ODESSA NATIONAL MEDICAL UNIVERSITY

Microbiology,virology and immunology department

MEDICAL FACULTY

Lecture 15
Human immunodeficiency virus.

Odessa-2021
HIV probably entered the United States around 1970
CDC in 1981 noticed unusual clusters of Kaposi’s
sarcoma in gay men in NY and San Francisco, which
led to the disease to be called GRID (Gay Related
Immune Deficiency).
By 1982 the disease was found in heterosexuals and
was renamed AIDS (Acquired Immune Deficiency).
1984- Scientists (Dr. Luc Montagnier, Dr. Robert Gallo) identify
HIV (initially called LAV or HTLV-III) as the cause of AIDS

1987- AZT is the first drug approved for treating AIDS

Nobel Prize in Physiology and Medicine in 2008

Luc Antoine Montagnier Francoise Barre-Sinoussi Нarald zur Hausen

Virus classification:
Group: Group VI (ssRNA-RT)
Family: Retroviridae
Genus: Lentivirus
Species : Human immunodeficiency virus 1
Human immunodeficiency virus 2
• Types : HIV1 & HIV2
• HIV1: HIV-1A & HIV-1B
• HIV-1A & HIV-2 are spread heterosexually, but
HIV-1A is more virulent than HIV-2
• HIV-1B dominates in Europe & the United States

Comparison of HIV species

Species Virulence Infectivity Prevalence Inferred origin

HIV-1 High High Global Common chi

mpanzee

HIV-2 Lower Low West Africa Sooty manga

bey
HIV geographic distribution
HIV transmission
3D- model of HIV virion
Enveloped RNA retrovirus
Spherical 120 nm in diameter envelope proteins
make the spikes on the membrane.
Truncated conical capsid
Electron dense core
Two copies of the single stranded (+) RNA
Enzymes: Reverse transcriptase, Integrase &
Protease
Structural genes: gag, pol and env
Regulatory genes: LTR (long terminal repeats) rev
and neg
HIV genome
Viral replication
Role of coreceptors in viral
replication
 Electron micrograph of subsequent
stages of assembly and budding of HIV
1993 y.
HIV course
WHO Clinical Staging of HIV for Adults and
Adolescents with Confirmed HIV Infection
Clinical Stage 1
• Asymptomatic
• Persistent generalized lymphadenopathy
 Clinical Stage 2
• Unexplained moderate weight loss (<10% of presumed or measured
body weight)
• Recurrent respiratory tract infections (sinusitis, tonsillitis, otitis media
and pharyngitis)
• Herpes zoster
• Angular cheilitis
• Recurrent oral ulceration
• Papular pruritic eruptions
• Seborrhoeic dermatitis
• Fungal nail infections
 
WHO Clinical Staging of HIV for Adults and
Adolescents with Confirmed HIV Infection
Clinical Stage 3
• Unexplained severe weight loss (>10% of presumed or measured
body weight)
• Unexplained chronic diarrhoea for longer than one month
• Unexplained persistent fever (above 37.5C intermittent or constant
for longer than 1 month)
• Persistent oral candidiasis
• Oral hairy leukoplakia
• Pulmonary tuberculosis
• Severe bacterial infections (e.g. pneumonia, empyema, pyomyositis,
bone or joint infection, meningitis or bacteraemia)
• Acute necrotizing ulcerative stomatitis, gingivitis or peridontitis
• Unexplained anaemia (<8 g/dl), neutropenia (<0.5 X 109 per litre)
and/or chronic thrombocytopenia (<50 X 109 per litre)
 WHO Clinical Staging of HIV for Adults and
Adolescents with Confirmed HIV Infection
Clinical Stage 4
• HIV Wasting syndrome
• Pneumocystis pneumonia
• Recurrent severe bacterial pneumonia
• Chronic herpes simplex infection (orolabial, genital or anorectal of more than one month’s duration or visceral
at any site)
• Oesophageal candidiasis (or candidiasis of trachea, bronchi or lungs)
• Extrapulmonary tuberculosis
• Kaposi’s sarcoma
• Cytomegalovirus infection (retinitis or infection of other organs)
• Central nervous system toxoplasmosis
• HIV encephalopathy
• Extrapulmonary cryptococcosis including meningitis
• Disseminated non-tuberculous mycobacterial infection
• Progressive multifocal leucoencephalopathy
• Chronic cryptosporidiosis
• Chronic isosporiais
• Disseminated mycosis (extrapulmomary histoplasmosis or coccidiodomycosis)
• Recurrent septicaemia (including non-typhoidal salmonella)
• Lymphoma (cerebral or B-cell non-Hodgkins)
• Invasive cervical carcinoma
• Atypical disseminated leishmaniasis
• Symptomatic HIV-associated nephropathy or symptomatic HIV-associated cardiomyopathy.  
Development of opportunistic infections
Sarcoma Kaposhi on the hand.
Points of action of antiretroviral drugs
Antiretroviral drugs
Inhibitors of entrance and fusion

