1. WHEN TO START ANTI-RETROVIRAL
THERAPY IN ADULTS AND
ADOLESCENTS
BY GROUP 16
2. BROAD OBJECTIVES
• By the end of this presentation learners should be
able to know and understand the criterias for ART
initiation
3. SPECIFIC OBJECTIVES
• To explain when to start antiretroviral therapy in adults and
adolescents
• To explain the clinical assessment of HIV infected adults and
adolescents
• To describe the benefits and risks of starting ART
• To describe WHO clinical staging of HIV
4. OBJECTIVES CONTINU…
• To explain the immunological assessment of HIV infected
adults and adolescents
• To explain the virological assessment of HIV infected adults
and adolescents
• To explain the consideration for treatment on the basis of a
public health approach
5. OBJECTIVES CONTI….
• To construct first line regimens
• To describe important points before adapting the ARV regimens
by nations
• To describe the recommendations by WHO
• To describe pathophysiology and management of IRIS
6. WHEN TO START ART IN ADULTS AND
ADOLESCENTS?
• All HIV confirmed infected people should start ART as soon as
possible for their own health and to prevent passing the virus on
to others.
7. CLINICAL ASSESSSMENT OF HIV- INFECTED
ADULTS AND ADOLESCENTS
• clinical assessment should be carried out to determine existing
conditions which will help in selecting suitable ARV regimen,
such conditions include hepatitis, Tuberculosis, pregnancy,
major psychiatric illness, anemia etc.
• Medical history should also be considered (including traditional
and herbal medication) to avoid drug interaction.
• weight measurement for drug dosages
8. ASSESSMENT CONTINUE…
• patient readiness for therapy
• Hemoglobin measurement if Zidovudine(AZT) is
considered
• pregnancy test if EFV is considered (Efavilins)
• CD4 COUNT cell testing
• Viral load Testing
9. BENEFITS OF STARTING ART TREATMENT
• ART for all HIV infected people is the most effective
prevention method available: Successful ART leads to very
low levels of virus in the blood and in body fluids (viral
suppression).
• There is high treatment coverage and high adherence
• Reduced Viral load in Patients on ART. transmission
• Viral suppression greatly reduces the risk of sexual or
mother-to-child.
10. BENEFITS CONTINUE…
• Earlier initiation and time spend on ART may
provide impetus to shift to less toxic first line
regimen
• Reduces the risks of Tuberculosis and invasive
bacterial diseases due to decline of viral load
11. RISKS OF EARLY INITIATION OF ART
• increases ART cost
• people who urgently in need of the drugs may be displaced by
those who do not need the drug urgently
• early initiation will put someone longer exposure to ART and
may face more ART - Related side effects and ARVS
resistance
• the impact of earlier initiation on adherence is uncertain
12. WHO CLINICAL STAGING OF HIV DISEASE
• The world health organization (WHO) has a method of describing the
different stages of the HIV disease based on clinical symptoms, known as
the WHO staging system for HIV disease.
• It is used when HIV infection has been confirmed by HIV antibody
testing, and it forms part of the baseline assessment on entry into care.
• Untreated HIV infection leads to gradual destruction of the immune
system, leading to different HIV-related diseases
13. CONTI…
• Most of the HIV-related diseases can also occur in HIV negative
patients, but they are more common and more severe in HIV infected
patients.
• Most WHO stage defining conditions apply to all ages ,but some are
only for children under 15years and others are for adults.
• WHO clinical staging requires confirmed HIV infection and is
mandatory for all HIV patients regardless if a CD4 count is available.
