Human immuno virus infection treatment.pptx

1
HUMAN
IMMUNODEFICIENCY
VIRUS DISEASE
Dr AWIL ABDI
January 25, 2024

2
Introduction
HIV disease
 An infectious disease caused by HIV, a human retrovirus
 HIV disease should be viewed as a spectrum ranging from
primary infection, with or without the acute syndrome, to an
asymptomatic stage, to advanced disease characterized by
profound immunodeficiency and susceptibility to opportunistic
infections.
AIDS
 Late stage of infection with HIV
 Current case definition
 Any HIV-infected person with a CD4+ T-cell count <200/μL
 Development of an AIDS-defining clinical condition
January 25, 2024

3
Mode of Transmission
 Sexual intercourse with an HIV-infected person
 Transfusion with HIV-infected blood
 Mother-to-child transmission during pregnancy, delivery, or
through breastfeeding
 HIV-contaminated sharp instruments, e.g., dental and surgical
equipment, needles, scalpels, razors, hair shaving equipment,
nail cutters, and other sharp objects
 Exposure to HIV-infected materials through an open wound or
cut
January 25, 2024

4
Epidemiological risk factors for
HIV
1. Present or past high-risk behavior (multiple sexual partners)
2. Loss of a spouse or partner from HIV disease
3. Having sexually transmitted infections, especially Herpes
simplex virus type 2
4. Being an uncircumcised man
5. Being in an HIV-discordant sexual relationship or marriage
6. History of blood transfusion between 1975 and 1986
January 25, 2024

5
Structure of HIV
Envelope
Core p24
RNA
Reverse
Transcriptase
January 25, 2024

6
Pathogenesis of HIV
January 25, 2024

7
PATHOGENESIS
 HIV has several targets including
 dendritic cells,
 macrophages,
 CD4+ T cells
January 25, 2024

8
Target cells
 HIV most often enters the host through the anogenital mucosa.
 The viral envelope protein, glycoprotein (GP)-120, binds to the
CD4 molecule on dendritic cells.
 Interstitial dendritic cells are found in cervicovaginal
epithelium as well as tonsillar and adenoidal tissue, which may
serve as initial target cells in infection transmitted via genital-
oral sex.
 Newly acquired HIV infection is more commonly due to
transmission of macrophage tropic rather than T cell tropic
viruses.
January 25, 2024

9
 Viral entry into these cells is mediated by different co-receptors.
 In order to enter macrophages, GP-120 must bind to the
chemokine receptor CCR5 as well as CD4 Macrophage tropic
viruses are designated as R5 in comparison to T cell tropic
viruses, which are called X4, based upon the CXCR4 receptor on
these cells
 HIV infected cells fuse with CD4+ T cells, leading to spread of the
virus. HIV is detectable in regional lymph nodes within two days of
mucosal exposure and in plasma within another three days
 Once virus enters the blood, there is widespread dissemination to
organs such as the brain, spleen, and lymph nodes .
January 25, 2024

10
…
 The intestinal mucosa is also a primary target during initial
infection .
 destruction occurred preferentially in CD4+ memory T cells,
which may result from direct infection as well as through
apoptosis.
Cellular immune response
 At the time of initial infection with HIV, patients have a large
number of susceptible CD4+ T cells and no HIV-specific immune
response.
 Viral replication is therefore rapid; plasma HIV RNA levels may
climb to more than 10(7) copies/mL and p24 antigen levels may
exceed 100 pg/mL.
January 25, 2024

11
…
 Concomitant with the evolution of HIV specific immunity, primarily
due to the emergence of virus-specific CD8+ cytotoxic T lymphocytes,
plasma RNA levels fall precipitously by 2 to 3 logs, and symptoms of
the acute retroviral syndrome resolve.
 In the absence of antiretroviral therapy, plasma HIV RNA levels will
stabilize at an individual's given "set-point" within six months of .
 Thehost factors, virus factors, and pharmacologic interventions,
which determine this set point, are active issues for ongoing
investigations.
 A few HIV-positive individuals may, even in the absence of
antiretroviral therapy, retain normal CD4 counts and low or
undetectable plasma viremia. Those with persistent viral suppression
are sometimes referred to as "elite controllers." A large study from
France demonstrated that this clinical phenotype was quite rare
January 25, 2024

