News Briefs
by Mark Bowers
Nucleoside Analogs
New
300 Mg Tablet of AZT
The Food and Drug Administration (FDA) has approved a new 300 mg tablet
of AZT (Retrovir), making twice-daily dosing possible. The previous and
still available 100 mg formulation requires most people to take 2 tablets
3 times a day. Twice-daily dosing can simplify the dosing schedule for
those who take AZT in combination with other twice-daily drugs such as
3TC (Epivir).
PMPA
Clinical Testing
Gilead Sciences, of Foster City, CA, has announced the initiation of
Phase I/II clinical studies in humans of its nucleotide analog drug PMPA.
Two sites, San Francisco General Hospital and Johns Hopkins University
School of Medicine, were chosen to recruit 40 volunteers with CD4 cell
counts greater than 200 cells/mm3. Preclinical data on PMPA
made headlines last year when it was shown that subcutaneous injections
for 4 weeks either 48 hours before or up to 24 hours after exposure provided
100% protection against the development of simian immunodeficiency virus
(SIV) infection in primates. PMPA also reduced SIV RNA levels in chronically
infected primates by 99%. In addition, PMPA intravaginal gel completely
protected primates from vaginal transmission of SIV.
Antibody Therapy
CytoDyn
Receives Study Approval
FDA has approved a Phase I/II study of the injectable monoclonal antibody
Cytolin (made by CytoDyn Corporation) in HIV positive individuals. The
patented antibody targets a subset of CD8 cells (cytotoxic T-lymphocytes)
and has been administered to at least 188 patients for up to 2 years.
Treated individuals showed significantly reduced levels of HIV, clinical
improvement and increased numbers of CD4 cells. Side effects included
serious allergic reactions in about 1% of treated individuals.
Protease Inhibitors
Norvir
plus Saquinavir Data
A report presented at the 36th Interscience Conference on Antimicrobial
Agents and Chemotherapy (ICAAC) showed a 99.9% reduction in viral load
with a combination of 2 protease inhibitors, ritonavir (Norvir, made by
Abbott Laboratories) and saquinavir (Invirase, made by Hoffmann-LaRoche).
The 12-week data reflect a comparison of 136 participants with 100-500
CD4 cells/mm3 who were randomized to receive one of 4 treatments:
400 mg ritonavir plus 400 mg saquinavir twice daily; 600 mg ritonavir
plus 400 mg saquinavir twice daily; 400 mg ritonavir plus 400 mg saquinavir
3 times a day; and 600 mg ritonavir plus 600 mg saquinavir 3 times a day.
The first 2 regimens reduced viral load by 99.9%, while the other 2 regimens
reduced it by 99.3%. The combination regimens were generally well tolerated.
Only 7% of participants in the study discontinued due to drug toxicities.
See Research Notes for more ICAAC coverage.
Agouron
to File NDA for Nelfinavir
Agouron Pharmaceuticals announced on October 25 that they will file a
new drug application (NDA) with FDA by March 1997. The NDA will be for
nelfinavir (Viracept), a protease inhibitor currently in 3 clinical studies
with more than 700 participating volunteers. Results of these studies
are expected soon.
Drug
Interaction Warning
The Centers for Disease Control and Prevention (CDC) issued a warning
in October that combining protease inhibitors with drugs widely used to
treat tuberculosis (TB) could result in subtherapeutic levels of the protease
inhibitors. The drugs are called rifamycins, and include rifabutin, a
prophylaxis and treatment drug for Mycobacterium avium complex
(MAC), and rifampin, an essential component of TB treatment. CDC recommends
that protease inhibitors be withheld from patients receiving treatment
for TB. In the future, it may be possible to combine rifamycins with protease
inhibitors once dose modifications are proven safe and effective.
Viral Load
HIV
Eliminated from Lymph Tissue
Sven Danner, MD, and colleagues from the University of Amsterdam reported
that 6 patients who received a cocktail of antiretroviral drugs including
AZT, 3TC and ritonavir had no sign of HIV in their tonsils after 6 months
of treatment. In the November 8 issue of Science, Ashley Haase,
MD, and colleagues at Minnesota Medical School developed a new method
for measuring levels of HIV in lymphoid tissue. Cellular sources of viral
production can now be studied and quantified over the course of natural
infection and treatment.
