ACQUIRED

IMMUNODEFICIENCY
SYNDROME
CHARLENE NOELLE B. PARCIA
FIRST YEAR INTERNAL MEDICINE
DEFINITION
• “the presence of a reliably diagnosed disease that is at least
moderately indicative of an underlying defect in cell-mediated
immunity in the absence of any known cause for such a defect.”
• Clinical conditions associated with HIV infection and CD4+ T
lymphocyte counts
• The definition and staging criteria of AIDS are complex and
comprehensive and were established for surveillance purposes rather
than for the practical care of patients.
STAGES

0 A negative HIV test within 6 months of

the first HIV infection diagnosis, the
stage is 0 and remains 0 until 6 months
after diagnosis.
1 acute HIV infection
2 chronic HIV infection
3 acquired immunodeficIency syndrome
(AIDS).
unknown
CD4+ T lymphocyte count takes precedence over the CD4+ T lymphocyte percentage
ETIOLOGY
• AIDS is caused by infection with the human retroviruses HIV-1 or 2.
• HIV-1 is the most common cause worldwide. (HIV-1 M - AIDS
pandemic)
• HIV-2 viruses have been thught have caused much more localized
epidemics.
• HIV-2 was first identified in 1986 in West African patients and was
originally confined to West Africa but is now found throughout the
world.
TRANSMISSION
HIV is transmitted primarily by:
• Sexual contact (both
heterosexual and male to male);
• Blood and blood products;
• Infected mothers to infants
intrapartum, perinatally, or via
breast milk.
SEXUAL INTERCOURSE
• Most common mode of transmission
• Male - Male - most common
• Male - Female (most common mode of transmission in developing countries)
• Female genitals
• The most common way that HIV is transmitted is through unprotected vaginal
intercourse, due to the following mechanisms:
• Tear - HIV can enter the body through small tears in the vaginal lining.
• Direct Penetration - can also be absorbed by the lining of the vagina and cervix
• Male genitals
• HIV can enter through the urethra, small cuts, abrasions, inner foreskin
tissue, and open sores of the penis (such as those who have untreated syphilis
or herpes infection)
SEXUAL INTERCOURSE
• Unprotected receptive anal intercourse (URAI)
1) direct inoculation into blood in cases of traumatic tears in the mucosa; and
2) infection of susceptible target cells, such as Langerhans cells, in the mucosal layer in the
absence of trauma
• Vaginal mucosa is several layers thicker than the rectal mucosa and less likely to
be traumatized during intercourse
• Male-to-Female > Female-to-Male
• prolonged exposure of the vaginal and cervical mucosa to infected seminal
fluid; the endometrium also can be exposed to virus when semen enters
through the cervical os.
• penis and urethral orifice of the uninfected male partner are exposed
relatively briefly to infected vaginal fluid
SEXUAL INTERCOURSE
• HETEROSEXUAL TRANSMISSION
• There is a close relationship between genital ulcerations and transmission
• Treponema pallidum, Haemophilus ducreyi, and herpes simplex virus are important
causes of genital ulcerations linked to transmission of HIV.
• Nonulcerative inflammatory STI are also linked with the transmisssion
• Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis
• Treating STIs and genital tract syndromes may help prevent transmission of
HIV (Except for HSV infections)
• Male circumcision is associated with a lower risk of acquisition of HIV
infection for heterosexual men (protective)
SEXUAL INTERCOURSE
• Oral contraceptives was associated with an increase in incidence of
HIV infection
• Adolescent girls might also be more susceptible to infection upon
exposure due to the properties of an immature genital tract with
increased cervical ectopy or exposed columnar epithelium
• Oral sex is a much less efficient mode of transmission of HIV: fellatio
or cunnilingus. Therefore, the assumption that oral sex is completely
safe is not warranted.
• Risky practices (ALcohol, drugs) increases risk of HIV infection
TRANSMISSION THROUGH INJECTION
DRUG USE
• Injection drug users (IDUs)
• Through sharing injection paraphernalia such as needles, syringes, the water in
which drugs are mixed, or the cotton through which drugs are filtered
• It does not require IV puncture; subcutaneous (“skin popping”) or intramuscular
(“muscling”) injections can transmit HIV as well, even though these behaviors are
sometimes erroneously perceived as low risk.
