ADULT MANAGEMENT

MM
REVIEW THE HIV CYCLE
HIV LIFECYCLE
1.BINDING
• A glycoprotein is a molecule that consists of a protein plus one or more
carbohydrates.
• The attachment of the virus occurs through the gp 120 and gp 41 to the
CD4 cell receptor of the host cell.
• Thereafter, there is an interaction between a CD4 cell coreceptor and the
gp120 complex.
• This works like a key and a lock, allowing fusion of the viral envelope &
CD4 cell membranes
 2.FUSION AND ENTRY
• This step involves the fusion of the membranes of the host cell and
that of the virus.
• After HIV attaches itself to a host CD4 cell, the HIV viral envelope
fuses with the CD4 cell membrane.
• Fusion allows HIV to enter the CD4 cell.
• Once inside the CD4 cell, the virus releases HIV RNA and HIV
enzymes, such as reverse transcriptase, integrase and protease
3.REVERSE TRANSCRIPTION
• Once inside the CD4 cell, reverse transcriptase to convert HIV RNA
into HIV DNA.
• The conversion of HIV RNA to HIV DNA allows HIV to enter the CD4
cell nucleus
4.INTEGRATION
5.REPLICATION
• Now HIV is integrated into the host CD4 cell DNA, the infected host
cell’s mechanisms are then taken over by the virus which uses the
CD4 cell to create long chains of HIV proteins.
• The protein chains are the building blocks for more HIV
6.ASSEMBLY
• During assembly, new HIV RNA and HIV proteins and enzymes made
by the host CD4 cell move to the surface of the cell and assemble into
immature (as yet noninfectious) HIV .
7.BUDDING
• During budding, immature (noninfectious) HIV pushes itself out of the
host CD4 cell. (Noninfectious HIV can't infect another CD4 cell.)
• Once outside the CD4 cell, the new HIV releases protease.
• Protease acts to break up the long protein chains that form the
noninfectious virus.
• The smaller HIV proteins combine to form mature, infectious HIV
 CLASS ACTIVITY.
• Having been through the steps in replication of the HIV virus, where in
the life cycle do you think ART drugs can act in preventing the
replication of the virus?
ENROLMENT INTO CARE AND INITIAL ASSESSMENT
OF ADULTS LIVING WITH HIV Outline
By the end of the topic students should be able to describe
• Components of Enrolment into HIV Care
• Initial Clinical Assessment of an Adult Living with HIV
• Initial Laboratory Assessment of an Adult Living with HIV
• Readiness Assessment process in context of Test and Start
Components
1.Initial clinical assessment for an adult living with HIV.
• Proper history taking medical, psychosocial history, sexual and
reproductive history.
• Comprehensive physical examination.
• Lab assessment.-The CD4 count will no longer determine the eligibility
for ART but will determine the need serum cryptococcal antigen
(sCRAG) test if CD4 count ≤ 200 cells/mm3.
2.Lab assessments
• Confirm and document positive HIV test result
• CD4 cell count-If CD4≤200 cells/mm3 then laboratory should perform
a serum cryptococcal antigen (sCrAg) on the same sample to rule out
cryptococcal meningitis before starting ARV.
• Viral load (HIV-1 RNA) - Baseline Viral Load (VL) is only recommended
(where applicable) for HEIs after 1st PCR test if positive.
• Specimen for Baseline VL can be drawn before or at time of initiating
ART; obtaining a VL should not delay ART initiation
• Serum Cryptococcal Antigen (sCrAg)
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• Hb (preferably full blood count if available) -If hb<9.5g/dl then AZT
should be avoided
• Pregnancy status -Pregnancy status should be determined for all
women of reproductive.
• Creatinine -Calculate Creatinine Clearance (CrCL) and if CrCL≤
50mil/min then TDF should be avoided.
