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
    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

            Key points
    • PIs can cause hypertriglyceridaemia and elevated low-density lipoprotein cholesterol (LDL-C).
    • ATV/r and DRV/r are associated with less significant lipid abnormalities than LPV/r.
    • EFV can cause elevated total cholesterol (TC) and mild hypertriglyceridaemia.
    • DTG does not significantly affect cholesterol.
    • Lipids should be assessed routinely after 3 months on a PI regimen.

    PIs can cause hypertriglyceridaemia and elevated LDL-C. ATV/r and once-daily DRV/r (800 mg/100 mg DRV/r once daily) are associated with less severe dyslipidaemia than other boosted PIs; AZT can cause mild hypertriglyceridaemia, and EFV can cause elevated total cholesterol (TC) and mild hypertriglyceridaemia.

    We suggest that lipids should be assessed routinely after 3 months on a PI regimen. If normal at this stage, then reassessment should be performed only in those with cardiovascular risk factors. Diet and lifestyle modification should always be advised. Diet is more effective for controlling hypertriglyceridaemia than hypercholesterolaemia. Other cardiovascular risk factors should be addressed. Clinicians should consider and investigate secondary causes of hypertriglyceridaemia and hypercholesterolaemia (e.g. diabetes, nephrotic syndrome, alcohol abuse and hypothyroidism).

    If patients receiving LPV/r develop significant dyslipidaemia, then they should be switched to DRV/r or ATV/r, rather than adding lipid-lowering therapy. However, lipid-lowering therapy is indicated in patients with persistent elevations despite switching to DRV/r or ATV/r. Switching the PI to DTG is another option, because DTG has a more favourable lipid profile than PIs. However, DTG should only be used in a regimen in which at least one other ART drug is known to be fully active. In patients with hyperlipidaemia on EFV, the drug should be switched to DTG or RPV.

    Marked hypertriglyceridaemia (> 10 mmol/L) can cause pancreatitis and requires urgent treatment with diet modification (restrict total TG intake to < 30 g/day), fibrates and switching of LPV/r to DRV/r, ATV/r or DTG. (Fibrates can be stopped after 1 month, followed by reassessment within 4–6 weeks.)

    Indications for statin therapy in HIV-positive patients should be the same as in HIV-negative patients, using the Framingham heart disease risk score. As a general rule, in young patients with isolated elevated cholesterol but no other cardiovascular risk factors, a threshold of TC > 7.5 mmol/L (or LDL-C > 5.0 mmol/L) should be used for initiating statin therapy; and the patient should be referred to a lipid clinic for investigation if feasible. In patients with cardiovascular risk factors (e.g. smoking, diabetes, hypertension), decisions should be made using the Framingham heart disease risk score. All patients with established atherosclerotic disease (coronary, cerebral or peripheral) or familial hypercholesterolaemia should be started on statin treatment. In addition, type 2 diabetics should also be started on a statin if they have chronic kidney disease, or if they are aged > 40 years (or have had diabetes for > 10 years) and have one or more additional cardiovascular risk factors.91

    Many statins have interactions with PIs that can lead to potentially toxic statin concentrations, with the exception of pravastatin and fluvastatin. Atorvastatin concentrations are significantly raised by PIs, but low doses (maximum 10 mg daily) can be used with monitoring for symptoms of myalgia. Lovastatin and simvastatin should not be co-administered with PIs, as their concentrations are dramatically increased, and severe rhabdomyolysis has been reported. We also advise against the use of rosuvastatin with PIs due to a complex drug-drug interaction: PIs increase the plasma concentrations of rosuvastatin while reducing their efficacy in the liver.

    Common pitfall: Not routinely assessing lipids while the patient is receiving PI-based ART.
    Common pitfall: Failure to recognise that many statins have interactions with PIs that lead to toxic statin concentrations.
    Common pitfall: Monitoring of LDL-C in patients on a high-dose statin for secondary prevention. Such monitoring is not necessary.