Approved
at the Chair of Infection diseases and
epidemiology
meeting on
The Head of the Chair
Prof . G. M. Dubynska
The subject under the study
is
Infectious diseases
Methodical Instruction No. 19
For the 5th year students’ self – preparation work
(at class and at home)
in studying Infectious diseases
Topic: HIV-infection
Hours:
1. Urgency of the issue:
Today it is generally recognized that the HIV infection has become a medical and social problem of
vital importance, for apart from its social consequences (millions of people infected and dying from
AIDS) the disease seriously affects a countrys economic and political welfare.
This has made the HIV infection one of the most considerable modern sociopathies. It is universally
acknowledged that social and ecological characteristics are the most important
factors influencing peoples health. To this extent the effect of any infectious disease, the HIV infection
among them is to be assessed in terms of epidemiological surveillance. However when it is question of
HIV/AIDS everybody is primarily concerned with the issues of real HIV/AIDS prevalence and the
absolute number of HIV-infected individuals. Another key issue is the efficiency of efforts taken at
different levels to hold the global spread of the disease.The overview of the global situation on
HIV/AIDS lets us state that the HIV/AIDS crisis in a number of African countries continues to deepen,
while Eastern Europe and East Asia have had the most rapid spread of the HIV-infection among the
population.
2. Training tasks of the class (indicating the level of learning to be reached):
2.1. The student should be familiar with (study):
а–1
۰ have general idea about position of HIV/AIDS in the structure of virulent diseases, prevalence in
different areas of the world and different age groups; study statistic data related to case rate, case
mortality, event frequency, long-term effects of infections;
۰ get familiar with history of scientific study of HIV/AIDS, have an idea of scientific contribution
of native scientists in the history of scientific research in this field.
2.2. The student should know:
а–2
-the main characteristics of HIV/AIDS
-аetiology, еpidemiology, сlinical picture of HIV/AIDS
-anti–epidemiological measures and methods of treatment of HIV/AIDS.
2.3. The student should be able to:
а–3
1. Make up medical history estimating epidemiological data
2. Examine the patient and find out the main symptoms and syndromes of HIV/AIDS and solve the
issue of necessary inpatient treatment
3. based on clinical examination define possible complications of HIV/AIDS
4. Fill in medical documentation based on previously stated diagnosis HIV/AIDS.
5. Make up a plan of patient’s laboratory and instrumental examination
6. Analyze the results of laboratory examination
7. Give a proper estimate to the results of specific methods of diagnostics
8. Make up an individual treatment plan taking into account epidemiological data, stage of disease,
available complications, severity of the condition, allergic anamnesis, comorbidity, provide rescue
emergency care
9. Make up a preventive measures plan for the centre of infections
10. Provide recommendations related to mode of treatment, diet, examination and medical supervision
during recovery period
3. Information to be obtained during pre-classroom independent work.
3.1.Basic knowledge and skills necessary for subject learning (interdisciplinary integration)
Discipline
Microbiology
Propedeutics of
medical diseases
To know:
To be able to:
Features of HIV, rules and terms for Take samples of material for
sampling for specific diagnostics
virological and serological testing,
analyze the results
Main stages and methods of patient clinical Make up medical history, perform
examination
clinical examination of the patient by
Epidemiology
Immunology and
allergology
Physiology
Dermology
Neurology
Clinical
pharmacology
Family practice
Virulent diseases
different organs and systems, define
clinical symptoms of pathology
Epidemic process (source, mechanism of Make up an epidemiological history,
infection
introduction,
ways
of perform antiepidemic and preventive
transmission) of HIV/AIDS; prevalence of measures
pathology in Ukraine and in the world.
WHO’s strategy related to liquidation of
these infections.
The key terms of the subject, role of Analyze data of immunological
immunity system in infectious process,
examinations
Aspects of physiological standards of
Estimate data of laboratory
human organs and systems; aspects of
examination
laboratory examination in standard
condition
Various types of exanthema and enanthema Define the nature of rash on skin and
mucous membranes
Clinical, laboratory and instrumental signs
of meningitis, encephalitis and toxic
encephalopathy
Pharmacokinetics and pharmacodynamics,
adverse effects of antivirals and means of
nosotropic therapy
Perform clinical examination of the
patient with affected central nervous
system. Make a lumbar puncture
Prescribe treatment with regard to age,
individual symptoms of the patient,
chose an optimum mode of drug intake
and dosage, provide prescriptions
Other disciplines
Pathogenesis, epidemiology, intensiveness
of clinical signs, possible complications of
HIV/AIDS .Principles of prophylactics and
treatment.
Integration between subjects
Features of infectious diseases. Methods of
diagnostics, treatment and prophylactics of
infectious diseases. Pathogenesis,
