ART Guidelines

ART Guidelines


Please review the disclaimer before proceeding with these guidelines

×

×





  • ×
  • 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








    Preamble
    Key principles

    Although many antiretroviral therapy (ART) guidelines are available internationally, the current guidelines have been written to address issues relevant to southern Africa. A major spur for the current guidelines is the introduction of dolutegravir (DTG) into first- and second-line ART regimens. DTG-based ART regimens hold much promise, although the transition inevitably challenges existing paradigms and generates additional complexities. These guidelines aim to address many of these and to update the text in general to reflect the latest evidence.

    As with previous iterations, these guidelines take affordability into account, as countries in the region vary between low- and middle-income countries. Hence, only the treatment and diagnostic options that are available in southern Africa are included. In addition, these guidelines recognise the need to bridge the gap in treatment recommendations between public and private sector programmes, considering that many patients transition between the two sectors for treatment. The format of this iteration of the guidelines has been modified to highlight each sections’ key points and common pitfalls

    Goals of antiretroviral therapy
    • Provide maximal and durable suppression of viral load
    • Restore and/or preserve immune function
    • Reduce HIV-related infectious and non-infectious morbidity
    • Prolong life expectancy and improve quality of life
    • Prevent onward transmission of HIV
    • Minimise adverse effects of the treatment.

    These goals are achieved by suppressing viral replication completely for as long as possible, using well-tolerated and sustainable treatment taken with good adherence. With prolonged viral suppression, the CD4+ lymphocyte count usually increases, which is accompanied by a restoration of pathogen-specific immune function. For most patients, this results in a dramatic reduction in the risk of HIV-associated morbidity and mortality. In patients who start ART with preserved CD4+ counts, ART is able to prevent the decline in CD4+ count observed in untreated patients and prevent clinical complications of HIV infection. It is still unclear whether immune function ever returns to full normality, though long-term cohorts show that patients who adhere well to ART have a near-normal life expectancy.1 Patient adherence to their ART regimen remains a key focus and challenge.

    Stopping antiretroviral therapy

    ART should not be stopped unless there is an extremely compelling reason to do so. In most cases where drug toxicities develop, switching the culprit drug(s) should be attempted instead. If non-nucleoside reverse transcriptase inhibitor (NNRTI)-based therapy is stopped, then we generally do not recommend ‘covering the tail’ with an additional 5–7 days of nucleoside reverse transcriptase inhibitors (NRTIs). There is little evidence for this in patients on long-term ART, and the intracellular half-life of drugs such as tenofovir disoproxil fumarate (TDF) in any case approximates that of the NNRTIs.2 It is important to ensure that the viral load (VL) is suppressed before substituting a single drug for toxicity, otherwise resistance may develop to the new drug, consequently compromising future regimens. However, single-drug substitutions can be done in the first few months of ART without measuring the VL, as the VL may take up to 6 months to become suppressed.

    We strongly advise against lamivudine (3TC) monotherapy ‘holding regimens’ in patients who have virological failure. Such regimens can be associated with a rapid fall in CD4+ count. The objective when prescribing ART should always be to provide a regimen that is most likely to achieve virological suppression.