2.

Recognize risk factors for acquiring HIV infection

Classic risks - Most common transmission through sexual contact. Transmission rates highest for
anal sex and transmission is more likely from male to female when having vaginal intercourse
(although Uptodate says male to female and female to male transmission rates are the same). Risk
is obviously increased with risky behaviour like not using condoms and sex with multiple partners.
Male to male transmission is a serious risk for those reasons, however the transmission rate seems
to have steadied off in this category and the most rapidly rising group of new patients are females
having heterosexual intercourse. Another classic risk group are IV drug users. There has been a
significant reduction amongst this group since the implementing of needle exchange programs
educating the patient in this case is important.
Viral Load - The mean viral load was significantly higher in those who transmitted HIV to their partner
(90,254 compared to 38,029 copies/mL). Furthermore, there were no cases of transmission among
the 51 subjects with HIV RNA levels less than 1500 copies/mL. Based on study quoted on Uptodate.
STDs - The risk of aquiring HIV is higher in those with an STD. Especially those with genital ulcers
(i.e. herpes, syphilis, chancroid, thrush, HPV genital warts).
Lack of circumcision.
Mother to child either in utero, during delivery or during breast feeding. This risk has gone down a lot
with proper treatment to the point of being all but eliminated during labor and delivery according to
Kochar.
Transfusion - Since HIV testing began in 1988 the risk of receiving HIV through a transfusion is very
low. A donor may be in the preseroconversion infectious window period making it possiblebut risk
is very low. With improvements in testing in 1999, science has shrunken the window where a
patient will not test positive for HIV, but will have HIV RNA. The chance of getting HIV from a
transfusion is now 1 in 3 million.
Genetic Background - Genetics may play a role in the fact that similar HLA Class-I alleles between
partners may select for viral strains that are more likely to escape the immune containment of the
seronegative partner.
3 Describe the pathogenesis of HIV infection.
HIV has several targets including dendritic cells, macrophages, and CD4+ T cells.
Target cells HIV-1 most often enters the host through the genital mucosa. The viral envelope
protein, glycoprotein (GP)-120, binds to the CD4 molecule on dendritic cells. Interstitial dendritic cells
are found in cervicovaginal epithelium as well as tonsillar and adenoidal tissue, which may serve as
initial target cells in infection transmitted via genital-oral sex.
Newly acquired HIV infection is more commonly due to transmission of macrophage tropic rather than
T cell tropic viruses. Viral entry into these cells is mediated by different coreceptors. In order to enter
macrophages, GP-120 must bind to the chemokine receptor CCR5 as well as CD4. Macrophage
tropic viruses are designated as R5 in comparison to T cell tropic viruses, which are called X4, based
upon the CXCR4 receptor on these cells. Patients homozygous for a deletion in CCR5 are relatively
resistant to R5 infection, but cases of X4 infection have rarely been reported in these individuals.

HIV infected cells fuse with CD4+ T cells, leading to spread of the virus. HIV is detectable in regional
lymph nodes within two days of mucosal exposure and in plasma within another three days. Once
virus enters the blood, there is widespread dissemination to organs such as the brain, spleen, and
lymph nodes.
The intestinal mucosa is also a primary target during initial infection. Massive CD4 T-cell depletion
during acute infection has been demonstrated with simian immunodeficiency virus (SIV) in rhesus
macaques. Both studies documented that destruction occurred preferentially in CD4+ memory T cells,
which may result from direct infection as well as through apoptosis. This can lead to an early and
disproportionate loss of CD4+ T cells in the gastrointestinal compartment, compared to peripheral
blood. It has also been proposed that microbial translocation, due to changes in the gut mucosal
barrier, may be the etiology of chronic immune activation in HIV infection.
Viremia Studies in primates suggest viral penetration of mucosal epithelium, followed by infection
of submucosal CD4+ T cells, dendritic cells, and macrophages with subsequent spread to lymph
nodes and ultimately, plasma. Viremia was documented between 5 to 30 days after experimental
intravaginal HIV exposure.
HIV RNA levels rapidly increase from the earliest quantifiable measure to a peak level that usually
coincides with seroconversion. However, a period of low-level viremia preceding ramp-up viremia,
may be more common than originally thought. A study of serial samples from patients with confirmed
primary HIV infection was performed to determine if low levels of viremia were present in samples
that were negative by prior quantitative PCR. On retesting with a sensitive qualitative reverse
transcriptase PCR assay with sensitivity of 4 copies/mL, 23 of 69 samples were subsequently
positive. These specimens preceded the first sample with >100 copies/mL by 9 to 25 days. Whether
blood is infectious at this low level of concentration is not known.
The HIV DNA level in peripheral blood mononuclear cells provides an estimate of the cellular HIV
reservoir, which is established soon after infection. In one study of 163 patients who did not start
immediate antiretroviral therapy after diagnosis of acute infection, the HIV DNA level and initial CD4
cell count were found to be independent predictors of disease progression.
Cellular immune response At the time of initial infection with HIV, patients have a large number of
susceptible CD4+ T cells and no HIV-specific immune response. Viral replication is therefore rapid;
plasma HIV RNA levels may climb to more than 10(7) copies/mL and p24 antigen levels may exceed
100 pg/mL.
Concomitant with the evolution of HIV specific immunity, primarily due to the emergence of virusspecific CD8+ cytotoxic T lymphocytes, plasma RNA levels fall precipitously by 2 to 3 logs, and
symptoms of the acute retroviral syndrome resolve. In the absence of antiretroviral therapy, plasma
HIV RNA levels will stabilize at an individual's given "set-point" within six months of infection. The host
factors, virus factors, and pharmacologic interventions, which determine this set point, are active
issues for ongoing investigations.
A few HIV-positive individuals are classified as long-term nonprogressors because, in the absence of
antiretroviral therapy, they have normal CD4 counts and low or undetectable plasma viremia. A newer
term for these individuals is "controller", implying their ability to control viral replication without
antiretroviral therapy. There is no official definition of long term non-progressors, but some have
defined it by the following criteria: HIV infection 8 years, a CD4 count >500/mm3, and no intervening
antiretroviral therapy. These individuals are distinguished from regular and rapid progressors by the
persistence of HIV-specific T-helper cell proliferative responses. In one model, these proliferative
responses allow for ongoing HIV-specific cytotoxic T lymphocyte activity and hence containment of