epidemiology, intensiveness of clinical signs,
laboratory diagnostics, possible complications
specific features of clinical progress of
HIV/AIDS. Prophylactics and treatment
methods
3.2. Structure and logic scheme of class content
Perform differential diagnostics
HIV/AIDS with other infectious
diseases. Prescribe treatment.
Provide rescue emergency care in
pre-hospital stage.
AIDS is an acronym for Acquired Immunodeficiency Syndrome or Acquired Immune Deficiency
Syndrome and is defined as a collection of symptoms and infections resulting from the depletion of
the immune system caused by infection with HIV. Although treatments for both AIDS and HIV exist,
there is no known cure. The rate of clinical disease progression varies widely between individuals and
has been shown to be affected by many factors such as host susceptibility, immune function, health
care, the presence of co-infections and peculiarities of the viral strain.
The official date for the beginning of the AIDS epidemic is marked as June 18, 1981, when the US
Center for Disease Control and Prevention reported a cluster of Pneumocystis carinii pneumonia (now
classified as Pneumocystis jiroveci pneumonia) in five gay men in Los Angeles in the early 1980s.
Originally dubbed GRID, or Gay Related Immune Difficiency, health authorities soon realized that
nearly half of the people identified with the syndrome were not gay. Reporter Randy Shilts discovered
the name of an extremely sexually active man, Gaetan Dugas, who epidemiologists at the time
suspected to be the first carrier of what was first called "gay-plague", but later research failed to track
the epidemic to any individual carrier. In 1982, the CDC introduced the term AIDS to describe the
newly recognized syndrome.
Three of the earliest known instances of HIV infection are as follows:
1. A plasma sample taken in 1959 from an adult male living in what is now the Democratic
Republic of Congo.
2. HIV found in tissue samples from an American teenager who died in St. Louis in 1969.
3. HIV found in tissue samples from a Norwegian sailor who died around 1976.
Two species of HIV infect humans: HIV-1 and HIV-2. HIV-1 is more virulent and more easily
transmitted. HIV-1 is the source of the majority of HIV infections throughout the world, while HIV-2
is less easily transmitted and is largely confined to West Africa. Both HIV-1 and HIV-2 are of primate
origin. The origin of HIV-2 has been established to be the sooty mangabey (Cercocebus atys), an Old
World monkey of Guinea Bissau, Gabon, and Cameroon. The origin of HIV-1 is a chimpanzee
subspecies: Pan troglodytes troglodytes.
HIV is transmitted through penetrative (anal or vaginal) and oral sex; blood transfusion; the sharing of
contaminated needles in health care settings and through drug injection; and, between mother and
infant, during pregnancy, childbirth and breastfeeding.
AIDS is thought to have originated in sub-Saharan Africa during the twentieth century and is now a
global epidemic. The World Health Organization estimated that, worldwide, between 2.8 and 3.5
million people with AIDS died in 2004.
Global epidemic
UNAIDS and the WHO estimated that between 36 and 44 million people around the world were living
with HIV in December 2004. It was estimated that during 2004, between 4.3 and 6.4 million people
were newly infected with HIV and between 2.8 and 3.5 million people with AIDS died. Sub-Saharan
Africa remains by far the worst-affected region, with 23.4 million to 28.4 million people living with
HIV at the end of 2004. Just under two thirds (64%) of all people living with HIV are in sub-Saharan
Africa, as are more than three quarters (76%) of all women living with HIV. South & South East Asia
are second most affected with 15%. AIDS accounts for the deaths of 500,000 children.
World region
Sub-Saharan Africa
Caribbean
Estimated adult prevalence of
HIV infection
(ages 15–49)
6.9% to 8.3%
1.5% to 4.1%
Estimated adult and child
deaths
during 2004
2.1 to 2.6 million
24,000 to 61,000
0.3% to 0.6%
Asia
Eastern Europe and Central Asia 0.5% to 1.2%
0.5% to 0.8%
Latin America
0.1% to 0.3%
Oceania
0.1% to 0.7%
Middle East and North Africa
North America, Western and
0.3% to 0.6%
Central Europe
350,000 to 810,000
39,000 to 87,000
73,000 to 120,000
fewer than 1,700
12,000 to 72,000
15,000 to 32,000
Source: UNAIDS and the WHO 2004 estimates. The ranges define the boundaries within which the
actual numbers lie, based on the best available information.
Prevention
The effective use of condoms and screening of blood transfusion in North America, Western and
Central Europe is credited with the low rates of AIDS in these regions. Adopting these effective
prevention methods in other regions has proved controversial and difficult. The Vatican opposes the
use of condoms and many countries do not screen blood transfusions for HIV antibodies.
Safer sex
The male latex condom is the single most efficient available technology to reduce the sexual
transmission of HIV and other sexually transmitted infections. With consistent and correct use of
condoms, there is a very low risk of HIV infection. Studies on couples where one partner is infected
show that with consistent condom use, HIV infection rates for the uninfected partner are below 1% per
year.
The US government and US health organizations both endorse the ABC Approach to lower the risk of
acquiring AIDS during sex:

