HIV

Prepared by:
Dr. Brian Gilbert Fernandez, DPCOM
 Facts about HIV
• HIV (human immunodeficiency
virus) is a virus that attacks the
body’s immune system.

• If HIV is not treated, it can lead to

AIDS (acquired immunodeficiency
syndrome).
• HIV infection in humans came from a
type of chimpanzee in Central Africa.

• The chimpanzee version of the virus

(called simian immunodeficiency virus,
or SIV) was probably passed to humans
when humans hunted these chimpanzees
for meat and came in contact with their
infected blood.
 Facts about HIV
 Retroviruses contain an RNA dependent DNA polymerase
that directs the synthesis of a DNA form of the viral
genome after infection of a host cell.
 2 of the Families of Retroviridae infect humans
 Deltaretroviruses: HTLV type 1 and II
 Lentiviruses: HIV 1 and 2
 Facts about HIV
 The surface glycoprotein is responsible for binding to
receptors of host cell
 The transmembrance protein anchors SU to the virus
 Aprotease cleaves the polyproteins encoded by the gag, pol
and env genes into their functional component
 Reverse transcriptase and IN is an integrase present in some
retroviruses (e.g HIV-1) that facilitated insertion of the
provirus into the host genome
 Facts about HIV
 AIDS is caused by infection with the human retroviruses HIV-1 or 2.

 HIV-1 is the most common cause worldwide.

 These viruses are passed through sexual contact; through transfusion of

contaminated blood or blood products; through sharing of contaminated
needles and syringes among injection drug users (IDUs); intrapartum or
perinatally from mother to infant; or via breast milk.

 As of November 1, 2017, an estimated 1.8 million people have been

infected with HIV and 1.1 million people are currently living with HIV in
the United States; approximately 13% of these individuals are unaware that
they are infected.

 Of new HIV/AIDs diagnoses, 68% were due to male to male sexual contact,
23% to heterosexual contact, and 6% to IDUs
 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.

 Essentially all pts undergo a viremic stage during primary infection; in some pts this
is associated with the “acute retroviral syndrome,” a mononucleosis-like illness (see
below).

 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.
 Continuation..
 The CD8 T cell response is thought to be important in
controlling virus levels, which peak and then decline, as the
CD4 T cell counts rebound.
 A good CD8 T cell response has been linked to slower
disease progression and a better prognosis, though it does
not eliminate the virus.
 The pathophysiology of Aids is complex.
 Ultimately, HIV causes AIDs by depleting CD4 T helper
lymphocytes
 Important points in
pathogenesis
 After the virus is acquired, a period of rapid viral replication
ensues leading to viremia.
 During primary infection, the level of HIV may reach several
million virus particles per ml of blood.
 This response is accompanied by a marked drop in the
numbers of circulating CD4 T cells
 This acute viremia is associated in virtually all people with
the activation of CD8 T cells, which kill HIV –infected cells,
and subsequently with antibody production or seroconversion
Manifestations of HIV
 Facts about HIV
 The stages of HIV infection are acute infection (also known as
primary infection), latency and AIDS.

 Acute infection lasts for several weeks and may include

symptoms such as fever, swollen lymph nodes, inflammation of
the throat, rash, muscle pain, malaise, and mouth and
esophageal sores.

 The latency stage involves few or no symptoms and can last

anywhere from two weeks to twenty years or more, depending
on the individual.

 AIDS, the final stage of HIV infection, is defined by low CD4+

T cell counts (fewer than 200 per μL), various opportunistic
infections, cancers and other conditions.
 Facts about AIDS
1. The symptoms of AIDS are primarily the result of conditions that do not
normally develop in individuals with healthy immune systems.

2. Most of these conditions are opportunistic infections caused by bacteria,

viruses, fungi and parasites that are normally controlled by the elements
of the immune system that HIV damages. These infections affect nearly
every organ system.