plasma viremia. However, it is not clear whether these HIV immune responses directly cause, or
alternatively, are the result of HIV control.
Early research suggests that initiation of aggressive combination antiviral therapy during acute
infection protects activated HIV-specific T helper cells from infection by HIV and thereby preserves
the HIV-specific cytotoxic T lymphocyte response to virally infected cells a situation analogous to
the long-term nonprogressors.
Studies of T cell responses in primary HIV infection help to delineate how early therapy might improve
clinical outcomes. In one study, patients with primary HIV infection who were identified early in the
course of their acute disease demonstrated a 10- to 20-fold increase in the proportion of highly
activated (CD38+) and proliferating (Ki-67+) CD4 T cells that expressed CCR5. CD4 T cells that
produced interferon gamma in response to HIV antigens were readily detected in this patient subset.
However, in patients with primary HIV infection who presented later in their clinical course, antigenspecific CD4+ T cells could not be readily detected. This observation coincided with lower frequencies
of activated and proliferating T cells, suggesting that apoptosis and cytopathic infection with HIV leads
to their rapid decline. Regulatory T cells may also play a role in suppressing HIV-specific CD4 T cell
responses in early infection.
Preservation of the immune response to HIV may also shorten the duration of symptoms associated
with acute infection, prevent dissemination of virus to other organs, and establish a lower virologic
"set-point." Nevertheless, eradication of virus seems unlikely with currently available agents based
upon studies which show that replication-competent HIV may be recovered even from patients with
completely suppressed viral loads.
This concept was well-illustrated in a case report of an infant girl who was diagnosed with HIV
infection at birth after her mother had primary seroconversion two weeks earlier. The baby was
initiated on combination antiretroviral therapy within one week of birth. Antiretroviral therapy led to full
suppression of HIV viremia, undetectable HIV-specific antibodies, and lack of detection of proviral
DNA in peripheral blood mononuclear cells and tonsillar tissue. In light of these findings and her
strong HIV-specific T cell proliferative responses, antiviral therapy was stopped. Within one month,
the CD4 count dropped from 3674 to 2174/microL and HIV plasma viremia rose to 46,000 copies/mL.
Genetic susceptibility Cohorts of individuals who are highly exposed (injection drug users or
commercial sex workers) but who remain HIV-seronegative have been described. A nested casecontrol study of 266 HIV-seropositive patients and 532 seronegative controls was conducted to
examine whether any of nine candidate host genes may play a role in susceptibility to HIV infection.
Self-reported risk behaviors were analyzed from data collected at semi-annual visits. Four singlenucleotide polymorphisms (CCR-2, CCR5, MIP1A, and IL2) were significantly associated with HIV
infection susceptibility in different genetic models.
The most extensively studied of these genetic factors is the C-C chemokine receptor 5 (CCR5), a
major coreceptor for HIV. CCR5 (delta) 32 is an allele that contains a 32-base pair deletion and codes
for a nonfunctional coreceptor. CCR5 (delta) 32 homozygotes (people who inherited the allele from
both parents) are highly resistant to HIV infection. Patients who are heterozygous for the 32-base pair
deletion can acquire HIV infection, but have a slower rate of progression.
4. Describe the stages and natural history of HIV infection.
Infection with Human Immunodeficiency Virus (HIV) eventually leads to Acquired Immune Deficiency
Syndrome (AIDS). This process typically takes several years and can be broken down into four

stages: primary infection, asymptomatic, symptomatic, and AIDS. Knowing what stage of HIV
infection an individual is in can help physicians design treatment plans.
In order to diagnose an individual as being in a specific stage of HIV, the World Health Organization
(WHO) developed a set of criteria that can be used worldwide. The criteria rely on symptoms, instead
of viral load test, since many developing countries do not have the facilities to perform these
complicated tests.
Stage 1: Primary HIV Infection
The first stage of HIV infection is called primary infection. Primary infection begins shortly after an
individual first becomes infected with HIV. This stage lasts for a few weeks. During this time period,
individuals experience symptoms similar to the flu. Very few individuals seek treatment during this
time, and those who do are usually misdiagnosed with a viral infection.
Often, if an HIV test is performed, it will come back negative, since antibodies are not yet being
produced by the individuals immune system. Those who believe they have been exposed to HIV
should repeat the test again after six months.
Stage 2: Asymptomatic HIV
In the second stage, individuals are free from any symptoms of HIV. Levels of HIV in the blood are
very low, but are detectable. If an HIV test is performed, it will come back positive. While the
individual is asymptomatic, the HIV in their blood is reproducing constantly. This stage lasts about ten
years, but can be much longer or shorter depending on the individual.