12
Clinical Features
January 25, 2024

14
Differential diagnosis
1. TB
2. Untreated diabetes mellitus
3. Malnutrition
4. Cancer
5. Other chronic diseases
January 25, 2024

16
Management
Entry inhibitors (HIV fusion inhibitors)
 Anti-Gp41
 Enfuvirtide
CCR5 antagonists
 Anti-GP120 (attachment inhibitor)
 Maraviroc
 Block the CCR5 co-receptor molecules that HIV uses to infect
new target T-cells. Some forms of HIV use a different coreceptor
January 25, 2024

17
…
Nucleoside reverse transcriptase inhibitors (NTRTIS)
Incorporate them selves into the DNA of the virus, thereby
stopping the building process
 Tenofovir (TDF)
 Zidovudine (AZT)
 Lamivudine (3TC)
 Abacavir (ABC)
Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
 Stop HIV production by binding directly onto the reverse
transcriptase enzyme, and prevent the conversion of RNA to
DNA
 Efavirenz (EFV)
 Nevirapine (NVP)
 Etravirine (ETV)
January 25, 2024

18
…
Protease inhibitors (PIs)
 Prevent HIV from being successfully assembled and released
from the infected CD4 cell:
 Atazanavir (ATV)
 Lopinavir (LPV)
 Darunavir (DRV)
 Ritonavir (RTV, abbreviated as ”r” ifboosting other PIs, e.g.
ATV/r, LPV/r.
Integrase inhibitors
 Interfere with the HIV DNA’s ability to insert itself into the host
DNA and copy itself.
 Dolutegravir (DTG)
 Raltegravir (RAL) January 25, 2024

24
ANTIRETROVIRAL THERAPY FOR
PEOPLE LIVING WITH HIV
THE GOAL OF ART
The aim of antiretroviral therapy is to
1. Suppress viral load levels amongst all PLHIV to undetectable levels,
2. Reduce the risk of morbidity and mortality associated with HIV,
3. Reduce transmission of HIV
 ART should be initiated at the earliest opportunity in all people with
confirmed HIV infection, regardless of clinical stage or CD4 cell count
January 25, 2024

25
THE PROCESS OF STARTING ART
 Although the program recommends starting all PLHIV on ART, the health
workers should do the following ;
 Assess all clients for opportunistic infections especially TB and cryptococcal
meningitis.
 If the patient has TB or cryptococcal meningitis, ART should be deferred and
initiated after starting treatment for these OIs.
 For patients without TB or cryptococcal meningitis, offer ART on the same
day through an opt-out approach
January 25, 2024

26
Principles for selecting the ARV regimens
The first-line ART regimens for treating HIV infection in Uganda were selected
based on the following principles:
• Regimen with lower toxicity
• Better palatability
• Increased durability and efficacy
• Sequencing: spares other available formulations for use in the 2nd line regimen
• Harmonization of regimen across age and population
• Lower cost
• Help the country to achieve a recommended regimen for the vast majority of
PLHIV
January 25, 2024

28
When to use TDF+3TC+EFV
 If the weight does not allow for use of the currently available DTG
formulations because DTG 50mg should only be given to adults and
adolescents weighing 40kg and above.
When to use ABC+3TC+DTG
 TDF is contraindicated, including the following conditions:
 1. Kidney disease and estimated glomerular filtration rate (GFR) below 60
ml/min
 2. Adolescents below 35 kg of weight
January 25, 2024

29
MONITORING RESPONSE TO ART
The purpose of monitoring patients on ART is to assess:
1. Response to ART and diagnose treatment failure
2. Safety of the medicines- side effects and toxicity
3. Adherence to ART
January 25, 2024

30
CLINICAL MONITORING
Clinical monitoring involves taking a medical history and doing a physical
exam;
 Demographics (age, sex etc.)
 Screen for signs and symptoms of OIs (e.g. TB, cryptococcal meningitis),
hepatitis B and C infections, malaria, and other infections
 Screen for pregnancy (women of reproductive age)
 Screen for co-morbidities
 Screen for STIs
 Screen for symptoms of depression
January 25, 2024

31
 Obtain previous history of chronic illnesses (hypertension, DM, COPD,
kidney disease)
 Obtain a list of current medication(s)
 stablish family planning methods currently in use
 Assess development, sexual awareness and behavioral issues in
adolescents .
January 25, 2024

