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Chair of Microbiology, Virology, and Immunology
Human Immunodeficiency
Virus
The first indication of new disease – Acquired Immunodificiency
Syndrom (AIDS) began, when reports came from great cities of
USA (New York, Los Angeles, San Francisco) of a sudden
increase in the incidence of two very rare diseases:

1981- 5 cases of Pneumocystis carinii pneumonia in 8
months in young homosexuals ((before described as
epidemics at the closed children’s establishments, 1967 to
1979 treatment was sought for 2 cases).

1981- In 30 months time 26 cases of Kaposi’s sarcoma
in young
They appeared to have lost their immnune competence, rendering
them vulnerable to overwhelming and fatal infections with
relatively avirulent microorganisms, as well as to lymphoid and
other malignancies.
Kaposi’s Sarcoma
Pneumocystis carinii
New retrovirus from Lymphadenopathy in a homosexual in
1983 Prof. Luc Montagnier Pasteur institute, Paris named
Lymphadenopathy Associated Virus (LAV)
Dr. Robert Gallo, National Cancer Institute confirmed that a
retrovirus was the causative agent of AIDS in 1984, named
HTLV-III (Human T-lymphotropic Virus).
LAV = HTLV-III (Gallo et. al)
Human Retroviurs subcommittee of the International
committee on taxonomy of viruses (ICTV) recommended the
name Human Immunodeficiency virus (HIV).
1986 - One HIV was isolated from a west African patient in Pasteur
Institute.
1986 - Another HIV was isolated from a patient from Senegal in
Harvard School of Public health.
Difference antigenicity and clinical manifestations between
Western HIV and African HIV.
Human retrovirus sub committee on taxonomy of viruses (ICTV)
subsequently recommended that HIV-isolated from western patient
to be named-HIV-1.
HIV isolated from African patient was named HIV-2 (1986).
A.I.D.S.
A.I.D.S. stands for Acquired Immunodeficiency Syndrome.



Acquired – means that the disease is not hereditary but
develops after birth from contact with a disease causing
agent (in this case, HIV).
Immunodeficiency – means that the disease is
characterized by a weakening of the immune system.
Syndrome – refers to a group of symptoms that
collectively indicate or characterize a disease.
A global view of HIV infection
33 million people [30–36 million] living with HIV, 2007
Children (<15 years) estimated to be living with HIV, 2007
2.0 million (1.9 – 2.3 million)
More than 25 million people died of
AIDS since 1981 and AFRICA has more
than 12 million orphans
Over 7400 new HIV infections a day in 2007
More than 96% are in low and middle income countries
About 1000 are in children under 15 years of age
About 6300 are in adults aged 15 years and older
of whom:
— almost 50% are among women
— about 45% are among young people (15-24)
Regional HIV and AIDS statistics and features, 2007
Adults & children
living with HIV
Sub-Saharan Africa
Middle East & North Africa
South and South-East Asia
East Asia
Latin America
Caribbean
Eastern Europe & Central Asia
Western & Central Europe
North America
Oceania
TOTAL
Adults & children
Adult prevalence
newly infected with HIV
(15‒49) [%]
Adult & child
deaths due to AIDS
22.0 million
1.9 million
5.0%
1.5 million
[20.5 – 23.6 million]
[1.6 – 2.1 million]
[4.6% – 5.4%]
[1.3 – 1.7 million]
380 000
40 000
0.3%
27 000
[280 000 – 510 000]
[20 000 – 66 000]
[0.2% – 0.4%]
[20 000 – 35 000]
4.2 million
330 000
0.3%
340 000
[3.5 – 5.3 million]
[150 000 – 590 000]
[0.2% – 0.4%]
[230 000 – 450 000]
740 000
52 000
0.1%
40 000
[480 000 – 1.1 million]
[29 000 – 84 000]
[<0.1% – 0.2%]
[24 000 – 63 000]
1.7 million
140 000
0.5%
63 000
[1.5 – 2.1 million]
[88 000 – 190 000]
[0.4% – 0.6%]
[49 000 – 98 000]
230 000
20 000
1.1%
14 000
[210 000 – 270 000]
[16 000 – 25 000]
[1.0% – 1.2%]
[11 000 – 16 000]
1.5 million
110 000
0.8%
58 000
[1.1 – 1.9 million]
[67 000 – 180 000]
[0.6% – 1.1%]
[41 000 – 88 000]
730 000
27 000
0.3%
8000
[580 000 – 1.0 million]
[14000 – 49 000]
[0.2% – 0.4%]
[4800 – 17 000]
1.2 million
54 000
0.6%
23 000
[760 000 – 2.0 million]
[9600 – 130 000]
[0.4% – 1.0%]
[9100 – 55 000]
74 000
13 000
0.4%
1000
[66 000 – 93 000]
[ 12 000 – 15 000]
[0.3% – 0.5%]
[<1000 – 1400]
33 million
2.7 million
0.8%
2.0 million
[30 – 36 million]
[2.2 – 3.2 million]
[0.7% - 0.9%]
[1.8 – 2.3 million]
The ranges around the estimates in this table define the boundaries within which the actual numbers lie, based on the best available information.
HIV, the etiologjcal agent of AIDS, belongs to the lentivirus subgroup
of the family Retroviridae. The Lentivirus subgroup (L. lentus =
slow) includes the causative agents of the slow virus diseases
visna/maedi in sheep and others. Besides HIV, the related animal
immunodeficiency viruses also are assigned to this group.
HIV-1 isolated in 1984, and HIV-2 in 1986
Human Immunodeficiency Virus
Knob engages CD4 receptor on lymphocyte; virus carries preformed RT and integrase
enzymes; 107 particles/mL; 0 billion made per day as opposed to 2 billion CD4 cells/day
12
HIV-1 Virion
HIV can be inactivated by
- Boiling-water in seconds
- 70% Ethanol
- 2% Glutaraldehyde
- 1% House hold bleach (available in the market as 3.5%)
- Soap and Water
- 5% Formaldehyde
- 10% Sodium hypochlorite
- 3% Hydrogen peroxide
- 35% Isopropyl alcohol
- 0.5% Lysol
- 2.5% Tween-20
(<Minute)
30 minutes
Viral genes and antigens. The genome of HIV contains the three
structural genes (gag, pol and env) characteristic of all retroviruses, as
well as other nonstructural and regulatory genes specific for the virus.
The products of these genes, both structural and nonstructural, act as
antigens. Sera of infected persons contain antibodies to them. Detection
of these antigenes and antibodies is of great value in the diagnosis and
prognosis of HIV infections.