Stage 3: Symptomatic HIV

In the third stage, the immune system has become so damaged by HIV that symptoms begin to
appear. Symptoms are typically mild at first, and then slowly become more severe. Opportunistic
infections, infections that take advantage of the immune systems vulnerable state, begin to occur.
These infections affect almost all the systems of the body and include both infections and cancers.
Some common opportunistic infections include tuberculosis, cytomegalovirus, and shingles.
Stage 4: Acquired Immune Deficiency Syndrome
In the fourth and final stage, a person is diagnosed as having AIDS. To be diagnosed as having AIDS,
a person has to exhibit certain opportunistic infections, such as HIV wasting syndrome, pneumocystis
pneumonia, or Kaposi sarcoma. Once a person is diagnosed with AIDS, they can never return to a
stage of HIV, even if the individual gets better.
HIV, the virus that causes AIDS, originated in non-human primates in sub-Saharan Africa and was
transferred to humans during the late 19th or early 20th century.
Two types of HIV infect humans: HIV-1 and HIV-2. HIV-1 is more virulent, is easily transmitted and is
the cause of the majority of HIV infections globally. HIV-1 is closely related to a virus found in

chimpanzees, and molecular phylogenetics indicates that the HIV-1 virus appeared sometime
between 1884 and 1924 in equatorial Africa. HIV-2 is less transmittable and is largely confined to
West Africa, along with its closest relative, a virus of the Sooty Mangabey (Cercocebus atys), an Old
World monkey of Guinea-Bissau, Gabon, and Cameroon.
Most HIV researchers agree that HIV evolved from the closely related Simian Immunodeficiency Virus
(SIV), and that HIV was transferred from non-human primates to humans in the recent past (as a type
of zoonosis). Research in this area is conducted using molecular phylogenetics, comparing viral
genomic sequences to determine relatedness.
HIV-1 spread from chimpanzees
Where: Because most groups of HIV-1 are most closely related to a strain of the simian
immunodeficiency virus that infects the chimpanzee subspecies Pan troglodytes troglodytes (SIVcpz),
scientists generally accept[3][4] that the virus originated in populations of wild chimpanzees in WestCentral Africa.[5] Exactly where this occurredin the southeastern rain forests of Cameroon (modern
East Province) near the Sanaga River, or further south near Kinshasa in the Democratic Republic of
the Congohas been a matter of scientific discussion.[6][5][7]
When: Using HIV-1 sequences preserved in human biological samples along with estimates of viral
mutation rates, scientists calculate that the jump from chimpanzee to human probably happened
during the late 19th or early 20th century, a time of rapid urbanisation and colonisation in equatorial
Africa. Exactly when the zoonosis occurred is not known. Some estimates suggest that HIV-1 (group
M) entered the human population in the early 20th century, probably between 1915 and 1941.[8][9] A
study published in 2008, analyzing viral sequences recovered from a recently-discovered 1960 biopsy
along with previously-known sequences, suggested a common ancestor between 1884 and 1924.[2]
[10]
Genetic recombination had earlier been thought to "seriously confound" such phylogenetic analysis,
but later "work has suggested that recombination is not likely to systematically bias [results]",
although recombination is "expected to increase variance".[2] The results of phlyogenetics study
supported the later work and indicated that HIV evolves "fairly reliably".[2][11]
How: According to the 'Hunter Theory', the "simplest and most plausible explanation for the crossspecies transmission",[3] the virus was transmitted from a chimpanzee to a human when a bushmeat
hunter was bitten or cut while hunting or butchering an animal. The resulting exposure of the hunter to
blood or other bodily fluids of the chimpanzee could have resulted in infection.[12]
Method of spread
Zoonosis (transfer of a pathogen from non-human animals to humans) and subsequent spread of the
pathogen between humans, requires the following conditions:
a human population;
a nearby population of a host animal;
an infectious pathogen in the host animal that can spread from animal to human;

interaction between the species to transmit enough of the pathogen to humans to establish a
human foothold, which could have taken millions of individual exposures;
ability of the pathogen to spread from human to human (perhaps acquired by mutation);
some method allowing the pathogen to disperse widely, preventing the infection from "burning
out" by either killing off its human hosts or provoking immunity in a local population of humans.
Conditions that facilitated the establishment and spread of infection in human populations may have
included the reuse of needles for injectable antibiotics, antimalarial drugs and vaccines;[13] an
increase in bushmeat hunting and immune suppression as a result of the harsh conditions, forced
labor and displacement associated with colonialism, particularly in French Equatorial Africa;[14] rapid
urbanisation that brought infected people into close contact with others; and colonial commerce that
provided opportunities for further geographical spread.[10]
SIV in non-human primates tends to cause a non-fatal disease. Comparison of the gene sequence of
SIV with HIV should therefore give us information about the factors necessary to cause disease in
humans. The factors that determine the virulence of HIV as compared to most SIVs are only now
being elucidated. Non-human SIVs contain a nef gene that down-regulates CD3, CD4, and MHC
class I expression; most non-human SIVs therefore do not induce immunodeficiency; the HIV nef
gene however has lost its ability to down-regulate CD3, which results in the immune activation and
apoptosis that is characteristic of chronic HIV infection.[15]
History of known cases and spread:
19551957: British printer (possible AIDS death)
Main article: David Carr (history of AIDS)
The oldest documented possible case of the then-unknown syndrome was thought to have been
detected in 1959, when a 25-year-old British printer who had travelled in the navy between 1955 and
1957 (but apparently not to Africa) sought help at the Royal Infirmary of Manchester, England. He
reported to have been suffering from puzzling symptoms, among them purplish skin lesions, for
nearly two years. His condition had taken a turn for worse during Christmas 1958, when he started
suffering from shortness of breath, extreme fatigue, rapid weight loss, night sweats and high fever.
The doctors thought he might be suffering from tuberculosis and, even though they found no
evidence of bacterial infection, they treated him for tuberculosis just to be safe, to no avail. The printer
continued to weaken and he died shortly after in August 1959. His autopsy revealed evidence of two
unusual infections, cytomegalovirus and Pneumocystis carinii pneumonia (PCP, later, when
redetermined as P. jirovecii, renamed Pneumocystis pneumonia), very rare at the time but now
commonly associated with AIDS patients. His case had puzzled his doctors, who preserved tissue
samples from him and for years retained some interest in solving the mystery.
Sir Robert Platt, then president of the Royal College of Physicians, wrote in the printer's hospital chart
that he wondered "If we are in for a new wave of virus disease now that the bacterial illnesses are so
nearly conquered". It was only 31 years later, after the AIDS pandemic had become well-known and
widespread, that they decided to perform HIV-tests on the preserved tissues of the printer, which
initially turned out a positive result. While the case was reported in the July 7, 1990 issue of the

British medical journal The Lancet, their claim was retracted in a letter in the January 20, 1996 issue,
in which they reported that the tissue sample had
1959: Congolese man
One of the earliest documented HIV-1 infections was discovered in a preserved blood sample taken
in 1959 from a man from Leopoldville, Belgian Congo (now Kinshasa, Democratic Republic of the
Congo). However, it is unknown whether this anonymous person ever developed AIDS and died of its
complications.
5. List indications for HIV testing.
Indications for HIV testing should be assessed on the basis of the following risk factors:
1.
2.
3.
4.
5.
6.

