This document provides an overview of HIV/AIDS, including its pathogenesis, diagnosis, management, and epidemiology. It begins with definitions of HIV and AIDS, noting that HIV attacks CD4 cells and destroys the immune system. Modes of HIV transmission are through five body fluids. Globally in 2021, 38.4 million people lived with HIV, with sub-Saharan Africa disproportionately affected. Diagnosis involves different tests for infants versus older children and adults. Management consists of supportive investigations like CD4 counts and viral loads, as well as antiretroviral drugs that target different stages of the HIV lifecycle like reverse transcriptase, integrase, and protease.

1. HIV /AIDS
Presenters :Dinabell Lutaka
Davies Silungwe
Henry Nyirong Jr
Frank Mtonga

2. CONTENT
• INTODUCTION
• PATHOGENESIS
• DIAGNOSIS
• Management

3. INTRODUCTION
• Definition
• HIV Human immunodeficiency virus (HIV) is an infection that attacks the
body’s immune system, specifically the white blood cells (CD4 cells). HIV
destroys these CD4 cells, weakening a person’s immunity against
opportunistic infections.
• AIDS Acquired immunodeficiency syndrome (AIDS) is a term that applies
to the most advanced stages of HIV infection. It is defined by the
occurrence of opportunistic infections due to a weakened immune system.

4. Contd
• For HIV to be transmitted from one person to another, one of the person
involved must be HIV-positive
The infectious is found in five body fluids: blood, semen, vaginal fluids,
secretions in the rectum, and breast milk.

5. EPIDEMIOLOGY
Global HIV statistics
• HIV continues to be a major global public health issue.
• Accoding to UNAIDS 38.4million people globally were living with HIV in 2021.
• 1.5million became newly infected with HIV in 2021.
650 000 people died from AIDS-related illnesses in 2021.
.

6. Epidemiology
• 28.7million people were accessing antiretroviral therapy in 2021.
• 84.2million people have become infected with HIV since the
start of the epidemic.
• 40.1million people have died from AIDS-related illnesses since
the start of the epidemic

7. Epidemiology
• An estimated 68% live in sub-Saharan Africa. Among this group 20.6 million are
living in East and Southern Africa . (UNAIDS)
• Zambian statistics according to UNAIDS 1.3 million people with HIV in 2021
• 10.8% adult HIV prevalence.
• 38,000 new HIV infections.
• 19,000 AIDS-related deaths.
• 1.2 million people on antiretroviral treatment.

8. MODES OF TRANSMISSION
• Sexually: vaginally ,oral or anal sex
• Blood exposure: drug users needle sharing occupational exposure and blood
transfusion
• Perinatal : transmission from mother to the child either during delivery or
breastfeeding
• Occupational transmission : health care workers
• Oher routes e.g. organ transplant and artificial insemination

9. Pathogenesis
HIV can infect immune cells such as CD4+ T cells, macrophages and
microglial cells.
HIV -1 entry to macrophages and CD4+ T Cells is mediated via the
virion envelope glycoproteins GP120 with the CD4 molecule on the
target cells membrane. also with the chemokine co-receptors CCR5.

10. HIV LIFE CYCLE
• They are about 6 stages in the life cycle of HIV and these are binding and
fusion ,reverse transcription ,intergration ,transcription, assembly and
budding.
• Binding and fusion

11. binding and fusion
• The HIV begins its life cycle when it binds to the CD4 receptors and one of
the two co- receptors on the surface of the CD4+ T helper cells.the virus
then fuses with the host cell and releases its own genetic material into the
host cell
• REVERSE TRANSCRIPTION
• The hiv enzyme reverse transcriptase helps to convert the ssRNA HIV TO
ds DNA HIV
• INTERGRATION

12. INTERGRATION
• The newly formed HIV DNA double stranded is intergreted into the host
cell nucleus by enzyme called intergrase. The newly intergreted HIV DNA is
called provirus and can be inactive or producing very few copies of virus for
several years.

13. transcription
• The host cell receives instructions / signals to become more active and
produce more copies .the provirus uses the host cells enzymes RNA
polymerase to create more copies of messenger RNA

14. ASSEMBLY
• An HIV enzyme called protease cuts of the long chains of HIV proteins
into shorter chains and they are easily assembled into a viral particle

15. budding
• The newly assembled viral particle easily buds off from the plasma
membrane of the hos cells and it contain the host cell membrane making it
easy to attach to other host cells for infection

16. Diagnosis
The definitive diagnosis of HIV infection at any age requires diagnostic
testing that confirms the presence of HIV
Confirmation of infection is different in infants (<18months) and
children > 18 months and adults

17. Types of tests
1.NATs
2.Ag/Ab Tests
3.Ab tests
4.Recency- HIV assays designed to detect recent infection
5.OraQuick In-Home HIV test
When is testing done?

18. Exposed infants-EID/NAT
Dried blood spots (DBS)
-Detects HIV in blood
• Blood specimens collected onto filter paper for the diagnosis of HIV
infection in infants.

19. DBS Contd
• DBS can be used for virological (HIV DNA or HIV RNA , testing and p24
Ag assays , some serological testing and HIV drug-resistance testing.

