HIV

MANAGEMENT
IN ADULTS…
2023
GUIDELINES
DR DM DILEBO
AUGUST 2024
CONTENTS
• SOME STATS
• REVISION: Replication
• Drug classes
• 2023 UPDATES
• MONITORING
• TREATMENT FAILURE
• PREENTION OF OIs
• IRIS
STATISTICS

• The estimated overall HIV prevalence rate is approximately 13,9% among

the South African population. The total number of people living with HIV
(PLWHIV) is estimated at approximately 8,45 million in 2022. For adults
aged 15–49 years, an estimated 19,6% of the population is HIV positive.

• Globally 44% of all new HIV infections were among women and girls (all ages) in 2023.
• In sub-Saharan Africa, women and girls (all ages) accounted for 62% of all new HIV
infections. In all other geographical regions, over 73% of new HIV infections in 2023
occurred among men and boys.
• Every week, 4000 adolescent girls and young women aged 15–24 years became infected
with HIV globally in 2023. 3100 of these infections occurred in sub-Saharan Africa.
REVISION
 Fusion
inhibitors

NRTIs
and
NNRTIs

Integrase
inhibitors

Protease
inhibitors
 Transcriptase Inhibitors
Competitive inhibitor of RT
NRTI They mimic the normal building blocks of HIV DNA

They do not allow additional nucleotides to be added, acting as DNA chain

terminators
Noncompetitive inhibitors of RT
NNRTI Bind to a region of the RT outside the active site

Prevent RT activity by distorting the active site

Low barrier to resistance

NRTI NNRTI
• Zidovudine (AZT, ZDV) • Efavirenz
• Lamivudine (3TC) • Nevirapine
• Abacavir (ABC) • Rilpivirine
• Emtricitabine (FTC) • Etravirine
• Tenofovir (TDF) [NtRTI] • Delavirdine
• Didanosine (ddI) • Dapivirine
• Zalcitabine (ddC) • Doravirine
• Stavudine (d4T)
Integrase Inhibitors (InSTIs)
Through the action of integrase enzyme, the viral DNA is
integrated into host cell chromosomes

As effective as EFV, more rapid reduction in VL and durable

response

Examples: Dolutegravir (DTG)

Raltegravir (RAL)
 Protease inhibitors (PIs)
Protease enzyme catalyses the cleavage of viral polyproteins to yield mature virions

Without effective cleavage, the virus remains immature and non-infectious

PIs prevents assembly of new, fully functional HIV virions

Lopinavir/ritonavir
Saquinavir
Indinavir
(Aluvia / Kaletra)
Atazanavir Darunavir Ritonavir (Fortovase (Crixivan)
/ Invirase)
PIs and treatment principles
Drug interactions need to be considered

• Drugs that ↓ PI level: rifampicin, anticonvulsants (Phenytoin, Carbamazepine,

Phenobarb)
• PI reduced the level of: oral contraceptive levels

Side effect profile regarding lipids and insulin resistance

Mostly now use boosted PI regimens

RTV increases levels of other PIs (1.5-40X)

• Ritonavir boosting
Fusion inhibitors (and co-receptor inhibitors)

• Fusion inhibitor
• Enfuvirtide (Fuzeon)
• CCR5 Antagonist
• Maraviroc
• selective and reversible CCR5 co-receptor antagonist
• no activity against non-CCR5 using virus
Therapeutic Strategies in HIV Management
Evidence of synergy
Selection
criteria for Absence of cross-resistance

combination Potential for resistance reversal and resistance

suppression

antiretroviral Absence of overlapping toxicities

therapy: Ease of dosing schedule

Tablet load (FDC)

Common side effects
AZT: anaemia, neutropenia
ABC: Hypersensitivity reactions, rash
3TC: Headache
FTC: Headache, hyperpigmentation of palms and soles
TDF: Renal, Osteopenia, osteoporosis
EFV: abnormal dreams, confusion, mood changes
NVP: elevated liber enzymes
DTG: headache, insomnia, mood changes
LP/r: Diarrhoea, dyslipidaemia
AZV: Diarrhoea, hyperbillirubinaemia, Gall stones, PR interval elongation
 • Updates introduced to improve patient care and
treatment outcomes
• Emphasis on immediate ART initiation upon
diagnosis regardless of CD4 count and clinical
stage
2023 ART • For all clients without contra-indications, ART
GUIDELIN should be initiated within 7 days, and on the
same day if possible.
ES • While rapid, and same-day ART initiation is
encouraged where possible, all clients,
particularly those with advanced HIV disease,
should be carefully assessed for opportunistic
infections (OIs) that may necessitate ART
deferral
 Medical indication to defer ART
TB symptoms

Drug-sensitive TB (non-neurological) Defer ART for 2 weeks if CD4 < 50 cells/μL

Defer ART for 8 weeks ≥ 50 cells/μL
Drug-resistance TB (Non-neurological) Initiate ART after 2 weeks of TB treatment

TB in neurological site Defer ART until 4-8 weeks after start of TB treatment

Signs of meningitis Investigate for meningitis before starting ART

+ve serum CLAT, no meningitis signs. Defer ART until the first 2 weeks of fluconazole prophylaxis has
been completed
Confirmed Crypto meningitis Defer ART until 4-6 weeks of antifungal treatment has been
completed
Sign of Liver disease

For those already on ART should NOT have their treatment interrupted upon diagnosis of these
Baseline clinical evaluation
Nutritional assessment
Screen for TB
Screen for depression and other mental d/o
Screen for other NCDs
Screen for pregnancy
Screen for STI
Neurodevelopmental screening
WHO staging
Baseline investigations
CD4 count
Viral load
Cr and eGFR
Hb
Gene Xpert
CLAT if CD4 less than 100
Pap smear
HbsAg
 TLD: Drug interaction
Rifampicin Rif ↓level of DTG