3. A declining CD4+/CD8+ ratio is predictive of the progression of HIV to

AIDS.

4. People with AIDS also have an increased risk of developing various

cancers such as Kaposi's sarcoma, cervical cancer and cancers of the
immune system known as lymphomas.

5. Additionally, people with AIDS often have systemic symptoms of

infection like fevers, sweats (particularly at night), swollen glands,
chills, weakness, and weight loss.
 Facts about CD4

 CD4 count is a good measure of your risk of opportunistic infections

and an indicator of how well your immune system is working.

 Treatment with antiretroviral therapy (ART), medications that control

the HIV, is recommended for everyone with HIV, no matter how high
or low their CD4 count is.

 However, a low CD4 count (below 200/mm3) increases the urgency

to start ART.
 Facts about Viral Load

 Viral Load (VL): An HIV viral load test, also called an HIV RNA
test, tracks how many HIV particles are in a sample of your
blood. This is called your viral load.

 Why it’s important: A goal of HIV treatment is to keep your viral

load so low that the virus can’t be detected by a viral load test.

 It’s important to get a viral load test to see the level of HIV in
your blood before starting treatment and help guide the choice of
HIV medications and then to get repeat tests to track your
response to HIV treatment.
 Facts about Drug
Resistance test

 Drug Resistance Tests: HIV can change form, making it resistant to

some HIV medicines.

 A drug resistance test helps your provider identify which, if any, HIV
medicines will not be effective against the strain of HIV you have.

 Why it’s important: Drug resistance test results help your provider
determine which HIV medicines are most likely to work for you.
Laboratory Tests…
 SEROLOGIC TESTS FOR DIAGNOSING HIV

 The major tests used as screening tests for diagnosing HIV

 (1) include HIV antigen-antibody laboratory-based tests,

 (2) HIV antigen-antibody point-of-care tests
 (3) HIV antibody laboratory-based tests
 (4) HIV antibody point-of-care tests.

 In addition, HIV diagnostic testing includes HIV-1/2

differentiation assays and HIV nucleic acid diagnostic tests.
 INTERPRETATION OF TEST RESULTS

 If the HIV-1/2 antigen-antibody immunoassay is nonreactive, then the

interpretation is no infection with HIV-1 or HIV-2, unless the individual
undergoing testing has acquired HIV within the past 30 days. If acute HIV is
suspected, then perform an HIV-1 RNA test.

 If the HIV-1/2 antigen-antibody immunoassay is reactive and the HIV-1/HIV-2

differentiation assay result is reactive for HIV-1 and nonreactive for HIV-2,
then conclude the patient has HIV-1 infection.

 If the HIV-1/2 antigen-antibody immunoassay is reactive and the HIV-1/HIV-2

differentiation assay result shows HIV-1 nonreactive and HIV-2 reactive, then
conclude the patient has HIV-2 infection.

 If the HIV-1/2 antigen-antibody immunoassay is reactive and the HIV-1/HIV-2

differentiation assay shows HIV-1 indeterminate (or negative) in conjunction
with a nonreactive HIV-2, then several possibilities exist. In this scenario,
follow-up testing with HIV-1 NAT is indicated.
Key Points

1. HIV is the virus that causes HIV infection. AIDS is the most advanced stage
of HIV infection.

2. HIV is spread through contact with the blood, semen, pre-seminal fluid,
rectal fluids, vaginal fluids, or breast milk of a person with HIV. In the
United States, HIV is spread mainly by having anal or vaginal sex or sharing
injection drug equipment, such as needles, with a person who has HIV.

3. Antiretroviral therapy (ART) is the use of HIV medicines to treat HIV

infection. People on ART take a combination of HIV medicines (called an
HIV regimen) every day.

4. ART is recommended for everyone who has HIV. ART can’t cure HIV
infection, but HIV medicines help people with HIV live longer, healthier
lives. HIV medicines can also reduce the risk of HIV transmission.