- unprotected male-to-male intercourse

- sharing of injecting equipment
- being the sexual partner of an HIV positive person
- being from a country with a high HIV prevalence
- having recently travelled overseas
- presenting for post-exposure prophylaxis (PEP) after occupational or nonoccupational exposure to HIV
7. - pregnancy
8. - requesting an HIV test in the absence of clear risk factors
9. - diagnosis of a sexually transmissible infection
Routine pre-operative testing for HIV is not supported at this time.
For a person presenting for primary health care, indications for HIV testing should be assessed on
the basis of a history of potential exposure and/or specific signs and symptoms. Clinical features of
HIV-related illness may be wide-ranging and non-specific, and can overlap with a range of other
potential diagnoses. The clinical manifestations have been well described.
In considering whether an HIV test is indicated, an assessment of a persons risk or history should
be made in the context of what is known about the history of HIV transmission and its epidemiology,
and any identifiable or known risk factors.
An HIV test should be offered following a sexual assault, in the context of adequate risk
assessment and counseling. A sexual assault is not necessarily a high-risk event for HIV
transmission; however, the psychological benefit in being offered a test is significant.

Risk assessment and indications for testing:

1. Unprotected male-to-male anal intercourse
By far the most frequent means of transmission of HIV is unprotected anal intercourse between men.
This mode of transmission accounts for around 80% of all HIV infections. A history of unprotected
male-to-male anal intercourse is a strong indication for offering testing.

2. People who share injecting equipment

A history of injecting drug use involving shared equipment is a strong indication for offering testing for
HIV and other blood borne viruses. The sharing of injecting equipment between injecting drug users
is a well-documented mode of HIV transmission. Whilst hepatitis C is common in injecting drug user
populations, the prevalence of HIV has remained less than 2% in this population, except in male
injecting drug users who also report homosexual contact.

3. Sexual partners of people with HIV

The sexual partners of people with HIV are at higher risk of HIV infection, and therefore HIV testing
should be offered.

4. People from countries with a high HIV prevalence and their sexual partners
People from countries with a high HIV prevalence and their sexual partners are at increased risk of
HIV infection. (High prevalence countries are those with HIV prevalence of about 1% or higher.) Such
countries now include: the Caribbean, Sub-Saharan Africa, Southeast Asian countries including
Thailand and Cambodia, as well as Papua New Guinea.

5. People who have recently travelled overseas

People who have recently travelled to countries with a high HIV prevalence, and have had
unprotected sex, injected drugs, had dental, medical or cosmetic treatment, or a blood transfusion
whilst in such countries, are at increased risk of HIV infection and should be offered an HIV test.

6. People presenting for post-exposure prophylaxis after occupational or non-occupational

exposure to HIV
People presenting for post-exposure prophylaxis must be tested for HIV prior to, and upon completion
of, any course of antiretroviral therapy. Follow up HIV antibody testing should be performed at 2-4
weeks, at 3 months and at 6 months post-exposure.

7. Pregnant women
Pregnancy, per se, is not an indicator of risk of HIV infection. However, undiagnosed HIV infection
during pregnancy has serious implications for the health of both the woman and her child. These
implications can be mitigated by appropriate management. As a consequence, routine offering of HIV

testing to this group is warranted.

8. People requesting an HIV test in the absence of clear risk factors

The incidence of HIV is very low where there is an absence of recognized risk factors. In people
without a clear history of risk or clinical indications of HIV infection, there is no basis for systematically
or routinely offering testing. A small number of people will request a test but will not disclose risk
factors. In this case, a persons preference not to disclose risk factors should be recognized and HIV
testing should be conducted. A small number of people will present repeatedly for HIV tests with no
risk factors displayed; this behavior should be addressed through appropriate discussion. Individual
factors should play a role in the discussion between doctor and patient, as well as in the decision
whether or not to proceed with an HIV test.

9. People diagnosed with a sexually transmissible disease (STD)

Diagnosis of an STD should be considered as an indication for HIV testing. People infected with an
STD, particularly ulcerative STDs, are generally at higher risk of acquiring and transmitting HIV, and
should be offered an HIV test.

10. Donor testing for blood transfusion and tissue transplantation

HIV testing is mandatory for a person who donates blood or tissue. The donation or a blood sample
from the donor is tested for HIV and other blood-borne pathogens. The present risk of acquiring HIV
infection through a transfusion has been estimated at approximately 1 in 7 million.

11. HIV testing in prison settings

Prisoners should be offered testing for HIV as part of the reception medical examination and prior to
release. This testing should be offered in accordance with the guiding principles of this policy, with the
issue of the special circumstances of disclosure of medical information clearly addressed during the
consent process.

12. Pre-operative testing

Consistent with the Infection Control Guidelines for the prevention of transmission of infectious
diseases in the health care setting:

Preoperative testing of a patient for infectious agents should be on the basis of clinical
indication, and medical practitioners should exercise their professional judgment in ordering

any clinically relevant test. Discretion and patient confidentiality must be maintained in all
circumstances.