Genome consists of 9200 nucleotides (HIV-1):

gag core proteins - p15, p17 and p24

pol - p16 (protease), p31 (integrase/endonuclease)

env - gp160 (gp120:outer membrane part, gp41: transmembrane part)

Other regulatory genes ie. tat, rev, vif, nef, vpr and vpu
PATHOGENESIS
PATHOGENESIS
Types (Genotypes) of HIV Virus
 HIV 1
 Most common in sub-Saharan Africa and throughout the
world
 Groups M (Main), N (New), and O (Outlayer)
 Pandemic dominated by Group M
Group M comprised of subtypes A – K

Recombinant forms - AE, AG, AB, DF, BC, CD
As yet, different HIV-1 genotypes are not associated
with different courses of disease nor response to
antiviral therapy.
 HIV 2
 Most often found in West Central Africa, parts of Europe
and India
Virus travels through
Bloodstream
HIV attacks t-cells
Killer T-cells destroy affected
cells
AIDS virus attaches to a CD4
receptor
Transcription
Reverse Transcription
Proteins cut and
packaged with RNA
Possible Infections
Budding new
viruses
HIV Life Cycle
RNA
Reverse
Transcriptase
HIV
RNA
Protease
RNA
RNA
RNA
CCR5
RNA
DNA
Nine (9) genes
in the virus; uses
nucleotides in
cell to make
DNA
CD4 T -Lymphocyte
RNA
RNA
RNA
Proviral
DNA
Enveloped virus;
Will not survive in
the environment
Fig.
20.24
PATHOGENESIS
1) PRIMARY INFECTION
2) LYMPHOID INFECTION
3) ACUTE SYNDROME
4) IMMUNE RESPONSE
5) LATENCY
6) AIDS
Pathogenesis of AIDS
A great number of different abnormalities of
the immune system are seen in AIDS.
 As a result of the biology of lentivirus
infections, the pathogenesis of AIDS is highly
complex.
 These mechanisms are not mutually
exclusive & it is probable that the underlying
loss of CD4+ cells in AIDS is multifactorial

'Trojan horse' mechanism - virus escapes recognition by
replication inside monocytes, from where it can spread to other
tissues and other hosts.
Direct Cell Killing:

