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

    Viral load

    HIV viral load (VL) monitoring is key to the success of ART. Decisions to change ART made on the basis of virological failure, rather than on clinical or immunological failure alone, have been shown to result in better patient outcomes. 74 If the VL is undetectable, then the virus cannot mutate and develop resistance. A sustained VL < 50 copies/mL is associated with the most durable benefit. A suppressed VL also prevents transmission of HIV to contacts: Undetectable = Untransmittable (U=U).

    FIGURE 2: Timing of viral load monitoring of the patient starting ART. For patients with a viral load > 50 copies/mL on two consecutive occasions, refer to text. For the timing of viral loads in pregnant women, consult the pregnancy module. (RPV, rilpivirine; VL, viral load)


    We recommend performing a baseline VL assessment for the following reasons:

    1. The 3-month VL can then be compared with the baseline VL to detect > 2 log10 drop, and if this has not occurred, then it allows for early adherence intervention
    2. It confirms the diagnosis of HIV (antibody tests may very rarely give a false-positive result).
    3. In rare cases where RPV is considered as initial therapy, it may guide selection (RPV should not be used if VL > 100 000 copies/mL)

    A 3-month VL is desirable to detect adherence problems early, before resistance develops. A subset of patients who start ART with a very high VL may not be fully suppressed at 3 months despite 100% adherence, but such patients would have had a > 2 log10 drop in VL from baseline if adherence is optimal and there is no resistance. Therefore, the 3-month result should be interpreted in relation to the baseline VL. (For instance, if the baseline viral load is 100,000 copies/mL, then the viral load should be down to 1000 copies/mL or less at 3 months). All patients who have a detectable VL at 3 months should receive additional adherence interventions. In general, a patient’s VL declines fastest on InSTI-based regimens.

    If the 3-month VL is undetectable, then VL monitoring is recommended at 6 months and every 6 months thereafter. In patients who have an undetectable VL for > 12 months, and who demonstrate reliable adherence and follow-up, it may be acceptable to reduce the frequency of VL monitoring to 12-monthly.

    If the VL is > 50 copies/mL at any stage, then this should be an indication for urgent action. The patient should receive counselling and interventions should be implemented to improve adherence. A repeat measurement of VL should then be done in 2–3 months.

    Interpreting viral load results
    Virological criteria for treatment success

    Treatment success is defined as a decline in VL to < 50 copies/mL within 6 months of commencing ART, and sustained thereafter. A VL > 50 copies/mL is robustly associated with subsequent virological failure. 75, 76 Sustained viral replication, even at these low levels, can lead to the accumulation of resistance mutations (although this has not yet been definitively established in the case of dolutegravir).

    Virological criteria for treatment failure

    Treatment failure is defined as a confirmed VL > 1000 copies/mL on two consecutive measurements taken 2–3 months apart. The implication of this depends on the regimen the patient is on. Patients on DTG-based therapy as their initial ART regimen are extremely unlikely to have developed resistance at the point of treatment failure, but this is not necessarily true of other regimens, or of DTG-based regimens when there has been a history of failure with a prior ART regimen.

    Viral blips

    Isolated detectable HIV VLs < 1000 copies/mL, followed by an undetectable VL, are termed ‘viral blips’ and alone are not a reason to change the ART regimen.

    • Viral blips can be caused by immune activation (such as from an acute infection), variability in the laboratory testing thresholds, or intermittent poor adherence. Provided they are infrequent, and the viral load returns to being undetectable at the next measurement, they are not regarded as consequential.
    Reasons for a high viral load

    A high VL can be attributed to one or more of these three factors:

    • Inadequate patient adherence (most commonly). This may sometimes be out of the patient’s control (e.g. stock-outs, unplanned facility closure). See Table 28.
    • Resistance to the prescribed ART – including both acquired and transmitted drug resistance.
    • Inadequate ART drug levels as a result of altered pharmacokinetics, such as absorption difficulties, or drug-drug interactions.

    These explanations are not mutually exclusive. For instance, inadequate patient adherence may lead to the development of drug resistance.

    Transmitted drug resistance is only likely to be a concern for the rare patients who initiate therapy on an NNRTI, as by far the commonest transmitted mutation is K103N, which has little effect on viral fitness and can therefore persist in the population even in the absence of drug pressure. 77 Transmitted drug resistance to other drug classes is unusual and often of minimal clinical importance; therefore firstline therapy with a DTG-based regimen is unlikely to be affected by this phenomenon.

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