HIV guidelines in Namibia- a guide on the approach

HIV Guidelines Overview
05 December 2023
Dr OA Davids

HIV Prevalence Rates in Namibia
NAMPHIA 2017

Prevalence of HIV by sex and age groups
among ages 15-64 years: NAMPHIA 2017

Types of White Blood Cells
• Phagocytic Cells
• Neutrophils
• Monocytes
• Macrophages
• Eosinophils
• Basophils
• Lymphocytes
• Natural killer cells
• T-cells
• CD4 cells
• CD8 cells
• B-cells
• Plasma cells

• There are two types of HIV causing similar illness:
• HIV 1
• Is found worldwide
• Is the main cause of the worldwide pandemic
• HIV 2
• Is mainly found in West Africa, Mozambique and Angola
• Less efficiently transmissible; rarely causing vertical transmission
• Less aggressive with slower disease progression
• Some ARV medicines are ineffective
Basic Virology

• Predominant strain found in Namibia is HIV-1 type C:
• Confirmed by NIP study
• This is the most virulent subtype
• It has higher multiplication rates
• Is associated with faster disease progression in adults
• In contrast, subtype B is the most common subtype in USA and
Europe
HIV 1 Subtype C

Natural Progression of CD4 Count, VL and Clinical Course of
Untreated HIV Infection in Adults

• Uninfected Adults:
• CD4 counts above 500 cells/mm3 are usually considered normal
• HIV Infected Adults:
• CD4 gradually declines to very low levels
• the body replaces CD4 cells but is eventually overwhelmed
• < 200 cells/mm3 indicates severe immune system damage
CD4 Lymphocyte Counts

• Quantity of viral particles per ml of blood:
• Measures how much virus is reproducing
• Quantifies HIV-1 and not HIV-2
• Range is highly variable:
• < 40 copies (usually on treatment) to > 1,000,000 copies/ml (in acute phase or
no treatment or failing treatment)
• The higher the viral load, the faster the CD4 count decreases
• The lower the viral load, the slower the CD4 count decreases
Viral Load

Acute Retroviral Syndrome
SYMPTOMS
• Fever 87%
• Rash 68%
• Pharyngitis 48%
• Myalgia 42%
• Headache 39%
• Diarrhoea 32%
• Abd. Pain 32%
• Arthralgia 29%
• Nausea/Vom. 29%
SIGNS
• Temp > 37.5°C 70%
• Macular Rash 63%
• Lymphadenopathy 57%
• Oral Ulcers 40%
• Genital Ulcers/Disch 36%
• Purulent Sputum 6%
• Urticarial Rash 6%
• Stiff Neck 6%
• Presents 2-4 weeks after infection, lasts 2-4 weeks

• Patients are typically highly infectious during acute HIV due to an
enormous viral burden in blood and genital secretions
• A large proportion of all HIV infections may be transmitted by
individuals with primary infection
• Unfortunately, the diagnosis of acute HIV infection is infrequently
made in clinical practice
• If suspected, counsel on safe sex practices
• Offer HIV test and if the result is HIV negative repeat after 3 months
Acute HIV Infection

• Tests for HIV antibodies:
• HIV antibodies develop 2-10 weeks after HIV infection in most cases
• False negative or indeterminate test results during primary HIV infection
• False positive in children younger than 18 months because of passive
immunity from a mother
Antibody Tests in Acute HIV Infection

• Assesses degree of immunosuppression by clinical
criteria:
• Separate lists for adults and for children <15 yrs
• Assess clinical stage on every visit
• Applied to confirmed HIV positive patients
• Used as risk assessment criteria when initiating ART
• A person with multiple clinical conditions, should be
categorized using the highest stage.
• Same staging list used to determine “T” (treatment)
staging when a patient is on ART
WHO Clinical Staging for HIV and AIDS

CD4 cells
> 500
CD4 cells
500-350
CD4 cells
350-200
CD4 cells
< 200
Stage 1: Asymptomatic
Stage 2: Minor Symptoms
Stage 3: Moderate
Symptoms
Stage 4: AIDS,
severe symptoms
Primary HIV Infection 5-10 years
Natural History: Classification of HIV/AIDS
by the WHO