Cell fusion resulting in syncytium formation is one of the major mechanisms of
cell killing by HIV in vitro.
Indirect Killing of HIV-Infected Cells:
Indirect effects of infection, e.g. disturbances in cell biochemistry and
cytokine production, may also affect the regulation of the immune system.
However, the expression of virus antigens on the surface of infected cells leads to
indirect killing by the immune system - effectively a type of autoimmunity.
The extent of this activity is dependent on the virus load and replication kinetics in
infected individuals.
Antigenic Diversity
 This theory proposes that the continual generation of new antigenic variants
eventually swamps and overcomes the immune system, leading to its collapse.
T-Cell Anergy:






Anergy is an immunologically unresponsive state in which
lymphocytes are present but not functionally active.
This is usually due to incomplete activation signals and may be
an important regulatory mechanism in the immune system, e.g.
tolerance of 'self' antigens.
In AIDS, anergy could be induced due to HIV infection, e.g.
interference with cytokine expression.
There is experimental in vitro evidence that gp120-CD4
interactions result in anergy due to interference with signal
transduction.
Many AIDS patients are anergic, i.e. fail to mount a delayedtype hypersensitivity (DTH) response to skin-test antigens.
Impaired DTH responses are directly related to decreasing
CD4+ T-lymphocyte counts.
Apoptosis:





Like T-cell anergy, apoptosis could potentially be induced in large
numbers of uninfected cells by factors released from a much
smaller number of HIV-infected cells.
In addition to clonal deletion as a normal part of the evolution of
the T-cell repertoire, apoptosis may be induced following T-cell
activation as a negative regulatory mechanism to control the
strength and duration of the immune response.
HIV infection of T-cells induces an activated phenotype, e.g.
surface expression of CD45 and HLA-DR markers, which
suggests that these cells may be inevitably doomed due to
activation of the apoptosis pathway.
Because HIV establishes a persistent infection, it is by no means
clear that apoptosis has an entirely negative effect - induction of
cell death may well limit virus production and slow down the
course of infection.
Several HIV proteins have been identified as both inducers and
repressors of apoptosis under various circumstances. However,
the proportion of CD4+ T cells in the later stages of apoptosis is
about twofold higher in HIV-1 infected individuals than in
uninfected people.
Superantigens:





Superantigens are molecules which short-circuit the immune system,
resulting in massive activation of T-cells rather than the usual, carefully
controlled response to foreign antigens.
It is believed that they do this by binding to both the variable region of the
b-chain of the T-cell receptor (Vb) and to MHC class II molecules, crosslinking them in a non-specific way.
This results in polyclonal T-cell activation rather than the usual situation
where only the few clones of T-cells responsive to a particular antigen
presented by the MHC class II molecule are activated.
The over-response of the immune system produced results in autoimmunity
as whole families of T-cells which bind superantigens are activated, &
immunosuppression as the activated cells are killed by other activated Tcells or undergo apoptosis.
No superantigen has been conclusively identified in HIV, despite intensive
investigation, thus the practical relevance of superantigens in AIDS is in
doubt.
Superantigens:
TH1/TH2 Imbalance:






Immunological theory suggests that there are two types of CD4+ T-helper
(TH) cell: TH1 cells which promote the cell mediated response and TH2 cells
which promote the humoral response.
This theory suggests that early in HIV infection, TH1-responsive T-cells
predominate and are effective in controlling (but not eliminating) the virus.
At some point, a (relative) loss of the TH1 response occurs and TH2 HIVresponsive cells predominate.
The hypothesis is therefore that the TH2-dominated humoral response is
not effective at maintaining HIV replication at a low level and the virus load
builds up, resulting in AIDS.
Although this is largely a theoretical proposal which has not been proved,
this thinking is shaping our understanding of the immune response to many
different pathogens, not just HIV.
However, no experimental study has demonstrated an actual switch from
the TH1 to TH2 pattern of cytokine expression and secretion that is
associated with disease progression, so there is no evidence for the
involvement of these mechanisms in AIDS.
TH1/TH2 Imbalance
Virus Load & Replication Kinetics:
 The
average half-life of an HIV particle in vivo is
2.1 days.
to 109-1010 HIV particles are produced each
day.
 Up
average of 2x109 new CD4+ cells are
produced each day.
 An
Some of the immune abnormalities in HIV infection
include:
 Altered cytokine expression
 Decreased CTL and NK cell function
 Decreased T-cell function
 Decreased humoral and proliferative response to antigens and mitogens
 Decreased MHC-II expression
 Decreased monocyte chemotaxis
 Depletion of CD4+ cells
 Altered monocyte/macrophage function
 Impaired DTH reactions
 Lymphopenia
 Polyclonal B-cell activation
It is not clear how much of the pathology of AIDS is directly due to the virus
and how much is caused by the immune system itself. There are numerous
models which have been suggested to explain how HIV causes immune
deficiency:
Transmission
Sexual
Parenteral
Perinatal
Sexual
Male
Female
·
·
·
·
·
·
·
Large surface area
Higher concentration of HIV in semen
Recipient of infectious material
Menstruation
Trauma is more frequent
Dendritic cell
Social cause
Route of Sexual Transmission
Factors increase the rate of HIV
transmission in STD
Concentration of HIV is increased in
sexual fluid.
Disruption of normal barrier of skin and
mucus membrane.
Parenteral transmission
 Blood
and blood product
 Syringe, needle, surgery,
tattooing
ear-nose
acupuncture, razor.
dentistry,
piercing,
Perinatal
 Intrauterine
 During
delivery
 Breast
feeding
What body fluids transmit HIV
blood
semen
vaginal fluid
breast milk
You cannot become infected with HIV by:
 Kissing, hugging or shaking hands
 Sharing cups, glasses or knifes and forks
 Using the same toilet
Clinical Chronology after exposure to HIV
Exposure
Incubation period
(Window period)
Acute infection
Carrier state
Constitutional symptoms
Opportunistic infections
Malignancy
Incubation period

2 weeks to 12 weeks
(Incubation period must not be
confused with window period)
Window period

