Loma Linda University

Physician Assistant
Program
Summer 2015

HIV/AIDS
Scott A. Denny, MSPA, PA-C
Director of HIV/Transgender Services
HIV Specialist, Infectious Diseases
Kaiser Permanente Hawaii Region

AN ELEPHANT IN THE ROOM

A fable tells of six blind men invited to examine an elephant and
report what they believed it to be. Each touched the elephant at a
different part and reported something completely unlike the others.
In the early AIDS years, physicians and researchers saw the disease
in different ways, without ever really assembling all the different
pieces together.

THE UNOFFICIAL BEGINNING

On June 5th, 1981, the Centers for Disease Control and

Prevention (CDC) published a brief but significant article in its
weekly bulletin, Morbidity and Mortality Report (MMWR).

The article, randomly appearing between discussions of dengue

fever and measles, described the case reports of 5 young men
treated in Los Angeles, California.

Symptoms included: sweats, fever,

cough, rash, diarrhea, lymphadenopathy,
fatigue, wasting, among others.

THE UNOFFICIAL BEGINNING

ALL FIVE MEN
Gay
Sexually active with multiple partners.
Suffering from a rare type of pneumonia -

Pneumocystis pneumonia (PCP) from a then thought

of protozoa Pneumocystis carinii.

Later on, it would be determined that Pneumocystis

carinii was in fact a yeast-like fungus newly named
Pneumocystis jirovecii.

THE UNOFFICIAL BEGINNING

In this same CDC article, the writer observed that three of
the patients had,

profoundly depressed numbers of thymus-dependent lymphocyte cells and profoundly

depressed responses to mitogens and antigens.
(AIDS The Biological Basis, B. Weeks, I.E. Alcamo, 2010)

THE UNOFFICIAL BEGINNING

All we could derive then...
Lymphocyte cells = immune system
Response to Mitogens and Antigens = function of the immune system.

Therefore, the immune system was under stress.

Upon release of the CDC article,

physicians were encouraged to be
on alert for any unusual or
strange illness, or immune
occurrences.

More and more reports would be

arriving quickly.

THE UNOFFICIAL BEGINNING

On July 3, 1981,
another article
appeared in the
CDCs MMWR, this
time describing
Kaposis Sarcoma (a
rare and potentially
deadly skin cancer) as
well as pneumocystis
pneumonia
concurrently affecting
26 homosexual young
men in New York and
California.

INITIAL (UNOFFICIAL) THEORIES

Gay-Related-Immune-Deficiency (GRID)
Homosexual men
associated with:
Amyl nitrate (poppers)
Cytomegalovirus (CMV)
Barrage of other STDs
suppressing the immune
system.

Hepatitis B Vaccine

BEYOND HOMOSEXUAL
By late 1981, the CDC was receiving numerous reports

Heterosexual IV drug users

Blood transfusion recipients

ALL WERE AFFLICTED WITH PCP AND SEVERE

IMMUNE COMPROMISE.

VERTICAL TRANSMISSION
Panic came to an all time high when a California woman
contracted AIDS through sexual intercourse with her hemophiliac
husband and then passing the disease to her newborn child.
IN SUMMARY
Not just homosexuals and IV drug users were susceptible.

FROM GRID TO AIDS

In 1982, the CDC, acting on the recommendations from renowned
virologist, Bruce Voeller, renamed the disease:
Acquired Immune Deficiency Syndrome (AIDS)
Group of clinical entities, along with its specific immune deficiency.
(AIDS A Biological Basis, S. Weeks, I.E. Alcamo, 2010)

1982: In June, the CDC had gathered details on 355 cases

in 5 different states.
1983: 16 countries and 34 states were reporting cases
(half had already died by this time).

SO...
WHAT IS AIDS?
A severe immunological disorder resulting in a defect in cellmediated immune response that is manifested by increased
susceptibility to opportunistic infections and to certain rare cancers,
especially Kaposi's sarcoma.

A PANDEMIC

By 1988, the World Health Organization (WHO) had received

reports of AIDS defining illnesses in 175 countries.
2003: AIDS cases worldwide reached 4.8 mil.
2004: the total global number of people with AIDS or living with
HIV rose to 39.4 mil, with the highest infection rates seen in Subsaharan Africa and South and Southeast Asia.

MONITORING AIDS
World Health Organization (WHO)
Supports AIDS prevention and tracks the disease
United Nations Programme on HIV-AIDS (UNAIDS)
Coordinates the UNs efforts in dealing with the pandemic.

CAUSE OF AIDS?
MORE THEORIES

African swine fever.

A viral escapee from a genetics laboratory.
Failed biological warfare against Cuba.
Mutations arising from secret Soviet Union electromagnetic
warfare against the United States.

or... simply a virus?

HIV
On April 23, 1984, Robert C. Gallo from the US
National Cancer Institute announced that his
research group had identified a virus in the blood
of 48 persons with AIDS.
Gallo named the virus: T-Cell Lymphotropic Virus
Type III (HTLV-III).
French researcher Luc Montagnier also claimed to
have discovered the AIDS causing virus, calling it
Lympadenopathy-Associated Virus (LAV).
In 1986, Gallo and Montagnier agreed to share
credit for the discovery of the virus, now officially
called Human Immunodeficiency Virus (HIV-1).
Soon afterward, a new HIV strain was isolated,
appropriately coined HIV-2.

HIV-2
Uncommon in the United States.
Common in Africa, Nigeria, Ghana, and the Ivory Coast.
Less pathogenic than HIV-1 and progresses to AIDS more slowly.
Takes longer to damage the immune system.
Same modes of transmission as HIV-1.
Same opportunistic infections.
Same medications are used as HIV-1, though less effective.
Requires a specific antibody test to test for infectivity. Traditional
ELISA antibody test for HIV-1 does not work.
The immune system mounts a more effective response against
HIV-2 than HIV-1.

SUBTYPES OF HIV
HIV-1 is related to viruses found in chimpanzees and gorillas living
in western Africa, while HIV-2 viruses are related to viruses found
in sooty mangabeys.

HIV-1 viruses may be further divided into groups:

The HIV-1 group M (Major) viruses predominate

and are responsible for the AIDS pandemic.

90% of HIV/AIDS cases deriving from infection

with HIV-1are group M.

The M group is subdivided further into subtypes.

B is the most common subtype.

SUBTYPES OF HIV
Subtype A is common in West Africa.
Subtype B is the dominant form in Europe, the Americas, Japan, Thailand, and Australia.
Subtype C is the dominant form in Southern Africa, India, and Nepal.
Subtype D is generally only seen in Eastern and central Africa.
Subtype E has never been identified as a non-recombinant.
Subtype F has been found in central Africa, South America and Eastern Europe.
Subtype G (and the CRF02_AG) have been found in Africa and central Europe.
Subtype H is limited to central Africa.
Subtype I describes a strain that is now accounted for as CRF04_cpx.
Subtype J is primarily found in North, Central and West Africa, and the Caribbean.
Subtype K is limited to the Democratic Republic of Congo and Cameroon.

A 10-year study completed in 2005 found a strain of

Simian Immunodeficiency Virus (SIV) in a number of

chimpanzee colonies in south-east Cameroon that was a
viral ancestor of the HIV-1 that causes AIDS in humans.

It is believed that a perfect storm combination of 2

distinctly separate versions of SIV (from a Red Cap

Mangabey and a Greater Spot Nose Guenon) combined to
create a new strain of SIV that would become HIV in
humans.