• Asymptomatic: no symptoms or signs of any illness OR
• Persistent Generalised Lymphadenopathy (PGL):
• Painless enlarged LN, >1cm, in 2 or more non-contiguous sites (excluding
inguinal) in the absence of known cause and persisting for 3 months or more
WHO Clinical Stage 1: Asymptomatic

• Unexplained moderate weight loss:
• <10% of presumed or measured body weight
• Recurrent respiratory tract infections:
• sinusitis, tonsillitis, otitis media and pharyngitis
• Herpes zoster
• Angular cheilitis
• Recurrent oral ulceration
• Papular pruritic eruptions
• Seborrhoeic dermatitis
• Fungal nail infections
WHO Clinical Stage 2: Mild Symptoms

• Unexplained severe weight loss:
• >10% of presumed or measured body weight
• Unexplained chronic diarrhoea for longer than one month
• Unexplained persistent fever:
• above 37.6°C intermittent or constant, for longer than one month
• Persistent oral candidiasis
• Oral hairy leukoplakia
WHO Clinical Stage 3: Advanced Symptoms

• Pulmonary tuberculosis
• Severe bacterial infections (such as pneumonia, empyema,
pyomyositis, bone or joint infection, meningitis or bacteraemia)
• Acute necrotizing ulcerative stomatitis, gingivitis or periodontitis
• Unexplained anaemia (<8 g/dl), neutropaenia (<0.5 × 109 per litre)
and/or chronic thrombocytopaenia (<50 × 109 per litre)
WHO Clinical Stage 3: Advanced Symptoms (2)

• HIV wasting syndrome
• Pneumocystis pneumonia
• Recurrent severe bacterial pneumonia
• Chronic herpes simplex infection (orolabial genital or anorectal of
more than one month’s duration or visceral at any site)
• Oesophageal candidiasis (or candidiasis of trachea bronchi or lungs)
• Extrapulmonary tuberculosis
• Kaposi’s sarcoma
WHO Clinical Stage 4: Severe Symptoms

• Progressive multifocal leukoencephalopathy
• Chronic cryptosporidiosis (with diarrhoea)
• Chronic isosporiasis
• Cytomegalovirus infection (retinitis or infection of other organs)
• Central nervous system toxoplasmosis
• HIV encephalopathy
• Extrapulmonary cryptococcosis including meningitis
• Disseminated non-tuberculous mycobacterial infection
WHO Clinical Stage 4: Severe Symptoms (2)

• Disseminated mycosis (histoplasmosis or coccidiomycosis)
• Recurrent non-typhoidal Salmonella bacteraemia
• Lymphoma (cerebral or B-cell non-Hodgkin) or other solid HIV-
associated tumours
• Invasive cervical carcinoma
• Atypical disseminated leishmaniasis
• Symptomatic HIV-associated nephropathy or symptomatic HIV-
associated cardiomyopathy
WHO Clinical Stage 4: Severe Symptoms(3)

• Status should be recorded at each patient visit in the Patient Care
Card as:
• (W) Working
• Able to work, go to school, do housework, or harvest, or for children, normal activities or
playing. Working does not mean the patient is employed
• (A) Ambulatory
• Able to perform activities of daily living but not able to work or play
• (B) Bedridden
• Not able to perform activities of daily living
Functional Status

• Criteria for use in Namibia:
• CD4 count ≤350 cells/mm3
• Clinical Stage 3 or 4 irrespective of CD4 count
• If CD4 count is <200 cells/mm3 in patient with known allergy or who
develops allergy to CTX:
• Give Dapsone 100mg once daily as an alternative
• Re-check CD4 every 6-months and discontinue once the CD4 is >200 for 2
consecutive readings
Co-trimoxazole Preventative Therapy in Adults

• Reduces risk of active tuberculosis by 60% in HIV positive patients
with latent TB infection
• Can be used in pregnancy
• Due to high rate of endemic TB in Namibia, all HIV positive patients
are assumed to be latently infected
• Tuberculin Skin Test (TST) is not necessary
• All HIV positive patients who do not have a contraindication should
have a course of IPT
Isoniazid Preventive Therapy (TB-IPT)

