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HIV MANAGEMEMNT

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Title: HIV MANAGEMEMNT


1
HIV/AIDS MANAGEMENT
  • Dr. W. C. Lwabby (MMed, MD)
  • Lecturer Int. Med. Dpt

2
Learning Objectives
  • To describe important investigations in the
    management of HIV/AIDS
  • To describe the treatment of HIV/AIDS.

3
BASELINE INVESTIGATIONS
  • Are laboratory tests needed in HIV baseline
    evaluation.
  • HIV baseline evaluation
  • all important information collected during a
    persons initial visits by a health care
    provider.
  • They include
  • Persons health and medical history
  • Physical examination
  • Baseline laboratory tests

4
BASELINE INVESTIGATIONS.
  • The purpose of an HIV baseline evaluation is to
  • Determine how far HIV infection has progressed.
  • Evaluate whether the person is ready to start
    lifelong treatment with ART.
  • Collect information to decide what ART to start.

5
BASELINE INVESTIGATIONS
  • The following lab tests are included in an HIV
    baseline evaluation
  • CD4 cell count
  • The normal CD4 count is over 500 cells/mm3
  • Is the most useful laboratory indicator of the
    degree of immune suppression.
  • It is used(together with clinical staging) in
    decisions to start prophylaxis against
    opportunistic infections.

6
BASELINE INVESTIGATIONS..
  • CD4 cell count..
  • Is of great value in the differential diagnosis
    of clinical problems.
  • Is used to monitor the effectiveness of ART.
  • Should be performed every 36 months in patients
    on ART, together with measurement of the viral
    load
  • ART is recommended as soon as possible for
    everyone with HIV,
  • No matter what their CD4 count is

7
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8
BASELINE INVESTIGATIONS
  • Viral load
  • Measures how much virus is in the blood (HIV
    viral load)
  • A goal of HIV treatment is to keep a viral load
    so low,
  • that the virus cant be detected by a viral load
    test.
  • The CD4 count and viral load test,
  • are both used to monitor the effectiveness of ART.

9
BASELINE INVESTIGATIONS
  • Drug-resistance testing
  • Identifies which ART(if any),will not be
    effective against HIV strain.
  • Health care providers,
  • consider drug resistance test results when
    recommending an HIV regimen.
  • Other tests include
  • Complete blood count (Infection, Anaemia,
    Bleeding disorders)
  • Renal function tests (serum creatinine, BUN)
  • Liver function tests (liver enzymes, serum
    albumin, bilirubin, etc)
  • Urinalysis (UTIs, proteinuria)
  • Lipid profile (serum total cholesterol,
    lipoproteins)
  • Tests for co-STIs (viral hepatitis, syphilis,
    etc)

10
LIFE CYCLE OF HIV
11
ANTIRETROVIRAL THERAPY(ART)
  • ART has transformed HIV from a progressive
    illness with a fatal outcome,
  • into a chronic manageable disease with a
    near-normal life expectancy.
  • The goals of ART are to
  • Reduce the viral load to an undetectable level
    for as long as possible
  • Improve the CD4 count to over 200 cells/mm3 so
    that severe HIV-related disease is unlikely
  • Improve the quantity and quality of life without
    unacceptable drug toxicity
  • Reduce HIV transmission.

12
ANTIRETROVIRAL THERAPY(ART).
  • The management of HIV/AIDS,
  • normally includes the use of combination ARV
    drugs in an attempt to control HIV infection.
  • There are six classes of ARV agents
  • They act on different stages of the HIV
    life-cycle
  • ART aims zero death, zero new infection and OIs
  • WHO recommends offering ARVs treatment to all
    patients with HIV.

