PI Perspective #29
April 2000 View PDF En
español
New Information on
Opportunistic Infections and Co-Infections
Many reports have shown fewer opportunistic infections (OIs) and
deaths since the wide-scale availability and use of potent anti-HIV
therapy. Also, there have been many reports of people stopping preventive
therapies for OIs. Now several studies further confirm that it may
be safe for some people to stop preventive therapies when their
CD4+ cell count increases are sustained over time. In addition,
ongoing research into hepatitis co-infection (with HIV) is beginning
to show progress.
Despite success in these areas, there also appear to be increases
in the rate of certain AIDS-related cancers. Moreover, a major hospital
is beginning to document new increases in the rates of OIs.
Stopping MAC Prevention
An AIDS Clinical Trial Group (ACTG) study examined the safety of
stopping MAC (Mycobacterium avium complex) preventive therapy in
people who had significant increases in their CD4+ cell count from
highly active antiretroviral therapy (HAART). The study enrolled
643 people on MAC preventive therapy who at one time had CD4+ cell
counts below 50 but had over 100 cells at the start of the study.
Volunteers were either continued their current MAC preventive therapy,
azithromycin (Zithromax, 1,200mg once a week) or switched to a placebo.
About 60% of them had good control of HIV with HIV RNA below 500
copies.
After over a year, only two people got MAC, both of whom took the
placebo. These results imply that it’s safe to stop MAC preventive
drugs for people whose CD4+ cell counts increase to and remain over
100. If you wish to consider stopping your MAC preventive therapy,
discuss it with your doctor.
Stopping PCP Prevention
A Spanish study evaluated the safety of stopping PCP (Pneumocystis
carinii pneumonia) preventive therapy. Almost 500 people with a
history of CD4+ cell counts around 100 participated.
At the start, all volunteers had CD4+ cell counts over 200, HIV
RNA below 5,000 copies and were using HAART for at least three months.
About 20% had been previously diagnosed with PCP.
Volunteers either continued PCP preventive therapy or received
no preventive drugs. After almost a year, not a single case of PCP
was diagnosed.
These results suggest that it’s possible for people to stop
PCP preventive therapy if they have sustained CD4+ cell count increases
over 200 and stay on potent anti-HIV drugs that optimally control
HIV.
An early report from a similar study, ACTG 888, appears to confirm
these results. No cases of PCP have yet been reported in the 252
participants to date.
The federal guidelines for the treating opportunistic infections
suggest that it’s possible for people to stop primary PCP
preventive therapy (to prevent first PCP infection) if they have
sustained CD4+ cell counts over 200. However, the guidelines do
not recommend that people stop secondary preventive or maintenance
therapy (to prevent PCP from coming back). If you consider changing
your PCP preventive therapy, talk to your doctor.
Advances in Hepatitis C Virus Therapy
There is possible good news for people with hepatitis C virus (HCV).
Results from a small study of peg-interferon (Pegasys, a new formulation
of interferon-alfa) suggest that it’s far more effective in
treating HCV than the current formula of interferon-alfa. The new
formulation was compared to standard interferon-alfa in 271 people
with cirrhosis of the liver due to HCV. Cirrhosis is a permanent
scarring of the liver and indicates a decrease in the amount of
functioning liver tissue. Furthermore, the scarring interferes with
the normal flow of blood through the liver and results in poor liver
function.
The new version of interferon-alfa is bound to polyethylene glycol,
which helps the interferon to remain stable and active in the blood
for longer periods than standard interferon.
In the study, people received 48 weeks of anti-HCV therapy with
a follow-up period of 24 weeks when they did not take any therapy.
They received either 90 micrograms (µg) or 180µg of
peg-interferon once a week or three million international units
of interferon-alfa three times a week. Both formulas required injections
under the skin.
Results showed that at 72 weeks, 29% of the participants receiving
peg-interferon had undetectable blood levels of HCV compared to
only 6% using standard interferon-alfa. Side effects were similar
between the two formulas and included headaches, fatigue, flu-like
symptoms, nausea, vomiting, depression, fever and chills.
In truth, neither of these success rates are overly impressive.
Optimally, even the peg version of interferon may need to be used
in combination therapy approach. Another study is ongoing in people
who have both HIV and HCV to determine the effectiveness of peg-interferon
combined with ribavirin (Rebetol). Ribavirin combined with a standard
form of interferon is called Rebetron and is generally considered
the current standard for treating HCV. Also, HCV advocacy groups
including Project Inform are working with Hoffman-La Roche, the
developers of peg-interferon, in designing studies that include
complementary therapies. The new studies would determine if these
therapies (such as milk thistle, coenzyme Q10 and vitamin B12) really
benefit people with HCV infection.
AIDS-Related Cancer on the Rise?
Recently, the large EuroSIDA study highlighted the increasing rate
of non-Hodgkins lymphoma (NHL), an AIDS-related cancer. The study
enrolled over 7,000 people in Europe since 1994. While the overall
rate of opportunistic infections has declined dramatically, the
incidence of NHL has increased substantially.
It’s not entirely clear why this is occurring. But one theory
explains this may be a result of people living longer or that NHL
was seen less frequently in the time before protease inhibitors
because people died of other conditions before developing NHL. Immune
restoration (increases in CD4+ cell counts) among people on HAART
seemingly has little or no impact on NHL. Some researchers wonder
if the extensive use of anti-HIV drugs might be contributing to
the increase, but there is no clear evidence that this is the case.
Are OI Rates on the Rise?
One alarming trend observed over the past 18 months at the San Francisco
General Hospital (SFGH) is the rising numbers of OIs. In 1997 cases
of PCP, MAC, cytomegalovirus, and cryptococcal disease (a fungal
infection primarily of the brain) fell to an all-time low. However,
by 1998 the number of these infections diagnosed at SFGH grew above
1997 levels. The 1999 numbers are expected to be even higher.
Earlier HIV testing and better access to treatment and care may
have prevented many of these infections. It’s been noted that
what happens in San Francisco usually happens in the rest of the
country a year or two later. So, returns in rates of new AIDS-related
infections may be expected over the coming years.
Conclusion
We now have some clear data on the safety of stopping preventive
therapy. However, the more worrying issue is the apparent increase
in the number of OIs. This clearly indicates the need for newer
and more potent anti-HIV therapies, as well as more effective efforts
to get people into testing and treatment programs in earlier stages
of HIV infection. It also indicates the need for better third line
therapies so that we do not return to the situation in which we
were in 1996.
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