14. • HIV-related diseases are grouped into four WHO
clinical stages:
stage 1: Asymptomatic
stage 2: Mild symptoms
stage 3: advanced symptoms
stage 4: severe symptoms
15. WHO CLINICAL STAGING FOR CHILDREN AND
ADULTS WITH CONFIRMED HIV INFECTION
AND DEFINITION OF PRESUMMED SEVERE
HIV DISEASE FOR INFANTS
16. ADULTS AND CHILDREN ADULTS ONLY(15 YEARS OR
OLDER)
CHILDREN ONLY( BELOW 15
YEARS)
1. Asymptomatic
Persistent generalized
lymphadenopathy
2. Respiratory tract
infections,reccurent(sinusitis,
tonsillitis, otitis media,pharyngitis)
Herpes zoster
Angular chelitis
Oral ulcerations, reccurent
Papular prulitic eruptions/fungal
nail infections
Moderate weight loss
<10%,unexplained
Seborrhoeic dermatitis
Hepatosplenomegaly,persistent
unexplained
Lineal gingival erythema
Wart virus infection,extensive
Molluscum contagiosum,extensive
Parotid enlargement,persistent
unexplained
3. Fever, persistent unexplained,
intermittent or constant, >1month
Pulmonary tuberculosis(current)
Tuberculosis(PTB or EPTB) within
the
last 2 years
Anaemia, unexplained <8g/dl
Neutropaenia,unexplained<500/mm
3
Severe weight loss >10% and/or
BMI <18.5kg/m2
Diarrhoea, chronic(>month)
unexplained
Oral candidiasis
Severe bacterial
infections(pneumonia, empyema,
pyomyositis, bone/joint, meningitis,
bacteraemia)
Acute necrotizing ulcerative
Moderate unexplained
wasting/malnutrition not responding
to treatment ( weight for height /age
70-79% or MUAC 11-12mc)
Diarrhoea, persistent unexplained
(14 days or more)
Oral candidiasis (from age 2 months)
Acute necrotizing ulcerative gingivitis
or periodontitis
Lymph node tuberculosis
17. 4. Pneumocystis pneumonia
Candidiasis of oesophagus,
trachea, bronchi or lungs
Extrapulmonary tuberculosis
Kaposi’s sarcoma
HIV encephalopathy
Cryptococcal meningitis or
other
extrapulmonary
cryptococcosis
Disseminated non-
tuberculosis
mycobacterial infection
Cryptosporidiosis, chronic
with
diarrhea
Isosporiasis >1 month
Disseminated mycosis
(coccidiomycoooosis or
histoplasmosis)
Symptomatic HIV-associated
nephropathy or
cardiomyopathy
HIV wasting syndrome(severe
weight loss + persistent fever or
severe weight loss + chronic
diarrhea)
Baacterial pneumonia, recurrent
severe
Chronic herpes simplex infection
(orolabial genital/anorectal >1
month or visceral at any site)
Cytomegalovirus infection
(retinitis or infection of other
organs)
Toxoplasmosis of the brain
Non-typhoidal Salmonella
bacteraemia, recurrent
Invasive cancer of the cervix
Leishmaniasis, atypical
disseminated
Severe unexplained wasting/
malnutrition not responding to
treatment (weight for height/age
<70% or MUAC <11cm or
oedema)
Bacterial infections, severe
recurrent (empyema,
pyomyositis, bone/joint,
meningitis, but excluding
pneumonia)
Chronic herpes simplex infection
( orolabial or cutaneous >1
month or visceral at any site)
Cytomegalovirus infection:
retinitis or other organ (from age
1month)
Toxoplasmosis of the brain (from
age 1 month)
Recto-vaginal fistula, HIV-
associated
Presumed Severe HIV Disease
18. CONTINUE….
• Previously where CD4 testing was not available, the WHO staging
system was being used to determine whether to start
treatment(WHO 2009 treatment guidelines) or not.
• Where a patient is showing signs of WHO clinical stage 3 and 4
they were eligible to start treatment.
• Where a patient is showing signs of WHO clinical stage 1 and 2
they were not eligible to start treatment.
19. IMMUNOLOGICAL ASSESSMENT OF HIV-
INFECTED ADULTS AND ADOLESCENTS
• CD4 counts are the most direct routine measure for HIV immune
suppression.
• A normal CD4 count ranges from 500-1,200cells/mm3 in adults
and adolescents.
• A drop in the CD4 count below 200 cells/mm3 is associated with
a significant increase in opportunistic infections and/or the
disease is progressing.
20. CONTINUE….
• Targeted CD4 count is done to patients with suspected clinical
and/or confirmed treatment failure.
• If CD4 count is <200cells/ml routine urine LAM for disseminated
TB, and serum CrAg for cryptococcal meningitis is done.