Studies of primates in other continents did not find any

trace of SIV, leading to the conclusion that HIV originated in

Africa.

The chimpanzee version of the virus (SIV) most likely was

transmitted to humans when humans hunted these
chimpanzees for meat. This may have occurred in the early
1900s.

Tubes of blood dating circa 1908 that were unearthed in

2008 tested positive for HIV.

ETIOLOGY OF HIV

Upon butchering the animals, the

hunters came into contact with their

infected blood.

SIV mutated into HIV.

It was in Kinshasa in the 1970s that

the first epidemic of HIV/AIDS is

believed to have occurred. The
emerging epidemic in the Congolese
capital was signaled by a surge in
opportunistic infections.

It is speculated that HIV was brought

ETIOLOGY OF HIV

to the city by an infected individual

who travelled from Cameroon by river
down into the Congo and through
labor migration and illicit sexual activity.

The virus slowly spread across Africa

through intracontinental trafficking and

ultimately later on into other parts of
the world.

CURRENT
PANDEMIC
Since its official discovery in 1981, HIV has lead to the death of
more than 39 million people worldwide.
In 2013 - 2.5 million new infections worldwide.
As of 2013, there were 35 million people living with HIV/AIDS
in the world. 3.4 million are less than 15 years old.
- WHO 2015 Statistics

WORLDWIDE HIV/AIDS
Global 35 Million
Sub-Saharan Africa 21.6 mil 24.1 mil
South and South-East Asia 3.6 mil 4.5 mil
Eastern Europe and Central Asia 1.3 mil 1.7 mil
Latin America 1.2 mil 1.7 mil
North America 1.0 mil 1.9 mil
East Asia 580,000 1.1 mil
Western and Central Europe 770,000 930,000
Source: UNAIDS World Aids Day Report 2011

SUB-SAHARAN AFRICA
HIV infection is becoming endemic in sub-Saharan Africa,
which is home to just over 12% of the worlds population
but 67% of all people infected with HIV.
The adult HIV prevalence rate is 5.0% and between 21.6 mil and 24.1 mil
are affected.
Southern Africa is the hardest hit region,
with adult prevalence rates exceeding
20% in most countries in the region, and
30% in Swaziland and Botswana.
Across Sub-Saharan Africa, more women
are infected with HIV than men, with 13
women infected for every 10 infected
men.

SUB-SAHARAN AFRICA
Poor

economic conditions (dirty needles in clinics), poor

nutrition, lack of hygiene.

Lack

of sex education.

In

some African countries, 25% or more of the working adult

population is HIV-positive.

Slow

onset-emergencies, such as drought, or rapid onset

natural disasters and conflict can result in young women and
girls being forced into using sex as a survival strategy.

Women

are forced by clients to accept greater risks, such as

not using contraceptives.

UNITED STATES
The adult prevalence rate in the US is 0.7% with over 1
million people (1,218,400) currently infected with HIV.
Up to 50,000 new infections occurred in the US in
2013. This transmission rate remains consistent.

It is estimated that 156,300 (1 in 8) of those individuals

are not aware that they are infected with the virus.

As of 2013, the highest transmission rates continue to

occur between men having sex with men (MSM)

(30,000) with 72% of those new infections being MSM
aged 13-24 years old. A rate increased 22% from 2008.
- AIDS.gov 2015

UNITED STATES
After MSM, african-american women were the next
highest infectivity group with 5,300 new cases.

Rates of HIV infection in the US are highest in the

southern regions, with the exception of California.

Washington, D.C. also has the nation's highest rate of

infection, at 3%. Comparable to what is seen in west
Africa, this is considered a severe epidemic.

UNITED STATES
New HIV infections among women are primarily attributed to heterosexual contact
(84%) or injection drug use (16%). Women accounted for 1 in 5 new HIV infections
in 2013.

AIDS is one of the top three causes of death for African American men aged 2554
and for African American women aged 3544 years in the United States.

In the United States, African Americans make up about 44% of the total HIV-positive
population despite making up only 12% of the total population.

African American women are 19 times more likely to contract HIV than other
women.

Hispanics/Latinos represented 16% of the population but accounted for 21% of new
HIV infections in 2013.

Centers for Disease Control and Prevention Surveillance System

UNITED STATES
In the United States in particular, a new wave of
infection is being blamed on the use of
methamphetamine, known as crystal meth.

Research presented at the 12th Annual

Retrovirus Conference in Boston in February

2005 concluded that using crystal meth or
cocaine is the biggest single risk factor for
becoming HIV+ among US gay men, contributing
29% of the overall risk of becoming positive.

Methamphetamine is the catalyst for at least

80% of seroconversions currently occurring
across the United States.

In Los Angeles,

methamphetamine is regarded as
the main cause of HIV
seroconversion among gay men
in their late thirties.

The chemical

"methamphetamine", in and of
itself, can not infect someone
with the AIDS virus.

SO WHAT IS HIV?
HIV is the virus that ultimately causes Acquired
Immunodeficiency Syndrome (AIDS), a
condition in which progressive failure of the
immune system in humans allows lifethreatening opportunistic infections and
cancers to thrive.

VIROLOGY OF HIV
HIV is a Retrovirus
Retroviruses are enveloped viruses that belong to the viral family Retroviridae.
A retrovirus is an RNA virus.
This means
RNA virus is duplicated in a host cell using reverse transcriptase enzyme to
produce DNA from its RNA genome.
The DNA is then incorporated into the host's genome by an integrase enzyme.
The virus then replicates as part of the host cell's DNA.
The further subset of the Retroviridae family that HIV specifically belongs to is the
Lentivirus family.
Lentivirus (lente-, Latin for "slow") is a genus of slow viruses characterized by a long
incubation period. Lentiviruses can deliver a significant amount of genetic
information into the DNA of the host cell.

STRUCTURE OF HIV
HIV is roughly spherical with a diameter of about 120nm, around 60times
smaller than a red blood cell, yet still large for a virus.
It is composed of two copies of positive single-stranded RNA.
The single-stranded RNA is tightly bound to capsid proteins and enzymes
needed for the development of the virion such as:

reverse transcriptase

protease

integrase

ribonuclease

STRUCTURE OF HIV
Enclosed by a conical capsid composed of roughly 2,000 copies of the viral protein p24.
A matrix composed of the viral protein p17 surrounds the capsid ensuring the integrity of
the virion structure.
Matrix is surrounded by a viral envelope that is composed of two layers of fatty molecules
called phospholipids (taken from the membrane of a human cell when a newly formed
virus particle buds from the cell).
Embedded in this viral envelope are a mixture of proteins from the host cell and copies of
a complex HIV protein that protrudes through the surface of the virus particle.
This protein, known as Env, consists of a cap made of molecules:
glycoprotein (gp)120
a stem consisting of three gp41 molecules that anchor the structure into the viral
envelope (spikes).
This glycoprotein complex enables the virus to attach to and fuse with target CD4 cells to
initiate the infectious cycle.
Both these surface proteins, especially gp120, have been considered as targets of future
treatments or vaccines against HIV.