TB treatment: Add another dose of DTG (50mg) 12hr after the TLD

Anticonvulsants They ↓level of DTG

(Phenytoin,
Carbamazepine,
Phenobarb) Avoid these anticonvulsants (can use Valproate, lamotrigine)

Metformin DTG ↑level of Metformin

Do not exceed 500mg bd for metformin

(Mg2+, Fe2+, Ca and Fe supplement ↓ DTG on empty stomach, take with food
Ca2+) e.g.
antacids,
multivitamin Mg ↓ DTG, take at least 2 hrs apart
 • During labour, give a stat single fixed-dose
combination tablet of TLD and a stat single dose
ART of nevirapine (NVP).
Initiation in • Lifelong ART should be initiated the following
Women and day. TLD and a contraceptive method is
Adolescent recommended. Provide information on different
contraceptive methods available.
Girls • Appropriate ART literacy education should be
Diagnosed given to the woman before she leaves the
with HIV facility. Also provide her with information on
infant feeding, infant HIV prophylaxis, and
during follow-up infant HIV testing. Provide a 2-month
Labour supply of her ART regimen at discharge from
labour ward
Monitoring: clinical, virological, side-effects

Determine clinical response

• Trends in weight
• Screen for TB and other OIs
• Screen for pregnancy and desire for
children
Determine the virological & immunological
responses
• VL: At month 3 and month 12 on ART , then repeat every 12 months
• CD4 count: after 10 months/DCs on ART(aligned with VL) Thereafter, stop CD4
monitoring unless:
• CD4 still ≤ 200 cells/mm3: repeat every 6 months until CD4 > 200
• • VL ≥ 1000 c/mL: repeat CD4 every 6 months until VL < 1000 c/mL
• • A clinical indication arises, such as a new WHO Stage 3 or 4 condition in a
previously well client
• Repeat CD4 for clients returning > 90 days after missing a scheduled appointment
• Stop CD4 monitoring if client's VL remains below 1000 c/mL
Monitor drug side-effects:
• TDF: Cr & eGFR at months 3 and 10 , then
every 12 months
• PIs (Dyslipidaemia): Total cholesterol and
triglycerides (TGs) at month 3
• AZT (Anaemia and neutropenia): FBC and
WCC at months 1 and 3. Thereafter, repeat if
clinically indicated
Treatment Failure
Clinical Failure:

• New or recurrent clinical event indicating severe immunodeficiency (WHO clinical stage)
condition) after 6 months of effective treatment

Immunological failure

• CD4 count falls to the baseline (or below)

• or
• Persistent CD4 levels below 100 cells/mm3
• Without concomitant or recent infection to cause a transient decline in the CD4 cell count

Virological failure

• VL >1000 copies/mL on two occasions (3-months apart), despite intensive adherence support
What to do: VL 50-999, OR greater than 1000

Check: A: Adherence problem

B: Bugs
C: incorrect dose
D: Drug interactions
E: REsistance
Repeat VL after 3-month

• 50-999: continue adherence

support, repeat 6 month
• ≥1000: change to 2nd line
2nd line regimen
PREVENTION OF OIs: Cotrimoxazole prophylaxis

Advantages
↓ risk of PCP
↓ risk of Toxoplasmosis
↓ diarrhoea
↓ risk of pneumonia
PREVENTION OF OIs: Cotrimoxazole prophylaxis

When CD4 count ≤ 200 cells/μL

to start WHO Stage 2, 3 and 4

When CD4 count > 200 cells/μL,

to stop regardless of clinical stage
PREVENTION OF OIs: TB Preventive therapy
Considered in everyone starting ART, or already on ART,
and who have not yet received TB Preventive Therapy

Prior to initiating TPT, active TB should be ruled out by

screening for TB symptoms.

A Tuberculin skin test (TST) is not required prior to

starting TPT
Immune Reconstitution Inflammatory syndrome (IRIS)

Introduction of ART sometimes leads to worsening of

previously quiescent disorders to symptomatic disease.
The hallmark of the syndrome is paradoxical worsening of
an existing condition or disease process
or

Appearance of a new infection/disease process soon after

the initiation of ART
 IRIS definition (in a nutshell)
Temporal association between initiation of ART and subsequent development of
symptoms (usually within 3/12)

Evidence of immune restoration (VL reduced by >1log10 copies/ml and an

increase in CD4+ from baseline)

Clinical signs & symptoms consistent with an inflammatory process

Unmasking IRIS: immune response against a pathogen, previously undiagnosed,

that was not causing clinical disease before the initiation of ART
Risk factors for developing IRIS
Rapid decline in VL (esp. in first 3/12 of ART)

Low baseline CD4 count (esp. <50cells/µl or <10%) and rapid increase
after initiation of ART

Initiation of ART soon after initiation of treatment for an OI

Disseminated vs localized OI

ART- naïve patient

Types of TB IRIS
ART OUTCOME CASE DEFINITION

Patients on TB
Paradoxical
medication prior Paradoxical
Reaction within 3
to initiation of TB-IRIS
months
ART

ART
Patients not on
Unmasking
TB medication at Active tuberculosis TB IRIS
time of ART diagnosed on ART (ART associated TB)
initiation
 Treatment of the syndrome (IRIS)
Diagnosis
• to distinguish between an OI, drug toxicity and immune reconstitution syndrome

Difficult to diagnose

Treat the underlying infection

Continue with ART +/- steroids

Watch for drug interactions

NSAIDs (mild cases), steroids (more severe)

Surgical drainage of lymphadenitis/abscesses

Serial LPs etc.

 QUESTIONS WELCOME BUT
ANSWERS NOT
THANK YOU GUARANTEED