• Previously CD4 count was being used to determine on when to
initiate treatment.
• If CD4 is <200cells/mm3 treatment was being initiated
irrespective of clinical stage
21. CONTINUE…..
• If CD4 is 200-350cells/mm3 treatment was being
initiated before CD4 drops below 200
• If CD4 is >350cells/mm3, treatment was not being
initiated on client.
22. VIROLOCICAL ASSESSMENT OF HIV-INFECTED
ADULTS AND ADOLESCENTS
• Viral load (VL) is the number of viral particles per ml of blood.
• Viral load is the measure for the level of progression of HIV
infection.
• It is required to confirm suspected treatment failure.
• Successful treatment leads to low levels of HIV in the blood that
it can no longer be detected with viral load testing.
23. CONTINUE….
• undetectable viral load is also called viral suppression, which is
the aim of treatment
• From the public perspective, the expanded access to viral load
determination should be considered primarily for the diagnosis of
HIV infection in infants and children under 18 months.
24. CONTINUE…
• Currently the affordable methods of determining viral load are
not viable but it is hoped that more affordable methods of
determining viral load ideally to the point of care will be viable
to improve the standard of monitoring for patients on treatment,
especially in situations where treatment switching is being
considered.
25. CONSIDERATIONS FOR TREATMENT ON THE
BASIS OF PUBLIC HEALTH APPROACH
• Countries are encouraged to use public health approach to
support and facilitate wider access to treatment
• Among the key principles of this approach are standardizations
and simplifications of treatment regimens. Therefore it is
suggested that countries select limited number of first-line
regimens and suitable second-line regimens.
26. CONTINUE….
• The use of three ARVs medications is the current
standard treatment for HIV infection in order to achieve
the best possible suppression of viral replication and to
arrest the progression of HIV disease.
27. FACTORS TO BE CONSIDERED WHEN SELECTING
APPROPRIATE TREATMENT REGIMENS FOR PROGRAM
LEVEL:
• 1. Ability to treat all ages
2. Suitability of drug formulation, particularly the availability of
fixed-dose combination
3. licensing approval by national drug regulatory authorities for
the product and the recommended dose.
4. potential for maintenance of future treatment options
28. CONTI…
5. toxicity profile
6. laboratory monitoring requirement
7. promotion of adherence( ARVs taken once daily or twice daily
are well tolerated by clients)
8. special considerations for women of childbearing age and
pregnant women
29. CONTINUE…
9. prevalent coexisting conditions eg tuberculosis, hepatitis b
and c
10. availability from local and intentional manufacturers
11. price and cost-effectiveness
30. CONSTRUCTING THE FIRST LINE REGIMEN
• Regimen are numbered for ease of reference:
• Regimen 4, 5, 6, 13, 14, 15 and 17 are 1st line regimens
• Regimen 13 is the new standard 1st line regimen for males and
females weighing 30kg or above.
• Regimen 0 and 2 have been removed………..
• Regimen 1 and 3 contain stavudine (d4T). They are no longer
used and have been deleted.
31. CONTINUE…
• Regimen 7 – 11 are 2nd line regimens.
• Regimen 12 is the standard 3rd line regimen.
• An “A” is added to the regimen number for adult
formulations (e.g. Regimen 2A) and a “P” is added for
paediatric formulations (e.g. Regimen 2P).
35. HOW DO ARVS WORK
• They prevent multiplication of viruses within the body
TYPES OF ARVs
1. Nucleoside reverse transcriptase inhibitor(NRTIs)
- act by working defective blocks in the production of HIV within the body
2. Non Nucleoside reverse transcriptase inhibitor(NNRIs)
When HIV is multiplying within the body the process requires precise instructions
the medication works by giving Wrong instructions in HIV Manufacturing
36. CONTINUE….
3. Protease inhibitors
• Not most in developing countries.
• This group of medications functions like
preventing HIV from entering the T. cells
37. IMPORTANT POINTS BEFORE ADAPTING THE ARV
REGIMENS BY NATIONS
1. DO NO HARM
• Seek to maintain current progress of treatment programmes
without disrupting the care of those on treatment or
compromising PLHIV at highest risk for poor outcomes.
