Hiv Aids Management

HIV/AIDS MANAGEMENT
Dr. W. C. Lwabby (MMed, MD)

Lecturer Int. Med. Dpt
Sunday, March 6, 2022 1

Learning Objectives
• To describe important investigations in the management of

HIV/AIDS
• To describe the treatment of HIV/AIDS.

BASELINE INVESTIGATIONS
• Are laboratory tests needed in HIV baseline evaluation.
• HIV baseline evaluation;

– all important information collected during a person’s initial
visits by a health care provider.
– They include;
• Person’s health and medical history
• Physical examination
• Baseline laboratory tests
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.

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.

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 3–6 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
• 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 can’t be detected by a viral load test.
– The CD4 count and viral load test,

• are both used to monitor the effectiveness of ART.

• 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)
LIFE CYCLE OF HIV

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.

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.
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
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.

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

Classes of ARTs…
3:Non-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
Classes of ARTs…
4:Integrase 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,

Classes of ARTs…
5:Protease 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.
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.

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.
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.

Initiation of antiretroviral therapy
• The WHO/Tanzania preferred initial regimen for adults and

adolescents to be:
tenofovir + lamivudine + dolutegravir(TLD)
(TDF+3TC+DTG)

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;
– TDF+3TC+DTG
– TDF+3TC+EFV
– TDF+3TC+NVP
– TDF+FTC+EFV
– TDF+FTC +NVP
– AZT+ 3TC+EFV
– AZT+3TC+NVP
Common toxicity switches for first line drugs

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.

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 6–8 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.
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

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.
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
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.

REFERENCES
▪ Brian R, Walker N, Stuart H. Davdson’s Principle and Practice of

Medicine 23rd Edition. HIV Infection and AIDS , Pg 323-337.
▪ KASPER F,HAUSER LONGO. HARRISON’S PRINCIPLES OF INTERNAL

MEDICINE 19th Edition. Human Immunodeficiency Virus Disease:
AIDS and Related Disorders pg 1215-1283.

THANK YOU

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HIV/AIDS MANAGEMENT

Dr. W. C. Lwabby (MMed, MD)

Sunday, March 6, 2022 1

• To describe important investigations in the management of

• To describe the treatment of HIV/AIDS.

Sunday, March 6, 2022 2

• Are laboratory tests needed in HIV baseline evaluation.

• HIV baseline evaluation;

• 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

– Collect information to decide what ART to start.

Sunday, March 6, 2022 4

• CD4 cell count

– Is the most useful laboratory indicator of the degree of

– It is used(together with clinical staging) in decisions to start

Sunday, March 6, 2022 5

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 3–6 months in patients on ART,

• ART is recommended as soon as possible for everyone with HIV,

– A goal of HIV treatment is to keep a viral load so low,

– The CD4 count and viral load test,

Sunday, March 6, 2022 8

Sunday, March 6, 2022 10

• ART has transformed HIV from a progressive illness with a fatal

• The goals of ART are to:

– Reduce HIV transmission.

• The management of HIV/AIDS,

• 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

• In patients with major opportunistic infections,

• ARV drugs are broadly classified by,

• Typical combinations include:

Sunday, March 6, 2022 14

1: Entry inhibitors:(or fusion inhibitors)

2: Nucleoside/nucleotide reverse transcriptase inhibitors

Sunday, March 6, 2022 16

– Inhibit reverse transcriptase by binding to an allosteric site of the

– They affect the handling of substrate (nucleotides),

– Inhibit the viral integrase enzyme,

– It halts further spread of virus.

• E.g; Raltegravir, elvitegravir and dolutegravir,

5:Protease inhibitors. (PIs)

– Competitively inhibit the HIV protease enzyme,

– This inhibition prevents the maturation of virions capable of

– These drugs prevent the cleavage of gag and gag/pol precursor

• Resistance to some protease inhibitors is high.

Sunday, March 6, 2022 20

• No single ARV has been demonstrated to suppress an HIV

• The combination treatment includes:

• With a HAART regimen:

– Viral load reduced.

– Patient survival is prolonged.

• The WHO/Tanzania preferred initial regimen for adults and

Sunday, March 6, 2022 23

• The drug combinations are used.

Sunday, March 6, 2022 25

• Daily use of tenofovir plus emtricitabine,

• Regular HIV testing should be done in people on PrEP.