- The use of appropriate prophylaxis (primary or secondary) is essential in patients initiating ART.
- In general, prophylaxis can be discontinued once the CD4+ count has increased to > 200 cells/μL, but certain minimal durations of prophylaxis apply for secondary prophylaxis.
- Local and international guidelines should be consulted.
Cotrimoxazole primary prophylaxis
Prophylactic cotrimoxazole (CTX) is indicated for HIV-positive patients with a CD4+ count < 200 cells/μL, or with WHO stage 3 or 4 conditions (including TB). CTX offers protection against Pneumocystis jirovecii, toxoplasmosis, isosporiasis and certain bacterial infections. The recommended dose is 160 mg/800 mg daily. Patients who develop a hypersensitivity reaction to CTX can be given dapsone instead, although this is best avoided if the reaction to CTX was life-threatening. CTX can be discontinued once the patient’s CD4+ count > 200 cells/μL.
CTX is a common cause of cutaneous and systemic hypersensitivity reactions, indistinguishable from hypersensitivity reactions to ART drugs. CTX should be interrupted when treating mild suspected NNRTI cutaneous hypersensitivity rashes, and permanently discontinued if severe hypersensitivity reactions occur. If CTX is prescribed for secondary prophylaxis or used for primary prophylaxis in those with severe immunosuppression, then an alternative should be substituted.
|Common pitfall: Prescribing CTX for newly diagnosed HIV-positive patients with a high CD4+ count (> 200 cells/μL).|
Cryptococcal antigen screening and pre-emptive treatment
- CrAg screening should be done for all adults or adolescents with a CD4+ count < 200 cells/μL who are initiating or re-initiating ART.
- Reflex laboratory screening is the preferred approach in South Africa.
- LP is recommended for all patients with a new positive CrAg screening test.
Screening for subclinical cryptococcal disease has been shown to have a benefit in reducing mortality in HIV-infected patients with a CD4+ count < 200 cells/μL. It is recommended that HIV-seropositive adults or adolescents (≥ 10 years) with a CD4+ count < 200 cells/μL should be screened for cryptococcal antigenaemia (CrAg) on serum or plasma by reflex laboratory testing (preferred) or clinician-initiated testing. If clinician-initiated testing is performed, then it is recommended that screening should be restricted to adults or adolescents without prior cryptococcal disease who are initiating or re-initiating ART. For patients with a new positive CrAg result and an LP that rules out CM, oral fluconazole alone as induction therapy should be given (adults 1200 mg daily for 2 weeks). In these patients with a negative CSF CrAg result, ART can be started immediately with fluconazole. Patients diagnosed with CM should be managed as per the latest Southern African HIV Clinicians’ Society guideline for the prevention, diagnosis and management of cryptococcal disease among HIV-infected persons: 2019 update.
Common pitfall: Not performing an LP in all patients who are newly diagnosed as CrAg positive. The absence of any symptoms of meningitis does not exclude CM; approximately one in three patients with asymptomatic antigenaemia have concurrent CM.
Isoniazid preventive therapy
- Isoniazid preventive therapy (IPT) should be started at ART initiation or added to the treatment regimen of patients already on ART who have not yet received IPT, once active TB has been excluded.
- There is no need to test for latent TB prior to commencing IPT.
- IPT should not be started in pregnancy, except in pregnant women where the CD4+ count is < 350 cells/μL and who are at high risk of death from TB.
- Before commencing IPT, active TB infection should always be excluded.
Clinical trials conducted in South Africa and Cote d’Ivoire have shown that IPT has an additive effect with ART in preventing incident TB in HIV-infected patients.97,98 In the South African trial, there was a 37% reduction in incident TB when patients receiving ART were prescribed IPT (vs. placebo) for 12 months. This benefit applied irrespective of tuberculin skin test (TST) status, and the trial included patients established on ART. All patients receiving ART should be considered for IPT and screened for active TB using a symptom screen99 – IPT should be deferred and investigations conducted for active TB if any of the four symptoms (current cough, fever, night sweats or weight loss) are present. In patients receiving IPT, monitoring for neuropathy and hepatitis symptoms should be performed. Routine ALT monitoring is not indicated, but ALT should be tested if hepatitis symptoms occur.
A recent trial of IPT in pregnant women receiving ART, the TB APPRISE study, showed that IPT resulted in worse pregnancy outcomes.100 However, this was not confirmed in a larger observational study from the Western Cape, which showed that IPT use was associated with better pregnancy outcomes, and that incident TB was reduced in women on IPT who had CD4+ counts < 350 cells/μL.101 The duration of IPT is now 12 months irrespective of TST status as outlined in Table 28.
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|TABLE 28: Indications for isoniazid preventive therapy (provided that there are no tuberculosis symptoms nor contraindications to isoniazid).|
|Non-pregnant, regardless of CD4+ count||Indicated||12 months|
|Pregnant women with CD4+ count > 350 cells/μL||Not indicated||N/A|
|Pregnant women with CD4+ count < 350 cells/μL (at high risk for TB)||Indicated||12 months|
ART, antiretroviral therapy; CD4+, cluster of differentiation 4; IPT, isoniazid preventive therapy; N/A, not applicable; TB, tuberculosis.