This document discusses HIV infection and AIDS. It begins by noting that AIDS was first recognized in 1981 in homosexual men with immune deficiencies. It then discusses how HIV is transmitted, primarily through sexual intercourse, needle sharing, blood transmission, and from mother to child. The document outlines the structure of HIV, which is a retrovirus that infects CD4 cells. It explains how HIV replicates by converting its RNA to DNA and integrating into the host cell genome. This causes a depletion of CD4 cells over time, leading to immunosuppression and susceptibility to other infections and illnesses. The document covers clinical manifestations of HIV at different stages, as well as methods for testing, monitoring, and treating HIV, including antiretroviral drugs that

1. HIV INFECTION
AIDS
Hashmi Furqan
Final year, Pharm. D

2. Introduction
• Acquired immune deficiency syndrome (AIDS) was first recognized in 1981 in USA.
• Identified first time in young (previously healthy) homosexual men with profound
immunologic deficits (impairment of cellular immune response), Pneumocystis
carinii (now Pneumocystis jiroveci) pneumonia (PCP), and Kaposi sarcoma.
• The virus has been isolated from a number of body fluids as blood, semen, vaginal
secretions, saliva, breast milk, tears, urine, peritoneal fluid and cerebrospinal fluid
(CSF).
Transmission
• The pre-dominant routes of transmission: sexual intercourse, sharing of unsterilized
needles or syringes, blood or blood products, areas where people are not screened
or treated and vertical transmission in utero, during labor or through breast
feeding.

3. Structure of Human
Immunodeficiency
Virus (HIV)

4. Pathogenesis
• HIV retrovirus, possesses the enzyme reverse transcriptase and consists of a lipid
bilayer membrane surrounding the capsid.
• Its surface glycoprotein has a strong affinity for the CD4 (cluster of differentiation-
4) receptor protein found on the T-lymphocytes.
• Monocytes and macrophages may also have CD4 receptors hence can be infected.
• HIV virus also binds to co-receptors such as CCR-5 or CXCR-4.

5. Pathogenesis
• Membrane fusion also occurs.
• Penetration to host cell sheds its outer coat and releases its genetic material.
• The viral RNA with the help of Reverse Transcriptase is converted to DNA (utilizing
host nucleotides).
• Viral DNA is integrated into host genome in the cell nucleus undergo transcription
and translation resulting in new viral proteins.
• After integration, HIV preferentially replicates in activated cells. Activation by
antigens, cytokines, or other factors stimulates the cell to produce nuclear factor
kappa B (NF-κB), an enhancer-binding protein (pro-inflammatory factor).
• New virus particles (proteins)  assemble and bud out of the host cell releasing
mature infectious virions (under the influence of protease enzyme)

6. Pathogenesis
• Immediately after primary HIV infection (PHI) also known as seroconversion 
high turnover of viruses.
• Equilibrium is then achieved at which stage the infection may appear to be
clinically latent even though 10,000 million new virions are produced/day.
• With the chronicity of infection T-lymphocytes are depleted from the body
(immunosuppression / immunocompromised).
• As a result of suppression the individual becomes susceptible to a myriad infections
and tumors.
• The rate of immunosuppression is variable in individuals and the precise
mechanism of factors affecting is not fully understood.
• Some individuals rapidly develop severe immunosuppression while some infected
with HIV for many years possess intact immune system (viral-, host-genetic &
environmental factors).

8. Clinical Manifestation
The sequalae of untreated HIV infection can be considered in five categories:
1. Opportunistic infections
Infections that would not normally cause disease in immunocompetent host
e.g. P. jiroveci pneumonia and cytomegalovirus (CMV).
2. Infections in immunocompetent patient
Tend to occur more frequently, more severely and often atypically in the
context of underlying HIV infection e.g. Mycobacterium tuberculosis.
3. Malignancies
Occur rarely in immunocompetent people e.g. Kaposi’s sarcoma and non-
Hodgkin’s lymphoma.
4. Direct manifestation of HIV infection e.g. HIV encephalopathy, HIV myelopathy
and HIV enteropathy.

9. 5. Consequences of chronic immune activation including premature cardiovascular
disease, neurocognitive dysfunction, bone mineral density loss.
Additional manifestations
• 70% individuals  flu-like illness (during seroconversion), PHI  fever, arthralgia,
pharyngitis, rash and lymphadenopathy.
• CD4 count depletion leading to oropharyngeal / oesophageal candidiasis or P.
jerovici pneumonia.
• Patients may be characterized
– Asymptomatic
– Symptomatic
Fever, night sweats, lethargy, oral candidiasis, weight loss, and recurrent HZV infection.
– AIDS
– Defined by the diagnosis of one or more specific conditions such as; P. jerveroveci, M. tuberculosis
and CMV.

10. Investigation and Monitoring
• Initially detection of antibodies against HIV (ELISA) within 3—4
weeks of infection.
• After confirmation of HIV infection the patient is usually tested for
prior exposure to a number of potential pathogens such as; Syphilis,
Hepatitis-A, B & C, CMV, VZV and T. gondii.
• CD4 count  Normal level (500—1500 Cells/mm3)
• Patients with CD4 count < 200 Cells/mm prophylaxis against P.
jiroveci is recommended (major indictor to start ART)  makes the
basis of AIDS.

11. • Viral load  depicts plasma HIV RNA (estimates the amount of circulating virus in
the blood. Increased viral load  increased disease progression.
• Resistance testing  viruses which use CCR5 as a receptor for entry into the host
cell are termed and CCR5-tropic.

12. Pharmacological Treatment
Methods of therapeutic treatment
Four primary methods of therapeutic intervention against HIV are:
1. Inhibition of viral replication,
2. Virucides to prevent HIV infection,
3. Vaccination to stimulate a more effective immune response,
4. Restoration of immune system by immunomodulators.
Types of agents used for the treatment
1. Nucleoside reverse transcriptase inhibitors (NNRTI)
2. Protease inhibitors (PI)
3. Dual nucleoside reverse transcriptase inhibitors (dNtRTI)
4. Triple nucleoside reverse transcriptase inhibitors (tNtRTI)

13. Therapeutic Agents
Therapy Agents
NNRTI
Preferred
Alternative
Efavirenz
Nevirapine
PIs
Preferred
Alternative
Atazanavir + Ritonavir
Fosamprenavir + ritonavir (b.i.d)
Lopinavir/ritonavir (b.i.d)
Atazanavir
Fosamprenavir
Fosamprenavir + ritonavir (od)
Lopinavir/ritonavir (od)
Saquinavir
dNtRTI
Preferred
Alternative
Lamivudine + emtricitabine
Tenofovir + emtricitabine
Abacavir + lamivudine
Didanosine + lamivudine
tNtRTI