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Which
Offers the Greater Benefit: Immediate or Deferred Treatment for
Central Nervous System-related Opportunistic Infections?
With
60% of the world's population, Asia is home to one of the fastest
growing HIV epidemics in the world. Most HIV-infected patients in
Asia present with an opportunistic
infection (OI), most commonly tuberculosis or
cryptococcal
meningitis (CM), rather than with early disease, and
warrant antiretroviral therapy (ART) by virtue of their usually
severe immunosuppression.
The
optimal time to initiate ART in patients with HIV-associated central
nervous system (CNS) opportunistic infections (OI) is
unknown. There are concerns that immediate ART may worsen rather
than improve outcomes because of combined drug interactions and
toxicities or immune
reconstitution inflammatory syndrome occurring within
the confined space of the skull.
However,
mortality in HIV-associated tuberculous
meningitis (TBM) and CM is unacceptably high, and delaying
ART may result in an increased incidence of HIV-related deaths.
Currently, there are no randomized controlled trial data to guide
the decision as to the optimal time to commence ART. Clinical guidelines
exist for tuberculosis, but even these acknowledge the limited evidence
on which they are based.
We
conducted a survey of HIV physicians around the world to determine
their opinions about initiating ART in HIV-infected patients presenting
with CNS OI. A questionnaire containing two case histories of patients
who had presented to our unit with HIV-associated TBM and CM was
e-mailed to 20 HIV physicians around the world, of whom 12 responded
within a specified time period.
In
the TBM case, all 12 physicians commenced treatment with anti-tuberculous
chemotherapy (ATC), the majority (11/12) with a standard four-drug
regimen. Five physicians also commenced other drugs for potential
drug-resistant tuberculosis. In terms of timing of the initiation
of ART, there was a range of responses (2 weeks to 12 months), with
2 months being the most popular response.
The
majority of respondents chose a combination of zidovudine
(Retrovir), lamivudine
(Epivir) and efavirenz (Sustiva)
both in their own country (10/12) and in a developing country setting
(5/12). Eleven physicians commenced other medications, such as adjunctive
corticosteroids (8/12) or prophylactic cotrimoxazole (6/12).
In
the CM case, the majority of physicians (10/12) gave amphotericin
and flucytosine as the initial antifungal regimen. With regard to
the timing of ART, there was a range of responses (0-10 weeks),
with 2 weeks being the most common response. Again, the most popular
ART regimen in the physicians' own country was zidovudine, lamivudine
and efavirenz (9/12), whereas zidovudine, lamivudine and nevirapine
(Viramune) was the most popular regimen (5/12) in a developing
country setting. The majority of physicians (9/12) also gave prophylactic
cotrimoxazole.
In
terms of the optimal timing of the initiation of ART, there was
a wide range of responses. In the TBM case, the earliest time that
anyone would consider starting ART was at 2 weeks. The majority
of physicians would, however, commence ART at 2 months, which coincides
with the start of the continuation phase of ATC, when drugs are
usually rationalized to dual therapy.
There
is thus considerable variation in practice, even among experienced
HIV physicians, in the management of HIV-infected patients presenting
with CNS OI. This reflects the lack of evidence, and prospective
data from randomized controlled trials with clinical endpoints are
urgently needed.
Oxford University Clinical Research Unit and Hospital
for Tropical Diseases, Ho Chi Minh City, Vietnam.
03/23/05
Reference
M
Torok and others. Immediate or deferred antiretroviral therapy for
central nervous system opportunistic infections? (Correpondence)
AIDS 19(5): 535-536. March 25, 2005.
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