Definition of AIDS: Acquired Immunodeficiency Syndrome (AIDS) is a late stage of HIV (Human Immunodeficiency Virus) infection. It is characterized by a severe depletion of the immune system, making the individual susceptible to opportunistic infections and certain cancers. 2. Etiology (HIV): HIV Structure: HIV is a retrovirus that primarily targets CD4+ T cells, a crucial component of the immune system. The virus has two main types: HIV-1 and HIV-2, with HIV-1 being the most common and virulent worldwide. 3. Transmission: Modes of Transmission: HIV is primarily transmitted through unprotected sexual intercourse with an infected person. It can also be transmitted through sharing of contaminated needles, from an infected mother to her child during childbirth or breastfeeding, and through blood transfusions with infected blood (though this is rare now due to blood screening). 4. Clinical Stages: Acute HIV Infection: Occurs within the first few weeks after exposure. Presents with flu-like symptoms such as fever, fatigue, and swollen lymph nodes. Chronic HIV Infection (Asymptomatic Stage): Can last for several years with few or no symptoms. The virus is actively replicating, and the immune system is gradually compromised. Symptomatic HIV Infection (Symptomatic Stage): As the immune system weakens, symptoms such as persistent fever, weight loss, and diarrhea may occur. AIDS: Diagnosed when the immune system is severely compromised, typically when the CD4+ T cell count falls below a critical threshold. Opportunistic infections (e.g., Pneumocystis jirovecii pneumonia) and certain cancers (e.g., Kaposi's sarcoma) become more common. 5. Preventive Measures: Condom Use: Consistent and correct use of condoms during sexual intercourse helps prevent the sexual transmission of HIV. Pre-Exposure Prophylaxis (PrEP): Antiretroviral medications, when taken consistently by HIV-negative individuals at high risk, can prevent HIV infection. Post-Exposure Prophylaxis (PEP): Emergency treatment with antiretroviral drugs within 72 hours of potential exposure to HIV to prevent infection. Needle Exchange Programs: Reducing the sharing of needles among injecting drug users helps prevent the transmission of HIV.

1. BY
SRIRAM THIRUNAVUKKARASU,
PHARM.D,
PGP COLLEGE OF PHARMACY,
NAMAKKAL

2. • Human immunodeficiency virus (HIV) is an infection that attacks the body’s
immune system, specifically the white blood cells called CD4 cells. HIV destroys
these CD4 cells, weakening a person’s immunity against infections such as
tuberculosis (TB) and some cancers.
• If the person’s CD4 cell count falls below 200, their immunity is severely
compromised, leaving them more susceptible to infections. Someone with a CD4
count below 200 is described as having AIDS (acquired immunodeficiency
syndrome).
According to WHO;
INTRODUCTION:

3. Epidemiology:
• According to (WHO), the total number of people in the world living with HIV
is approximately 40 million.
• More than 4 million peoples are diagnosed in 2006.
• Approximately 25 million have died of AIDS, 3 million people in 2006 alone.
• It is now thought that around 2.5 million people in India are living with HIV.

4. TRANSMISSION OF HIV:

5. 1.Screening Tests: The initial step in HIV diagnosis involves screening tests. The
most common screening test is the enzyme-linked immunosorbent assay (ELISA)
or immunoassay. This test detects antibodies to HIV. If the result is positive, a
confirmatory test is necessary.
2.Confirmatory Tests: Upon a positive screening result, a confirmatory test is
conducted to verify the presence of HIV. The Western blot test is a widely used
confirmatory test. It identifies specific proteins of the virus and is considered highly
accurate.
3.Nucleic Acid Tests (NAT): In some cases, particularly during the early stages of
infection, nucleic acid tests (NAT) are employed. These tests directly detect the genetic
material of the virus (HIV RNA). NAT is more expensive and not routinely used for
screening but is highly sensitive and can identify HIV sooner after infection.
DIAGNOSIS OF HIV:

