AIDS TREATMENT NEWS #226, July 7, 1995
Margaret Poscher, M. D., is an internist in private practice
with Quest, a five-physician medical group in San Francisco.
Dr. Poscher is also Assistant Clinical Professor, University
of California Medical Center, and Director of HIV Clinical
Services, University of California Mt. Zion.
ATN: Which antiretroviral combinations do you most use or
Dr. Poscher: I am disappointed that there is still not much
published information on combination therapy. I was on the
fence about combinations for a number of years. But in the
last two years, and especially with viral load assays now
available, it has become clear that combination treatment is
incredibly important. I don't think I have any patients on
monotherapy, except for some on d4T.
My favorite combination now is AZT plus 3TC. I foresee that
as being initial therapy, when 3TC is approved; patients who
have CD4 (T-helper cell) counts below 500, or have a certain
threshold level of HIV RNA, will be started immediately on
At this point, with patients who are asymptomatic and have a
relatively high CD4 count, and a moderate viral load, between
10,000 and 100,000 copies of RNA, I am starting those
patients on AZT plus ddI, or AZT plus ddC. They make the
decision of ddC or ddI, based on my description of the two
drugs. I tend to prefer ddI, as I have not been impressed
with ddC as an antiviral.
This week I had a patient who recently seroconverted, and in
a big way -- with several million copies of HIV RNA, a big
dip in his CD4 count, and who continues to have over 100,000
copies of RNA. In 1995 there is concern about people
becoming infected with AZT-resistant virus. So we discussed
potentially starting him on d4T as initial therapy, and using
d4T with either ddI or 3TC. I think that d4T with ddI is a
very good combination, especially in people with higher
T-cells, who tend not to get neuropathy as easily as advanced
In patients I've had on AZT plus 3TC who have developed
complications -- especially anemia, the big complication I
have seen, especially in patients with more advanced disease
-- I've had success switching them to d4T plus 3TC.
Occasionally I will use the triple combination AZT plus 3TC
plus ddI; this is based on Dr. St. Clair's report at the 2nd
National Conference on Human Retroviruses and Related
Infections (January 29 -- February 2, 1995, in Washington, D.
C.) on laboratory studies with this combination. Since then
there has been a question raised about possible antagonism
between ddI and 3TC, but this is not yet substantiated. With
these untested combinations, we do have to be careful about
unknown potential antagonisms.
ATN: Any other thoughts about which patients are the best
candidates for which treatments?
Dr. Poscher: It is probably also important to look at the
viral load. People with very high levels of HIV RNA, I would
be more likely to put on a triple combination. Some patients
may want to start therapy very early; they may only have 15
or 20 thousand copies of RNA, and CD4 counts of 500 or above;
you might even consider monotherapy for somebody like that.
Or I might put them on AZT plus ddC, as ddC is easier to take
that ddI. With high viral loads, I would dose higher, and
give more drugs, at least initially, until the viral load
ATN: On doses, do you tend toward the lower end of the
Dr. Poscher: I tend to give low doses. For AZT, I give 300
or 400 mg per day total. With ddC, I refuse to use the 0.75
mg tablet; my experiences with ddC back when it was in
parallel track was that higher doses just meant more
neuropathy and more anemia when used with AZT. So I tend to
stick to 0.375 mg of ddC three times a day.
With ddI I also use low doses, because of problems with
pancreatitis which I saw when the drug was parallel track; my
cohort of patients had close to a 20 percent incidence of
pancreatitis. But that is when we were using total daily
doses of 750 to 900 mg. Now I tend to give 250 mg of ddI
once per day. I was sad to see the 375 mg sachet taken away,
because I had many patients on 375 mg once per day. I dose
it once a day for convenience for the patient; most patients
cannot find two times in a day when they have an empty
stomach, since usually they are trying to eat as much as they
can to maintain their weight. To try to fast for an hour to
be able to take ddI twice a day usually means missing a meal,
at one end of the day or other. So I encourage them to take
it in the middle of the night, if they wake up to urinate, as
they often do. If you make it easy for people, they are more
likely to take the drug; it is better for them to get one
good dose in than skip it altogether because it's
ATN: What differences do you see with therapy naive
patients, vs. those who have been on AZT for a long time?
Dr. Poscher: It's like night and day; it is significantly
different. I think 3TC is the one exception, where you can
add it to AZT and still get some mileage out of the AZT. I
have completely given up on adding either ddI or ddC to a
patient who is already on AZT; I think that is a waste of
time. When you start a naive patient on antiretroviral
treatment early on, that is where those two drugs have a role
-- but not in somebody who has been on AZT for three or four
years. The only drugs I could see adding then would be 3TC,
or potentially a protease inhibitor if that were available.