Amplicor
Expanded Access Backlog
FDA approved the Roche Molecular Systems Amplicor HIV-1 Monitor viral
load test in early June 1996. An expanded access program was set up to
provide 2 free baseline tests to all HIV positive persons in the U.S.
for a period of 60 days beginning on June 17. So far, about 24,000 (30%)
of the 80,000 specimens that were submitted for testing have not been
processed. A follow-through program has been agreed to by Roche and community
activists. Roche has committed to processing and returning all backlogged
specimens to physicians by December 4. Physicians who did not receive
test results by October 18 will receive 2 free coupons for each affected
patient, to be redeemed for 2 additional free tests (which will be processed
within 10 working days). These coupons will be distributed to physicians
in increments, with 25% being mailed in December 1996, and January, February
and March 1997.
Opportunistic Infections
Topical
Amphotericin B for Thrush
Bristol-Myers Squibb is now marketing amphotericin B oral suspension
(Fungizone) for the treatment of thrush (oral candidiasis). The recommended
dose is 1 mL (100 mg) 4 times per day between meals for 2 weeks, in a
swish-and-swallow fashion. The drug, when not swallowed, has few of the
usual side effects associated with other forms of amphotericin B. Studies
are underway to assess the utility of oral Fungizone in people with azole-resistant
Candida infections.
Injectable
Amphotericin B for Aspergillosis
Sequus Pharmaceuticals received FDA approval to market amphotericin B
choleseryl sulfate complex for injection (Amphotec) in November. The new
formulation of amphotericin B is indicated for the treatment of invasive
aspergillosis, a difficult to treat fungal infection, in people for whom
kidney damage or toxic side effects render standard amphotericin B ineffective
or unacceptable.
Albendazole
Available by Prescription
SmithKline Beecham announced the commercial availability of albendazole
(Albenza) tablets for the treatment of hydatid disease and neurocysticercosis,
2 rare parasitic diseases caused by tapeworms. Studies are underway to
determine the usefulness of albendazole in people with microsporidiosis,
an AIDS-related opportunistic infection with no satisfactory treatment.
The prescription of albendazole for the treatment of microsporidiosis
currently represents off-label use of the drug.
Genital
Herpes Drug Study
Famciclovir (Famvir, made by SmithKline Beecham) was shown to be safe,
well-tolerated and effective in suppressing herpes simplex virus type
2 (HSV-2) outbreaks in HIV-infected individuals. About 80% of famciclovir
recipients did not experience recurrence of HSV-2 outbreaks compared to
29% of those receiving placebo. The randomized, double-blind, placebo-controlled
study recruited 48 individuals with both HIV and HSV-2. Participants received
either 500 mg famciclovir twice daily or placebo for 8 weeks, took no
drug for 7 days, then switched to the other regimen for 8 weeks. Famciclovir
reduced the frequency and duration of episodes of herpes reactivation.
Herpes
in the Eye
Researchers at the University of California Proctor Foundation in San
Francisco have identified herpes simplex virus (HSV) as the sole cause
of retinal infections in 2 people with AIDS. Todd Margolis, MD, observed
that HSV infection of the eye is extremely rare, but treatments for HSV
differ from treatments for the other possible causes of AIDS-related retinitis,
cytomegalovirus (CMV) and varicella-zoster virus. Accurate diagnosis can
help clinicians choose the most effective treatment. Polymerase chain
reaction (PCR) technology was used to find HSV in the eye.
Depression
Depression
Linked to Increased Risk of Death
The Center for AIDS Prevention Studies (CAPS) at the University of California
at San Francisco reported in the October 28 issue of Archives of Internal
Medicine that chronic depression increases the risk of death among
HIV-infected gay and bisexual men. CAPS studied 405 men between the ages
of 25 and 54 over an 8-year period. Using a 20-item inventory of symptoms
of depression, CAPS identified 230 (58%) of the men as depressed at least
once during the study. For men who were more depressed at each 6-month
measurement, the risk of death was 1.67 times greater than for men who
did not report depression. The association between depression and death
did not seem to be linked to CD4 cell counts. Possible explanations for
the increased mortality include increased risky sexual practices, smoking,
drinking and substance abuse.
VACT UP
Vaccine Advocates Committed to Universal Prevention (VACT UP) is a community-based,
nonprofit organization dedicated to speeding the development of a vaccine
for HIV. Vaccine advocacy efforts are also directed at increasing public
awareness of the complex issues involved in vaccine development and testing.
VACT UP is working to set up a web site (http://www.vactup.org)
that will feature materials about current vaccine efforts and provide
links to governmental, corporate, educational and medical sources of information.
Activists will be able to use the web site as a forum for global communication
and to increase community involvement. For more information, call 800-789-6854.
Mark Bowers is Managing Editor of Treatment Publications
at the San Francisco AIDS Foundation.
Page last updated 17 December 1996
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