AIDS Treatment Strategies: Interview With Lisa Capaldini, M.D.

Several years ago, AIDS TREATMENT NEWS decided to seek out
the experiences of physicians who had been treating HIV long
enough and intensively enough that their opinions might be
especially valuable for people living with HIV or AIDS, as
well as for researchers and other physicians. Lisa Capaldini,
M.D., General Internal Medicine, was the first physician we
interviewed (see AIDS TREATMENT NEWS issue # 100, April 6,
1990). Dr. Capaldini continues to treat many patients with
HIV, and to teach HIV care as an Assistant Professor of
Medicine at the University of California San Francisco. We
asked Dr. Capaldini again to share her experiences treating
symptomatic HIV disease -- especially what she has learned in
her practice and believes should be more widely known.

Opportunistic Infection Prophylaxis

DS: Everyone knows to prophylax against Pneumocystis
pneumonia, but beyond that, there isn't a solid consensus.
When do you initiate the different prophylaxes, and what do
you use?

LC: I try to have a structured routine with my HIV patients;
those with very low CD4 [T-helper cell] counts (less than 50-
100) get regular eye checks, MAC prophylaxis and of course,
PCP prophylaxis. I think AZT can actually be used as a
prophylactic measure, in that it seems to help prevent
dementia. [AZT, unlike many drugs, is known to cross the
blood/brain barrier.] AZT also seems to reduce the incidence
of HIV enteropathy, which can cause serious diarrhea and
weight loss.

For MAC prophylaxis, you can make a good argument for single-
drug therapy, with either rifabutin, clarithromycin, or
azithromycin when CD4 counts fall below 100. I have been
using clarithromycin, 1000 mg a day for people who can
tolerate it. It's important not to combine this with Seldane,
which can lead to a cardiac rhythm complication called
prolonged QT syndrome. A good thing about clarithromycin is
that it may also prevent some of the respiratory infections
that people with HIV are prone to, like pneumococcus, and
haemophilus, and staphylococcus. The cousin of
clarithromycin, azithromycin, is probably just as good. If
rifabutin is used, it's important to explain to patients that
their body fluids, especially urine, will turn orange. But
none of these drugs can be expected to control MAC
indefinitely.

I think that detecting early, even asymptomatic, CMV disease
is really important. By the time CMV causes an identifiable
retinitis, it is already a disseminated infection, capable of
causing fevers and wasting. People with CD4 cells less than
200 should have their eyes checked every three months, and if
the CD4s drop below 100, then every two months. If you catch
CMV disease early, you may prevent some of the constitutional
symptoms associated with a disseminated infection; if you
notice visual symptoms but wait to treat them, you may
compromise someone's vision, as anti-CMV therapy does not
fully reverse visual symptoms.

DS: Are you recommending anything for prophylaxis of fungal
infections?

LC: Yes, I'm suggesting that people with less than 200 CD4s
take ketoconazole, fluconazole, or itraconazole, daily. We're
seeing much less cryptococcal meningitis than we used to,
probably because so many people have already been taking one
of these drugs for Candida infections. Even though
ketoconazole does not cross the blood-brain barrier, I
believe it can prevent CNS fungal disease by decreasing
extra-CNS fungal burden. Fluconazole does cross the blood-
brain barrier, but is much more expensive. In my experience,
it is rare for someone taking daily ketoconazole prophylaxis
to develop cryptococcal meningitis.

With ketoconazole, it's important to take the drug on an
acidic stomach, so I tell people to take it with an acidic
beverage, like orange juice, coffee or a cola. This is
especially important if they are also on an acid-lowering
drug like cimetidine or ranitidine. Another precaution about
ketoconazole is that, rarely, it can interfere with androgen
binding and androgen receptors, which can cause a situation
that's clinically indistinguishable from androgen or adrenal
hormone deficiency.

On the other hand, there is a danger in overdoing preventive
medicine in not individualizing recommendations, and scaring
people. I try to streamline my prophylaxis recommendations
for my patients, so they don't feel like they're a carton of
eggs and one little misstep will mean disaster.
Psychologically that can wear people out. I am seeing more
and more people with lower and lower CD4 cells who do not
have any opportunistic infections and whose overall health is
quite good.

Cervical and Anal Cancer

DS: The incidence of cervical and anal cancer has been
reported at the last two International Conferences on AIDS to
be increased in people with HIV. Has this been true in your
patients?

LC: The more mucosal infections someone's had -- whether it's
warts, herpes, chlamydia, syphilis -- the more prone that
individual will be to have dysplasia [precancerous cells] on
that mucosal surface. If I'm caring for an HIV-positive woman
who has never had a sexually transmitted disease [STD], her
risk for cervical or anal dysplasia is probably no greater
than for a comparable HIV-negative woman. But a woman who's
had multiple sexual partners, and multiple STDs, should be
having regular pelvic exams and colposcopic exams.
Analogously, for men or women, anal dysplasia will be seen
more in individuals who have a history of chronic rectal
infections, with HIV added as a cofactor that reduces immune
surveillance and allows the dysplasia to emerge and perhaps
develop into cancer.