In a person with an identified risk of HIV infection and/or clinical indications of infection, pre-operative
HIV testing should be performed only if it will benefit the patient, and informed consent has been
obtained after pre- and post-test discussion. The use of rapid testing pre-operatively for elective
surgery is not supported.
6. Describe the significane of CD4 counts
A CD4+ count is a blood test to determine how well the immune system is working in people who
have been diagnosed with human immunodeficiency virus (HIV). The lower the count, the greater
damage HIV has done. Anyone who has less than 200 CD4 cells, or a CD4 percentage less than
14%, is considered to have AIDS according to the US Centers for Disease Control.
The number of CD4+ cells with the viral load helps determine whether opportunistic infections may
occur. The pattern of CD4+ counts over time is more important than any single CD4+ value because
the values can change from day to day. The CD4+ pattern over time shows the effect of the virus on
the immune system. In people infected with HIV who are not getting treated, CD4+ counts generally
decrease as HIV progresses. A low CD4+ count usually indicates a weakened immune system and a
higher chance of getting opportunistic infections.
CD4 counts are also used to indicate when to start antiretroviral therapy (ART). When the CD4 count
goes below 350, most health care providers begin ART. Also, some health care providers use the
CD4% going below 15% as a sign to start aggressive ART, even if the CD4 count is high. More
conservative health care providers might wait until the CD4 count drops to near 200 before starting
treatment. A recent study found that starting treatment with a CD4% below 5% was strongly linked to
a poor outcome.
Additionally, CD4 counts are used to start treatment for opportunistic infections. Most health care
providers prescribe drugs to prevent opportunistic infections at the following CD4 levels:
Less than 200: pneumocystis pneumonia (PCP)
Less than 100: toxoplasmosis and cryptococcosis
Less than 75: mycobacterium avium complex (MAC).
7. Describe treatment protocols for the initiation of HIV therapy
For patients with a history of an AIDS-defining illness or a CD4 T-cell count <200 cells/mm3,
antiretroviral therapy should be initiated. For patients with CD4 T-cell counts between 200 and 350
cells/mm3, antiretroviral therapy is also recommended. Antiretroviral therapy may be considered in
some patients with CD4 T-cell counts >350 cells/mm3.
Potential benefits and risks of early (CD4 counts >350 cells/mm3) therapy initiation for the
asymptomatic patient are outlined below.
Potential Benefits of Early Therapy Include:
Maintenance of a higher CD4 count and prevention of potentially irreversible damage to the immune
system

 Decreased risk for HIV-associated complications that can sometimes occur at CD4 counts >350
cells/mm3, including tuberculosis, non-Hodgkins lymphoma, Kaposis sarcoma, peripheral
neuropathy, HPV-associated malignancies, and HIV-associated cognitive impairment
Decreased risk of nonopportunistic conditions, including cardiovascular disease, renal disease, liver
disease, and nonAIDS-associated malignancies and infections
Decreased risk of HIV transmission to others, which will have positive public health implications
Potential Risks of Early Therapy Include:
Development of treatment-related side effects and toxicities
Development of drug resistance because of incomplete viral suppression, resulting in loss of future
treatment options
Less time for the patient to learn about HIV and its treatment and less time to prepare for the need
for adherence to therapy
Increased total time on medication, with greater chance of treatment fatigue
Premature use of therapy before the development of more effective, less toxic, and/or better studied
combinations of antiretroviral drugs
Transmission of drug-resistant virus in patients who do not maintain full virologic suppression
Antiretroviral therapy should also be initiated in the following groups of patients regardless of CD4 Tcell count:
Pregnant Women All HIV-infected pregnant women should be started on antiretroviral therapy to
manage maternal HIV infection and to maximize viral suppression, in order to reduce the risk for
perinatal HIV transmission
HIV-Associated Nephropathy (HIVAN) HIVAN is the most frequent cause of chronic renal failure in
persons living with HIV infection. This entity, which is more common in black than in white patients, is
not clearly related to CD4 T-cell depletion. Ongoing viral replication appears to be directly involved in
renal injury.
Hepatitis B virus (HBV) coinfection requiring treatment of HBV HIV-infected patients may also
be coinfected with HBV. The two-NRTI combination of tenofovir plus either lamivudine or emtricitabine
is a component of many recommended first-line antiretroviral regimens and is also an effective
treatment for HBV infection. In the HIV-infected patients, if therapy for either HIV or HBV infection is
indicated, initiation of a fully suppressive antiretroviral regimen that includes tenofovir and either
lamivudine or emtricitabine is recommended in order to prevent development of antiretroviral drug
resistance (BIII). If antiretroviral therapy is not initiated, HBV therapy should include only agent(s) with
the least potential of selecting HIV resistance mutations.
8. Recognize the complications of HIV infections.
HIV infection weakens your immune system, making you highly susceptible to a large number of
bacterial, viral, fungal and parasitic infections. You may also be vulnerable to certain types of cancers.
But treatment with anti-retroviral drugs has markedly decreased the number of opportunistic
infections and cancers affecting people with HIV. It's now more likely these infections will occur in
people who have not had treatment.
Bacterial infections
Bacterial pneumonia. Dozens of types of bacteria can cause bacterial pneumonia, which may
develop on its own or after you've had an upper respiratory infection such as a cold or the flu.

