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Page 34 of 39 Guideline

The use of prophylactic prednisone for the prevention of ÿ Reflex laboratory screening is the preferred approach in
paradoxical TB-associated IRIS in adults with a CD4 count ≤ South Africa.
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100 cells/μL has been shown in a randomised trial to be ÿ Lumbar puncture is recommended for all patients with a
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associated with a 30% lower relative incidence of TB-IRIS. new positive CrAg screening test.
Importantly, this did not come at the expense of any excess
risk of severe infections or cancers. The recommended Screening for subclinical cryptococcal disease has been
prednisone regimen is 40 mg daily for 14 days, followed by shown to have a benefit in reducing mortality in HIV-infected
20 mg daily for 14 days, and prednisone should be started patients with a CD4 count < 200 cells/μL. It is recommended
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concurrently with ART. Certain patient groups should be
excluded from receiving prednisone; however, including that HIV-seropositive adults or adolescents (≥ 10 years) with
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patients with Kaposi’s sarcoma and patients with RIF-resistant a CD4 count < 200 cells/μL should be screened for CrAg on
TB, or whose TB has not improved prior to starting ART. serum or plasma by reflex laboratory testing (preferred) or
clinician-initiated testing. If the clinician-initiated testing is
° Common pitfall: Using prophylactic prednisone in performed, then it is recommended that screening should be
patients who are not improving on TB therapy.
restricted to adults or adolescents without prior cryptococcal
27. Opportunistic infection disease who are initiating or re-initiating ART. For patients
with a new positive CrAg result and an LP that rules out CM,
prophylaxis oral fluconazole alone as induction therapy should be given
Key points (adults 1200 mg daily for 2 weeks). In these patients with a
negative CSF CrAg result, ART can be started immediately
ÿ The use of appropriate prophylaxis (primary or with fluconazole. Patients diagnosed with CM should be
secondary) is essential in patients initiating ART. managed as per the latest Southern African HIV Clinicians’
ÿ In general, prophylaxis can be discontinued once the Society guideline for the prevention, diagnosis and management of
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CD4 count has increased to 200 cells/μL, but certain cryptococcal disease among HIV-infected persons: 2019 update.
minimal durations of prophylaxis apply for secondary
prophylaxis. ° Common pitfall: Not performing an LP in all patients
ÿ Local and international guidelines should be consulted. who are newly diagnosed as CrAg positive. The absence
of any symptoms of meningitis does not exclude CM;
Cotrimoxazole primary prophylaxis approximately one in three patients with asymptomatic
antigenaemia has concurrent CM.
Prophylactic CTX is indicated for HIV-positive patients with a
CD4 count < 200 cells/μL, or with WHO stage 3 or 4 conditions Isoniazid preventive therapy
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(including TB). Cotrimoxazole offers protection against
Pneumocystis jirovecii, toxoplasmosis, isosporiasis and certain Key points
bacterial infections. The recommended dose is 160 mg/800 mg ÿ Isoniazid preventive therapy should be started at ART
daily. Patients who develop a hypersensitivity reaction to CTX initiation or added to the treatment regimen of patients
can be given dapsone instead, although this is best avoided if already on ART who have not yet received IPT, once
the reaction to CTX is life-threatening. Cotrimoxazole can be active TB has been excluded.
discontinued once the patient’s CD4 count is > 200 cells/μL.
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ÿ There is no need to test for latent TB prior to commencing
IPT.
Cotrimoxazole is a common cause of cutaneous and
systemic hypersensitivity reactions, indistinguishable from ÿ Isoniazid preventive therapy should not be started during
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hypersensitivity reactions to ART drugs. Cotrimoxazole pregnancy, except in pregnant women where the CD4
should be interrupted when treating mild suspected NNRTI count is < 350 cells/μL and who are at high risk of death
cutaneous hypersensitivity rashes, and permanently from TB.
discontinued if severe hypersensitivity reactions occur. If ÿ Before commencing IPT, active TB infection should
CTX is prescribed for secondary prophylaxis or used for always be excluded.
primary prophylaxis in those with severe immunosuppression,
then an alternative should be substituted. Clinical trials conducted in South Africa and Cote d’Ivoire
have shown that IPT has an additive effect with ART in
° Common pitfall: Prescribing CTX for newly 97,98
diagnosed HIV-positive patients with a high CD4 preventing incident TB in HIV-infected patients. In the
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count (> 200 cells/µL). South African trial, there was a 37% reduction in incident TB
when patients receiving ART were prescribed IPT (vs. placebo)
Cryptococcal antigen screening and pre-emptive for 12 months. This benefit applied irrespective of tuberculin
treatment skin test (TST) status, and the trial included patients
Key points established on ART. All patients receiving ART should be
considered for IPT and screened for active TB using a symptom
ÿ Cryptococcal antigenaemia screening should be screen – IPT should be deferred and investigations should be
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performed for all adults or adolescents with a CD4 count conducted for active TB if any of the four symptoms (current
< 200 cells/μL who are initiating or re-initiating ART. cough, fever, night sweats or weight loss) is present. In patients

http://www.sajhivmed.org.za 52 Open Access