• Risk factors: INCREASES
• increases with the duration of injection drug use;
• the frequency of needle sharing;
• the number of partners with whom paraphernalia are shared,
• comorbid psychiatric conditions such as antisocial personality disorder;
• the use of cocaine in injectable form or smoked as “crack”; and
• the use of injection drugs in a geographic location with a high prevalence of HIV infection
TRANSMISSION BY TRANSFUSED BLOOD AND
BLOOD PRODUCTS
• HIV-contaminated blood transfusions, blood products, or transplanted
tissue.
• >90% of individuals exposed to HIV-contaminated blood products
become infected.
• Transfusions of whole blood, packed red blood cells, platelets,
leukocytes, and plasma are all capable of transmitting HIV infection
• However, hyperimmune gamma globulin, hepatitis B immune
globulin, plasma-derived hepatitis B vaccine, and Rho immune
globulin have not been associated with transmission of HIV infection
TRANSMISSION BY TRANSFUSED BLOOD AND
BLOOD PRODUCTS
• Screening of blood donations for antibodies to HIV-1 and
HIV-2 and determination of the presence of HIV nucleic acid
• health history questionnaires to exclude individuals with risk
behavior; and opportunities for self-deferral and the screening out
of HIV-negative individuals with serologic testing for infections that
have shared risk factors with HIV, such as hepatitis B and C and
syphilis.
• Transmission of HIV (both HIV-1 and HIV-2) by blood or blood
products is still an ongoing threat in certain developing countries
where routine screening of blood is not universally practiced.
OCCUPATIONAL TRANSMISSION OF HIV: HEALTH
CARE WORKERS, LABORATORY WORKERS, AND THE
HEALTH CARE SETTING
• There is small but definite occupational risk of HIV transmission particularly when
sharp objects are used.
• Exposures that place a health care worker at potential risk of HIV infection are:
• percutaneous injuries (e.g., a needle stick or cut with a sharp object)
• contact of mucous membrane or nonintact skin (e.g., exposed skin that is chapped, abraded,
or afflicted with dermatitis) with blood, tissue, or other potentially infectious body fluids.
• Large, multi-institutional studies have indicated that the risk of HIV transmission
following skin puncture from a needle or a sharp object that was contaminated
with blood from a person with documented HIV infection is ~0.23% and after a
mucous membrane exposure it is ~0.09% if the injured and/or exposed person is
not treated within 24 hours with antiretro viral drugs.
• Rare HIV transmission after nonintact skin exposure has been documented, but
the average risk for transmission by this route has not been precisely determined;
however, it is estimated to be less than the risk for mucous membrane exposure.
• Transmission of HIV through intact skin has not been documented.
• Treatment: combination antiretroviral therapy (ART) (postexposure prophylaxis or
PEP)
• potentially infectious: cerebrospinal fluid, synovial fluid, pleural fluid, peritoneal
fluid, pericardial fluid, and amniotic fluid. (lower than the risk after blood
exposures)
• Breaches in infection control and the reuse of contaminated syringes, failure to
properly sterilize surgical instruments, and/or hemodialysis equipment also have
resulted rarely in the transmission of HIV from patient to patient in hospitals,
nursing homes, and outpatient settings.
MOTHER-TO-CHILD TRANSMISSION OF
HIV
• Persistent form of transmission of HIV infection in certain developing
countries.
• Transmitted to the fetus during the first or second trimesters of
pregnancy.
• Maternal transmission to the fetus occurs most commonly in the
perinatal period.
MOTHER-TO-CHILD TRANSMISSION OF
HIV
• Higher rates of transmission have been reported to be associated with
many factors—the best documented of which is the presence of high
maternal levels of plasma viremia
• It is very unlikely that mother-to-child transmission will occur if the
mother’s level of plasma viremia is <1000 copies of HIV RNA/mL of blood
and extremely unlikely if the level is <50 copies/mL
• Risk factors: prolonged interval between membrane rupture and delivery
presence of chorioamnionitis at delivery; STIs during pregnancy; illicit
drug use during pregnancy; cigarette smoking; preterm delivery; and
obstetrical procedures (amniocentesis, amnioscopy, fetal scalp electrodes,
and episiotomy)
MOTHER-TO-CHILD TRANSMISSION OF
HIV
• All HIV-infected pregnant women should receive life-long ART for the
health of the mother (regardless of plasma HIV RNA copy number or
CD4+ T-cell counts) as well as to prevent perinatal transmission
• Breast-feeding is an important modality of transmission of HIV infection in
certain developing countries, particularly where mothers continue to
breast-feed for prolonged periods.