HIV AFFINITY
HIV-1 entry to macrophages and CD4+ T cells is mediated
through the interaction of glycoproteins gp120, gp41 and the
CD4 molecule on the target cells. This interaction is supported
by chemokine coreceptors.
gp120 attracts to and binds to the CD4 cell, alters the cells
shape, which allows gp41 to spike through.
This alteration enables the HIV virion to further interact with the
CD4 cell surface proteins - CCR5 and CXCR4.

HIV VIRAL CYCLE

Dendritic cells are the first cells
encountered by the virus during sexual
transmission.
Dendritic cells capture HIV in the mucosa.
DCs then target the nearest macrophages, which transport HIV to
CD4+ T cells.
Macrophages appear to be the first cells actually infected by HIV and
perhaps the source of HIV production when CD4+ cells become
depleted in the patient.

In tonsils and adenoids of HIV-infected patients, macrophages produce

huge amounts of virus.

HIV TROPISM: CCR5 & CXCR4

HIV Tropism refers to which cell types HIV infects.
These are proteins (coreceptors for chemokines) on the surface
of white blood cells that enable HIV entry into the cell.
HIV Trophile co-receptors are:
CCR5 (Chemokine Receptor Type 5) - targets macrophages.
CXCR4 (Chemokine Receptor Type 4) - targets lymphocytes.
HIV initially uses CCR5 to infect host cells, later CXCR4.
R5, R4, Dual-Mixed (both)
A few individuals carry a mutation known as CCR5 delta 32 in
the CCR5 gene, protecting them against these strains of HIV.

HIV VIRAL CYCLE

Once gp120 is bound with the

CD4 protein, the envelope

undergoes a structural change,
allowing for a more stable twopronged attachment, using gp41 to
penetrate the cell membrane.

This interaction causes the

collapse of the extracellular portion

of gp41 into a hairpin.

This loop structure brings the virus and cell membranes close together,
allowing fusion of the membranes and entry of the viral capsid.

After HIV has bound to the target cell, the HIV RNA and various enzymes,
including reverse transcriptase, integrase, ribonuclease, and protease, are
injected into the cell.

HIV VIRAL CYCLE

After the viral capsid enters the cell,
reverse transcriptase liberates the
single-stranded RNA genome from the
attached proteins and copies it into a
complementary DNA (cDNA) molecule.
The process of reverse transcription is
error-prone, and the resulting mutations
may cause drug resistance or allow the
virus to evade the body's immune system.

Together, the cDNA and its complement form a double-stranded viral

DNA that is then transported into the cell nucleus.
The integration of the viral DNA into the host cells nucleus is carried
out by another viral enzyme called integrase.

HIV VIRAL CYCLE

Newly created HIV genetic
material and other polyproteins
are then transported to the host
cell surface, where assembly of
new HIV virions begins at the
plasma membrane.
Maturation of new HIV virions now begins in the forming
bud as it buds from the host cell.
During maturation, viral enzyme protease cleaves the
polyproteins into individual functional HIV proteins and
enzymes.
The various structural components then assemble to
produce a mature HIV virion.

HIV VIRAL CYCLE

HOW IS HIV SPREAD?

Unprotected sex with someone HIV positive. Greater risk with elevated viral load.
Unprotected anal sex is riskier than unprotected vaginal sex.
Unprotected receptive anal sex is riskier than unprotected insertive anal sex.
Multiple sex partners or the presence of other sexually transmitted diseases (STDs).
Unprotected oral sex can also be a risk for HIV transmission, but rare.
Sharing needles, syringes, rinse water, used to prepare illicit drugs for injection.
An infected mother can pass HIV on to her child during pregnancy, birth, or breast-feeding.

LESS COMMON MODES OF TRANSMISSION

Being stuck with an HIV-contaminated needle or other sharp object.
Eating food that has been pre-chewed by an HIV-infected person.
Being bitten by a person with HIV.
Contact between broken skin, wounds and contaminated body fluids.
Deep, open-mouth kissing; if the HIV-infected persons mouth or gums are bleeding.
Tattooing or body piercing are a potential risk, but no cases have been documented.
There have been a few documented cases in Europe and North Africa where infants
have been infected by unsafe injections and then transmitted HIV to their mothers
through breastfeeding. No documented cases in the U.S.

MYTHS ABOUT HIV TRANSMISSION

HIV CANNOT BE SPREAD
Air or water.
Insects, including mosquitoes.
Shaking hands or sharing dishes.
Closed-mouth or social kissing.
Saliva, tears, or sweat.
There is no documented case of
HIV being transmitted by spitting.

RISKS FOR TRANSMISSION (%)

CDC, July 2012
Blood transfusion 90% (9 in 10)
Mother-to-child (without treatment) 25%
Mother-to-child (with treatment) 1%2%
Needle-sharing drug use 0.67% (1 in 149)
Percutaneous needle stick 0.30% (1 in 333)

Receptive anal intercourse, with

ejaculation1.43% (1 in 70)

Receptive anal intercourse, without

ejaculation 0.65% (1 in 154)

Low-income country female-to-male 0.38%

(1 in 263) - High Income: 0.04%

Fellating a man -0% (zero)

Low-income country male-to-female 0.30%

Man being fellated 0 - 0.04% (1 in 2500)

Receptive penile-vaginal intercourse 0.1%

Insertive anal intercourse, circumcised

Insertive penile-vaginal intercourse 0.05%

0.11% (1 in 909)

Insertive anal intercourse, uncircumsized

0.62% (1 in 161)

(1 in 333) - High Income: 0.08%

RISKS FOR TRANSMISSION

Increasers Decreasers

Acute infection (12 weeks after contracting HIV) can increase transmission likelihood 26 times,
raising a 1.43% risk to 37% - higher than 1 in 3.

Presence of other sexually transmitted infections can amplify risk of transmission 8 times.

Intimate partner violence can raise a womans risk of transmission 1.5 times.

Circumcision can lower heterosexual mens risk by 60%.

Treatment as prevention (TasP), when HIV+ people compliant on meds maintain an undetectable
viral load can reduce transmission by 96%.

Condoms lower risk by 80%

SeroSorting - condom-less sex with known positive partners only - limited data.

CRITERIA FOR TESTING

High Risk populations: MSM, IVDU, sex workers, other STDS, TB, or partners/
contacts with HIV.
Pregnant women, people with occupational exposure.
CDC initially recommended risk-based testing based on the behavior of certain
populations.
2006 - CDC now suggests: opt out testing. Intended to reduce barriers to testing.

Routine testing as component of

health care for persons 13-64 years
of age.

Consent for testing would be implied.

High risk populations should be

tested annually.

Counseling and education provided.

DIAGNOSTIC TESTING FOR HIV

HIV Antibody Test (Enzyme-linked immunosorbent assay-ELISA):

New 4th Generation ELISA (Duo, Combi) - detects both antigen

and antibodies with higher sensitivity - average 5 days.

Reduces the Window Period - time between infection with HIV

and the ability to detect it with antibody tests .

Time to seroconversion: 2 to 8 weeks (the average is 25 days).

Ninety-seven percent (97%) of persons will develop detectable

antibodies by 3 months. In rare case, It can take up to 6 months to

develop antibodies to HIV.

2% false positive rate with ELISA (syphilis).

99.994% sensitivity and specificity 3 months after transmission.

DIAGNOSTIC TESTING FOR HIV

WESTERN BLOT
All positive ELISA antibody tests - must be followed by
confirmatory testing using Western Blot (WB).
WB tests antibodies to HIV-1 proteins:
(p17, p24, p55, p31, p51, p66, and gp41, gp120, gp160)
WB is positive if: reactivity to gp120/160, plus gp41 or
p24.
0.0004% false positive rate for WB.
False positives due to: certain vaccines (flu), technical error.