32
 Determine progress with disclosure if not done already
 Perform nutritional assessment
 Ensure examination of vital signs, skin, eyes, oropharynx (presence of
thrush), lymph nodes, lungs, heart, abdomen, genital tract (for STIs),
extremities, nervous system
 Determine WHO clinical staging
January 25, 2024

33
LABORATORY MONITORING
 Viral load monitoring ;
 Uganda adopted viral load monitoring as the preferred approach for
monitoring response to ART and to diagnose/confirm ART treatment
failure. Compared to clinical or immunological monitoring
 Adults: the first VL test should be done at six months after initiating ART,
then at 12 months and thereafter, annually,
January 25, 2024

34
When viral load is not suppressed (VL >1000
copies per ml)
For non-suppressed PLHIV, the following should be done
Contact the patient to return to facility within one week after facility receives
results.
• Ensure that facility ART team holds case discussions on patients with non-
suppressed VLs to determine possible causes of non-suppression.
• Discuss results with the patient and assess for barriers to adherence.
January 25, 2024

35
• Do intensive adherence counseling support monthly for three months.
• Repeat VL test one month after the last (3rd) intensive adherence counseling
session (the repeat viral load test should be done within 6 months of the last
unsuppressed VL test).
• If the repeat VL is suppressed, follow the standard algorithm.
• If repeat VL is not suppressed, and the ART team is confident that the
patient is adherent, then the patient is failing on the current ARV regimen
and should be switched according to the guidance
January 25, 2024

36
CD4 monitoring
 Although CD4 cell count is no longer the mainstay for ART response
monitoring and is not a precondition for initiating ART, it is still
recommended in the following scenarios:
• At baseline when initiating ART. Baseline CD4 helps to screen for risk for
opportunistic infections, e.g. cryptococcal infection in patients with CD4 less
than 100 cells/mm3
• PLHIV who are on treatment or prophylaxis for cryptococcal infection to
inform decision on when to stop fluconazole
• PLHIV re-engaging in care after treatment interruption
• ART patients with VL >1000 copies/ml and/or WHO clinical Stage 3 or 4
disease
January 25, 2024

37
IMMUNE RECONSTITUTION INFLAMMATORY
SYNDROME (IRIS)
 IRIS is a spectrum of clinical signs and symptoms thought to be associated
with immune recovery brought about by a response to ART. It is a widely
recognized phenomenon that occurs among 10–30% of the people initiating
ART, usually within the first 4–8 weeks after initiating therapy.
 IRIS should be considered only when the presentation cannot be explained by
a new infection, the expected course of a known infection, or drug toxicity.
The most serious and life-threatening forms of IRIS occur in patients co-
infected with TB, cryptococcus, Kaposi’s sarcoma and herpes zoster
January 25, 2024

38
Risk factors for IRIS include
1. A low CD4+ cell count (<50 cells/mm3) at ART initiation.
2. Disseminated opportunistic infections
3. Tumors
4. A shorter duration of therapy for opportunistic infections before ART starts.
January 25, 2024

39
Managing IRIS
 IRIS is generally self-limiting, and interruption of ART is rarely indicated.
 Treat any co-infections to reduce morbidity and symptoms.
 If the symptoms are protracted, reassure the patient to prevent
discontinuation of, or poor adherence to ART.
January 25, 2024

40
Steps to reduce development of IRIS
 Diagnose HIV early and initiate ART before CD4 declines to below 200
cells/mm3.
 Screen and optimally manage opportunistic infections before initiating ART,
especially TB and cryptococcus.
 The timing of ART in people with opportunistic infections requires balancing
a greater risk of IRIS after early initiation against continuing high mortality if
ART is delayed
January 25, 2024

41
ARV DRUG TOXICITY
 Antiretroviral drugs can cause a wide range of toxicities, from
low-grade intolerance that may be self-limiting to life-
threatening side effects. Differentiating between ART toxicity
(also known as adverse reactions) and complications of HIV
disease is sometimes difficult
January 25, 2024

43
Important drug interactions
January 25, 2024

45
WHEN TO SWITCH ART DUE TO TREATMENT FAILURE
January 25, 2024

46
The recommended sequence is:
▪ After failing on TDF + 3TC or ABC+3TC based regimen, use AZT+3TC
▪ After failing on AZT+3TC based regimen, use TDF + 3TC
January 25, 2024