• 2 Accessibility
• Ensure that all clinically eligible people infected with HIV are
able to enter treatment services.
• .
38. CONTINUE….
• 3 Quality of care
• Ensure that care achieves the highest standards possible
• 4 Equity of access
• Ensure fairness and justice in access to treatment
services.
• 5 Efficiency in resource use
• Aim to achieve the greatest health impact with the optimal
use of available human and financial resources.
40. RECOMMENDATIONS BY WHO
• Strengthen health systems
In making decisions, priority should be given to interventions that
will directly or indirectly strengthen health systems.
• Implement in phases
It may not be possible to implement every new recommendation
in every setting. A phased approach may be necessary if only
some recommendations can be implemented.
41. CONTINUE….
• Understand the perspectives of PLHIV
The toxicity of d4T is of concern to the majority of PLHIV and its
continuing use may undermine confidence in ART. If d4T has to
be included in ongoing regimens, strategies should be devised to
allow for substituting an alternative drug in cases of toxicity.
There should be a plan to eventually avoid the routine use of this
drug.
42. CLASSIFICATION OF ARVS
Mode of action Biochem. structure Abbrev. ARVs Dosing interval
Reverse
Transcriptase
Inhibitors
Nucleosides NRTI
AZT 12-hourly
3TC, ABC
12- or 24hourly
Entecavir (ETV)* 24-hourly
Nucleotide NtRTI TDF 24-hourly
Non-Nucleosides NNRTI
NVP 12-hourly
EFV 24-hourly
Protease Inhibitors PI
ATV/r 24-hourly
DRV 12-hourly
LPV/r 12-hourly
Integrase Strand Transfer
Inhibitor
INSTI
DTG 24-hourly
RAL 12-hourly
43. IMMUNE RECONSTITUTION INFLAMMATORY
SYNDROME (IRIS)
• DEFINITION
• IRIS is an over-aggressive response of the immune system caused by a
sudden recovery on ART.
• A small number of patients may get worse in the first 6 months after
starting ART.
• •
•
•
44. CAUSES
The most common causes for this are (in the order
of likelihood):
• Undiagnosed / untreated OI, mainly TB
• Poor adherence to ART
• Drug-resistant TB (if on TB treatment)
• IRIS
45. CONTINUE…
IRIS appears as a severe bout / worsening of an Opportunistic
Infection:
• TB
• Cryptococcal meningitis
• Herpes zoster
• Kaposis Sacoma
• Hepatitis
46. MANAGEMENT OF IRIS
• Confirm that ART is actually taken as prescribed.
• Continue ART if ART toxicity has been ruled out as the
underlying cause.
• Treat the OI.
• Remember that in case of any CNS infections (e.g.,
cryptococcal and TB meningitis cerebral toxoplasmosis)
ART should be started 5 weeks after initiating treatment of
CNS infection.
47. CONT…
• Consider TB treatment failure if worsening occurs
after more than one month on TB treatment.
• Admit severe cases to hospital.
• NSAIDs may be given in mild and moderate cases.
Consider prednisolone (e.g., 1mg/kg for 2 weeks then
0.5mg/kg for 2weeks) only in severe IRIS.
48. REFFERENCES
DR Mbiri, 2016, Advanced HIV/AIDS, Module, Malawi
Malawi Clinical HIV Guidelines 2021
Malawi comprehensive HIV testing and counselling
training October 2013
National Health research agenda,2012-2016
https://www.aidsmap.com
49. GROUP MEMBERS
1. Agness Gundo BScNM/UP/21/19
2. Richard Mathias BScNM/21/086
3. Anny Simbota BScNM/21/150
4. Ruth Chikweza BScNM/21/019
5. Immaculee Tuyisenge
BScNM/21/155
6. Precious Bulambo BScNM/21/010
7. Daniel Chilombo
BScNM/UP/21/012
8. Mervis Magwaza BScNM/21/078
9. Misheck Khondowe BScNM/21/068
10. Mercy Banda BScNM/21/004
11. Christiana Nthondowa
BScNM/21/127