• NRTIs:
• Nucleoside reverse transcriptase inhibitors
• Nucleotide reverse transcriptase inhibitors (NtRTI)
• NNRTIs – non-nucleoside reverse transcriptase inhibitors
• PIs – protease inhibitors
• Integrase inhibitors
• Fusion inhibitors (eg: Maraviroc) – not available in public sector
• CCR5 entry inhibitors - not available in public sector
Classes of Antiretrovirals

• Nucleoside/tide analogues - block transcription of HIV RNA into DNA
by inhibiting HIV Reverse Transcriptase:
• Tenofovir (TDF) (nucleotide)
• Zidovudine (AZT)
• Lamivudine (3TC)
• Abacavir (ABC)
• Emtricitabine (FTC)
• Stavudine (D4T)
• Didanosine (DDI)
Nucleoside Reverse Transcriptase Inhibitors
(NRTIs)

Unit 4: Slide 29
• Nucleoside/tide analogues - block transcription of HIV RNA into
DNA by inhibiting HIV Reverse Transcriptase:
 Tenofovir (TDF) (nucleotide)
 Zidovudine (AZT)
 Lamivudine (3TC)
 Abacavir (ABC)
 Emtricitabine (FTC)
 Stavudine (D4T)
 Didanosine (DDI)
Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

Unit 4: Slide 30
• Atazanavir (ATV)
• Lopinavir (LPV) (comes formulated with ritonavir as Kaletra® and
Aluvia®)
• Ritonavir (RTV) (used to boost levels of other PIs)
• Darunavir (DRV)
• Indinavir (IDV)
• Tipranavir (TPV)
Protease Inhibitors (2)

Unit 4: Slide 31
• Enfuvirtide (T-20, Fuzeon®):
 Fusion inhibitor
 Administered by subcutaneous injection
 Used only in salvage therapy
• Maraviroc:
 CCR5 chemokine Inhibitors
Entry and Fusion Inhibitors (2)

Unit 4: Slide 32
• A combination of 3 or more ARV medicines, to achieve viral
suppression usually:
 2 NRTIs (eg: TDF/3TC/FTC/ABC/AZT/TAF)
PLUS
 1 INSTI (eg: DTG / RAL) or 1 PI (eg: ATV/LPV/r)
• Highly Active Antiretroviral Therapy
 Antiretroviral Therapy is highly active in suppressing viral replication
 “Highly Active” is no longer needed as a qualification
• Therapy with only one or two agents allows for selection of
resistance mutations
Antiretroviral Therapy (ART)

Unit 4: Slide 33
• Management of co-morbidities
• Recognise new OIs and immune reconstitution
• HIV resistance can be avoided by optimal viral suppression
• Adherence counselling and support network vital throughout
treatment
Principles of Successful ART (2)

Unit 4: Slide 34
• The patient should have the following taken:
 a complete medical history
 physical examination
 appropriate baseline laboratory tests
 rule out the presence of opportunistic infections
 determine readiness to start ART
ART: Assessment at the Time of Diagnosis

Unit 4: Slide 35
Recommended First Line ART Regimens
Preferred 1st line Regimens Alternative 1st line Regimens
TDF + 3TC (or FTC) + DTG*
(TLD1)**
TAF*** +3TC (or FTC) + DTG*
TAF +3TC (or FTC) + DTG
ABC+3TC+DTG****
TDF + FTC (or 3TC) + ATV/r
AZT + 3TC + DTG*
1st line regimens applicable to:
• Adult males and adolescent boys ≥10 years and weighing at least
30kg
*TB patients on Rifampicin to receive DTG twice daily (b.d)
**TLD1 means patient is on TLD as first line
***TAF is not currently suitable for pregnant women, TB/HIV coinfected and CrCl<30
****ABC/3TC/DTG can be used from weights of 20kg.
Alternative regimens should only be used if the preferred first line regimen is not an option