Mycobacterium avium complex (MAC). The mycobacteria normally cause an infection of the
respiratory tract. But if you have advanced HIV infection and your CD4 lymphocyte count is less than
50, you're more likely to develop a systemic infection that can affect almost any internal organ,
including your bone marrow, liver or spleen. MAC causes nonspecific symptoms such as fever, night
sweats, weight loss, stomach pain and diarrhea.
Tuberculosis (TB). In resource-poor nations, TB is the most common opportunistic infection
associated with HIV and a leading cause of death among people living with AIDS. Having HIV makes
you more susceptible to TB and far more likely to progress from dormant to active HIV infection. At
the same time, TB increases the rate at which the AIDS virus replicates. What's more, TB often
strikes people with HIV years before other problems associated with HIV develop. One of the first
indications of HIV infection may be the sudden onset of TB often in a site outside the lungs.
Salmonellosis. You contract this bacterial infection from contaminated food or water. Symptoms
include severe diarrhea, fever, chills, abdominal pain and, occasionally, vomiting. Although anyone
exposed to salmonella bacteria can become sick, salmonellosis is far more common in people who
are HIV-positive. You can reduce your risk by washing your hands carefully after handling food and
animals and by cooking meat and eggs thoroughly.
Bacillary angiomatosis. This infection, caused by Bartonella henselae bacteria, first appears as
purplish to bright red patches on your skin. It often resembles Kaposi's sarcoma, but it can cause
disease in other parts of your body, including your liver and spleen.
Viral infections
Cytomegalovirus (CMV). This common herpesvirus is transmitted in body fluids such as saliva,
blood, urine, semen and breast milk. But a healthy immune system inactivates the virus, and it
remains dormant in your body. If your immune system weakens, the virus resurfaces, causing
damage to your eyes, digestive tract, lungs or other organs. Most commonly, CMV causes infection
and inflammation of your retina (CMV retinitis). If not treated, CMV retinitis can lead to blindness.
Viral hepatitis. Viral hepatitis is a viral infection of the liver. Signs and symptoms include yellowing of
your skin and the whites of your eyes (jaundice), fatigue, nausea, abdominal pain, loss of appetite
and diarrhea. There are several types of viral hepatitis, but the most common are hepatitis A, B and
C. Hepatitis B and C can lead to persistent or chronic infection and put you at risk of long-term
complications such as cirrhosis or liver cancer. If you are HIV-positive and also have hepatitis, you
may be more likely to develop liver toxicity from your medications.
Herpes simplex virus (HSV). HSV, which usually causes genital herpes, may be transmitted during
unprotected anal or vaginal sex. Initial symptoms include pain or irritated skin in the genital area.
Later, sores that ooze and bleed erupt on the genitals, buttocks and anus. Although these sores
eventually heal, the virus periodically reappears, causing the same symptoms. If you have HIV, your
skin infection is likely to be more severe than it would be in people who don't have HIV, and the sores
may take longer to heal. Systemic symptoms may also be more severe. Although the herpes virus
isn't life-threatening in adults, it may cause brain damage and blindness.
Human papillomavirus (HPV). This is one of the most common causes of sexually transmitted

disease. Some types of this virus cause common warts. Other types cause warts on the genitals. If
you're HIV-positive, you're especially susceptible to infection with HPV and more prone to recurrent
infections. HPV infection is especially serious because it significantly increases a woman's risk of
cervical cancer. Infection with both HPV and HIV increases a woman's risk even further cervical
cancer seems to occur more often and more aggressively in women who are HIV-positive.
Progressive multifocal leukoencephalopathy (PML). PML is an extremely serious brain infection
caused by the human polyomavirus JC virus. Signs and symptoms vary and may include speech
problems, weakness on one side of the body, loss of vision in one eye, or numbness in one arm or
leg. PML usually occurs only when your immune system has been severely damaged.
Fungal infections
Candidiasis. Candidiasis is a common HIV-related infection. It causes inflammation and a thick white
coating on the mucous membranes of your mouth, tongue (thrush), esophagus (Candida esophagitis)
or vagina.
Cryptococcal meningitis. Meningitis is an inflammation of the membranes and fluid surrounding
your brain and spinal cord (meninges). Cryptococcal meningitis is a common central nervous system
infection associated with HIV, caused by a fungus that is present in soil. It may also be associated
with bird or bat droppings. Symptoms include headache, high fever, a stiff neck and sensitivity to light.
Meningitis is a serious disease that can cause severe complications or prove fatal in a short period of
time.
Parasitic infections
Pneumocystis carinii pneumonia (PCP). Although anti-retroviral drugs have helped reduce the
number of cases of PCP, it remains one of the most common opportunistic infections affecting people
with AIDS in the United States. PCP attacks the lungs, making it difficult to breathe. Signs and
symptoms include a cough that doesn't go away, fever and trouble breathing.
Toxoplasmosis. This potentially deadly infection is caused by Toxoplasma gondii, a parasite spread
primarily by cats. Infected cats pass the parasites in their stool, and the parasites may then spread to
other animals. Humans generally contract toxoplasmosis by touching their mouths with their hands
after changing cat litter or by eating raw or undercooked meat, especially pork, lamb and venison. For
many people with AIDS, toxoplasmosis leads to encephalitis. Signs and symptoms may include
disorientation, seizures, and difficulty walking or speaking.
Cryptosporidiosis. This infection is caused by an intestinal parasite that's commonly found in
animals. You contract cryptosporidiosis when you ingest contaminated food or water. The parasite
grows in your intestines and bile ducts, leading to severe, chronic diarrhea in people with AIDS.
Cancers
Kaposi's sarcoma. Kaposi's sarcoma is a tumor of the blood vessel walls. Although rare in people
not infected with HIV, it's common in HIV-positive people. Kaposi's sarcoma usually appears as pink,

red or purple lesions on the skin and mouth. In people with darker skin, the lesions may look dark
brown or black. Kaposi's sarcoma can also affect the internal organs, including the digestive tract and
lungs.
Non-Hodgkin's lymphoma. This cancer originates in lymphocytes. The most common early sign is
painless swelling of the lymph nodes in your neck, armpit or groin.
Other complications
Wasting syndrome. It is defined as a loss of at least 10 percent of body weight and is often
accompanied by diarrhea, chronic weakness and fever.
Neurological complications. Although AIDS doesn't appear to infect the nerve cells, it can still
cause neurological symptoms such as confusion, forgetfulness, changes in behavior, depression,
anxiety and trouble walking. One of the most common neurological complications is AIDS dementia
complex, which leads to behavioral changes and diminished mental functioning.