Abstinence or delay of sexual activity, especially for youth,

Being faithful, especially for those in committed relationships,

Condom use, for those who engage in risky behavior.
This approach has been very successful in Uganda, where HIV prevalence has decreased from 15% to
5%. However, the ABC approach is far from all that Uganda has done, as "Uganda has pioneered
approaches towards reducing stigma, bringing discussion of sexual behavior out into the open,
involving HIV-infected people in public education, persuading individuals and couples to be tested and
counseled, improving the status of women, involving religious organizations, enlisting traditional
healers, and much more." (Edward Green, Harvard medical anthropologist). Also, it must be noted that
there is no conclusive proof that abstinence-only programs have been successful in any country in the
world in reducing HIV transmission. This is why condom use is heavily co-promoted. There is also
considerable overlap with the CNN Approach. This is:

Condom use, for those who engage in risky behavior.

Needles, use clean ones

Negotiating skills; negotiating safer sex with a partner and empowering women to make smart
choices
The ABC approach has been criticized, because a faithful husband or wife of an unfaithful partner is
at risk of AIDS. Many think that the combination of the CNN approach with the ABC approach will be
the optimum prevention platform.
HIV blood screening
In those countries where improved donor selection and antibody tests have been introduced, the risk of
transmitting HIV infection to blood transfusion recipients has been effectively eliminated. According
to the WHO, the overwhelming majority of the world's population does not have access to safe blood
and "between 5% and 10% of HIV infections worldwide are transmitted through the transfusion of
infected blood and blood products."
Medical procedures
Medical workers who follow universal precautions or body substance isolation such as wearing latex
gloves when giving injections and washing the hands frequently can help prevent infection of HIV.
The risk of being infected with HIV from a single prick with a needle that has been used on an HIV
infected person though is thought to be about 1 in 150 (see table above). Post-exposure prophylaxis
with anti-HIV drugs can further reduce that small risk.
Universal precautions are frequently not followed in both sub-Saharan Africa and much of Asia
because of both a shortage of supplies and inadequate training. The WHO estimates that approximately
2.5% of all HIV infections in sub-Saharan Africa are transmitted through unsafe healthcare injections.
Because of this, the United Nations General Assembly, supported by universal medical opinion on the
matter, has urged the nations of the world to implement universal precautions to prevent HIV
transmission in health care settings.
Universal precaution gets its name from the idea that precautions are to be used every single time, and
not merely when the healthcare worker thinks that a patient might be high-risk for a transmissable
disease.
Intravenous drug use
HIV can be transmitted by the sharing of needles by users of intravenous drugs. Cumulative data from
1981 to 2001 has shown that 31.5% of people with AIDS in the United States are injection drug users.
All AIDS-prevention organisations advise drug-users not to share needles and to use a new or properly
sterilized needle for each injection. Information on cleaning needles using bleach is available from
health care and addiction professionals and from needle exchanges. In the United States and other
western countries, clean needles are available free in some cities, at needle exchanges or safe injection
sites.
Mother to child transmission
There is a 30% risk of transmission of HIV from mother to child during pregnancy, labour and
delivery. A number of factors influence the risk of infection, particularly the viral load of the mother at
birth (the higher the load, the higher the risk). Breastfeeding increases the risk of transmission by
10–15%. This risk depends on clinical factors and may vary according to the pattern and duration of
breastfeeding.
Studies have shown that antiretroviral drugs, cesarean delivery and formula feeding reduce the chance
of transmission of HIV from mother to child. (Sperlin et al., 1996)
When replacement feeding is acceptable, feasible, affordable, sustainable and safe, HIV-infected
mothers are recommended to avoid breast feeding their infant. Otherwise, exclusive breastfeeding is
recommended during the first months of life and should be discontinued as soon as possible.
Transmission and infection
Scanning electron micrograph of HIV-1 budding from cultured lymphocyte.
Patterns of HIV transmission vary in different parts of the world. In sub-Saharan Africa, which