DIAGNOSTIC TESTING FOR HIV

DIAGNOSTIC TESTING FOR HIV

HIV RNA PCR (Viral Load)

P24 Antigen Assay

Measures HIV viral load.

May detect virus within one

week of transmission.

Detects the presence of p24

protein of HIV.

Less expensive.

Used to monitor virus during

lifelong treatment.

Only 30-90% sensitive.

Specificity is 100%.

98% sensitivity.

Used less often.

False positive 2% - 9%,

depending on viral load.
Expensive.

DIAGNOSTIC TESTING FOR HIV

DNA PCR Assay (Proviral)

Detects cell-associated proviral DNA, in peripheral

CD4 cells.
Sensitivity is 99%.
Not FDA approved.
Very expensive.
Can detect early.
Best to use for newborns.

DIAGNOSTIC TESTING FOR HIV

Other Hiv Tests: Saliva, Urine, Serum
Rapid tests:

OraQuick
OraSure
Clearview
Uni-Gold
Reveal G2
Multispot
VITROS

Rapid tests recommended with: occupational exposure,

pregnant women in labor, outreach settings, and patients
unlikely to return again.
All should be confirmed with a Western Blot.

CASE STUDY

31 y/o homosexual male presents with 5 days of swollen glands,

fever, rash on torso, muscle aches, malaise, and cough. Has a history
of unprotected receptive anal intercourse with a random partner
roughly 7 weeks ago.

DIFFERENTIAL DIAGNOSIS
Mononucleosis (Epstein-Barr)
Bacterial Pharyngitis
Lymphoma
Cytomegalovirus
Influenza
Viral Syndrome
Viral Hepatitis
Drug Reaction
Secondary Syphilis

HIV ACUTE INFECTION

Acute HIV Infection, also known as
Acute Seroconversion Syndrome.
Second stage of HIV infection, after the incubation stage and before
the latency stage.
If it occurs, it will usually occur 2-4 weeks post exposure.
Influenza-like, mononucleosis-like illness, lasting roughly 10-14 days.
It is estimated that an acute infection/illness will occur
50-70% of the time.
Often subtle symptoms may come and go without notice.

HIV ACUTE INFECTION SIGNS AND SYMPTOMS

fever
lymphadenopathy
pharyngitis
generalized rash
myalgia
malaise
headache

mouth/esophageal sores
nausea and vomiting
enlarged liver/spleen
weight loss
thrush
neurological symptoms

Infected individuals may experience all,

some, or none of these symptoms.

CAUSE OF ACUTE HIV ILLNESS

A period of rapid viral replication that immediately follows the individual's
exposure to HIV, leading to an abundance of virus in the peripheral blood.

This response is accompanied by a marked drop in the numbers of circulating

CD4+ T cells.

Activation of CD8+ T cells, which kill HIV-infected cells, and subsequently with
antibody production, when seroconversion occurs.

A good CD8+ T cell response has been linked to slower disease progression and
a better prognosis, though it does not eliminate the virus.

A strong immune defense reduces the number of viral particles in the blood
stream, marking the end of the acute HIV infection.

The start of the infection's clinical latency stage, which, in turn, may be succeeded
by true AIDS.

WHEN TO TREAT?
2012 DHHS Guidelines
US Dept. Of Health and Human Services
now recommends that

ALL HIV + people be started on HAART

when confirmed with a positive diagnosis,

regardless of CD4 count or viral load.

WHEN IS IT AIDS?
HIV confirmed positive
(through WB)
plus
CD4 count <200
or
An AIDS Defining Illness

AIDS DEFINING ILLNESS AND

OPPORTUNISTIC INFECTIONS
Candidiasis of

bronchi, trachea, or
lungs, esophageal

Encephalopathy

Lymphoma,

Herpes simplex:

Lymphoma, primary,

(HIV-related)

Cervical cancer
(invasive)

chronic ulcer/s
(> than 1 month)

Coccidioidomycosis

Histoplasmosis

Cryptococcosis

Isosporiasis, chronic

Cryptosporidiosis,

chronic intestinal for

longer than 1 month

Cytomegalovirus

intestinal (>1 month)

Kaposi's sarcoma
Lymphoma, Burkitt's

disease

immunoblastic
of brain

Mycobacterium

avium complex or
Mycobacterium
kansasii

Pneumocystis jiroveci
pneumonia (formerly
Pneumocystis carinii)

Progressive multifocal
leukoencephalopathy
(PML)

Salmonella
septicemia

Mycobacterium

Toxoplasmosis of the

Pneumonia

Tuberculosis,

tuberculosis
(recurrent)

brain

disseminated

Wasting syndrome

Cytomegalovirus

retinitis (w/vision loss)

due to HIV

OPPORTUNISTIC INFECTIONS
Cytomegalovirus (CMV) Viremia

Exposure to CMV or reactivation of previous CMV exposure

with low CD4 count.

Flu-like illness (similar to Mono), fatigue, myalgias, fever, N/V.

Testing: CMV PCR, IgG, IgM through serum

Check the eyes!

Tx: Valganciclovir 900mg BID for 4 weeks - only if confirmed

in serum.

Monitor PCR for resolution

OPPORTUNISTIC INFECTIONS
Cytomegalovirus (CMV) Retinitis

Inflammation of the eye's retina caused by exposure to

Cytomegalovirus or reactivation of the virus from a
previous exposure.
Can lead to blindness.
Emergent: opthomalogical exam and ocular surgeon.
Tx: IV Gangciclovir or Foscarnet (Antivirals).

OPPORTUNISTIC INFECTIONS
Kaposis Sarcoma
Kaposis sarcoma (KS) is a systemic disease that can present with
cutaneous lesions, with or without internal involvement.

Herpes Virus 8 (HHV8)

May be sexually transmitted
and through saliva.

OPPORTUNISTIC INFECTIONS
Kaposis Sarcoma
KS lesions are nodules or blotches.
Red, purple, brown, or black, and are usually
papular.
They are typically found on the skin, but
spread elsewhere is common, especially the
mouth, gastrointestinal tract and respiratory
tract.

OPPORTUNISTIC INFECTIONS
Kaposis Sarcoma

Oral KS: 30% of the time.

Initial site in 15% of AIDS-related KS.
Hard palate, gums.
GI KS:
Lesions may be silent, cause weight loss, pain, nausea/vomiting,
diarrhea, bleeding, malabsorption, or intestinal obstruction.
Respiratory KS:
Shortness of breath, fever, cough, hemoptysis, or chest pain, or
as an incidental finding on chest x-ray.
Confirmed by bronchoscopy.

OPPORTUNISTIC INFECTIONS
Kaposis Sarcoma

Tx: KS is not curable.

Initiating HAART is number one treatment. HAART alone can
eradicate the lesions.
Local skin lesions can be treated with cryosurgery.
Disemminated KS can be treated with systemic therapy,
including interferon alpha, liposomal anthracyclines, or paclitaxel.
No prophylactic medication.