9. Describe therapeutic interventions to prevent mother to child transmission of HIV.

HIV AND PREGNANCY OVERVIEW The most common way for infants to become infected with
human immunodeficiency virus (HIV) is from his or her mother during pregnancy, labor and delivery,
and, to a lesser degree, through breastfeeding. Fortunately, the use of certain medications during
pregnancy and labor (zidovudine, also called AZT or ZDV) can reduce the risk of passing HIV to the
infant by nearly 70 percent.
CARE BEFORE PREGNANCY Women who have HIV and want to become pregnant should talk
to their HIV specialist before trying to become pregnant. Several HIV medications are not safe to take
during pregnancy, and it may be necessary to switch before trying to conceive.
Pregnancy does not appear to worsen HIV or increase the risk of death from HIV. However, it is not
clear if HIV or HIV treatments increase the risk of pregnancy complications, such as prematurity, low
birth weight, and stillbirth.
It is clear that certain HIV medications, such as zidovudine (ZDV or AZT), can significantly reduce the
risk that the newborn will become infected with HIV when the medication is taken during pregnancy
and labor, and then given to the newborn after delivery. ZDV is given with other medications for HIV
as part of a three-drug regimen.
CARE DURING PREGNANCY
Initial evaluation
During the initial evaluation, you will have blood tests to determine the amount of HIV virus in your

blood (eg, HIV viral load) and the strength of your immune system (eg, the number of CD4 T cells).
These numbers affect the choice of HIV treatments and the likelihood of passing HIV to the baby
during pregnancy or delivery.
HIV treatment regimens During pregnancy, most women with HIV are advised to take
combination antiretroviral therapy using three antiretroviral drugs, also called highly active
antiretroviral therapy or "HAART". When possible, zidovudine (ZDV) is included because it has been
shown to significantly reduce the risk of passing HIV to the infant and is thought to be safe to take
during pregnancy.
Timing of HIV treatment When you start HAART will depend on your immune status. If you need
to take HIV treatment for your health, then HAART is started (or continued) immediately. If HIV
treatment is not needed right away, then HAART is started after the first trimester of pregnancy to
avoid unnecessary drug exposure to the baby. Once medications are started, HAART is continued
throughout pregnancy to prevent HIV transmission to the baby.
Even if zidovudine is not used during pregnancy, it is still recommended during labor and for the
newborn for six weeks after birth.
Medication adherence during pregnancy It is extremely important to take your medications
exactly as prescribed during pregnancy to decrease the risk of developing drug resistance.
Furthermore, taking your medications on time can lessen the risk of HIV transmission to the baby.
Medications to avoid There are several antiretroviral drugs that should not be used in pregnancy:
these include efavirenz during the first trimester; the combination of stavudine(d4T) and didanosine
(ddI) used together; and nevirapine in women with CD4 count >250/mm3.
Delavirdine, which is rarely used today due to the number of pills required daily, is also not
recommended during pregnancy.
LABOR AND DELIVERY WITH HIV The safest way for women with HIV to deliver a baby (ie, by
vaginal or cesarean delivery), depends upon her HIV viral load during pregnancy. Women with low
HIV viral loads (<1000 copies/mL) may be able to deliver vaginally while women with higher HIV viral
loads (1000 copies/mL) are usually encouraged to schedule a cesarean delivery at 38 weeks of
pregnancy.
The antiretroviral drug zidovudine is usually given during labor, regardless of how the woman
delivers, because zidovudine helps to reduce the risk of HIV transmission. Other antiretroviral drugs
are also continued on schedule during labor or before a cesarean section; this helps to provide
maximal protection to the mother and infant and to minimize the risk that the mother could develop
drug resistance due to a missed dose of medication.
CARE AFTER DELIVERY

For women after delivery After delivery, women who took antiretroviral medications during
pregnancy need to be evaluated to determine if antiretroviral therapy should continue.
Breastfeeding Women with HIV who breastfeed can pass HIV to the infant.In the United States
and other resource-rich countries, clean water and infant formulas are readily available and are safe
alternatives to breastfeeding. Therefore, the United States Public Health Service recommends that
women in resource-rich countries who are infected with HIV not breastfeed their babies, even if the
woman is taking antiretroviral medications. HIV can be transmitted through breastmilk, even if the
woman is taking antiretroviral medications.
For newborns and infants
HIV treatment regimens Newborns of women with HIV are usually treated with zidovudine for the
first six weeks of life. Zidovudine can help to prevent the infant from becoming infected with HIV as a
result of exposure to the mother's blood during delivery.
10 )Recommendations for prevention of HIV Prevention
Vaccines against HIV have been difficult to develop because HIV surface proteins mutate
easily, resulting in an enormous diversity of antigenic types. Nonetheless, research continues,
and various candidates are under study. At the present time, there is no effective AIDS vaccine.
Prevention of transmission: Vaginal microbicides (including antiretroviral drugs) inserted
before sexual contact have proved ineffective, and some appear to increase risk for women,
perhaps by damaging natural barriers to HIV.
Effective measures include the following:

Public education: Education is effective and appears to have decreased rates of infection in
some countries, notably Thailand and Uganda. Because sexual contact accounts for most
cases, teaching people to avoid unsafe sex practices is the most relevant measure

Safe sex practices: Unless both partners are known to be free of HIV and remain
monogamous, safe sex practices are essential. Safe sex practices are also advised when
both partners are HIV-positive; unprotected sex between HIV-infected people may expose a
person to resistant or more virulent strains of HIV and to other viruses (eg, cytomegalovirus,
Epstein-Barr virus, herpes simplex virus, hepatitis B virus) that cause severe disease in AIDS
patients. Condoms offer the best protection. Oil-based lubricants should not be used
because they may dissolve latex, increasing the risk of condom failure.

Counseling for parenteral drug users: Counseling about the risk of sharing needles is
important but is probably more effective if combined with provision of sterile needles,
treatment of drug dependence, and rehabilitation.

Confidential testing for HIV infection: Testing should be offered routinely to adolescents
and adults in virtually all health care settings. In order to facilitate routine testing, some states
no longer require written consent or extensive pretest counseling.