• Risk factors: mother-to-child transmission of HIV via breast-feeding include
detectable levels of HIV in breast milk, the presence of mastitis, low maternal
CD4+ T-cell counts, and maternal vitamin A deficiency. highest in the early months
• exclusive breast-feeding has been reported to carry a lower risk of HIV
transmission than mixed feeding
TRANSMISSION OF HIV BY OTHER
BODY FLUIDS
• Saliva - HIV can be isolated typically in low titers from saliva of a small
proportion of infected individuals.
• There is no convincing evidence that saliva can transmit HIV infection.
• secretory leukocyte protease inhibitor (SLPI) blocks HIV infection in several cell
culture system
• higher salivary levels of SLPI in breast-fed infants were associated with a
decreased risk of HIV transmission through breast milk
• submandibular saliva reduces HIV infectivity by stripping gp120 from the
surface of virions, and that saliva-mediated disruption and lysis of HIV-infected
cells occurs because of the hypotonicity of oral secretions
• No evidence that HIV transmission can occur as a result of exposure to
tears, sweat, or urine
EPIDEMIOLOGY
• In Asia and the Pacific, an estimated 5.8 million people were living
with HIV at the end of 2020. HIV infections in Asia and the Pacific
declined by 21% between 2010 and 2020, with reductions in Thailand
and Vietnam offset by increases in Pakistan and the Philippines.
• In this region, HIV prevalence is highest in southeast Asian countries,
with wide variation in trends between different countries.
• Among countries in Asia, only Thailand has an adult seroprevalence
rate that reaches 1%.
Epidemiology
• However, the populations of many Asian nations
are so large that even low infection and
seroprevalence rates result in large numbers of
people living with HIV.
• China, India, and Indonesia
• Key populations and their partners accounted for
an estimated 94% of new HIV infections in the
region in 2020, and ~30% of new HIV infections
were among young people (age 15–24 years).
Rising numbers of new infections among gay men
and other men who have sex with men are a
major concern.
PATHOPHYSIOLOGY AND
IMMUNOPATHOGENESIS
• The hallmark of HIV disease is a profound immunodeficiency resulting
from a progressive quantitative and qualitative deficiency of the
subset of T lymphocytes referred to as helper T cells that are defined
phenotypically by the expression on the cell surface of the CD4
molecule, which serves as the primary cellular receptor for HIV.
• A co-receptor must be present with CD4 for efficient entry of HIV-1
into target cells.
• The two major co-receptors for HIV-1 are the chemokine receptors
CCR5 and CXCR4. The CD4+ T lymphocyte and less so cells of
monocyte lineage are the principal cellular targets of HIV.
Primary Infection
• Following initial transmission, the virus infects CD4+ cells, predominantly T
lymphocytes, but also monocytes, or bone marrow–derived dendritic cells.
• Both during this initial stage and later in infection, the lymphoid system is a
major site for the establishment and propagation of HIV infection.
• The gut-associated lymphoid tissue (GALT) plays a role in the establishment of
infection and in the early depletion of memory CD4+ T cells.
• All patinetts undergo a viremic stage during primary infection; in some patients
this is associated with the “acute retroviral syndrome,” a mononucleosis-like
illness. This phase is important in disseminating virus to lymphoid and other
organs throughout the body, and viral replication is ultimately contained only
partially by the development of an HIV-specific immune response.
Establishment of Chronic and Persistent
Infection
• When the virus is not cleared from the body despite the robust immune response that
is mounted following primary infection
• A chronic infection develops that persists for a median time of 10 years before the
untreated patient becomes clinically ill. During this period of clinical latency, the
number of CD4+ T cells gradually declines, and few if any clinical signs and symptoms
may be evident.
• However, active viral replication can almost always be detected as plasma viremia and
in lymphoid tissue.
• The level of steady-state viremia (referred to as the viral set point) at ∼6 months to 1
year post-infection has important prognostic implications for the progression of HIV
disease; individuals with a low viral set point at 6 months to 1 year after infection
progress to AIDS more slowly than do those whose set point is very high at this time.
Advanced HIV Disease
• In untreated patients or in patients in whom therapy has not controlled
viral replication, after some period of time (often years), CD4+ T cell
counts will fall below a critical level (∼200/µL) and pts become highly
susceptible to opportunistic diseases.