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• Syphilis serology-Recommended (for all PLHIV with a history of being
sexually active)
• Glucose -All patients
• Plasma lipid profile - All patients
• HBsAg -All adolescent and adult patients (plus children who did not
complete routine childhood immunizations)
• HCV antibody -PWID or for patients with history of injection drug use
2.Readiness Assessment process in
context of Test and Start
• It is absolutely vital that a readiness assessment is conducted to ensure
there has been adequate treatment preparation and the patient is ready
start life-long ARVs before ART is initiated.
• On the same day of enrolment into the HIV care services, newly
diagnosed HIV patients should undergo HIV education and adherence
preparation.
• Thereafter, the patients should undergo an ART readiness assessment to
guide whether they are ready to start on ART if the responses are all
positive and the patient has no objections, initiate ART with the standard
package of care.
• ART should ideally be initiated within 2 weeks
Assignment !!!
• Check on ART readiness assessment tool/form
By the end of this unit, you should
be able to:
• By the end of this unit, you should be able to:
I. Describe the eligibility for ART
II. Describe the timing for initiating ART
III. Describe goals and principles of antiretroviral therapy
IV. Outline the classification of antiretroviral drugs
V. Describe the first-line ART regimens in kenya.
VI. Outline the appropriate ART regimens in special populations
Introduction
• The primary goal of ART is to reduce HIV-associated illness and death
by suppressing the HIV viral replication as much as possible and for as
long as possible.
Other goals of ART include
• Restoring and preserving immunologic function
• Improving quality of life
• Preventing transmission of HIV
Principles of ART in the
management of HIV:
1. ART is only one part of comprehensive care
2. ART should be a potent combination of ARVs to achieve durable
viral suppression
3. The initiation of ART is based on diagnostic evaluation and informed
discussion with the patient.
4. The design of a regimen should take into consideration factors
related to the patient as well as the virus.
Note
• Patients should not be denied ART based on predicted non-
adherence.
• Anticipated difficulties in adhering to a regimen should be proactively
and empathically managed by appropriate selection of ARVs, intensive
counselling and disease monitoring, and correction of factors
contributing to non-adherence.
 Classification of Antiretroviral Drugs
Antiretroviral drugs are classified based on their site of action.
• Reverse Transcriptase Inhibitors
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)
• Protease inhibitors (PIs)
• Integrase Strand Transfer Inhibitors (INSTIs)
• Entry Inhibitors
Fusion inhibitors (FIs)
Chemokine receptor antagonists (CCR5 antagonists)
1.Reverse Transcriptase Inhibitors
• The class of ARVs that blocks this enzyme are broadly classified into two
groups: NRTIs and NNRTIs.
a) Nucleoside Reverse Transcriptase Inhibitors (NRTIs).
• The NRTI class of drugs include Abacavir (ABC), Didanosine (ddI),
Emtricitabine (FTC), Lamivudine (3TC), Stavudine (d4T), Zalcitabine (ddC),
Zidovudine (AZT), and Tenofovir disoprovil fumarate (TDF) which is a
nucleotide Reverse Transcriptase inhibitor.
b) Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs).
Currently, there are four approved NNRTIs: Delavirdine (DLV), Efavirenz (EFV),
Etravirine (ETR), and Nevirapine (NVP), and several in development, including
rilpivirine.
Assignment !!!
• Differentiate between nucleoside and non nucleoside reverse
transcriptase inhibitors
• Differentiate between nucleotide and nucleoside reverse transcriptase
inhibitors
2.Protease Inhibitors (PIs)
• Examples of PIs include Amprenavir (APV), Atazanavir (ATV),
Darunavir (DRV), Fosamprenavir , Indinavir (IDV), Lopinavir (LPV),
Nelfinavir (NFV), Ritonavir (RTV), Saquinavir (SQV, ), and Tipranavir
(TPV).
• PIs are preferably combined as two PIs in one.
• Ritonavir is the preferred second PI in the combination of two PIs. An
example is LPV/r - a combination of Lopinavir and Ritonavir.
Assignment!!!