OPPORTUNISTIC INFECTIONS
Cryptosporidiosis (Cryptosporidium parvum)
Protozoan parasite that can cause gastro-intestinal
illness.
Human-to-human fecal-oral transmission (oral-anal).
Also, animal-to-person transmission and waterborne
transmission.
Profuse watery diarrhea, cramps, nausea, vomiting.
Symptoms usually improve when CD4 is >100.
Tx: if stool cultures positive.
Rx: HAART and sometimes anti-protozoal
medications (Nitazoxanide).

OPPORTUNISTIC INFECTIONS
Cryptococcus Neoformans

Found in the droppings of wild birds, often pigeons; when dust of the
droppings is stirred up it can infect humans or pets that inhale the dust.
Infected humans and animals do not transmit their infection to others.
Usually enters through respiratory tract and presents as a lung infection.
Fungal meningitis and encephalitis common in AIDS patients.
Presenting as subacute meningitis: fever, headache, malaise.
Risk of death is increased with intracranial pressure (ICP).
Positive serum cultures, and CSF through LP.
Prophylactically treat: CD4 < 100.
Rx: Fluconazole 100-400mg daily.
If fulminant meningitis: treat with IV Ampho B.
Ongoing maintenance medication until patient has CD4 >200 for 3 months.

OPPORTUNISTIC INFECTIONS
Esophagitis Candidiasis

Diagnosis is clinical.
White patchy overgrowth on oral mucosa, and into
esophagus.
Tx: Fluconazole 100-400mg daily along with HAART.
Nystatin oral washes may improve symptoms.
Ongoing maintenance needed for recurrence.

OPPORTUNISTIC INFECTIONS
Mycobacterium Avium Complex (MAC)
Mycobacterial infection similar to TB.
AKA: Lady Windemere Syndrome (Oscar Wilde)
Symptoms of cough, fever, malaise, weight loss,
diarrhea, and night sweats.
Diagnosed through serum and sputum cultures.
CXR: may show infiltrates.
Prophylactically Treat: CD4 <50.
Rx: Azithromycin 1200mg PO Weekly
Discontinue Rx when CD4 >100 for 3 months.

OPPORTUNISTIC INFECTIONS
Mycobacterium tuberculosis
Treat:

Positive PPD (>5mm)

Negative PPD, but close

TB contact

Hx of untreated TB

Latent TB Rx: INH 300MG QD + Pyridoxine 50MG QD x 9

months.

OPPORTUNISTIC INFECTIONS
Toxoplasmosis
Toxoplasma gondii, a parasitic protozoa.
The definitive host of T. gondii is the cat.
Over half of the world's human population is estimated to
carry a Toxoplasma infection.
In HIV, it can cause encephalitis, neurologic diseases, and can
affect the heart, liver, inner ears, and eyes (chorioretinitis).
Prophylactically treat: if positive Toxo IgG test and CD4 <100.
Rx: Bactrim DS Daily.
Discontinue treatment when CD4 >200 for 3 months.

OPPORTUNISTIC INFECTIONS
Herpes Simplex 1 or 2
Treat: upon diagnosis with serum
HSV 1 & 2 or clinical exam.
Flare-ups can be worse with HIV
and lead to herpes viremia.
Preventative: Valcyclovir 1gm daily
or Acyclovir 800mg daily. Use
higher dose for flare-up.

OPPORTUNISTIC INFECTIONS
Pneumocystic carinii Pneumonia (PCP), Pneumocystis jirovecii

Fungal infection affecting the lungs.

Can lead to deadly fulminant
pneumonia.
Prophylactically treat: CD4 <200.

Bactrim (TMP-SMX) DS
Daily
Rx or
Dapsone 100mg daily
May discontinue Rx when
CD4 >200 for 3 months.

OPPORTUNISTIC INFECTIONS
Histoplasmosis (Histoplasma capsulatum)
H. capsulatum is a fungus that grows in soil and material
contaminated with bird or bat droppings.
Has been found in poultry house litter, caves, areas harboring
bats, and in bird roosts.
Usually endemic in Ohio and Missisippi River Valleys, Puerto
Rico and Latin America.
Transmitted through inhalation.
CD4 <300
Initial symptoms: often silent.

OPPORTUNISTIC INFECTIONS
Histoplasmosis (Histoplasma capsulatum)
The acute phase of histoplasmosis is characterized by nonspecific respiratory symptoms, often cough or flu-like.
Chest X-ray findings are normal in 4070% of cases.
Chronic histoplasmosis cases can resemble tuberculosis.
Disseminated disease: fever, weight loss, fatigue.
Test positive urine or serum for Histoplasmosis.
Tx: IV Ampho B followed by Itraconazole for at least a year.

OPPORTUNISTIC INFECTIONS
Coccidiomycosis (Valley Fever)

Fungal disease caused by C. immitis or C.

posadasii.

Some patients fail to recover and

develop chronic pulmonary infection
or widespread disseminated
infection (affecting meninges, soft
tissues, joints, and bone).

Severe pulmonary disease may

develop in HIV-infected persons.

Diagnosis through sputum and

serum cultures.

Endemic in certain parts of Arizona,

California, Nevada, New Mexico, Texas,
Utah and northwestern Mexico.
Symptomatic infection (40% of cases)
usually presents as an influenza-like illness
with fever, cough, headaches, rash, and
myalgia (muscle pain).

Tx: typically only treated if disseminated disease

Rx: IV Ampho or Fluconazole orally.

No prophylactic Tx for HIV.

OPPORTUNISTIC INFECTIONS
New Fears
Bacterial Meningitis?

Several homosexual men in the New York City and

Los Angeles areas with bacterial meningitis.

All were at the White Party in Palm Springs.

Eerily reminiscent of the first known cases of HIV/AIDS.
2014 - new report of 8 confirmed cases - conflicting
information.

HIV ASSOCIATED STDS

Syphilis
HSV 1 or 2
Chlamydia
Gonorrhea
HPV

Hepatitis A, B, & C
Trichomoniasis
Molluscum Contagiosum
Chancroid

SCREENING TESTS
HIV VL/CD4 Count

Anti-Toxoplasma IgG

PPD/CXR

Varicella IgG

LFTS

Geno/Pheno

CMP

Mammography
(if indicated)

HLA-B5701

CBC

Tropism Test
(CCR5/CXCR4)

LIPIDS

Hepatitis Panel
Syphilis Screen
(RPR.VDRL)

Anal Pap
Cervical Pap
Gonorrhea/
Chlamydia
(Urine, Rectum,
Pharynx)

Urinalysis

PSA (if indicated)

Dexa Scan (if indicated)
Colonoscopy (if indicated)
HSV Screening
G6-PD Screening

VACCINE PROPHYLAXIS
Tetanus Diptheria vaccine(TDap, Adacel)
Prevnar, Pneumovax vaccines (CD4 >200)
Varicella vaccine (non-immune and CD4 >200) Herpes Zoster vaccine (CD4 must be >200)
Influenza vaccine (NOT the live virus)
HPV vaccine (Gardasil) women and men ages 13-26.
Meningitis vaccine (Menactra) - when indicated.

COCKTAIL ANYONE?
HAART: Highly Active Antiretroviral Therapy
Combination of three or more medications used collectively to
suppress HIV viral load and raise CD4 counts in an HIV positive
patient.

PURPOSE:
to target the integration and
replication
of HIV from multiple points
of entry and division.