This period covers the terminal part of the
incubation period. Longer incubation period
shows longer window period. This period is
associated with appearance of HIV but not
anti-HIV in patient serum.
So, the period of time from the date of infection
until antibodies are produced.
Time period ranges from 6 weeks to 6 months.
Evolution of Antibodies
Window Period
Acute infection
Following HIV transmission, approximately 50% of
individuals will develop a febrile, flu-like illness with
some or all of the following conditions:
- Swollen glands
- Rash
- Oral ulcers
- Muscle aches
- Sore throat
- Headache
- Diarrhea
- Nausea or vomiting
Acute infection
Following HIV transmission, approximately 50% of
individuals will develop a febrile, flu-like illness with
some or all of the following conditions:
- Swollen glands
- Rash
- Oral ulcers
- Muscle aches
- Sore throat
- Headache
- Diarrhea
- Nausea or vomiting
Asymptomatic infection
All persons infected with HIV, whether they experience
seroconversion illness or not, pass through a phase of
symptom1ess infection; lasting for several months or years. They
show positive HIV antibody tests during this phase and are
infectious. In some, the infection may not progress any further,
while in others it may lead to full brown AIDS, either directly or
through cytopenias, minor opportunistic infection, persistent
generalized lymphadenopathy or AIDS related complex (ARC) as
described below.
Persistant Generalised Liphadenopathy (PGL)
This has been defined as the presence of enlarged lymph nodes, at
least 1,0 cm, in diameter, in two or more noncontiguous extrainguinal
sites, that persist for at least three months, in the absence of any
current illness or medication that may cause lymphadenopathy. This
by itself is benign but a proportion of the cases may progress to ARC
or AIDS.
AIDS Related Complex (ARC)
This group inc1udes patients with considerable immunodeficiency,
suffering from various constitutional symptoms or having minor
opportunistic infections. The typical constitutional symptoms are
fatigue, unexplained fever, persistent diarrhea and parked weight
loss of more than 10 per cent of body weight. The common
opportunistic infections are oral candidiasis,
herpes zoster,
salmonellosis or tuberculosis. Generalized lyrnphadenopathy and
splenomegaly are usually present. ARC patients are usually severely
ill and many of them progress to AIDS in a few months.
AIDS
This is the end stage disease representing the irreversible
breakdown of immune defense mechanisms, leaving the patient a
prey to progressive opportunistic infections and malignancies. The
clinical severity of AIDS varies with the type of infection or
malignancy present. In early AIDS, many patients are ill only
during episodes of infection which may respond to treatment.
Between episodes they may be relatively well and able to resume
normal life.
Constitutional symptoms
Fever for >2 months
Diarrhoea for >2 months
Loss of weight > 10% of body wait within short
period.
Night sweat
Loss of appetite
CD4 cell count low
P24 positive
Opportunistic infections of AIDS
1. Protozoal infections:
a)
Pneumocystis carinii
b)
Toxoplasma gondii
c)
Cryptosporidium
d)
Isospora belli
e)
Malaria
Opportunistic infections of AIDS
2. Fungal infections:
a) Candida
b) Cryptococcus
c) Aspergillus
Opportunistic infections of AIDS
3. Bacterial infections:
a)
Mycobacterium
b)
Salmonella
c)
Pyogenic bacteria
Opportunistic infections of AIDS
4. Viral infections:
a)
Herpes simplex virus (HSV)
b)
Herpes zoster virus
c)
Cytomegalovirus (CMV)
Malignancy
1.
Kaposi’s sarcoma
2.
Non-hodgkin’s lymphoma
According to the system most affected patients
present with various complaints, some of which
are as follows:
A. The commonest presentation is with increasing dry cough,
dyspnea and fever. In the USA and other Western countries, the
characteristic pathogen initially was P. carinii but now M. tuberculosis or
an atypical mycobacterium such as M. avium-intracellulare is more
often responsible. In the developing countries, the most important
pathogen is M. tuberculosis, with many strains being multidrug
resistant. In fact the poor nations are facing a double epidemic, jointly
with HIV and tuberculosis. Pneumonia may be viral (CMV) or fungal
(cryptococcus, histoplasma). Recurrent pneumonia is considered to
be indicative of AIDS.
Pneumocystis carinii
Histoplasma capsulatum
Cryptosporidium
(intestinal epithelium)
Cryptococcus neoformans
(nervous system)
B. Gastrointestinal system. The mouth is
often involved in AIDS, with thrush,
herpetic stomatitis, gingivitis, Kaposi's
sarcoma. Dysphagia may be due to
esophageal candidiasis. A characteristic
intestinal pathogen in AIDS is
cryptosporidium. Salmonellae,
mycobacteria, CMV or adenoviruses also
frequently cause intestinal infections.
Systemic strongyloidosis may occur.
Chronic colitis is common in male
homosexuals («gay bowel syndrome»),
from which ameba, lamblia and a host of
diarrheagenic bacteria have been
reported.
Candidiasis
C. Central nervous system: The typical CNS opportunistic infections
are toxoplasmosis and cryptococcosis. Infections are also seen with
CMV, herpes simplex, papovaviruses, mycobacteria, aspergillus and
Candida. Lymphomas of the central nervous system are common.
D. Malignancies: Kaposi's sarcoma is the characteristic lesion
seen in male homosexuals. It is an indolent multifocal
nonmetastasising is mucosal or cutaneous tumor, probably of
endothelial origin. The other tumors commonly seen are lymphomas,
both the Hodgkin and non Hodgkin types.
E. Cutaneous. Besides Kaposi's sarcoma, herpes lesions,
candidiasis, xeroderma, seborrheic dermatitis, prurigo, folliculitis,
impetigo and molluscum contagiosumn are common cutaneous
lesions.
F. Dementia. HIV may cause direct cytopathogenic damage in tire
central nervous system. It can cross the blood brain barrier and
cause encepfialopathy leading to loss of higher functions,
progressing to dementia.
G. Pediatric AIDS. About one third to one half the number of babies
born to infected mothers are infected with HIV. Many of them may
not survive for a year. Children may also acquire the infection from
b1ood transfusions or blood products.
The definition of AIDS has since been broadened to include all
seropositive persons (irrespective of clinical manifestations) with
CD4 T cell counts of less than 200 per mm3.
Kaposi's sarcoma
Dermatomycosis
Dermatitis
Herpes zoster
Herpes
Warts
Sarcoma
Еczema
Herpetic infection
AIDS patients
Laboratory diagnosis
Laboratory procedures for the diagnosis of HIV infection include tests
for immunodificiency as well as specific tests for HIV.
A. Immunological tests. The following parameters help to establish
the immunodeficiency in HIV infection:
l. Total leucocyte and lymphocyte count to demonstrate leucopenia
and a lymphocyte count usually below 2,000 /c.mm.
2. T cell subset assays. Absolute T4 cell count will be usually less than
200/c.mm. T4: T8 cell ratio is reversed.
3. Platelet count will show thrombocytopenia.
4. Raised IgG and IgA levels.
5. Diminished CMI as indicated by skin tests.
6. Lymph node biopsy showing profound abnormalities.
B. Specific tests for HIV infection. These include demonstration of
HIV antigens and antibodies and isolation of the virus.
I. Antigen detection. The time course of appearance of detectable
antigens and antibodies after НV infection is generally as follows:
Following a single massive infection, as by blood transfusion, the virus
antigens (p24) may be detectable in blood after about two weeks. IgM
antibodies appear in about 4-6 weeks, to be followed by IgG antibodies.
2. Virus isolation. Once infected with HIV, a person remains infected
for life. The virus is present in circulation and body fluids, mostly within
the lymphocytes but some are also cell free. Virus titres are high early
in infection, about a week before antibodies start appearing. Antibodies
do not neutralize the virus and the two can coexist in the body.
Laboratory Diagnosis
3. Antibody detection. Demonstration of antibodies is the simplest and
most widely employed technique for the diagnosis of HIV infection.