• Why is ritonavir combined with other PIs
3.Integrase Inhibitors
• Examples of INSTIs include Dolutegravir (DTG) Elvitegravir (EVG) and
Raltegravir (RAL)
4.Entry Inhibitors
• Fusion Inhibitors Example of FI is Enfuvirtide
• Chemokine receptor antagonists Example of CCR5 antagonists is
Maraviroc
First-line ART Regimens in Kenya
• ARVs are usually administered as a combination of 3 drugs from two
different classes.
• The recommended first line therapy will usually consist of a
combination of 2 NRTIs and 1 INSTI
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• Recommended First Line ART Regimens in Kenya TDF+3TC+DTG is the
recommended first line regimen for all adults and adolescents
15years old or ≥30kg, including: including: pregnant women (at any
gestational age), breastfeeding women, patients with TB/HIV co-
infection, and patients with HBV/HIV co-infection.
• Where TDF+3TC+DTG cannot be used due to contraindications or
other reasons the following can be used as alternatives in patients
starting ART
• ABC+3TC+DTG
• TDF+3TC +EFV
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• Dolutegravir (DTG) containing Regimens DTG containing regimens are
newer antiretroviral therapies (ART) used as first line drugs due to
superior efficacy and tolerability and higher threshold for resistance
compared to EFV.
• Tenofovir/Lamivudine/Dolutegravir (TLD) is the recommended first
line ART in Kenya.
Note
• ABC can be considered for initiation of first line ART in adult patients if
they have contraindications to both TDF (renal impairment) and AZT
(anaemia).
Appropriate ART Regimens in
Special Populations
• There are special categories of people we will consider when
determining the drug regimen for a patient who needs to start ART.
They are:
1. Women with a previous exposure to NVP as part of PMTCT
2. Patients with TB
3. Patients with HBV
4. Patients with renal disease
1.Patients with TB/HIV Co-infection
• The treatment of TB is the same for HIV negative and positive
patients.
• As with all PLHIV, those who are diagnosed with TB/HIV co-infection
should be on ART and CTX as part of the comprehensive package of
care for PLHIV.
• For TB meningitis delay ART for 4 to 8 weeks
Timing of ART for TB/HIV Co-
infection
• TB treatment should be started immediately regardless of being on
ART or not. Patients who are not yet on ART, initiate ART as soon as
anti-TB medications are tolerated, preferably within 2 weeks.
• Patients with CM should delay ART for 5 weeks and until symptom
have resolved due to the high risk of IRIS.
• Patients with TB meningitis should delay ART for 4-8 weeks.
Points to note
• Anti-TB treatment should always be initiated first
• Early initiation of ART has been associated with reduced mortality and
improved TB outcomes
• ART should be started as soon as TB treatment is tolerated,
irrespective of CD4 cell count (preferably within 2 weeks)
2. Patients with Hepatitis B and HIV
Co-infection
• All HIV-positive patients co-infected with HBV (HBsAg positive) should
have a regimen containing TDF and 3TC/FTC which are active against
HBV.
• Once a patient with HBV starts TDF+3TC they should continue for life;
stopping either drug can lead to rapid HBV resistance and viral
rebound causing acute hepatitis.
• TDF+3TC+DTG is the preferred regimen.
3. Patients with Renal Disease
• All PLHIV should be screened for renal disease with urinalysis as a
baseline investigation and estimating the creatinine clearance for
patients with proteinuria or glycosuria in urine.
• TDF should be avoided in patients with renal impairment at the time
of ART initiation.
• ABC is the preferred NRTI for patients with moderate to severe renal
impairment.
ADHERENCE TO ART
Adherence to ART
Adherence simply means:
• The extent to which a patient’s behaviour matches the prescribed
healthcare regimen determined through a shared decision-making
process between the patient and healthcare provider.
• It is important to note that this is a shared decision-making process and
not an imposition by the HCW.
• According to WHO, the term adherence encompasses more than just
following the treatment regimen.
