These new European recommendations have
been developed in view of the efficacy and safety issues outlined below.
Efficacy issue:
A high rate of early virological failure
and emergence of resistance has been observed in several clinical studies
in which didanosine and tenofovir DF were co-administered with a
non-nucleoside reverse transcriptase inhibitor (NNRTI) in
antiretroviral-naïve HIV-1 infected adults with high baseline viral loads
and low CD4 cell counts. [1-3]
Similar findings had previously been
reported in the context of triple combination involving didanosine and
tenofovir DF with another nucleoside reverse transcriptase inhibitor
(NRTI).
Although all these reports have been
reported in specific situations (i.e. antiretroviral naïve patients and
co-administration with NRTI or NNRTI), it could not be ruled out that such
worrying findings could be observed in other contexts (such as in
antiretroviral experienced patients and/or in combination with protease
inhibitors).
Therefore, co-administration of didanosine
and tenofovir DF is not recommended within any antiretroviral treatment
regimen unless judged strictly necessary.
Safety issue:
Separate pharmacokinetic studies showed
that co-administration of didanosine and tenofovir DF resulted in 40-60%
increase in systemic exposure to didanosine that may increase the risk for
didanosine-related adverse events. Rare cases of pancreatitis and lactic
acidosis, sometimes fatal, have been reported.
The European Summary of Product
Characteristics (SmPC) for ddI (Videx) and tenofovir DF (Viread) are
currently being updated with these new recommendations.
New information to be included in Sections
4.4 (Special Warnings and Special Precautions for use) and 4.5
(Interactions with other medicinal products) is summarised in the
attachment to this letter.
Bristol-Myers Squibb and Gilead are
committed to providing you with current product information for the
management of your patients for HIV infection. You can assist us by
monitoring the safety of our products and reporting adverse reactions,
which should be sent to the local representatives listed below or to the
Medicines and Healthcare products Regulatory Agency (MHRA).
Rutgers
researchers may have stopped HIV
Researchers
at Rutgers University have developed a trio of drugs they believe can
destroy HIV, the virus that causes AIDS, according to a published report.
The drugs, called DAPYs, mimic the virus by changing shape, which enables
them to interfere with the way HIV attacks the immune system.
Tests conducted in conjunction with Johnson and Johnson have shown the
drug to be easily absorbed with minimal side effects. It also can be taken
in one pill, in contrast to the drug
cocktails currently taken by many AIDS patients.
"This could be it," Stephen Smith, the head of the department of
infectious diseases at Saint Michael's Medical Center in Newark, said.
"We're all looking for the next class of drugs."
A research team led by Rutgers chemist Eddy Arnold pre-published details
of the most promising of the three drugs, known as R278474, last month in
the electronic edition of the Journal of Medicinal Chemistry. Full details
will be published in the journal in early 2005.
Dr. Arnold, 47, has worked at dismantling the AIDS virus over the last 20
years. He uses X-ray crystallography, a technique to determine the
structure of molecules, the smallest particles that can retain all the
characteristics of an element or compound.
The research has targeted reverse transcriptase, a submiscroscopic protein
composed of two coiled chains of amino acids. It is considered HIV's key
protein.
"Reverse transcriptase is very important in the biology of
AIDS," Dr. Smith said. "If you can really inhibit reverse
transcriptase, you can stop AIDS."
The optimism about R278474 stems from its potential to interfere with an
enzyme that the virus needs to copy and insert itself into a human cell.
"We're onto something very, very special," Dr. Arnold said. Dr.
Arnold established his lab at Rutgers' Center for Advanced Biotechnology
and Medicine in 1987. His current 30-member
research team is partnered with Johnson and Johnson subsidiaries Janssen
Pharmaceutica and Tibotec-Virco NV. An important advancement in Dr.
Arnold's research came in 1990
when Belgian scientist Paul Janssen was added to the collaboration. Dr.
Janssen, considered a drug pioneer, published a paper that year that
described a new drug that blocked reverse transcriptase but caused
resistant strains of the virus to pop up too quickly.
Dr. Janssen sought out Dr. Arnold, who used crystallography to detail the
structure of RT. Their work ultimately led to the RT inhibitors. "We
may eventually win the war against HIV/AIDS. That would be an extremely
rewarding and satisfying outcome," Dr. Arnold said.
IRISH
HIV FIGURES FOR FIRST SIX MONTHS (Q1&2) OF 2004*
HIV Infections, Cumulative total
The cumulative total of HIV cases
reported to the end of June 2003 is 3,590. A breakdown of the cumulative
cases can be seen in Table 75. This table is regularly updated as
further information is received.
Below shows a graph of the number of
HIV infections newly diagnosed annually from 1994 to 2003 in the three
major risk group, heterosexuals, MSM and IDUs.
HIV infected patients in Ireland by
exposure category (Cumulative to end of June 2004)