Reverse transcriptase inhibitors

- Nucleoside analogue reverse transcriptase inhibitors (NRTIs)

- Non-nucleoside reverse transcriptase inhibitors (NNRTIs)

Integrase inhibitors

Protease inhibitors

Inhibitors of maturation
Inhibitors of fusion
Nucleoside analogue reverse transcriptase
inhibitors (I)
Nucleoside analogue reverse transcriptase inhibitors
 Non-Nucleoside analogue reverse transcriptase
inhibitors(I)

* François Clavel, M.D., et al.5N Engl J Med. 2004;350(10):1023-1035.

Non-Nucleoside analogue reverse transcriptase
inhibitors(II)
Integrase inhibitors
Protease inhibitors
Inhibitirs of maturation
 Treatment (ART)
The most commonly used antiretroviral drugs fall into three classes:
• (a)     Nucleoside analogue reverse transcriptase inhibitors (NRTIs)
which were the first type of drugs available to treat HIV infection in
1987
• (b)    Non-nucleoside reverse transcriptase inhibitors (NNRTIs)
became available in 1997. Like NRTIs, non-nucleosides also
interfere with HIV’s ability to infect cells by targeting reverse
transcriptase
• (c)     Protease inhibitors (PIs) were first approved in 1995. PIs
interfere with viral replication by binding to the viral protease
enzyme and preventing it from processing viral proteins into their
functional forms.
• Several new classes of antiretroviral drugs are now available in
resource-rich countries such as fusion inhibitors, integrase inhibitors
and CCR5 inhibitors. These are rarely used in the developing world,
but drug availability is a fast changing field.
 Treatment (ART)
Nucleoside Reverse Non-Nucleoside Reverse Protease Inhibitors (PIs)
Transcriptase Inhibitors ( Transcriptase Inhibitors
(NNRTIs)
Zidovudine (AZT) Nevirapine (NVP) Lopinavir/r
Lamuvudine (3TC) Efavirenz (EFV) (Aluvia/Kaletra)
Didanosine (ddI) Saquinavir (SQV)
Stavudine (d4T) Ritonavir (RTV)
Abacavir (ABC) Atazanavir (ATV)
Tenofovir (TDF)* Darunavir (DRV)
Emtricitabine (FTC) Nelfinavir (NFV)
Indinavir (INV)
 ELISA (Enzyme-Linked Immuno Sorbent Assay):
Done to detect HIV antibodies in patient’s serum
(antigens used are p24, p17, gp160, gp120, and gp41).
 Anti-p24 is the first reliably detected antibody but declines as
viral titers rise in late infection
 Envelope antibodies rise more slowly but stay high at the end
 Env antigens show major antigenic variation
 ELISA for p24 useful early
 Western blot for antibodies specific to HIV
 Indirect Immunofluorescence Assay (IFA)
 HIV DNA PCR (Polymerase Chain Reaction):
◦ Qualitative to detect HIV infection in newborns of mothers are
HIV+
◦ Quantitative HIV DNA PCR to determine viral load to assess
treatment
◦ Useful in detecting HIV during window period ( i.e. no
antibodies in serum even though infected with HIV; 3-6
months)
Culture for HIV (with antigen detection in culture):
 HIV infection in newborns whose mothers are HIV+
 To assess drug resistance