• It also constitutes the extent to which a client executes lifestyle changes
as agreed with the healthcare provider. Which may include reduction in
risky behaviour e.g. multiple sexual partners and substance abuse.
Importance of adherence
• It leads to clinical effectiveness. Remember that one of the cardinal
goals of ART is maximal and durable viral suppression.
• There are few drug options and therefore limited options for changing
regimens. With every missed dose of ART there is a reduced
concentration of medication in the patient’s blood. When this
concentration is persistently low, the virus tends to develop resistance
to the medication. ,
• Good adherence gives patients a chance to maintain or return to a
productive and healthy life
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• Sustained HIV suppression
• Reduced risk of drug resistance,
• Improved quality of life and survival
• Decreased risk of HIV transmission.
Consequences of poor
adherence
• Exposure of the virus to sub-optimal concentrations of ARVs leads to
on-going viral replication and continued CD4 destruction.
• Development of OIs and increases the risk of death.
• Sub-optimal levels of ARVs leads to development of resistance.
• There is a limited choice of affordable combinations, so they may not
have good options for future treatment.
• Resistant strains can be transmitted in the population
Calculation of level of adherence.
Successful HIV therapy requires adherence of > 95%.
• This percentage can be determined in two ways:
i. Adherence from pill counts:
• # Pills taken X 100 = % Adherence
# Pills should have taken
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• Adherence from self-report (e.g. for past 4 days):
• # Doses that should have been aken – # missed doses X 100 = %Adherence
• # Doses that should have been taken
Factors Influencing Adherence
• 1.Patient Factors
Patient factors that are likely to affect adherence to medication include:

a)Psychological and social issues (stigma and non-disclosure, substance

abuse, and depression and other psychiatric illnesses).
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b)Cultural and religious beliefs. Some patients may stop taking their
medications if they believe they have been cured through prayer or
traditional medicines.
c)Poverty. A patient may opt not to take medication because they do
not have food. Some patients are unable to afford transport to the
clinic causing them to miss appointments and medication refills.
d)Occupational factors such as work schedules etc.
2.Healthcare Worker Factors
• It is essential that you have a good understanding of the medications the
patient needs and a good understanding of the importance of
adherence.
• You cannot convince a patient about the importance of adherence if you
are not convinced yourself.
• You also need to be able to prepare patients for common and serious
side effects of drugs so they can recognize them and so they understand
what action/s they should take if they experience side effects.
• You also need sufficient time to transfer the knowledge, address
concerns, and confirm understanding. If this is rushed, chances of
miscommunication are very high.
3.Disease Factors
• HIV itself and its associated OIs can also influence adherence.
• HIV-Associated Neurocognitive Disorder (HAND), previously called
AIDS Dementia) is common and underdiagnosed In PLHIV.
• HAND can affect understanding and also increase forgetfulness.
• HIV associated OIs and co-morbidities can affect adherence e.g. OIs
that affect feeding, or cause nausea.
4.Drug Factors
• Pill burden, side effects, and overlapping toxicities between ARVs, OI
prophylactic drugs, and treatment for OIs and co-morbidities can all
interfere with adherence and need to be considered whenever
prescribing a new drug
5. Patient-Provider Relationship
• Adherence can be facilitated when a patient-provider relationship
incorporates trust, good communication, adequate education about
medications, and an overall perception of caring, including a culturally
and linguistically appropriate approach to the relationship.
• If any of these lacks, the relationship may be compromised hindering
any further communication
 6. Clinical Setting factors
Numerous clinic characteristics have an impact on adherence to ART, including:
• Proximity to patient’s home or place of work
• Expense of getting to the clinic
• Lengthy delays between appointments
• Clinic opening and closing times
• Long waiting times
• Lack of child care services
• Privacy and confidentiality issues
• Unsympathetic / inconsiderate staff
Tools for monitoring adherence
• MMAS 4 –assignment
• MMAS 8-assignment
• Self-reports-Patients recall of missing a dose or Can be done using a
series of nonjudgmental questions at clinic visits
• Pill counts- Providers count remaining pills during clinic / home visit and
Adherence is then calculated.