HAART
Initial treatment against HIV targets three key enzymes:

Integrase
Protease
Reverse transcriptase

HAART
The life cycle of HIV can be as short as about 1.5 days from viral
entry into a cell, through replication, assembly, and release of
additional viruses to infection of other cells.
HIV lacks proofreading enzymes to correct errors made when it
converts its RNA into DNA via reverse transcription.
Its short life-cycle and high error rate cause the virus to mutate
very rapidly, resulting in a high genetic variability of HIV.
Some of them are able to slip past defenses such as the human
immune system and antiretroviral drugs.
When antiretroviral drugs are used improperly, these multi-drug
resistant strains can become the dominant genotypes very rapidly.
Some can lead to the development of multi-drug resistant
mutations.

HAART
Antiretroviral combination therapy defends against resistance by
suppressing HIV replication as much as possible.
Combinations of antiretrovirals create multiple obstacles to HIV
replication to keep the number of offspring low and reduce the
possibility of a superior mutation.
Therefore, if a mutation that conveys resistance to one of the
drugs arises, the other drugs continue to suppress reproduction
of that mutation.
No individual antiretroviral drug has been demonstrated
to suppress an HIV infection for long.
These agents must be taken in combination in order to have
a lasting effect. As a result, the standard of care is to use
combinations of antiretroviral drugs.

HAART
Nucleoside/tide
Reverse Transcriptase Inhibitor (NRTI)

NRTIs inhibit activity of reverse transcriptase.

lamivudine (Epivir, 3TC)

emtricitabine (Emtriva, FTC)

abacavir (Ziagen, ABC)

zidovudine (Retrovir, ZDV)

stavudine (Zerit, Z4T)

didanosine (Videx, DDI)

tenofovir D. (Viread, TDF)

tenofovir A. (TAF prodrug of TDF)

- Nov, 2015

HAART
Non-Nucleoside
Reverse Transcriptase Inhibitor (NNRTI)
NNRTIs block reverse transcriptase by binding at a different site
on the enzyme, compared to NRTIs.
NNRTIs are not incorporated into the viral DNA but instead
inhibit the movement of protein domains of reverse transcriptase
that are needed to carry out the process of DNA synthesis.
NNRTIs are therefore classified as non-competitive inhibitors of
nevirapine (Viramune, NVP)
reverse transcriptase.

delavirdine (Rescriptor, DLV)

efavirenz (Sustiva, EFV)
etravirine (Intelence, ETR)
rilpivirine (Edurant, RPV)
doravirine (Phase 3 Trials)

HAART

Protease Inhibitor

PIs prevent viral replication by inhibiting

the activity of protease enzyme. Typically PIs are boosted
with ritonavir.

amprenavir (Agenerase)

indinavir (Crixivan, IDV)

atazanavir (Reyataz , ATV)

nelfinavir (Viracept, NFV)

darunavir (Prezista, DRV)

fosamprenavir (Lexiva, f-APV)

ritonavir (Nor vir, RTV)

lopinavir/ritonavir (Kaletra, LPV/r)

darunavir/cobicistat (Prezcobix, DRV/c)

tipranavir

TMB-607 (unboosted monthly injectable)

saquinavir (Invirase, SQV)

(Aptivus, TPV)

atazanavir/cobicistat (EvoTaz, ATV/c)

HAART
Integrase Inhibitor (INI)
Block the action of enzyme integrase.

raltegravir (Isentress, RAL)*

elvitegravir (Vitekta, EVG)

dolutegravir (Tivicay, DTG

cabotegravir (oral and IM) - clinical trials

* being formulated as QD dosing now.

cobicistat Cobi
Inhibiter of cytochrome P450 liver enzymes that metabolize other
medications used to treat HIV, notably elvitegravir and PIs. Combining
cobicistat with certain ARVS, higher concentrations of are achieved in
the body with lower dosing.

HAART
Other HIV Medications
Due to resistance and multiple viral mutations,
salvage therapy is often necessitated.

Fusion Inhibitors

CCR5 Antagonists

Interferes with the binding,

fusion and entry of an HIV
virion to a human cell.
enfuvirtide (Fuzeon,T-20)
weekly dosing

Prevents HIV-1 from entering and

infecting immune cells by blocking CCR5
cell-surface receptor.

maraviroc (Selzentry, MRV)

cenicraviroc (CCR2/CCR5
antagonist)

aplaviroc (no longer used)

PRO-140 (weekly/biweekly injection)

HAART
Injectable Formulations
A study sponsored
by Glaxo Smith
Kline, published
final results in the
March, 2014 issue
of Science:

Long-acting integrase
inhibitor protects
macaques
from intrarectal
simian/HIV
(Aaron Diamond AIDS Research Center,
Rockefeller University)

Long-acting INI (cabotegravir) and NNRTI (rilpivirine) are being

formulated for monthly and/or quarterly IM injections.
Clinical trials in progress.

HAART
Injectable Formulations
TMB-360
An-CD4 Monoclonal Antibody

Monthly injection

fostemsavir (BMS-663068)
Attachment Inhibitor (AI)

Binds directly to the gp120 protein that

makes up part of the 'spikes' on HIV's outer
surface, thereby preventing viral attachment
and entry into CD4 T-cells.
Phase 3 clinical trials. 2017-18?

3BNC117
Anti-HIV neutralizing antibody

Injection of isolated and cloned

broadly neutralizing antibodies from
HIV infected individual to provide passive
immunity.

Concerns for incremental toxicity and drug resistance

due to pharmacological tailing and suboptimal dosing,
or missed injections.

HAART
New approaches and Kick and Kill

BMS-955176
Maturation inhibitor

Targets the point in which

the HIV virus changes
structure and becomes
infectious.

Bind to Gag polyprotein

of the budding virus and
block protease cleavage
(past the point where PIs
work).

In clinical trials. 2020-21?

TLR7 GS-9620
Toll-like receptor agonist

TLRs are receptors on immune system cells,

producing proteins that regulate an immune
response.

GS-9620 targets latent HIV infected cells

sleeping in HIV reservoirs.

Kicks the virus out of its hiding spot,

reversing latency, to be destroyed by HIV
treatment.

HAART
Single Tablet Regimens (STR)
Atripla
(emtricitabine, tenofovir, efavirenz)

Complera
(emtricitabine, repilvirine, tenofovir D.)
Stribild
(emtricitabine, cobicistat, tenofovir, elvitegravir)
Triumeq
(dolutegravir, abacavir, lamivudine)

HAART
Combined Regimens
Coming Soon!
(emtricitabine, tenofovir A.)
November, 2015

(elvitegravir, cobicistat, emtricitabine, tenofovir A.)

November, 2015
(rilpivirine, emtricitabine, tenofovir A.)
2017
(darunavir, cobicistat, emtricitabine, tenofovir A.)
2016-17

HAART
Newly Updated in 2015
First line HIV ARV Combinations

TWO
nucleoside-analogue reverse transcriptase inhibitors (NRTI)
AND

ONE
integrase inhibitor (INI) or
a boosted protease inhibitor (PI)

HAART
The preferred initial regimen in the US
is one of the following:
tenofovir/emtricitabine and raltegravir
tenofovir/emtricitabine and dolutegravir
abacavir/lamivudine and dolutegravir
tenofovir/emtricitabine, elvitegravir and
cobicistat (Stribild)
tenofovir/emtricitabine, ritonavir, and darunavir
(both latter are protease inhibitors)

OTHER HIV RELATED MEDS

Egrifta (tesamorelin)
The first FDA approved medication to reduce VAT
(Visceral Adipose Tissue), or lipohypertrophy from the
long term effects of HIV/HAART.
No longer available.