accounts for an estimated 60% of new HIV infections worldwide, controversy rages over the
respective contribution of medical procedures, heterosexual sex and the bush meat trade. In the United
States, sex between men (35%) and needle sharing by intravenous drug users (15%) remain prominent
sources of new HIV infections. In January 2005, Anthony S. Fauci, M.D., director of NIAID said,
"Individual risk of acquiring HIV and experiencing rapid disease progression is not uniform within
populations". NIH press release Some epidemiological models suggest that over half of HIV
transmission occurs in the weeks following primary HIV infection before antibodies to the virus are
produced. Investigators have shown that viral loads are highest in semen and blood in the weeks before
antibodies develop and estimated that the likelihood of sexual transmission from a given man to a
given woman would be increased about 20-fold during primary HIV infection as compared with the
same couple having the same sex act 4 months later. Most people who are infected typically suffer
from days to weeks of fever with or without muscle and joint aches, fatigue, headache, sore throat,
swollen glands and sometimes rash. This "acute retroviral syndrome" is rarely diagnosed because it is
difficult to distinguish from other very common ailments.
The Centers for Disease Control (CDC) in the United States reported a cluster of HIV infections in 13
of 42 young women who reported sexual contact with the same HIV infected man in a rural county in
upstate New York between February and September 1996
The risk of oral sex has always been controversial. Most of the early AIDS cases could be attributed to
anal sex or vaginal sex. As the use of condoms became more widespread, there were reports of AIDS
acquired by oral sex. Unprotected oral sex is widely understood to be less risky than unprotected
vaginal sex, which in turn is less risky than unprotected anal sex.
Heterosexual transmission of HIV-1 depends on the infectiousness of the index case and the
susceptibility of the uninfected partner. Infectivity seems to vary during the course of illness and is not
constant between individuals. Each 10 fold increment of seminal HIV RNA is associated with an 81%
increased rate of HIV transmission. During 2003 in the United States, 19% of new infections were
attributed to heterosexual transmission.
The argument about the exact incidence of HIV transmission per act of intercourse is academic.
Infectivity depends critically on social, cultural, and political factors as well as the biological activity
of the agent. Whether the epidemic grows or slows depends on infectivity plus two other variables: the
duration of infectiousness and the average rate at which susceptible people change sexual partners.
Genetic susceptibility
CDC has released findings that genes influence susceptibility to HIV infection and progression to
AIDS. HIV enters cells through an interaction with both CD4 and a chemokine receptor of the 7 Tm
family. They first reviewed the role of genes in encoding chemokine receptors (CCR5 and CCR2) and
chemokines (SDF-1). While CCR5 has multiple variants in its coding region, the deletion of a 32-bp
segment results in a nonfunctional receptor, thus preventing HIV entry; two copies of this gene provide
strong protection against HIV infection, although the protection is not absolute. This gene is found in
up to 20% of Europeans but is rare in Africans and Asians; researchers and scientists believe that HIV
had a similar viral shell as the bacteria which caused the black plague (1347-1350), leading to the
decimation of one-third of the European population, possibly explaining why the CCR5-32 receptor
gene is more prevalent in Europeans than Africans and Asians. Multiple studies of HIV-infected
persons have shown that presence of one copy of this gene delays progression to the condition of
AIDS by about 2 years. And it is possible that a person with the CCR5-32 receptor gene will not
develop AIDS, although they will still carry HIV.
Diagnosis
The majority of people infected with HIV, if not treated, develop signs of AIDS within 8-10 years.
However, 1-2% of HIV-infected individuals retain functional immune systems, despite being infected
with HIV for a number of years. These individuals are known as HIV longterm non-progressors.
The Centers for Disease Control has, since 1993, defined an AIDS diagnosis in adults and adolescents
in the USA as when a person presents with HIV infection and either a CD4+ T cell count below
200/ВµL or one of 26 of AIDS defining clinical conditions. This is different for children.
In developing countries, AIDS in adults and adolescents is identified on the basis of certain infections,
grouped by the World Health Organization (WHO):