Unit 4: Slide 36
• TB patients on Rifampicin to receive DTG twice daily
(b.d)
• TAF is not currently suitable for pregnant women,
TB/HIV coinfected and CrCl<30
• ABC/3TC/DTG can be used from weights of 20kg.
• TLD1 means patient is on TLD as first line
• TDF based regimens should be initiated on the same
day of HIV diagnosis and the clinician should draw blood
for baseline creatinine clearance to be reviewed within 2
weeks
• Alternative regimens should only be used if the preferred
first line regimen is not an option
Specific considerations for First Line ART Regimens

Unit 4: Slide 37
• Drug mutations and VLs should guide switching of ARVs:
• Mutation Classes
 TAM (Thymidine Analogue Mutations)
o Reduce NRTI susceptibility
o First reported in persons receiving AZT monotherapy
 K65R mutation
o Rarely selected (1.7 – 4%)
o Increases AZT susceptibility (except in combo with Q151M)
o Rarely occurs with most TAMs due to bidirectional antagonism (TAMs can restore susceptibility to AZT).
o Reduces susceptibility of ABC (two-fold) and TDF
 M184V mutation
o Most common NRTI mutation
o Causes high-level resistance 3TC and FTC
o Increased susceptibility to AZT and TDF
 NNRTI Drugs - NVP and EFV
• ONLY switch between classes, (e.g. TAM to K65R) if viral load <40
• If viral load >40 you may keep the same drug if not toxicity or switch within class ( e.g TDF to ABC)
Switching of ARVs Between Classes in First Line
ART Regimen

Unit 4: Slide 38
• Before changing to second line:
 Determine and address reasons for first-line failure
 Determine the treatment history (all the regimens the patient has
been exposed to)
 Address adherence issues and solve them
 Each case should be discussed with a clinical mentor or a HIV
experienced physician
• Anticipate cross-resistance (e.g. ABC and TDF)
Second-Line Therapy

Unit 4: Slide 39
Recommended Second line Regimen
Failing first-line Regimen Preferred second-line Regimen
TDF(or TAF) + 3TC + DTG
or
ABC + 3TC + DTG
AZT + 3TC + ATV/r or (LPV/r)
TDF(or TAF) + 3TC + EFV
or
TDF + 3TC + ATV/r
AZT + 3TC + DTG*
AZT + 3TC + EFV or
AZT + 3TC + ATV/r
TDF (or TAF) + 3TC + DTG**
*For HIV/TB coinfection on rifampicin based regimen, use LPV/R (super booster) instead of ATV/r and
DTG B.D instead of DTG O.D
** Maintain TDF in the second line for patients with chronic HBV coinfection

Unit 4: Slide 40
• For patients with true previous AZT toxicity, consult clinical mentor
or HIV experienced physician
• Super-boosted LPV/R is poorly tolerated in some patients due to
GIT side effects
 Discuss management options with an HIV experienced provider or
clinical mentor
Recommended Second line Regimen (2)

Unit 4: Slide 41
• A means to determine the clinicial siginificance of a change in
viral load
• Difference of 0.5 is considered significant in RSA
• In Namibia we use 1.0
Log Value

Unit 4: Slide 42
• Given to patients who have failed available 1st and 2nd line
regimens
• All patients failing Second-Line Regimen should undergo HIV
resistance testing following consultation with clinical mentor or a
HIV experienced physician
• This regimen is designed based on resistance testing results
 A special laboratory request form is used for this and must be
authorized by a clinical mentor or specialist
Third-Line Regimen for Adults

Unit 4: Slide 43
• All HIV infected individuals are eligible for ART irrespective of
CD4 count or WHO staging
• Accelerate ART initiation
 If READY initiate same day or within one week
• Adherence to therapy and potency of regimen are main factors
that determine effectiveness of ART
• Adherence issues should be address before switching to 2nd line
regimen
• Consult a clinical mentor or HIV experienced physician before
changing therapy
Key Points

Unit 4: Slide 44
Phase of HIV
management
Tests Frequency
At initial clinic visit CD4
HBsAg
CrAg
Hb
CrCl
HIV NAT
Repeat
Once
Once; if positive, repeat after 6
months. If HBsAg is reactive,
then the lab will automatically
do ALT
Once if CD4<200
Once
Once IF regimen is TDF based
Once If <18 months old-Do not
wait for results to initiate ART
Laboratory Monitoring For PLHIV