13
Criteria for starting ART
  • Guidelines now recommend starting ART in all
    people with confirmed HIV infection,
  • irrespective of CD4 count or clinical status.
  • Early initiation of ART
  • has been shown to reduce morbidity and mortality
  • has the additional benefit of reducing the risk
    of transmission
  • In patients with major opportunistic infections,
  • ART should generally be started within 2 weeks,
    with two important exceptions
  • in cryptococcal meningitis,
  • ART should be deferred for 5 weeks, as earlier
    initiation increases the risk of death.
  • in tuberculosis,
  • ART should be deferred until 8 weeks as earlier
    initiation increases the risk of the immune
    reconstitution inflammatory syndrome

14
Classes of ARTs
  • There are six classes of drugs,
  • which are usually used in combination, to treat
    HIV infection.
  • ARV drugs are broadly classified by,
  • the phase of the retrovirus life-cycle that the
    drug inhibits.
  • Typical combinations include
  • 2 NRTIs as a "backbone,
  • along with 1 NNRTI,or PIs or INSTI as a "base.

15
Classes of ARTs
  • 1 Entry inhibitors(or fusion inhibitors)
  • Interfere with binding, fusion and entry of HIV
    to the host cell,
  • by blocking one of several targets.(CD4-cell and
    its co-receptor-CCR5 or CXCR4)
  • e.g Maraviroc and Enfuvirtide.
  • 2 Nucleoside/nucleotide reverse transcriptase
    inhibitors
  • Are nucleoside and nucleotide analogues which
    inhibit reverse transcription.
  • Inhibit viral RNA-dependent DNA polymerase
    (reverse transcriptase) enzyme.

16
Classes of ARTs
  • Nucleoside reverse transcriptase inhibitors.
  • Examples of currently used NRTIs /NtRTI include
  • Zidovudine (AZT)
  • Lamivudine (3TC)
  • Abacavir (ABC)
  • Emtricitabine (FTC)
  • Tenofovir (TDF).

17
Classes of ARTs
  • 3Non-Nucleoside reverse transcriptase inhibitors
    (NNRTI)
  • Inhibit reverse transcriptase by binding to an
    allosteric site of the enzyme
  • act as non-competitive inhibitors of reverse
    transcriptase.
  • They affect the handling of substrate
    (nucleotides),
  • by reverse transcriptase by binding near the
    active site.
  • There two subclasses
  • First generation Nevirapine(NVP) and
    Efavirenz(EFV)
  • available in Tz.
  • Second generation etravirine and rilpivirine

18
Classes of ARTs
  • 4Integrase inhibitors
  • Also known as integrase nuclear strand transfer
    inhibitors
  • ( INSTIs)
  • Inhibit the viral integrase enzyme,
  • which is responsible for integration(combining)
    of viral DNA into the DNA of the infected cell
  • It halts further spread of virus.
  • E.g Raltegravir, elvitegravir and dolutegravir,

19
Classes of ARTs
  • 5Protease inhibitors. (PIs)
  • Block the viral protease enzyme, necessary to
    produce mature virions.
  • Competitively inhibit the HIV protease enzyme,
  • whose activity is critical for the terminal
    maturation of infectious virions.
  • This inhibition prevents the maturation of
    virions capable of infecting other cells.
  • These drugs prevent the cleavage of gag and
    gag/pol precursor proteins.

20
Classes of ARTs
  • Protease Inhibitors (PIs) ,Examples are
  • Lopinavir
  • Indinavir
  • Nelfinavir
  • Amprenavir
  • Ritonavir
  • usually used as a booster with other PIs
  • Darunavir and atazanavir(ATV)
  • are currently recommended as first line therapy.
  • Resistance to some protease inhibitors is high.

21
Combination therapy
  • Combinations of ARVs
  • Create multiple obstacles to HIV replication to
    keep the number of virus low
  • Reduce the possibility of a superior mutation
  • No single ARV has been demonstrated to suppress
    an HIV infection for long
  • so must be taken in combinations in order to have
    a lasting effect.
  • Combinations usually consist of three drugs from
    at least two different classes.

22
Classes of ARTs
  • The combination treatment includes
  • 2 NRTIs 1 NNRTI,
  • OR
  • 2 NRTIs 1 PI, OR 2NRTIs 1INSTIs, OR 3NRTIs
  • With a HAART regimen
  • HIV replication is inhibited.
  • Viral load reduced.
  • Patient survival is prolonged.