20. P24 Ag test
• Studies done in Macha Zambia (2015) concluded that this test is of help in
diagnosis of HIV in infants below or 4 weeks

21. Molecular based tests
1.HIV DNA testing
Qualitative HIV DNA/RNA PCR
 Currently widely used as the standard method for diagnosis of HIV infection in infants and
is the assay against which other assays are usually compared in research settings
The main characteristics of this assay relevant to infant diagnosis can be summarized
as follows:
• HIV proviral DNA is integrated in the cell's genome, and so detection of cell-associated
HIV DNA within PBMCs by PCR is one of the most sensitive methods for establishing
HIV infection.

22. Infants >18months & Adults
Serological testing
Serological testing identifies HIV antigen and/or antibody generated as part of the
immune response to infection with HIV.
2 tests to comfirm diagnosis
None of these detect HIV itself, but rather detect an immune response to the virus,
and therefore take some time to develop and become reactive (or positive) after HIV
infection has been acquired

23. Contd
• HIV determine
• SD Bio line
• OraQUICK in house test
• Recency

24. ELISA
• Most commercially available EIAs have a high sensitivity and specificity and
are able to detect all subtypes of HIV-1 and HIV-2.
• Enzyme immunoassay is a common immunological technique that has been
adapted for the detection of HIV antibodies.

25. EIAs contd
• Specific Abs bind the target Ag and detect the presence and quantity of Ag
binding. The most recent advances in
• EIA technology allows simultaneous detection of HIV antigen and
antibodies using a single test.
• This approach has further shortened the window period, i.e. the interval
between HIV infection and detectable HIV antigen/antibodies

26. Western blot (WB) tests
• The WB assay consists of a multilayer process similar to that of the EIA.
HIV antigens are laid out – from the highest in molecular weight to the
lowest – on a strip of nitrocellulose.
• When a specimen is incubated with the strip, any existing HIV antibodies
bind to these HIV antigens.
• Addition of enzyme leads to an antibody–enzyme complex. In a final step, a
chemical is added that changes color when it comes into contact with the
protein–antibody–enzyme layers.

27. Managemet

28. INVESTIGATIONS
DIAGNOSTIC INVESTIGATIONS
RDT
PCR ( Viral load )
CD4 count

29. • SUPPORTIVE INVESTIGATIONS
• FBC
• LFts
• Renal function tests
• Urea and Electrolytes

30. HIV ANTIRETROVIRAL DRUGS (
CLASSES, MECHANISM OF ACTION AND
SIDE EFFECTS )
• RECEPTOR Blockers include Maraviroc and Ibalizumab
• MOA: Maraviroc blocks CCR5 receptors on the CD4 cells preventing entry into the
cell while ibalizumab is a monoclonal antibody.
• Side Effects: Hepatotoxicity and rash (Maraviroc)

31. contd
• FUSION Inhibitors e.g Enfuvirtide
• MOA: Inhibits fusion by competitively binding to the viral protein GP41
thereby preventing the virus’s fusion with the cell.
• Side Effects: Localised skin reaction

32. • REVERSE TRANSCRIPTASE Inhibitors: These are divided into nucleoside
reverse transcriptase inhibitors and nucleotide reverse transcriptase inhibitors
• Nucleoside reverse transcriptase inhibitors (NRTIs) include, Abacavir,
Lamivudine and Zidovudine (AZT )
• MOA: These are primarily thymidine analogues. Incorporated to viral DNA
via Reverse Transcriptase leading to termination of DNA chain
• Side Effects: Abacavir ( Hypersensitivity reactions, Increases the risk of
cardiovascular disease )

33. • Nonnucleoside reverse transcriptase inhibitors (NNRTIs) include Efavirenz,
Nevirapine.
• MOA: Binds directly to reverse transcriptase inhibiting its function (it is not
an analogue).
• Side Effects: Neuropsychiatric effects, bizzare or vivid dreams.

34. contd
• Nucleotide reverse transcriptase inhibitors include, Tenofovir.
• MOA: Adenosine nucleotide analogue which acts as a chain terminator when
incorporated into viral DNA.
• Tenofovir comes in two forms mainly tenofovir disoproxil fumerate(TDF)
AND tenofovir alafenamide(TAF). Both are oral tablets which differ in half
life effects on the bones and kidneys
• Side Effects: Nephrotoxicity and bone toxicity.

35. Contd
• Integrase Inhibitors examples include, Raltegravir and Dolutegravir.
• MOA: Inhibits integrase enzyme thereby preventing transfer and insertion of
viral DNA unto host DNA.
• Side Effects: Causes myopathy (Raltegravir) and increased creatinine
(Dolutegravir).

36. Contd
• PROTEASE Inhibitors examples include , Atazanavir, Darunavir.
• MOA: Blocks viral protease enzyme resulting in immature non infectious
HIV.
• Requires a boost e.g Ritonavir
• Side Effects: Nausea, Diarrhoea, Hyperlipidemia , insulin resistance,
lipodystrophy etc

38. Twalitumela
• Zikomo,Twalumba,twatasha