Stage I HIV disease is asymptomatic and not categorized as AIDS

Stage II (includes minor mucocutaneous manifestations and recurrent upper respiratory tract
infections)

Stage III (includes unexplained chronic diarrhoea for longer than a month, severe bacterial
infections and pulmonary tuberculosis) or

Stage IV (includes Toxoplasmosis of the brain, Candidiasis of the oesophagus, trachea, bronchi
or lungs and Kaposi's Sarcoma) HIV disease are used as indicators of AIDS.
Treatment
There is currently no cure or vaccine for HIV or AIDS. Current optimal treatment options consist of
combinations ("cocktails") consisting of at least three drugs belonging to at least two types, or
"classes," of anti-retroviral agents. Typical regimens consist of two nucleoside analogue reverse
transcriptase inhibitors (NRTIs) plus either a protease inhibitor or a non nucleoside reverse
transcriptase inhibitor (NNRTI). This treatment is frequently referred to as HAART (highly-active
anti-retroviral therapy). Anti-retroviral treatments, along with medications intended to prevent AIDSrelated opportunistic infections, have played a part in delaying complications associated with AIDS,
reducing the symptoms of HIV infection, and extending patients' life spans. Over the past decade the
success of these treatments in prolonging and improving the quality of life for people with AIDS has
improved dramatically.
However, treatment guidelines are changing constantly. The current guidelines for antiretroviral
therapy from the World Health Organization reflect the 2003 changes to the guidelines and
recommend that in resource-limited settings (i.e., developing nations), HIV-infected adults and
adolescents should start ARV therapy when HIV-infection has been confirmed and one of the
following conditions is present:

Clinically advanced HIV disease:

WHO Stage IV HIV disease, irrespective of the CD4 cell count;

WHO Stage III disease with consideration of using CD4 cell counts <350/Вµl to assist
decision-making.

WHO Stage I or II HIV disease with CD4 cell counts <200/Вµl
The US Department of Health and Human Services, the federal agency responsible for overseeing
HIV/AIDS healthcare policies in the United States, have recently stated on April 7, 2005 that:

All patients with history of an AIDS-defining illness or severe symptoms of HIV infection
regardless of CD4+ T cell count receive ART.

Antiretroviral therapy is also recommended for asymptomatic patients with <200 CD4+ T
cells/Вµl

Asymptomatic patients with CD4+ T cell counts of 201 - 350 cells/Вµl should be offered
treatment.

For asymptomatic patients with CD4+ T cell of >350 cells/Вµl and plasma HIV RNA
>100,000 copies/ml most experienced clinicians defer therapy but some clinicians may
consider initiating treatment.