23
Initiation of antiretroviral therapy
  • The WHO/Tanzania preferred initial regimen for
    adults and adolescents to be
  • tenofovir lamivudine
    dolutegravir(TLD)
  • (TDF3TCDTG)

24
First Line ARVs for Adults and Adolescent
  • The drug combinations are used.
  • Based on indications and contraindications,
  • that govern the use of ARVs to minimize side
    effects and drug-drug interactions.
  • They include
  • TDF3TCDTG
  • TDF3TCEFV
  • TDF3TCNVP
  • TDFFTCEFV
  • TDFFTC NVP
  • AZT 3TCEFV
  • AZT3TCNVP

25
Common toxicity switches for first line drugs
26
Pre-exposure prophylaxis(PrEP)
  • Daily use of tenofovir plus emtricitabine,
  • has been shown to reduce the risk of HIV
    acquisition in people at ongoing high risk (e.g.
    from sex or injecting drug use)
  • Is well tolerated.
  • Regular HIV testing should be done in people on
    PrEP.

27
Post-exposure prophylaxis (PEP)
  • Is recommended when the risk is deemed to be
    significant,
  • after a careful risk assessment(both
    occupational and non-occupational settings).
  • The first dose should be given as soon as
    possible,
  • preferably within 68 hours.
  • There is no point in starting PEP after 72
    hours.
  • Tenofovir together with emtricitabine is the most
    widely used dual NRTI combination.
  • PEP should not be given if the exposed person is
    HIV-infected.
  • HIV antibody testing should be performed at 3
    months after exposure.

28
Changing ART
  • The reasons to change ART can be grouped into
    two major categories
  • Drug Adverse Events or Toxicities
  • Intolerable side effects
  • Drug interactions
  • Treatment Failure
  • Clinical failure Occurrence or persistence of
    HIV related Ois
  • Immunologic failure Decrease in CD4 cell count
  • Virological failure Increase in viral load

29
Treatment Failure
  • Virological Failure
  • There is less than 10 fold drop in viral load
    after 6-8 weeks of ART.
  • or
  • When the viral load (VL) is persistently above
    5,000 copies/ml.
  • Immunologic Failure
  • 50 drop in CD4 count from peak value
  • Or
  • Return to pre-ART baseline CD4 count or lower
  • Clinical Failure
  • There are development of opportunistic
    infections, or malignancies,
  • occurring three months or more after initiation
    of ART.

30
ART complications
  • Immune reconstitution inflammatory syndrome
    (IRIS)
  • Is a common early complication of ART,
  • especially in patients who start ART with CD4
    counts below 50 cells/mm3.
  • Is often characterised by an exaggerated immune
    response,
  • with pronounced inflammatory features
  • Presents either with,
  • Paradoxical deterioration of an existing
    opportunistic disease or
  • The unmasking of a new infection.
  • Is associated with a mortality of around 5
  • Management
  • To continue with ART and to ensure that the
    opportunistic disease is adequately treated.
  • Symptomatic treatments are helpful
  • Glucocorticoids are often used for more severe
    IRIS manifestations

31
ART complications.
  • Lipodystrophy
  • Is due to long-term use of ART
  • Is associated with changes in body fat
    distribution
  • can present with
  • Fat accumulation (e.g. visceral fat, buffalo
    hump) or
  • Subcutaneous fat loss (lipoatrophy)
  • or with both fat loss and accumulation.
  • Others
  • Hypersensitivity rashes, insomnia, euphoria,
    anaemia, neutropenia etc.

32
REFERENCES
  • Brian R, Walker N, Stuart H. Davdsons Principle
    and Practice of Medicine 23rd Edition. HIV
    Infection and AIDS , Pg 323-337.
  • KASPER F,HAUSER LONGO. HARRISONS PRINCIPLES OF
    INTERNAL MEDICINE 19th Edition. Human
    Immunodeficiency Virus Disease AIDS and Related
    Disorders pg 1215-1283.

33
  • THANK YOU
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