Fulyzaq (crofelemer)
The first FDA approved anti-diarrheal medication for
symptomatic relief of non-infectious diarrhea related to
HIV/AIDS and HAART.

IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME (IRIS)

A condition in which the immune system begins to recover, but then

responds to a previously acquired opportunistic infection with an
overwhelming inflammatory response that paradoxically makes the
symptoms of infection worse.
The suppression of CD4 T-cells by HIV causes a decrease in the
body's normal response to certain infections.
Therefore, the level of infection that would normally produce
symptoms is instead undetected.
If the CD4 count rapidly increases (due to HAART) a sudden
increase in the inflammatory response produces symptoms, and in
some cases a worsening of damage to the infected tissue.
Tx: supportive care and sometimes appropriate antibiotics/ant-virals,
depending on the underlying cause.

RESISTANCE AND FAILURE

The "wild type" virus is the most common form of HIV.

Any HIV different from the wild type is considered

mutated.

Changes (mutations) in the virus cause resistance.

HIV mutates almost every time a new copy is made.

Not every mutation causes resistance.

GENOTYPE/PHENOTYPE
Genotypic resistance testing is used to detect the presence of
one or more mutations in the HIV virus by comparing it to the
wild-type virus or natural HIV virus
Phenotype resistance testing is used to determine the growth of
the particular strain when exposed to ARV medications, as
compared to the wild-type virus.
The mutations will specify the drugs to which the virus is
resistant.

GENOTYPE/PHENOTYPE
Indications for HIV resistance testing include:

Primary/New HIV infection.

Virological Failure
Super-infection
Patient Non-Compliance
Test requires an HIV viral load of >500-1000.
Test measures only dominant species at time of testing.
(if pt is on HAART - remain on it through testing).

FURTHER TESTING
Trophile
Detects the specific tropism of the individuals HIV virus (CCR5,
CXCR5, or Mixed).
ONLY a CCR5 type virus can be treated with Selzentry
(Maraviroc), a CCR5 antagonist.
HLA B5701
Genetic test to identify carrier of HLA B5701 gene.
Associated with a hypersensitivity reaction to Abacavir (ABC),
a common initial HIV medication.
A positive HLA B5701 test, EXCLUDES Abacavir from the
patient regimen.

VIROLOGIC RESPONSE TO HAART

Virologic response to HAART is decreased VL to <5000 at 4 weeks and
<500 at 8-16 weeks.
Should be non-detectable by 24-48 weeks.
Treatment failure: not ND by 4 months.
Time to nadir of being non-detectable depends on beginning viral load
and CD4 count.
Failure is usually associated with: patient non-compliance, or resistance to
medications.
Viral Blips: sudden minor elevation in VL after being ND.
Usually inconsequential, but sustained VL >50 may indicate failure of
HAART.

FACTORS INFLUENCING CD4 COUNT

Seasonal changes

Diurnal changes

Acute infections

Major surgery

Steroids

Interferon treatment

Chronic conditions: sjogren syndrome, sarcoidosis, radiation,

collagen-vascular disease, lymphoma.

Acute changes in CD4 counts may simply be due to the

recirculation of lymphocytes between the marrow, spleen, and
lymph nodes.

HIV PROGNOSIS
Without treatment, the net median survival time after
infection with HIV is estimated to be 9 to 11 years.
HAART reduced the death rate from this disease by 80%.
Life expectancy for a newly diagnosed HIV-infected
person is now anywhere from 2050 years.

LONG TERM COMPLICATIONS

Osteoporosis

Kaposis Sarcoma

Pysch disorders

Lactic Acidosis

Avascular Necrosis

HPV

Neuropathy

Drug/ETOH abuse

Vitamin D def

STDs

Weakness

Lymphoma

Hypogonadism

CV disease

General Fatigue

Edema

Dementia

Renal disease

Chronic Diarrhea/
IBS

Cardiomyopathy

Lipodis (at) rophy

Hyperlipdemia

Wasting syndrome

Hepatotoxicity

Anemia
Pancreatitis
Thrombocytopenia
Malignancies

HIV PATIENT FOLLOW UP

Quarterly Visits: every 3-6 months, after
stable HAART.
Check VL and CD4 counts.
Monitor LFTS, renal, chemistry, thyroid,
vitamin D, testosterone.
New treatment or changes in regimen:
every 4 weeks until stable.

ELITE CONTROLLERS AND

SLOW PROGRESSORS
Elite Controllers (Long-Term Non-Progressors):
viral loads less than 50 without therapy >1 year.
Viremic Controllers (Slow-Progressors):
viral load < 2000 without therapy >1 year.
1 in 300 with HIV infection. Usually have a high CD4 count.
Genetic? R5 tropic?

CO-INFECTION/SUPERINFECTION
Co-Infection refers to two strains that appear to have been
acquired at the same time (or too close to distinguish).
Reinfection (orSuperinfection) is infection with a second strain at
a measurable time after the first.
Both forms of dual infection have been reported for HIV in both
acute and chronic infection around the world.

COMPLICATED PATIENT
Psychological Issues
Drug Abuse/Alcoholism
Non-Compliance
Risky Behavior

PREVENTION EFFORTS
PEP
Post-Exposure Prophylaxis

Rx: Truvada (with or without Isentress).

Recommended only within 72 hours of high risk exposure.
Data does not support longer than one month of treatment.
Reduces risk of transmission by 80-90%.
Must be HIV tested before starting treatment.
Risk of mutation/resistance.
Good for discordant couples.
Counseling.
Follow up testing at 4 weeks, and 12 weeks.

PREVENTION EFFORTS
PrEP
Pre-Exposure Prophylaxis
Truvada was approved in 2012 by the CDC as a once daily HIV

medication to be taken as added prevention against transmission of HIV.

Indicated for high risk behavioral individuals (MSM, with multiple sex
partner, seri-discordant couples).

May reduce risk of transmission by 90% - ONLY if taken on a consistent

basis.

Very controversial - a party drug??

Must be HIV tested before starting treatment, with follow-up testing

every three months to ensure no seroconversion to HIV positive. Other

STD tests should be performed as well.

Risk of mutation/resistance?
Counseling and barrier protection with condoms is still advised.

PREVENTION EFFORTS
PrEP
Pre-Exposure Prophylaxis
New injectable formulations of
ARVs, currently in clinical trials
are being considered for targeting
the PrEP population specifically.

PREVENTION EFFORTS
ABC Campaign:

Abstinence

Be faithful

Condom

Dr ug
(PreP,
PE

"HIV fatigue", where populations who were not around

to witness the effects of AIDS in the 1980s are not
interested in hearing anything about the disease now.
Theres a pill for it now.
The TeachAIDS prevention education software,
developed at Stanford University will be distributed to
every primary, secondary, and tertiary educational
institution in the country.

Circumcision:
Can lower a heterosexual mans risk of acquiring HIV up to 60%

P)

A CURE?
Berlin Patient
Received two bone marrow transplants to treat leukemia from a donor with the
CCR5delta-32 mutation.

Underwent apheresis, in which blood is withdrawn from the body, T-cells are filtered
out, and the rest of the blood is returned.

His own immune cells were destroyed by chemotherapy to wipe out the leukemia,
and his immune system was reconstituted with cells that lacked CCR5.

