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








     
    Renal disease
    Antiretroviral drug dose adjustment in renal disease
            Key points
     
    • Renal function is estimated by the modified Cockgraft-Gault or modification of diet in renal disease (MDRD) formulae.
    • For haemodialysis, the ART prescribed should be taken after dialysis.

    In HIV-positive patients on chronic haemodialysis, there are a number of important ART considerations. The NRTI class is eliminated through the kidneys, thus most NRTIs require dose adjustment as per Table 25. For suggested TDF dosing in patients with chronic hepatitis B see Module 20.
     

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


    Antiretroviral drug choice and dosing in patients on chronic haemodialysis
            Key points
     
    • Patients with HIV may develop end-stage renal failure owing to HIV-associated nephropathy or an HIV-unrelated cause, necessitating chronic haemodialysis.
    • TDF can be used in patients on chronic haemodialysis, but with once-weekly dosing which can be difficult for patients to remember.
    • AZT is generally avoided because of anaemia associated with renal failure.
    • InSTIs and NNRTI drugs do not require dose adjustment.
    • ATV concentrations are reduced in patients on haemodialysis to a greater degree than LPV concentrations.
    • LPV/r requires twice-daily dosing in patients on haemodialysis.
    • ART drugs taken once daily, or the evening doses of drugs taken twice daily, should be given after the haemodialysis session on dialysis days, to prevent the drug from being dialysed out.
    • Patients on chronic haemodialysis should be reviewed by a clinician experienced in ART management at least 6-monthly, to monitor treatment efficacy and side-effects and to adjust the regimen when needed.

    We recommend the following first-line option for patients on chronic haemodialysis: ABC (600 mg daily) + 3TC (50 mg first dose and thereafter 25 mg daily) + DTG (50 mg daily). On the days when haemodialysis is performed, the drugs should be given after the haemodialysis session.

    Common pitfall: Not giving daily doses or the evening doses of a twice-daily regimen after the haemodialysis session on dialysis days, to prevent the drug from being dialysed out.

    Antiretroviral therapy in patients with acute kidney injury
            Key points
     
    • In patients with acute kidney inury (AKI), NRTI dose adjustments should be implemented based on estimated CrCl calculation. 
    • TDF should be interrupted even if it is not thought to be the cause of the AKI.
    • Re-challenge with TDF may be considered in patients 1 month post resolution of AKI if TDF was not the cause and renal function returns to normal.
    • In patients with AKI who are not yet receiving ART, initiation is preferably deferred until AKI has resolved. But avoid significant delays.
    • Once renal function is improving (creatinine is on a downward trend), standard NRTI doses should be reintroduced to avoid under-dosing.


    In patients with AKI, NRTI dose adjustments should be implemented based on estimated CrCl calculation (see Table 25). TDF should be interrupted even if it is not thought to be the cause of the AKI. Care should be taken to identify other drugs which may affect renal function, such as aminoglycoside antibiotics, nonsteroidal anti-inflammatory drugs, co-trimoxazole and iodinated radiocontrast; these drugs should be avoided where possible, including temporary discontinuation.

    Once there is clear evidence that renal function is improving (i.e. creatinine is on a downward trend), standard NRTI doses should be reintroduced to avoid under-dosing. In patients with AKI who are not yet receiving ART, initiation is preferably deferred until AKI has resolved. However, ART should not be delayed for longer than 2 weeks for this reason. If renal function does not show any improvement after treating an acute event (e.g. sepsis) and this persists beyond 3 months, then the patient should be assessed for chronic kidney disease and referred to a physician who can evaluate and investigate further.

    Common pitfall: Not performing NRTI dose adjustment in patients with AKI.