I have some concerns about the emphasis on gynecological care
for women with HIV. There are some women who very much need
thorough, regular gynecological examinations, and there other
women for whom that emphasis could be unnecessary and
somewhat misfocused. In other words, some women may get their
negative Pap smears and normal gynecological checks every six
months and think they're OK overall, when really they may
need to be more concerned about the standard problems for
which everyone with HIV, men and women, are at risk
(vaccinations, PCP prophylaxis, diet education, etc.). HIV
can get misconstrued as a gynecological condition in women
because in some women, that may be how the disease first
shows up. But women who are HIV infected need to have a
primary practitioner with HIV expertise, someone other than
solely a gynecologist, directing their care. Women in this
country are accustomed to getting their primary care from a
gynecologist, but gynecologists cannot be expected to be
completely familiar with HIV care in women any more than a
proctologist would be for HIV-infected men. So we need to
stretch the model -- HIV-primary care practitioners
(internists, family practitioners) are already familiar with
working closely with oncologists, but it may take some
getting used to these clinicians working collaboratively with
the gynecologist.

DS: There was some commotion in the activist community around
the phenomenon of false-negative Pap smears. Because of the
incidence of misleading smears, shouldn't women with HIV just
be given a regular colposcopy [a more aggressive technique
than the Pap smear]?

LC: I think again you have to consider the individual's
history. A reasonable approach is that women should have a
baseline colposcopy; in HIV-positive women without risk
factors for cervical dysplasia beyond HIV, six-month Pap
smears should be sufficient. But if a woman has had multiple
STDs, she should have an annual colposcopy, and Pap smears
every six months. If at any point either test finds something
abnormal, then the screening can be intensified according to
what the gynecologist recommends.

Fatigue: Hormone Replacement, Other Treatments

DS: One of the most common problems for some people with AIDS
is unremitting exhaustion. I understand you have used
androgenic steroids (male hormones like testosterone) for
some of your male patients who are chronically fatigued.

LC: Some fatigue, I believe, is attributable to adrenal
insufficiencies, either of glucocorticoids (like prednisone)
or androgens/anabolic steroids (like testosterone). If
someone becomes suddenly tired by just standing up, or
walking a few steps, they probably have orthostatic
hypotension, or low blood pressure. This can be caused by
adrenal insufficiency, which in turn is treatable.
(Incidentally, prednisone can be extremely useful for helping
people cope with end-stage respiratory distress, such as that
caused by pulmonary KS.)

But fatigue accompanied by muscle wasting and low libido
probably results from androgen insufficiency. Borderline low
testosterone levels are often seen in men with ARC or AIDS,
and replacing that testosterone can help reverse weight-loss
and appetite as well as problems with erections and fatigue.
Testosterone cypionate, 200 mg every two to four weeks, has
helped some of my debilitated patients, and has not caused
any serious side-effects. It has also, I feel, reversed
anemia and low platelets in some of my patients. Because of
its potential masculinizing effects, I prefer to offer women
Megace or Marinol rather than androgens, to treat refractory
weight loss and fatigue. In men, Megace or Marinol can
supplement testosterone therapy. Of note, the dose of
testosterone I use is far below the amounts of anabolic
steroids used by body builders.

Another possible treatment for either women or men who are
emotionally as well as physically fatigued is
dextroamphetamine. This can help people through difficult
days, make them brighter and more interactive.

Survival Trends

DS: The statistics on AIDS say that people are living longer.
Have you seen that empirically in your practice?

LC: Yes, certainly, although in my practice there is a
definite bias, because I think my patients tend to have more
resources than the average patient with AIDS in this country.
I don't just mean money -- I also mean having friends, family
or neighbors who will be supportive and will look out for my
patients' welfare. As far as statistical survival goes, I see
two trends. Many people are living longer, learning how to
live with CMV and MAC or other illnesses, but some people are
deciding when to stop treatments, which may silently alter
the statistics. The issue isn't always how long did someone
live after an AIDS diagnosis but how long did they choose to
live.

Depression and Its Treatment

DS: What particular measures would you say might enhance
someone's life such that they would choose to live?

LC: I have never seen enough emphasis on treating reversible
affective disorders, like depression and panic attacks. I
have been amazed at how many people with AIDS, people who are
dealing with multiple infections and really difficult times,
function better day to day with antidepressants. Absolutely.
Some clinicians may be hesitant to "cross over" into
practicing psychiatric medicine, but we who treat HIV already
treat a number of clinical situations that we once would have
referred to a specialist. Who doesn't prescribe amphotericin,
or erythropoietin, when indicated, rather than referring
every symptom to an infectious-disease specialist, or a
hematologist? There is an aura around antidepressants that
misleadingly implies they are in a completely different
realm.

I think if primary-care providers only feel comfortable
referring psychiatric symptoms to a psychiatrist, they should
at least become familiar with recognizing depression and
anxiety in their patients. It would be great if those
providers also became comfortable treating the patient
directly. For logistic and reimbursement reasons alone, it's
helpful for patients to not have to go to a number of
providers for their care. More importantly, the primary-care
physician is often in the best position to pick the right
medication. The main concern with antidepressants is not
their efficacy, but their side-effect profile. Sometimes you
may actually want to exploit side effects, like drowsiness
for insomiac patients, or stimulant effects for lethargic
patients.

You may not always know for sure if the depression or anxiety
will respond to medication, but you can't know if you don't
try it. If the stigma around using antidepressants comes out
of the provider's unfamiliarity with the drugs, then they
should familiarize themselves.

Perhaps their discomfort stems from talking to their patients
about personal, emotional issues; a lot of health-care
providers may be dealing with their own depression, since
many of them have lost loved ones to this disease. But it's
good for the provider to open up so that the patient can open
up. And the benefit of doing that is being able to offer the
patient a positive healing message: I am looking at you as a
whole individual, with dreams and struggles and worries and
hopes, and not just a collection of opportunistic infections.
In medicine it's actually good to have double vision: to be
able to see the ordinary as well as the extraordinary.