The man stopped antiretroviral therapy, and three years later researchers are unable
to find any trace of HIV.
Bone marrow transplants are not feasible on a large scale, investigators are exploring
other ways to achieve a similar outcome.

A FUNCTIONAL CURE?
The Mississippi Baby

Mother learned she was HIV+ only during labor.

Mother is usually given ZDV during labor to decrease risk of exposure to baby. The
newborn is typically treated prophylactically with 1-2 medications (ZDV, NVP).

This baby was found to have HIV infected blood shortly after birth.
This baby was given a cocktail of 3 medications within 30 hours of its birth. The
baby was continued on these medications for 18 months, before she and her
mother went missing from care.

When they returned, after 5 months with no medicine, the baby was found to be
HIV negative, despite a barrage of tests. 3 years later, the girl was still HIV negative.

After five years, HIV was found detected in the young girls blood, indicating
infection.

A FUNCTIONAL CURE?
The Long Beach Baby

In 2011 an HIV+ mother, who did not receive

ARVs during pregnancy gave birth.

Baby was given a high dose combination of 3 ARVs

after birth.

At 15 months old, the baby still tested negative for

HIV.

After being lost to care, the child was tested again

at four years of age and found to be infected with
HIV.

A FUNCTIONAL CURE?
The Visconti Cohort
A group of 14 patients known as the Visconti Cohort all began HAART
within 10 weeks of contracting HIV.

Aged between 34-66, the group stopped treatment 3 years in.

Currently, they still have traces of HIV in their blood, but no indication of
advancing viral replication or illness. The virus is kept at bay.

Early treatment in these patients may have limited the establishment of viral
reservoirs, the extent of viral mutations, and preserved immune responses.

Highlights the importance of immediate treatment, so as to target newly

formed HIV reservoirs and their latent inhabitants, so as to potentially
create a functional cure.

A FUNCTIONAL CURE?
Gene Editing

Mirroring similar curative effects of the Berlin Patient, scientists

are taking stem cells from HIV-infected individuals and using a
gene editing tool to cause them to form into white blood cells
with a specific mutation (CCR5 Delta 32).

The mutation affects aprotein known as CCR5, and interferes

with the viruss ability to latch onto blood cells.
The mutation occurs naturally in a small percentage of the
worlds population and gives these individuals a life-long
resistance to HIV infections.
Although the virus may remain in their body, without being
able to enter the T cells, it cannot replicate and therefore will
stay at low numbers, uncompromising the immune system.

A FUNCTIONAL CURE?
Vaccine Trials

Initial trials were on rhesus macaque monkeys, which involved exposing them to a simple
bacteria to create an immune response.
Scientists then gave the monkeys incremental exposures to inactivated SIV, which is the
monkey form of HIV. Even after repeated exposure to SIV at extremely high doses, the
monkeys did not become infected with the virus.
The vaccine appears to work by stimulating a class of CD8 cells which apparently prevent
CD4 cells from recognizing SIV as a pathogen. Consequently, the body did not produce an
immune response and deliver the CD4 cells that SIV needs to infect and thrive in the body.
In human trials, this new vaccine uses a common cold virus called adenovirus 26. As it
spreads, it should activate an immune response. Then a second vaccine is given with bits of
HIV attached. The immune system cells will also "see" the attached bit of HIV and, the
researchers hope, react against any HIV virus should the vaccinated person ever be
exposed.

ON THE HORIZON
Zinc Finger Proteins
Zinc fingers are small protein structures that can mimic.
Gene therapy to interfere with co-receptors on the surface of T-cells to
protect these cells from HIV infection.
HIV uses two different surface co-receptors
CCR5 and CXCR4 to enter CD4 T-cells. If
the co-receptors are blocked or disrupted,
the virus is unable to enter cells.
Ultimately, the hope is that gene therapy will
create cells that lack these receptor proteins
and therefore are protected from infection.

ON THE HORIZON
HIV Resistant Cells
Stanford researchers have created HIV-resistant T-Cells.
Molecular splicing of HIV resistant genes into T-Cells.
Inactivation of a receptor gene and insertion of additional anti-HIV genes,
blocking the virus from entering the cells.
Creates multiple layers of protection,
called stacking.
Potentially eliminates the need for
medicinal treatment.

ON THE HORIZON
HIV bNABs
Broadly Neutralizing HIV-1 Antibodies are neutralizing antibodies which
neutralize multiple HIV-1 viral strains.

Research has shown that BNAs can block HIV from entering into or
replicating inside of CD4 cells in a laboratory setting. The findings
suggest the possible feasibility of passive immunotherapy, in which
people living with the virus would receive periodic administrations of
BNAs instead of antiretroviral treatment.
Similar to routine allergy shots.

LGBTQ
Lesbians, Gays, Bisexuals, Transgender, Queer
An estimated 4% of adults in the United States identify as lesbian,
gay, or bisexual andan estimated 0.3% of adults are transgender.
There are approximately 9 mil LGBT Americans, roughlyequivalent
to the population of New Jersey.
Bisexuals comprise a slight majority (1.8% comparedto 1.7% who
identify as lesbian or gay).
Women are substantially more likely than men to identify as bisexual.
Bisexualscomprise more than half of the lesbian and bisexual
population among women in eight of the nine surveys considered in
the brief.
An estimated 19 mil Americans (9%) report that they have engaged
in same-sex sexual behavior and nearly 25.6 mil Americans (13%)
acknowledge at least some same-sex sexual attraction.
A patients gender identity, sexual identity and desires can impact
their health and well-being through the added stressors of stigma,
potential lack of family and societal support, confusion if the identity
or desires are new or reemerging, and other unique health issues
related to being LGBT.

LGBTQ
All your patients are heterosexual.
All patients use traditional labels.
Sexual identity based on appearance.
Sexual orientation is based on behavior.

Dont
Assume
Anything!

Sexual behavior is based on identity.

Sexual behavior or identity havent changed
since last visit.
Bisexual identity is only a phase.
Transgender patients are gay, bisexual, or
lesbian.

LGBTQ
Gender is not binary.
Gender binary describes the system in which a society splits its members of male and
female sexes into gender roles, gender identities and attributes. Gender role is one
aspect of a gender binary. Gender roles shape and constrain individuals life
experiences, impacting aspects of self-expression ranging from clothing choices to
occupation. Traditional gender roles continue to be enforced by the media, religion
and educational, political and social systems. Many societies have used the gender
binary to divide and organize people, though the ways this happens differs between
societies. Gender binaries exist as a means of bringing order, though I would argue
that gender binaries divide and polarize society.
Johnson, Joy; Repta, Robin (2002).Sex an Gender: Beyond the Binaries

LGBTQ
Educate yourself about these populations.
Genuine engagement in their health condition - will make
them comfortable and increase compliance and retention.
More likely to seek out to appropriate primary care.
Encourage patients to be engaged in their own health
education.

Be preventative.

RESEARCH
Evidence-based medicine.
Clinical trials and research.
Be an independent dependent provider.
Practice your medicine with supporting data and
research.
Know your medicine. Its always evolving.
You must evolve with it.

Loma Linda University

Physician Assistant
Program
Summer 2015

HIV/AIDS
Scott A. Denny, MSPA, PA-C
Director of HIV/Transgender Services
HIV Specialist, Infectious Diseases
Kaiser Permanente Hawaii Region