ART Guidelines

ART Guidelines


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  • ABBREVIATIONS
    /r ritonavir-boosted
    3TC lamivudine
    ABC abacavir
    ADR adverse drug reaction
    AKI acute kidney injury
    ALT alanine transaminase
    ANC antenatal care
    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
    CNS central nervous system
    CrAg cryptococcal antigen
    CrCl creatinine clearance rate
    CSF cerebrospinal fluid
    CTX cotrimoxazole
    d4T stavudine
    ddI didanosine
    DILI drug-induced liver injury
    DNA deoxyribonucleic acid
    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
    FTC emtricitabine
    GI gastrointestinal
    Hb haemoglobin
    HBsAg hepatitis B surface antigen
    HBV hepatitis B virus
    HIV human immunodeficiency virus
    ICU intensive care unit
    INH isoniazid
    INR international normalised ratio
    InSTI integrase strand transfer inhibitor
    IPT isoniazid preventive therapy
    IRIS immune reconstitution inflammatory syndrome
    LAM lipoarabinomannan
    LDL-C low-density lipoprotein cholesterol
    LFT liver function test
    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
    PAS p-aminosalicylic acid
    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
    QTc corrected QT interval
    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
    UDP uridine 5’-diphospho
    ULN upper limit of normal
    VL viral load
    WHO World Health Organization
    WOCP women of childbearing potential








    Malaria
            Key points
     
    • There are several drug interactions between antimalarial agents and ART drugs.
    • 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.
    • No artemether-lumefantrine dose adjustment is recommended for patients taking PIs or InSTIs.
    • PIs and NNRTIs exhibit several interactions with atovaquone-proguanil (Malanil) such that atovaquone concentrations are reduced – atovaquone-proguanil (Malanil) is best avoided in patients receiving these drugs.
    • No significant drug interactions are predicted between InSTIs (DTG) and antimalarial drugs.
    • Quinine is best avoided in patients on PIs or NNRTIs.


    There are several drug interactions between antimalarials and ART drugs (outlined in Table 26). While artemether-lumefantrine (Coartem) can be administered safely with NVP, EFV significantly lowers the concentrations of artemether (and its active metabolite) and lumefantrine, which is likely to increase the risk of failure of antimalarial therapy. There is no clear guideline 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.

    Quinine concentrations are significantly decreased by LPV/r, probably owing to induction of metabolism by RTV. It is likely that quinine concentrations will also be reduced by EFV and NVP; therefore, quinine should be avoided in patients receiving PIs or NNRTIs. Patients with severe malaria should receive artesunate, if available, and those with milder malaria should be treated with artemether-lumefantrine.

    Among drugs used for 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). 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.

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

    Tip: To best view this table, zoom in or rotate your mobile device into landscape orientation.

    TABLE 26: Important drug-drug interactions between antimalarial agents and antiretroviral drugs.
    Drug Antimalarial agent Direction of interaction Recommendation
    InSTI Coartem (artemether-lumefantrine) No interaction Safe to use
    Atovaquone-proquanil No interaction Safe to use
    EFV Coartem ↓ artemether and lumefantrine concentrations Use but might need to repeat the 3-day course of Coartem
    Atovaquone-proguanil ↓ atovaquone and proguanil concentrations Avoid co-administration
    NVP Coartem No interaction Use
    Atovaquone-proguani ↓ atovaquone concentrations Avoid co-administration
    PI/r Coartem ↑ 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 pitfall: Not advising patients receiving ART on chemoprophylaxis for malaria when travelling to malaria-endemic areas.
    Common pitfall: Not providing ART recipients with intravenous artesunate or Coartem for malaria treatment despite the potential drug interactions.