Unit 4: Slide 45
Phase of HIV
management Tests Frequency
Treatment
monitoring
VL
CrCl
6M,12M (then every 12 months)
Children and adolescents under 19
years routine VL every 6 months;
pregnant women 3 monthly until
delivery and BF women 6 weeks
after delivery then 3 monthly until
end of breast-feeding period
6w, 6M, 12M (then every 12
months) if on TDF
Laboratory Monitoring For PLHIV (2)

Unit 4: Slide 46
Phase of HIV
Treatment
monitoring
Hb 2w, 6w, M3 if on AZT.
No need to repeat Hb after
three months if there is no
anaemia
HBsAg positive ALT 2w, 6w, 3M (then every 12 months
if the second HbsAg remain
positive)
Suspected
treatment
failure
VL Repeat VL after 3 months of good
adherence to treatment and once
OIs are excluded

Unit 4: Slide 47
Phase of HIV
Virological
failure
1) CD4
2) HIV
Drug
Resistance
• After 3 months of suspected
virologic failure in Children <10
years old who have been on a PI
as part of 1st line with eMTCT
NVP exposure in infancy.
• Before Switching to a 3rd line
regimen all ages
Secondary
fluconazole
prophylaxis
following
cryptococcal
meningitis
CD4 • 6-monthly while on fluconazole
prophylaxis until 2 consecutive
values >200 cells/mm3

Unit 4: Slide 48
• If the creatinine clearance is <50ml/minute an alternative to TDF
should be included in the ART regimen unless the patient is co-
infected with HBV.
• In such cases TAF (if available) or dose adjusted TDF may be
considered.
• Other alternatives may include ABC and AZT
Use of TDF in Renal insufficiency

Unit 4: Slide 49
• Estimate CrCl with the patient’s weight, a serum
creatinine and the formula:
(140-age) x body weight (kg) x 1.22
serum creatinine (μmol/l)
For women, multiply above result by 0.85
NB. Mobile apps can be used to calculate CrCl
Calculating Creatinine Clearance (CrCl) for
Adults

Unit 4: Slide 50
Phase of HIV
Treatment
monitoring
VL 6M, 12M (then every 12
months) Children and
adolescents under 19 years
routine VL every 6 months;
pregnant women 3 monthly until
delivery and BF women 6 weeks
after delivery then 3 monthly
until end of breast-feeding
period
Second-Line ART: Laboratory Monitoring

Unit 4: Slide 51
Phase of
HIV
manageme
nt
Tests Frequency
Treatment
monitoring
CrCl
Hb
Baseline, 6w, 6m, 12m
(then every 12 months) if
on TDF for the first time
Baseline, 2w, 6w, M3
if on AZT for the first
time
Second-Line ART: Laboratory Monitoring (2)

Unit 4: Slide 52
Result (Copies per Ml) Interpretation
< 40 or Target Not
Detected (TND)
Virological suppression
40-1000 Low level viremia
> 1000 Treatment failure
Viral Load Results Interpretation

Unit 4: Slide 53
• Provides identification of HIV mutations that may have been
selected and which might be causing virological failure in a patient
who is adhering well to ART.
• A Specialist or Clinical Mentor can give approval for HIV
resistance testing on an individual patient basis.
Resistance testing

Unit 4: Slide 54
• Patients who return after being lost to follow up and did not take
ARVs for at least 6 months;
• Assess for OIs
• Do CD4 test
• Manage any co-infections and provide appropriate prophylaxis.
• After ART re-initiation, do VL following the routine monitoring
schedule.
• If the VL is not suppressed after 6 months, the SOP for high VL
monitoring should then be followed.
Lab Monitoring in Patients Restarting ART After
LTFU (NEW)!!!

Unit 4: Slide 55
• Laboratory monitoring is important for early detection of
treatment failure
• The VL monitoring schedule for children, pregnant women
and breastfeed mothers is different
• A specialist/clinical mentor needs to be consulted before
doing HIV genotype test
Key Points

HIV guidelines in Namibia- a guide on the approach

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