Serology is the usual method for diagnosing HIV infection. Serological
tests can be divided into screening and confirmatory assays. Screening
assays should be as sensitive whereas confirmatory assays should be
as specific as possible.
Screening assays - ELISAs are the most frequently used screening
assays. The sensitivity and specificity of the presently available
commercial systems now approaches 100% but false positive and
negative reactions occur. Some assays have problems in detecting HIV1 subtype O.
Confirmatory assays - Western blot is regarded as the gold standard
for serological diagnosis. However, its sensitivity is lower than screening
ELISAs. Line immunoassays incorporate various HIV antigens on
nitrocellulose strips. The interpretation of results is similar to Western
blot it is more sensitive and specific.
ELISA for HIV antibody
Microplate ELISA for HIV antibody: coloured wells indicate reactivity
Western blot for HIV antibody

There are different
criteria for the
interpretation of HIV
Western blot results
e.g. CDC, WHO,
American Red Cross.

The most important
antibodies are those
against the envelope
glycoproteins gp120,
gp160, and gp41

p24 antibody is
usually present but
may be absent in the
later stages of HIV
infection
Test-system for AIDS
diagnosis
IMMUNOPROPHYLAXIS
Types of HIV vaccines
1. Attenuated vaccines are made from genetically engineered strains
lacking some crucial genes, so that the resulting virus causes a harmless
infection. This approach has been tried successfully with simian
immunodeficiency virus (SIV)
2. Killed virus vaccines. In humans, it has been proposed that vaccination
with low doses of killed HIV enhances cellular immunity and favors (lie
development of cell-mediated cytotoxicity. Evaluation is difficult because the
end-point is a disease-free interval that is long and variable.
3. Recombinant viral particles made by inserting HIV glycoprotein
genes in, for example, vaccinia-virus genomes induce neutralizing
antibodies in animals.
4. Component vaccines have been prepared from isolated gpl20,
polymerized gpl20, or gpl20 peptides representing more conserved
regions (such as the CD4-binding domain)
Therapy of HIV Infection:



Nucleoside-Analog Reverse Transcriptase Inhibitors (NRTI). These drugs inhibit
viral RNA-dependent DNA polymerase (reverse transcriptase) and are incorporated into
viral DNA (they are chain-terminating drugs).

Zidovudine (ZDV, Retrovir) first approved in 1987

Didanosine (ddI, Videx)

Zalcitabine (ddC, Hivid)

Stavudine (d4T, Zerit)

Lamivudine (3TC, Epivir)
Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). In contrast to NRTIs,
NNRTIs are not incorporated into viral DNA; they inhibit HIV replication directly by
binding non-competitively to reverse transcriptase.

Nevirapine (Viramune)

Delavirdine (Rescriptor)
Protease Inhibitors. These drugs are specific for the HIV-1 protease and competitively
inhibit the enzyme, preventing the maturation of virions capable of infecting other cells.

Saquinavir (Invirase) first approved in 1995

Ritonavir (Norvir)

Indinavir (Crixivan)

Nelfinavir (Viracept)
 Fusion inhibitors e.g. Fuzeon (IM only)
Prevention



The spread of HIV through blood transfusion and blood products
had virtually been eliminated since the introduction of blood
donor screening in many countries.
AZT had been shown to be effective in preventing transmission
of HIV from the mother to the fetus. The incidence of HIV
infection in the baby was reduced by two-thirds.
The management of health care workers exposed to HIV through
inoculation accidents is controversial. Anti-viral prophylaxis had
been shown to be of some benefit but it is uncertain what is the
optimal regimen.
The
risk of contracting HIV increases with the
number of sexual partners. A change in the lifestyle
would obviously reduce the risk.
The
only methods which have strong evidence
supporting their efficacy to protect against HIV
infection are condoms and female condoms