47
THIRD-LINE ART REGIMENS
Eligibility for Third-Line ART
Patients on second-line ART who meet the following criteria are eligible
for third-line ARVs:
1. If they have a detectable viral load test result >1000 copies/ml at the repeat
viral load test following intensified adherence counseling.
2. The patient should have had three intensified adherence counseling
sessions one month apart after the initial detectable viral load.
3. The patient has three consecutive scores of adherence >95% as determined
by adherence support team.
4. They have major resistance to PIs, as confirmed through resistance profiling
January 25, 2024

48
What to do when a patient on second-line has
suspected resistance to second-line ART:
 Two samples of venous blood should be taken off and sent to CPHL (Central
Public Health Laboratories)
 The samples should be accompanied by the combined viral load and HIV
drug resistance form.
 All samples will be sent to CPHL. CPHL will be responsible for transporting
samples to the resistance testing laboratories.
 The resistance test results will be returned to CPHL and CPHL will forward
them to the national third-line ART clinical team. The team will review
the results along the patient details and make the decision to switch or not to
switch the patient to third-line ART.
January 25, 2024

49
 Through the Implementing partner, the decision made by the national third-
line ART clinical team will be sent to the regional/district and health facility
teams.
 The health facility team will follow up the patient to initiate them on third-
line ART
January 25, 2024

51
HIV PREVENTION
 In Uganda, the HIV epidemic is driven by multiple behavioral, biomedical,
and structural factors.
 There is thus no single HIV prevention intervention that is sufficient to
prevent all HIV transmissions..
 The country, therefore, adopted a combination HIV prevention approach
which uses a mix of biomedical, behavioral and structural interventions to
meet the HIV prevention needs of the population so as to have the greatest
possible impact on reducing new infections
January 25, 2024

52
BEHAVIORAL CHANGE AND RISK
REDUCTION INTERVENTIONS
1. Always follow safe sex practices (e.g. use condoms; avoid
multiple sexual partners)
2. Never share used needles, syringes, razors, hair shavers, nail
cutters, and other sharp objects
3. Avoid tattooing, body-piercing, and scarification unless
4. carried out under strictly hygienic conditions in properly
5. controlled premises
6. Delay start of sexual activity in adolescence
7. Discourage cross-generational and transactional sex
8. Avoid violence and abuse January 25, 2024

53
BIOMEDICAL PREVENTION INTERVENTIONS
1. Safe Male Circumcision
2. ART with viral suppression
3. PEP (Post Exposure Prophylaxis)
4. PrEP (Pre Exposure Prophylaxis)
5. Blood transfusion safety
6. STI screening and treatment
7. Safe infusion and injection practices
8. Adherence to infection control procedures
January 25, 2024

54
POST-EXPOSURE PROPHYLAXIS
 Definition: Post-exposure prophylaxis (PEP) is the short-term use of ARVs to
reduce the likelihood of acquiring HIV infection after potential exposure.
 Types of exposure:
 • Occupational exposures occur in the health care or laboratory setting and
include sharps and needlestick injuries or splashes of body fluids to the skin
and mucous membranes.
 • Non-occupational exposures include unprotected sex with an HIV
infected or person of unknown HIV status, exposure following assault like in
rape and defilement, and road traffic accidents.

January 25, 2024

55
ORAL PRE-EXPOSURE
PROPHYLAXIS (PrEP)
 Definition: PrEP is the use of ARV drugs by HIV uninfected persons to
prevent the acquisition of HIV before exposure to HIV.
Where will PrEP services be offered?
 PrEP is being offered in a few accredited ART sites that have the capacity
and funding to provide a complete package and whose outcomes will inform
further roll out.
January 25, 2024

57
Pre-Exposure Prophylaxis (PrEP)
 Definition: PrEP is the use
of ARV drugs by HIV-
uninfected persons to
prevent the acquisition of
HIV before exposure to
HIV.
January 25, 2024

60
References
1. UpToDate, 2024
2. Ugandan Clinical Guideline (UCG), 2023
January 25, 2024

Human immuno virus infection treatment.pptx

More Related Content

Similar to Human immuno virus infection treatment.pptx (20)

More from opio63309 (8)

Recently uploaded (20)

Human immuno virus infection treatment.pptx

Editor's Notes