6. STRUCTURE OF HIV VIRUS:

7. PATHOGENESIS OF AIDS:

8. HOW VIRUS ENTER INTO THE CELLS:

9. The virus is uncoated in preparation for replication. Reverse transcriptase first
synthesizes
a complementary strand of DNA using the viral RNA as a Template
Attachment of HIV to the cell promotes fusion and internalization (adsorption) of the
virus—a process mediated by the gp41 subunit
The glycoprotein consists of two subunits, gp120 and gp41. The gp120 subunit has
high affinity for CD4 receptors and is responsible for the initial binding of the virus to the
cell
Once HIV Enters the human body, the outer glycoprotein (gp160 ) expressed on the virus
allows HIV to bind to CD4 receptors, proteins present on the surface of T-helper
lymphocytes, monocytes, macrophages, dendritic cells, and brain microglia.
PATHOGENESIS

10. protein is a potent amplifier of HIV gene expression. Rev protein regulates posttranscriptional
T-lymphocyte genes involved in growth and activate replication of HIV. When HIV replication
is induced, the host DNA polymerase transcribes the integrated proviral DNA into messenger
RNA (mRNA) with subsequent translation of the mRNA into viral proteins.
The RNA portion of this DNA-RNA hybrid is then partially removed by ribonuclease H (RNase
H), allowing reverse transcriptase to complete the synthesis of a double-stranded DNA molecule

11. The mature virion is free to infect new host cells and subsequently produce
more infectious virus
The process-translate, transcribe, and produce immature viral particles that
bud and break from the infected cell.
Thus the Pro-viral DNA is incorporated into the host cell's genetic material
via the integrase enzyme

12. • Fever, sore throat, fatigue, weight loss, and myalgia
• 40% to 80% of patients will also exhibit a morbilliform or maculopapular
rash usually involving the trunk
• Diarrhea, nausea, and vomiting
• Lymphadenopathy, night sweats
• Aseptic meningitis (fever, headache, photophobia, and stiff neck) may be
present in a quarter of presenting cases
• High viral load (exceeding 50,000 copies/mL in the adult or 500,000
copies/mL in the child)
• Persistent decrease in CD4 lymphocytes
Clinical Presentation:

13. • Achieve maximum suppression of HIV replication.
• Increase in CD4 lymphocytes because this determines the
risk for developing opportunistic infections
• Decreased morbidity and mortality.
Treatment:

14. CLASSIFICATION OF AIDS ACCORDING TO CD4+ TCELLS:

15. Category A
Asymptomatic HIV infection
Persistent generalized lymphadenopathy
Acute HIV infection with accompanying illness or history of HIV infection.
Category B
Bacillary angiomatosis, Candidiasis, oropharyngeal (thrush)Candidiasis,
vulvovaginal; Cervical dysplasia/carcinoma in situ
Constitutional symptoms, such as fever >38°C ,diarrhea, Hairy leukoplakia,
Herpes zoster (shingles), involving at least two distinct episodes or more than one
dermatome Idiopathic thrombocytopenia purpura,Listeriosis Pelvic inflammatory
disease, particularly if complicated by tubo-ovarian abscess,Peripheral neuropathy
Category C
Candidiasis of bronchi, trachea, or lungs, esophageal
Cervical cancer, Encephalopathy Toxoplasmosis of brain
Wasting syndrome resulting from HIV

16. Classification of Anti-Retroviral drugs (Anti-HIV drugs):
The Anti-HIV drugs can be classified into
1. Nucleoside reverse transcriptase inhibitors (NRTIs):
Eg: Zidovudine, Stavudine, Lamivudine, Abacavir, Zalcitabine. Emtricitabine,
Didanosine.
2. Non nucleoside reverse transcriptase inhibitors (NNRTIs):
Eg: Efavirenz, Nevirapine, Delaviridine.
3. Nucleotide reverse transcriptase inhibitors (NTRTIs):
Eg: Tenofovir
4. Protease inhibitors (PIs):
Eg:Saquinavir, Indinavir, Nelfinavir, Amprenavir, Fosamprenavir, Ritonavir,
Lopinavir, Atazanavir.
5. Entry/Fusion inhibitors:
Eg:Enfuvirtide