Counseling for pregnant women: If pregnant women test positive for HIV, risk of
maternal-fetal transmission should be explained. Monotherapy with ZDV or nevirapine
reduces risk by 2/3, and 2- or 3-drug combination therapy probably reduces it even more.

Some drugs can be toxic to the fetus or mother and cannot be guaranteed to prevent transmission.
If treatment is indicated, combination therapy tailored to the woman's history and stage of
pregnancy should be used throughout pregnancy. Delivery by cesarean section can reduce risk
of transmission. Some women choose to terminate their pregnancy for this or other reasons.

Screening of blood and organs: Transmission by blood transfusion is still possible

because antibody results may be false-negative during early infection. Currently, screening
blood for antibody and p24 antigen is mandated in the US and probably further reduces risk of
transmission. Risk is reduced further by asking people with risk factors for HIV infection, even
those with recent negative HIV antibody test results, not to donate blood or organs for
transplantation.

Antiretrovirals: Giving antiretrovirals to HIV-infected people reduces risk of

transmission, but how much risk is reduced is unclear.

Circumcision of men: In several African countries, circumcision reduced incidence by

about 50%; it is probably also effective elsewhere.

Universal precautions: Medical and dental health care practitioners should wear gloves
in situations that may involve contact with any patient's mucous membranes or body fluids
and should be taught how to avoid needlestick accidents. Home caregivers of patients with
HIV infection should wear gloves if their hands may be exposed to body fluids. Surfaces or
instruments contaminated by blood or other body fluids should be cleaned and disinfected.
Effective disinfectants include heat, peroxide, alcohols, phenolics, and hypochlorite
(bleach). Isolation of HIV-infected patients is unnecessary unless indicated by an opportunistic
infection (eg, TB). Guidelines to prevent transmission from infected practitioners to patients have
not been established.

11) Management of healthcare workers exposed to HIV

Postexposure prophylaxis (PEP): Potential consequences of exposure to HIV have prompted the
development of policies and procedures, particularly preventive treatment, to decrease risk of
infection to health care workers. Preventive treatment is indicated after penetrating injuries
involving HIV-infected blood (usually needlesticks) or heavy exposure of mucous membranes
(eye or mouth) to infected fluids. Other body fluids of concern include

Semen

Vaginal secretions

Body fluids obviously contaminated with blood

After initial exposure to blood, the exposed area is immediately cleaned with soap and water
for skin exposures and with antiseptic for puncture wounds. If mucous membranes are
exposed, the area is flushed with large amounts of water.
The following are documented:
Nature of the exposure is defined by

Which body fluid was involved

Whether exposure involved a penetrating injury (eg, needlestick, cut with sharp object)

Whether the fluid had contact with nonintact skin (eg, abraded or chapped skin) or mucous
membrane

Risk of infection is categorized as high or low:

High: Involves a hollow-bore needle with visible blood, direct exposure to a needle from
a vein or an artery of the source patient, or mucocutaneous exposure with a large amount
of blood from a high-risk source (viral load > 1500 copies/mL)

Low: Involves a solid needle, superficial injury, or a low-risk source (viral load < 1500
copies/mL) and includes most mucocutaneous exposures

Risk is about 0.3% after percutaneous exposure and about 0.09% after mucous membrane exposure.
The source is qualified by whether it is known or unknown; if the source is unknown (eg, a
needle on the street or in a sharps disposal container), risk should be assessed based on the
circumstances of the exposure (eg, whether the exposure occurred in an area where injection drug
use is prevalent, whether a needle discarded in a drug-treatment facility was used). If the source is
known but HIV status is not, the source is assessed for HIV risk factors, and prophylaxis is
considered .
Table 5
Postexposure Prophylaxis Recommendations
Infection Status of
Source

Prophylaxis

HIV-positive

2-drug PEP for less severe exposure

class 1*

3-drug PEP for more severe exposure

HIV-positive

3-drug PEP

class 2
Unknown HIV status of Generally, no PEP warranted; however,
source or unknown
consideration of 2-drug PEP if source has HIV
source
risk factors or if setting is likely to involve
exposure to HIV-infected people
HIV- negative

No PEP warranted

PEP = Postexposure prophylaxis.

* Class 1: Asymptomatic HIV infection or known low viral load (<
1500 RNA copies/mL).

Less severe exposure may involve a solid needle or superficial

injuries.

More severe exposure may involve a hollow-bore needle, deep

puncture, visible blood on the device, or a needle used in patient's
artery or vein.

Class 2: Symptomatic HIV infection, AIDS, acute seroconversion,

or known high viral load.

PEP is optional and should be based on an individualized decision by

the exposed person and the treating clinician. If PEP is offered and
taken and the source is later determined to be HIV-negative, PEP
should be stopped.
The goal is to start PEP as soon after exposure as possible if prophylaxis is warranted. CDC
recommends providing PEP within 24 to 36 h after exposure; a longer interval after exposure
requires the advice of an expert.
Use of PEP is determined by risk of infection; guidelines recommend antiretroviral therapy
with 2 NRTIs (eg, ZDV(zidovudine) plus 3TC(lamivudine)) for low risk and the addition of one
or more drugs (eg, 2 NRTIs(nucleoside rev transcriptase inhibitors) plus a PI(protease
inhibitor) or an NNRTI) for high risk; drugs are given for 28 days. Nevirapine is avoided
because of the rare possibility of severe hepatitis. Although evidence is not conclusive, ZDV
alone probably reduces risk of transmission after needlestick injuries by about 80%..
If the source's virus is known or suspected to be resistant to 1 drug, an expert in
antiretroviral therapy and HIV transmission should be consulted. However, clinicians should
not delay PEP pending expert consultation or drug susceptibility testing. Also, clinicians should
provide immediate evaluation and face-to-face counseling and not delay follow-up care.