ART Guidelines

ART Guidelines

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    /r ritonavir-boosted
    3TC lamivudine
    ABC abacavir
    ADR adverse drug reaction
    AKI acute kidney injury
    ALT alanine transaminase
    ART antiretroviral therapy
    ARV antiretroviral
    AST aspartate transaminase
    ATV atazanavir
    ATV/r ritonavir-boosted atazanavir
    AZT zidovudine
    bd twice daily
    CD4+ cluster of differentiation 4
    CM cryptococcal meningitis
    CrAg cryptococcal antigen
    CrCl creatinine clearance rate
    CSF cerebrospinal fluid
    CTX cotrimoxazole
    CVS cardiovascular
    d4T stavudine
    DILI drug-induced liver injury
    DNA deoxyribonucleic acid
    DOR doravirine
    DRV darunavir
    DRV/r ritonavir-boosted darunavir
    DTG dolutegravir
    eGFR estimated glomerular filtration rate
    ELISA enzyme-linked immunosorbent assay
    ETR etravirine
    FBC full blood count
    FDC fixed dose combination
    FTC emtricitabine
    GI gastrointestinal
    Hb haemoglobin
    HBsAg hepatitis B surface antigen
    HBV hepatitis B virus
    HIV human immunodeficiency virus
    ICU intensive care unit
    InSTI integrase strand transfer inhibitor
    IPT isoniazid preventive therapy
    LAM lipoarabinomannan
    LDL-C low-density lipoprotein cholesterol
    LP lumbar puncture
    LPV lopinavir
    LPV/r ritonavir-boosted lopinavir
    MDRD modification of diet in renal disease
    MTCT mother-to-child transmission of HIV
    MVC maraviroc
    NGT nasogastric tube
    NNRTI non-nucleoside reverse transcriptase inhibitor
    NRTI nucleoside reverse transcriptase inhibitor
    NTDs neural-tube defects
    NtRTI nucleotide reverse transcriptase inhibitor
    NVP nevirapine
    OI opportunistic infection
    PCR polymerase chain reaction
    PI protease inhibitor
    PI/r ritonavir-boosted protease inhibitor
    PMTCT prevention of mother-to-child transmission of HIV
    PPIs proton pump inhibitors
    PrEP pre-exposure prophylaxis
    PWH people with HIV
    RAL raltegravir
    RCTs randomised controlled trials
    RIF rifampicin
    RFB rifabutin
    RNA ribonucleic acid
    RPV rilpivirine
    RTV or /r ritonavir
    sCr serum creatinine
    sCrAg serum cryptococcal antigen
    TAF tenofovir alafenamide
    TAM thymidine analogue mutation
    TB tuberculosis
    TB-IRIS tuberculosis immune reconstitution inflammatory syndrome
    TBM tuberculosis meningitis
    TC total cholesterol
    TDF tenofovir disoproxil fumarate
    TG triglycerides
    TST tuberculin skin test
    ULN upper limit of normal
    VL viral load
    VTP vertical transmission prevention of HIV
    WHO World Health Organization

            Key points
    • There are several drug interactions between antimalarial agents and ART drugs.
    • No artemether-lumefantrine dose adjustment is recommended for patients taking PIs or InSTIs.
    • EFV has a significant drug interaction with artemether-lumefantrine (Coartem) such that artemether (and its active metabolite) and lumefantrine concentrations are lowered, which can lead to failure of antimalarial therapy. Consider extending the course of artemether-lumefantrine to 6 days if administered concurrently with EFV.
    • PIs and NNRTIs exhibit several interactions with atovaquone-proguanil (Malanil) such that atovaquone concentrations are reduced – atovaquone-proguanil is best avoided in patients receiving these drugs.
    • There are no significant drug interactions between InSTIs (DTG) and antimalarial drugs.
    • Quinine is best avoided in patients on PIs or NNRTIs.

    No significant drug interactions are predicted between InSTIs and antimalarial drugs.

    However, there are several drug interactions between antimalarials and other ART classes (see Table 25). EFV significantly lowers the concentrations of artemether (and its active metabolite) and lumefantrine (the two components of Coartem), which is likely to increase the risk of failure of antimalarial therapy. There is no clear guidance on how to overcome this interaction, but some experts recommend repeating the 3-day course of artemether-lumefantrine (i.e. treat for 6 days). Boosted PIs dramatically increase the plasma concentrations of lumefantrine, but a dose reduction is not recommended, as the toxicity threshold of lumefantrine seems to be high. Close monitoring for toxicity is recommended when co-administering artemether-lumefantrine with ART.

    Among drugs used for malaria chemoprophylaxis, there are no clinically significant pharmacokinetic interactions between ARVs and mefloquine or doxycycline. However, mefloquine and EFV both cause frequent neuropsychiatric side-effects; therefore, doxycycline is the preferred chemoprophylactic agent for patients receiving EFV. There are several interactions with atovaquone-proguanil (Malanil) however. Atovaquone concentrations are reduced by PIs and EFV, and also likely by NVP. Proguanil concentrations are also reduced by PIs and EFV. Use of atovaquone-proguanil is therefore best avoided in patients receiving PIs or NNRTIs.

    TABLE 25: . Important drug-drug interactions between antimalarial agents and antiretroviral drugs.
    Drug Antimalarial agent Direction of interaction Recommendation
    InSTI Artemether-lumefantrine No interaction Safe to co-administer
    Atovaquone-proguanil No interaction Safe to co-administer
    EFV Artemether-lumefantrine ↓ artemether and lumefantrine concentrations Use but consider repeating the 3-day course of artemether-lumefantrine
    Atovaquone-proguanil ↓ atovaquone and proguanil concentrations Avoid co-administration
    PI/r Artemether-lumefantrine ↑ lumefantrine concentrations No dose adjustment necessary
    Atovaquone-proguanil ↓ atovaquone and proguanil concentrations Avoid co-administration

    ART, antiretroviral therapy; EFV, efavirenz; InSTI, integrase strand transfer inhibitor; NVP, nevirapine; PI/r, ritonavir-boosted protease inhibitor.

    Common pitfalls:

    • Not advising patients receiving ART on chemoprophylaxis for malaria when travelling to malaria-endemic areas
    • Not including malaria in the differential diagnoses in PLHIV presenting with an acute illness.
    • Not providing ART recipients with intravenous artesunate or artemether-lumefantrine for malaria treatment despite the potential drug interactions.