Page 25 - SAHCS HIVMed Journal Vol 20 No 1 2019

Page 12 of 16 Guideline

Flucytosine maintenance therapy should be communicated. The expert
Bone marrow suppression is uncommon at the panel recommends standard first-line ART regimens among
12
recommended induction flucytosine dose for 1 week only, patients with CM. If nephrotoxicity occurred on
especially if renal function is normal (dose adjustment is amphotericin B, the renal function should be checked before
important in case of significant renal impairment). Other starting ART to ensure that it has improved (to a creatinine
causes of a low neutrophil count should also be considered. clearance of > 60 mL/min) before commencing tenofovir.
However, if grade 4 neutropenia (< 400 cells/mm ) The panel advises that, among patients who present with
3
develops, then we recommend to reduce the flucytosine relapse of CM or a first CM episode after interrupting ART,
dose and repeat a neutrophil count as soon as possible. If ART should also be restarted after 4–6 weeks. One situation
where ART may be delayed further is if a patient is still
the neutropenia is confirmed, then withhold flucytosine symptomatic with headaches at the visit when ART is about
until counts recover. If the patient was on the preferred to be started. In such a situation, a LP should be repeated to
1-week amphotericin B and flucytosine regimen, fluconazole measure pressure and for fungal culture to exclude persistent
may be added to amphotericin B, and extension of culture positivity. Antiretroviral treatment should be
amphotericin B treatment to a second week should be deferred and such patients may require further LPs or
considered. amphotericin B to ensure control of symptoms before
starting ART (Table 9).
Recommendation 5: Timing of
antiretroviral therapy Cryptococcal antigenaemia
Detailed recommendations The panel advises starting ART immediately among ART-
naïve patients who are blood CrAg-positive on screening and
Cryptococcal meningitis have an LP that excludes CM (with a caveat that there is no
The expert panel recommends commencing ART 4–6 weeks evidence for this recommendation). Asymptomatic CrAg-
after the diagnosis of CM. The panel strongly advises that positive patients who decline consent for LP or for whom LP
ART must not be delayed beyond 6 weeks after diagnosis, is contraindicated should start ART after at least 2 weeks of
and most members of the panel advise that clinicians should antifungal treatment (Figure 1).
aim to start exactly 4 weeks after diagnosis of CM. Although
most patients with CM have advanced immunosuppression Recommendation 6: Management
with very low CD4 counts, two randomised clinical trials of raised intracranial pressure
conducted in sub-Saharan Africa have shown excess early
mortality when ART was commenced while patients were Background
still receiving induction phase treatment for CM. 22,58 In the Raised intracranial pressure occurs in up to 75% of
later trial conducted in Uganda and South Africa, patients patients with CM and results from physical obstruction of
who started ART 1–2 weeks after diagnosis of CM had a CSF outflow through the arachnoid villi/granulations
15% higher mortality than those who deferred ART until resulting in build-up of CSF pressure. 61,62 Raised pressure
5–6 weeks. Another small trial showed possible excess IRIS may be present at the diagnosis of CM or develop while the
59
60
in those patients who started ART early. The in-hospital patient is on treatment and may result in severe headaches,
stay associated with amphotericin B therapy should be used vomiting, confusion or depressed level of consciousness,
for pre-ART counselling, identification of a treatment ophthalmoplegia (particularly sixth cranial nerve palsies)
supporter and early referral to an ART clinic. Clinicians and visual disturbance/loss. Clinicians need to consider
should aim to set up an ART clinic appointment within a raised intracranial pressure and manage appropriately if a
week of discharge from hospital to prevent delays in ART patient exhibits these symptoms or signs at any stage of the
initiation beyond what is advised in this guideline. Patients management of CM. To alleviate raised pressure,
initiated on ART should be counselled regarding the risk of therapeutic LPs are indicated. New-onset hypertension
development of IRIS. If a patient is referred to another may be a sign of increased intracranial pressure (i.e. part of
facility for ART, the need for fluconazole consolidation or Cushing’s triad) and should prompt an LP to measure
opening pressure instead of anti-hypertensive medications
TABLE 9: Summary of recommendation 5. (Box 1).
Scenario Sub-recommendations
Following a first or relapse • Start ART 4–6 weeks after diagnosis of CM. The panel
episode of CM strongly advises that ART must not be delayed beyond BOX 1: Summary of recommendation 6.
6 weeks after diagnosis, and most members of the Sub-recommendations
panel advise that clinicians should aim to start exactly
4 weeks after diagnosis of CM Measure baseline opening pressure at the time of or shortly after the diagnosis
• No adjustment in first-line ART regimen is required for of CM using a manometer
patients who are ART-naïve (unless renal dysfunction If opening pressure is > 25 cm H O (manometer reading), remove 10 mL – 30 mL
precludes the use of tenofovir) CSF 2
Following a new diagnosis • If CM has been excluded, start ART immediately Repeat LP whenever there are symptoms or signs of raised intracranial pressure
of cryptococcal • Asymptomatic CrAg-positive patients who decline (headache, vomiting, drowsiness, confusion, sixth cranial nerve palsy, visual
antigenaemia consent for LP or for whom LP is contraindicated disturbance, etc.)
should start on ART after at least 2 weeks of
antifungal treatment Daily therapeutic LPs may be required
CM, cryptococcal meningitis; LP, lumbar puncture; ART, antiretroviral treatment. CM, cryptococcal meningitis; CSF, cerebrospinal fluid; LP, lumbar puncture.

http://www.sajhivmed.org.za 18 Open Access