Therapy should be deferred for patients with CD4+ T cell counts of >350 cells/Вµl and plasma
HIV RNA <100,000 copies/mL.
The preferred initial regimens are either:

efavirenz + lamivudine or emtricitabine + zidovudine or tenofovir; or

lopinavir boosted with ritonavir + zidovudine + lamivudine or emtricitabine.
The DHHS also recommends that doctors should assess the viral load, rapidity in CD4 decline, and
patient readiness while deciding when to begin treatment.
There are several concerns about antiretroviral regimens. The drugs can have serious side effects
(Saitoh et al., 2005). Regimens can be complicated, requiring patients to take several pills at various
times during the day. If patients miss doses, drug resistance can develop. Also, anti-retroviral drugs are
costly, and the majority of the world's infected individuals do not have access to medications and
treatments for HIV and AIDS.
Research to improve current treatments includes decreasing side effects of current drugs, simplifying
drug regimens to improve adherence, and determining the best sequence of regimens to manage drug
resistance.
Vaccine research
As there is no known cure for AIDS, the search for a vaccine against the etiological agent, HIV, has
become part of the struggle against the disease. Only a vaccine will be able to halt the pandemic. This
would possibly cost less, thus being affordable for developing countries, and would not require daily
treatments. However, after over 20 years of research, HIV remains a difficult target for a vaccine and
there is still no vaccine available; a June 2005 study estimates that $682 million is spent on AIDS
vaccine research annually.
3.3 Recommended literature
1. Principles and practice of infectious diseases /edited by Gerald L., Mandel R., Gordon
Douglas, John E Bennett. – 3rd ed. – Churchill Livingstone Inc. – New York. - 1990.
2. Infectious diseases/ Ed. By E. Nikitin, M. Andreychyn. – Ternipil. Ukrmedknyha, 2004. – 364 p.
3. Walter R. Wilson, Merle A. Sande. Current diagnosis and treatment in infectious diseases. - Mc
Graw Hill, New-York, 2001. - 979 p.
3.4. Materials for self-control
3.4.1. Questions for self-control
1. What immunodeficiency syndromes do you know?
2. Name the main characteristics of HIV/AIDS.
3. Name the clinical characteristics of HIV/AIDS
4. Name the measures of prevention and control of HIV/AIDS.
3.4.2. Tests for self-control
Choose the correct answer:
=2
. Where does replication of the HIV occur?
a) plasmocytes and macrophages;
b) macrophages and T-helpers;
c) T-helpers and В-lymphocytes;
d) В-lymphocytes and plasmocytes;
e) No one from mentioned.
2. What opportunistic infections and invasions are typical for AIDS?
a) generalized candidiasis and pulmonary coccididomycosis;
b) leishmaniasis and toxoplasmosis;
c) pneumocytosis and disseminated histoplasmosis;
d) extrapulmonary tuberculosis and leishmaniasis;
e) shigellosis and amebiasis.
3. What is the screening - method of diagnostics of HIV-infection?
a) immune-enzyme analysis (IEА);
b) radioimmune analysis(RIA);
c) immunoblot analysis;
d) molecular hybridization (DNA-PROBES);
e) polymerase chain reaction.
4. What clinical syndrome is characteristic for dementia in patients with HIV-infection?
a) syndrome of liquor hypertension;
b) multifocal leukoencephalopathy;
c) discirculatory infringements of a cerebral circulation;
d) edema of the brain;
e) spongiform encephalopathy.
5. What is the coefficient Т4/Т8 (the ratio of subpopulations of Т-lymphocytes) typical for AIDS?
a) 0,5;
b) 1,5;
c) 2,0;
d) 3,0;
e) 4,0.
4. Materials for classroom individual work
4.1. List of practical training tasks to be done during the practical class:
 Study methods of examination of patient with HIV/AIDS
 Examine the patient for HIV/AIDS
 Perform differential diagnostics of HIV/AIDS
 Make up a plan of laboratory examination
 Study the results of specific examination of patients with HIV/AIDS
 State the complications of HIV/AIDS
 Make up a treatment plan for the patient HIV/AIDS
 Define medical approach in case of emergencies.
№
1.
4.2. Professional algorithm of gaining knowledge and skills of HIV/AIDS
Task
Sequence of actions
Notices and warnings concerning self-control
Study
the
methods of
examination
of
patient
2.
3.
with
HIV/AIDS
Examine the
patient
Perform
laboratory
examination