern of immune responses was detected. All had detectable CTL activity, including three with in vivo activated CTL, yet all had weak to undetectable neutralising antibodies against the panel of primary isolates.
A strong CTL response alone was not enough: one subject with strong CTL activity and a high viral titre had HIV disease progression during the observation period. Our finding that vigorous CTL responses can be detected in persons with low viral loads and stable nonprogressing disease supports the hypothesis that CTL may contribute to maintenance of the asymptomatic state, although these and other studies indicate that progression can occur even in the presence of vigorous CTL activity, Harrer et al. noted.
Additional expanded studies in both progressors and nonprogressors will be required
to adequately address these issues, and to determine whether augmenting the cellular or humoral immune response may confer benefit
in infected persons. Source AIDSWEEKLY Plus, 3 June 1996 issue
In hopes of bolstering his immune system, an HIV-positive man from San Francisco received
a thymus transplant last week. Matthew Sharp, 39 years old, received the tissue from a one-year-old donor undergoing heart
surgery. Sharps doctor, Richard Hong, said he hopes to perform the procedure in eight more patients.
Funding for the surgery is provided by the Linda Greenberg Foundation of Southern California and is administered by Project
Inform, a patient advocacy group in San Francisco.
Source: Reuters (05/22/96)
HIV-1 can be detected in the brain early in infection, but replication of the virus
is constrained until the terminal phase of AIDS encephalitis, a group of European researchers report. Francesca Chiodi and colleagues
at the Karolinska Institute in Stockholm tested parenchymal tissue from eight HIV-infected patients in different stages
of infection. They found that an increased number of viral copies in the brain was associated with histopathological evidence of
HIV-1 encephalitis. The researchers suggest that, while the virus may enter the brain early in infection, replication is limited
until the terminal phase of AIDS encephalitis. Source: Reuters (05/21/96)
|
CONTRACEPTION
|
The sex hormone progesterone, which is especially prevalent in the second half of
the menstrual cycle, has been shown to make female monkeys much more vulnerable to SIV, the monkey version of HIV. Preston A. Marx
and others at the National Institute of Child Health and Human Development report that 14 of 18 monkeys given the hormone became
infected with SIV, compared to just one of 10 monkeys that did not receive the hormone. The results were reported Monday at
a meeting of the American Clinical Investigation and the American Federation for Clinical Research. The findings are not necessarily
applicable to humans, but experts say the results support earlier theories linking hormone levels and susceptibility. Two
contraceptives, the implant Norplant, and Depo Provera, which is injected, contain progesterone, but experts say the study does
not merit a woman changing her method of birth control.
Source: New York Times (05/07/96) P. C3; Kolata, Gina
|
EVENTS
|
|
TREATMENT ALERT
|