For patients who are on AZT and not eligible for 3TC today
because they have a CD4 count over 100, I usually switch them
to d4T, usually to a combination of d4T and ddI.
ATN: Do you switch them all at once to the combination, or
do you start one drug first?
Dr. Poscher: All at once. Some patients are hesitant; they
want to try one drug and start at a low dose and get used to
it. But I encourage people to go for it, take both drugs full
dose from day one.
ATN: What about other antivirals, such as acyclovir, or oral
Dr. Poscher: I'm pro acyclovir -- absolutely for people who
have a known history of herpes, or zoster. I have all of
them on suppressive doses of acyclovir, 400 mg twice daily.
A few patients don't want to take it; they are usually
patients who have never had herpes or zoster outbreaks.
Still I encourage them to consider it, as I think there are
other herpes viruses which are not clinically apparent which
are exerting some effect. And acyclovir is safe; there is no
major drawback to using it. In the six years I have been in
private practice, I have seen two cases of
acyclovir-resistant herpes, after treating many people with
Oral ganciclovir for CMV prophylaxis, I am still ambivalent
about. I am concerned about the potential for resistance; I
think it is far more likely with ganciclovir and CMV, than
with acyclovir and herpes. I have had a couple patients who
have been on protocols for oral ganciclovir prophylaxis and
have then developed CMV, and it has been a nightmare. One
patient was resistant to everything; oral ganciclovir led to
ganciclovir resistance, and before he saw foscarnet he was
foscarnet resistant, and he was also resistant to HPMPC.
My thinking now is that there are better therapies coming for
CMV, such as local therapies through injection or eye
implants. With these we have a better chance of conserving
retina, which I think is the important thing, than through
years of treatment with oral ganciclovir and its
complications. So I am leaning to not using oral ganciclovir
in patients who have no CMV whatsoever, and to be careful
with ophthalmologic followup -- frequent eye exams, and
alerting people to symptoms of CMV retinitis.
I would use oral ganciclovir in patients who had end-organ
CMV disease -- CMV esophagitis, colitis, gastritis -- but
have not yet developed retinitis. Here you might use oral
therapy as secondary prophylaxis essentially -- as those
patients will probably develop retinitis within six to 12
For treatment of CMV retinitis, people often do well with
oral ganciclovir, after an initial course of IV induction
treatment. I have had a couple patients recently who have
gone one year without a recurrence, on oral ganciclovir.
Potential HIV Treatments
ATN: Are there other therapies that many of your patients
are on, such as experimental immune modulators?
Dr. Poscher: I have probably a dozen who continue to use
DNCB. Many continue to be on the TP-5 protocol. A few are
interested in the Cytolin, a mouse monoclonal antibody; I
have not seen enough on that to form an opinion. I think the
enthusiasm for IL-2 has diminished; nobody has asked about it
Thalidomide is the newest. I used it several times over the
past several years, in patients with oral aphthous ulcers,
and found it to be a very easy drug to take. The patients I
had who were maintained on thalidomide seemed to do very
well; I used to wonder if maybe the thalidomide was doing
something for them [vs. HIV disease, not only vs. the
ulcers]. So I'm encouraged that we at least have access to
it now, as a potential treatment for wasting, and possibly
for MAC, since it has been used in the treatment of leprosy
for decades now. [See "Thalidomide and HIV: Several Possible
Uses," by Denny Smith, AIDS TREATMENT NEWS #221, April 21,
ATN: What kinds of changes are you seeing in CD4 and viral
load with the different combination therapies?
Dr. Poscher: One therapy naive patient had avoided starting
antiretroviral therapy for years, and his CD4 count kept
going down. Finally I insisted that he do the HIV RNA test.
His count was greater than 1,600,000. He decided to go into
a clinical trial of PMEA; when he finally started that
treatment, his viral load was still over a million, and his
CD4 count had dropped below 200. He was a perfect example of
an antiretroviral naive patient who was put on the mid dose
of PMEA, and his viral load went from over a million to
30,000, and his CD4 count went from less than 200 to over
500, after six weeks on PMEA. He is now on AZT plus 3TC, and
doing very well.
I have seen at least one log (ten fold) viral load reductions
with d4T and 3TC. And when the RNA goes down, the CD4 count
goes up. Usually it does not last -- but I find that people
often reach a new plateau. They get a big increase, and then
it comes down a little, and they stay at that new plateau, a
little higher than they originally were, for a good six
months, or longer in some cases. I've seen people go from
well over 100,000 copies of HIV RNA, to under 10,000 copies.
[Part II of this interview will look at possible side effects
of combination treatment, treating a sudden CD4 drop, and
reimbursement and managed-care issues.]