• Patient diaries -Diaries in which client’s record the time and date of
medication intake, missed doses, and reasons for missed doses.
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• Pharmacy records - Pharmacists / dispensers base next pick-up date
on number of drugs dispensed • Every visit must be accurately
recorded .
• Visual analogue scale (VAS)
Patient asked to place a mark along a linear scale of 1 to 10 that best
describes their adherence to ARVs
• Biological markers -VL testing and CD4 counts
Causes of non adherence
• Stigma: hinders patients from disclosing their HIV status and seeking
information about ARVs. It also prevents PLHIV from attending
recognized HIV/AIDS health centres, because they are afraid to be
seen.
• Blame: If a family judges or blames an individual for contracting HIV,
that individual may be less likely to adhere to ARV therapy.
• Fear: of side effects, of costs, and fear that treatment won’t work.
• Ignorance: People still lack proper information about ARVs, and this
can lead to inconsistency in taking them.
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• Negative Outlook: Some people believe that since ART is not a cure
for HIV/AIDS, there is no point in taking the drugs.
• Lack of disclosure: People fail to disclose to their spouses, children, or
their employers that they are taking ARV drugs.Those close to the
individual need to understand about the disease and therapy
regimen, so they can help the individual.
• Lack of proper counselling: PLHIV must receive counselling before
and during the treatment regimen. Without counselling, individuals
are more likely to give up on ARVs.
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• Reduced availability of ARVs in the rural settings: There are still a few areas
in Kenya which may have limited access; drug shortages at health facility or
long distances to health facility may lead to inconsistent usage of drugs.
• Discrimination and Gender issues: In households with limited resources,
infected males in the family may be given priority over the females.
• Religious beliefs: In some belief systems, obtaining medical treatment, such
as ART is considered sacrilegious.
• Violation of Human Rights: when children infected with HIV and are eligible
to receive ARV treatment, are not made aware of their condition:
Factors that improve adherence
among patients
• Using FDCs
• Using regimens with easier dosing schedules (e.g. TDF+3TC+EFV OR
TDF+3TC+DTG given once daily)
• Availability and affordability of ARV drugs
• Being warned about common side effects in advance
• Ensuring the patient is ready before starting ART
• Participation of the patient in the care plan
• Counseling
Strategies that can be used to
promote adherence
• Assisted disclosure
• Treatment buddies
• Support groups
• Electronic reminders
• Medication diaries
• DOTS
• Information education and communication materials on ART.
Medication use counselling .
• The exchange of information between a suitably trained healthcare
provider and a patient regarding the use of medicinal products that is
aimed at ensuring the product achieves its intended treatment goal
MUC requires the following:
• Up-to-date knowledge by the HCW who is dispensing the medication
• An open, trusting and non-judgmental relationship between the
pharmacist and patient
• Adequate time
• Use of updated patient education aids
Importance of MUC
• Promotes adherence
• Educates the patient
• Improves the patient’s confidence in the healthcare system
• Helps to assess the patient’s understanding of their therapy
• Helps to establish communication with the patient and get feedback
from them
ARV IN CHILDREN
ARV IN CHILDREN
• Infants who initiate ART at less than 4 weeks of age should initiate on
AZT+3TC+NVP irrespective of previous ART exposure; metabolism of
other ARVs is not well known for this age group.
• As soon as these infants become 4 weeks old, they should switch to
ABC/3TC+DTG.
• Consult the Regional or National HIV Clinical TWG in case of pre-term
infants
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• Once adolescents reach 30 kg, if virally suppressed they should be
considered for transition
• TAF may become the preferred NRTI once fixed-dose combinations
are available
• DTG/3TC dual therapy may be considered for HBV-negative patients
once fixed-dose combinations are available
The end
questions