17. MOA OF HIV DRUGS

18. MAIN TYPES:
Nucleoside/nucleotide reverse transcriptase inhibitors
• Reduce the growth of HIV
• Inhibit prolongation of DNA chain insert false nucleotide
Eg: Zidovudine, lamivudine
Non nucleoside reverse transcriptase inhibitors
• Keep HIV from making copies of itself
• Bind directly to reverse transcriptase preventing activity
eg: Nevirapine, efavirenz
Protease inhibitors
• Prevent HIV from being formed
• Inhibit cleavage of viral packaging prior to viral release
eg: Indinavir, saquinavir mesylate, nelfinar mesylate
Antivirals-Treatment

19. Integrase Inhibitors
(Integrase Strand Transfer Inhibitor)
 These drugs prevent or inhibit the binding of the pre-integration complex to
host cell DNA, thus terminating the integration step of HIV replication.
Ex:Raltegravir.
CCR5 Antagonist
Inhibit the attachment of HIV to the host cell by competitively and selectively
binding to CCR5 and blocking the interaction between gp120 and CCR5; this
prevents infection of the cell.
Unlike currently available HIV medications which act on HIV directly, CCR5
entry inhibitors are the first class of drugs that act on the human T-cell,
changing it in such a way that HIV is unable to bind and therefore continue the
replication process Ex:Maraviroc.

20. Fusion Inhibitor
36-amino-acid synthetic peptide that prevents completion of the HIV fusion
sequence.
 A synthetic analogue of HR2, binds to the HR1 region, preventing the formation
of the hairpin structure required for fusion of viral and cellular membranes
Ex:Enfuvirtide.

21. • ART regimen generally consists of two NRTIs (zidovudine as one of the preferred
NRTI options) + one active drug from one of the following classes: NNRTI, PI
(generally boosted with RTV), INSTI, or a CCR5 antagonist.
• Antiretrovirals (tenofovir, abacavir and emtricitabine) have been added as first-line
Choice of drugs.
• The use of triple NRTI – Co-treatment of tuberculosis and HIV, NNRTI
intolerance, coinfection with hepatitis B or C with hepatic dysfunction, in pregnant
and non-pregnant women with CD4 counts between 250 and 350 cells/mm3, and
the treatment of HIV-2 infection.
• Second-line therapy remains based on the PI class, ideally supported by an NRTI
backbone using two new (previously unused) agents to minimize cross-resistance;
ritonavir-boosted.
• PIs are recommended in order to enhance potency.
Anti Retroviral Therapy-WHO Guidelines

22. Four approved classes of drugs in the HAART regimens:
Nucleoside and nucleotide reverse transcriptase inhibitors
Non-nucleoside reverse transcriptase inhibitors
Protease inhibitors
Fusion inhibitors
Physicians consider 200 to 350 CD4 cells/mm3 as the range to consider starting
HAART.
HAART combines two types of antiretroviral drugs RTI’s (Reverse Transcriptase
Inhibitors): Zidovudine (AZT/ZDV), Didanosine (DDI), Zalcitabine (DDC), Stavudine
(D4T), Lamivudine (3TC)
NNRTI’s (Non-Nucleoside RTI’S) : Delavirdine, Nevirapine, Efavirenz Protease
Inhibitors: Indinavir, Ritonavir
Medical abortion
Regimen till 9 weeks pregnancy
200 mg Mifepristone
48 hours later 400 micrograms of Misoprostol vaginally
Follow up after 15 days to ensure completeness

23. THANK YOU