• The presence of a CD4+ T cell count <200/µL or an AIDS-defining
opportunistic disease establishes a diagnosis of AIDS.
• Control of plasma viremia by effective antiretroviral therapy, particularly
maintaining the plasma viral load consistently at <50 copies of RNA per
mL, even in individuals with low CD4+ T cell counts, has dramatically
increased survival in these pts, including those whose CD4+ T cell counts
may not increase significantly as a result of therapy.
IMMUNE RESPONSE TO HIV
INFECTION
• Both humoral and cellular immune responses to HIV develop soon after primary
infection.
• Humoral responses include antibodies with HIV binding and neutralizing activity, as well
as antibodies participating in antibody-dependent cellular cytotoxicity (ADCC).
• Cellular immune responses include the generation of HIV-specific CD4+ and CD8+ T
lymphocytes, as well as NK cells and mononuclear cells mediating ADCC.
• CD8+ T lymphocytes may also suppress HIV replication in a noncytolytic, non-MHC-restricted manner.
• This effect is mediated by soluble factors such as the CC-chemokines RANTES (CCL5), MIP-1α (CCL3),
and MIP-1β (CCL4).
• The natural immune response to HIV is not adequate.
• Broadly reacting neutralizing antibodies against HIV are not easily generated in
infected individuals, and eradication of the virus from infected individuals by
naturally occurring immune responses has not been reported.
DIAGNOSIS OF HIV INFECTION
• The CDC has recommended that screening for HIV infection be performed as a matter of
routine health care.
• Laboratory diagnosis of HIV infection depends on the demonstration of anti-HIV antibodies
and/or the detection of HIV or one of its components.
• The standard screening test for HIV infection is the detection of anti-HIV antibodies using an
enzyme immunoassay (EIA). This test is highly sensitive (>99.5%) and is quite specific.
• The Western blot detects antibodies to HIV antigens of specific molecular weights.
Antibodies to HIV begin to appear within 2 weeks of infection, and the period of time
between initial infection and the development of detectable antibodies is rarely >3 months.
• Plasma p24 antigen levels rise during the first few weeks following infection, prior to the
appearance of anti-HIV antibodies. A guideline for the use of these serologic tests in the
diagnosis of HIV infection is depicted in the next slide.
DIAGNOSIS
LABORATORY MONITORING OF
PATIENTS WITH HIV INFECTION
• Measurement of the CD4+ T cell count and level of plasma HIV RNA are
important components of the routine evaluation and monitoring of HIV-
infected individuals.
• The CD4+ T cell count is a generally accepted indicator of the immunologic
competence of the patient with HIV infection, and there is a close relationship
between the CD4+ T cell count and the clinical manifestations of AIDS.
• Patients with CD4+ T cell counts <200/µL are at higher risk of infection with
Pneumocystis jiroveci.
• Once the count declines to <50/µL, patients are also at higher risk for
developing cytomegalovirus (CMV) disease and infection with Mycobacterium
avium intracellulare.
LABORATORY MONITORING OF PTS
WITH HIV INFECTION
• Patients should have their CD4+ T cell count measured at the time of diagnosis and
every 3–6 months thereafter. (Measurements may be done more frequently with
declining counts.)
• While the CD4+ T cell count provides information on the current immunologic
status, the HIV RNA level predicts what will happen to the CD4+ T cell count in the
near future.
• Following the initiation of therapy or any change in therapy, HIV RNA levels should
be monitored approximately every 4 weeks until the effectiveness of the
therapeutic regimen is determined, ideally by achieving an undetectable plasma
viral load.
• During therapy, levels of HIV RNA should be monitored every 3–6 months to
evaluate the continuing effectiveness of therapy.
LABORATORY MONITORING OF PATIENTS WITH HIV
INFECTION

• The sensitivity of an individual’s HIV virus(es) to different

antiretroviral agents can be tested by either genotypic or phenotypic
assays
• The use of resistance testing to select a new antiretroviral regimen in
patients failing their current regimen leads to a ∼0.5-log greater
decline in viral load compared with the efficacy of regimens selected
solely on the basis of drug history.
• HIV resistance testing may also be of value in selecting an initial
treatment regimen in geographic areas with a high prevalence of
baseline resistance.
• HARRISON’S 21ST ED