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Page 30 of 39 Guideline

ÿ Once renal function improves (i.e. creatinine is on a frequently causes neuropsychiatric effects in the first few
downward trend), standard NRTI doses should be re- weeks of therapy, typically presenting with insomnia, vivid
introduced to avoid under-dosing. dreams and dizziness. Both dysphoria and euphoria may
occur. Fortunately, these features subside in the majority of
Antiretroviral therapy in acute kidney injury patients within the first 4–6 weeks. Psychosis may occasionally
In patients with AKI, NRTI dose adjustments should be occur. Dolutegravir may cause insomnia, headache and
implemented based on estimated CrCl calculation (see neuropsychiatric side effects. Raltegravir has been associated
Table 25). Tenofovir disoproxil fumarate should be with similar central nervous system side effects.
interrupted even if it is not thought to be the cause of AKI. ° Common pitfalls:
Care should be taken to identify other drugs that may affect ° Not warning patients starting ART about potential
renal function, such as aminoglycoside antibiotics, non- neuropsychiatric symptoms. Patients must be
steroidal anti-inflammatory drugs, cotrimoxazole and informed about potential side effects.
iodinated radiocontrast; these drugs should be avoided ° Unnecessary delays in initiating ART in patients
where possible, including temporary discontinuation. with psychiatric illness.

Once there is clear evidence that renal function is improving 23. Malaria
(i.e. creatinine is on a downward trend), standard NRTI doses
should be reintroduced to avoid under-dosing. In patients Key points
with AKI who have not yet received ART, initiation is
preferably deferred until AKI has resolved. However, ART ÿ There are several drug interactions between antimalarial
should not be delayed more than 2 weeks for this reason. If agents and ART drugs.
renal function does not show any improvement after treating ÿ Efavirenz has a significant drug interaction with
an acute event (e.g. sepsis) and this persists beyond 3 months, artemether–lumefantrine (Coartem) such that artemether
then the patient should be assessed for chronic kidney disease (and its active metabolite) and lumefantrine concentrations
and referred to a physician who can evaluate and investigate are lowered, which can lead to failure of antimalarial
further. therapy. Consider extending the course of artemether–

° Common pitfall: Not performing NRTI dose adjustment lumefantrine to 6 days if administered concurrently with
in patients with AKI. EFV.
ÿ No artemether–lumefantrine dose adjustment is
22. Psychiatric disease ÿ Protease inhibitors and NNRTIs exhibit several
recommended for patients taking PIs or InSTIs.
Key points interactions with atovaquone–proguanil (Malanil) such
that atovaquone concentrations are reduced –
ÿ Dolutegravir may cause insomnia, headache and
neuropsychiatric side effects. atovaquone–proguanil (Malanil) is best avoided in
ÿ Zidovudine and RAL frequently cause headaches when patients receiving these drugs.
started, but this usually resolves. ÿ No significant drug interactions are predicted between
ÿ The majority of patients who experience neuropsychiatric InSTIs (DTG) and antimalarial drugs.
features of EFV do so within the first 2–6 weeks, and ÿ Quinine is best avoided in patients on PIs or NNRTIs.
thereafter the drug is better tolerated. Late neurological
syndromes are described however (see section 4). There are several drug interactions between antimalarials
ÿ Most neuropsychiatric effects relating to ART occur in the and ART drugs (see Table 26). Whilst artemether–
first few weeks of therapy. lumefantrine (Coartem) can be administered safely with
ÿ Depression and other mental illnesses are often NVP, EFV significantly lowers the concentrations of
undiagnosed or undertreated in HIV-infected individuals artemether (and its active metabolite) and lumefantrine,
and may undermine adherence. which is likely to increase the risk of failure of antimalarial
ÿ Consider avoiding EFV- and RPV-based regimens in therapy. There is no clear guideline on how to overcome this
patients with psychiatric illness – these drugs can interaction, but some experts recommend repeating the 3-day
exacerbate psychiatric symptoms and may be associated course of artemether–lumefantrine (i.e. treat for 6 days).
with suicidality. Boosted PIs dramatically increase the plasma concentrations
of lumefantrine, but a dose reduction is not recommended, as
Mental health, especially mood and behaviour disorder, is the toxicity threshold of lumefantrine seems to be high. Close
associated with non-adherence to ART, leading to disability monitoring for toxicity is recommended when co-
and poorer HIV treatment outcomes. There is a higher administering artemether–lumefantrine with ART.
prevalence of depression in HIV-positive individuals, with a
reported range of 20% – 40% versus 10% in the general Quinine concentrations are significantly decreased by LPV/r,
population. 89 probably owing to induction of metabolism by RTV. It is likely
that quinine concentrations will also be reduced by EFV and
Zidovudine and RAL frequently cause headaches when NVP; therefore, quinine should be avoided in patients
started, but this usually resolves after sometime. Efavirenz receiving PIs or NNRTIs. Patients with severe malaria should

http://www.sajhivmed.org.za 48 Open Access