Human Immunodeficiency Virus Disease: AIDS

1. DR. JUAN CARLOS BECERRA MARTÍNEZ
CÁTEDRA DE MEDICINA INTERNA-MC3087
TECNOLÓGICO DE MONTERREY, CAMPUS GUADALAJARA

2. The Human Retroviruses
 Retroviruses contain an RNA-dependent
DNA polymerase (a reverse transcriptase)
that directs the synthesis of a DNA form of
the viral genome after infection of a host cell.
 The designation retrovirus denotes that
information in the form of RNA is transcribed
into DNA in the host cell.
Harrison’s. 18th Ed.

3. The Human Retroviruses
 The family Retroviridae includes seven
subfamilies.
 2 of the families infect humans:
○ Deltaretroviruses: HTLV type I and II
○ Lentiviruses: HIV 1 and 2
Harrison’s. 18th Ed.

4. The Human Retroviruses
Harrison’s. 18th Ed.

5. The Human Retroviruses
The surface glycoprotein
(SU) is responsible for
binding to receptors of host
cells. The transmembrane
protein (TM) anchors SU to
the virus.
A protease (PR) cleaves
the polyproteins encoded
by the gag, pol, and env
genes into their functional
components. RT is reverse
transcriptase, and IN is an
integrase present in some
retroviruses (e.g., HIV-1)
that facilitates insertion of
the provirus into the host
genome.
Harrison’s. 18th Ed.

6. HIV & AIDS
 AIDS was first recognized in the United States in 1981,
when the CDC reported the unexplained occurrence of
Pneumocystis jiroveci (formerly P. carinii) pneumonia in five
previously healthy homosexual men in Los Angeles and of
Kaposi's sarcoma (KS) in 26 previously healthy
homosexual men in New York and Los Angeles.
 In 1983, human immunodeficiency virus (HIV) was isolated
and by 1984 it was demonstrated clearly to be the
causative agent of AIDS.
 In 1985, a sensitive enzyme-linked immunosorbent assay
(ELISA) was developed.
Harrison’s. 18th Ed.

7. Definition
Harrison’s. 18th Ed.

8. Definition
CATEGORY A:
Harrison’s. 18th Ed.

9. Definition
CATEGORY B:
Harrison’s. 18th Ed.

10. Definition CATEGORY C:
Harrison’s. 18th Ed.

11. HIV & AIDS
 The most common cause of HIV disease
throughout the world is HIV-1.
 HIV-2 was first identified in 1986 in West
African patients.
 The currently defined groups of HIV-1
are M, N, O and P and HIV-2 groups are
from A through G.
 HIV-1 viruses likely came from
chimpanzees and/or gorillas, and HIV-2
from sooty mangabeys (mangabey gris).
Harrison’s. 18th Ed.

12. The replication cycle of
HIV
Harrison’s. 18th Ed.

13. Transmission
 Sexual contact
 Blood and blood products
 Infected mothers to infants intrapartum,
perinatally, or via breast milk.
 There is no evidence that HIV is
transmitted by insects, such as by a
mosquito bite.
Harrison’s. 18th Ed.

14. Epidemiology
Harrison’s. 18th Ed.

15. Pathophysiology
Typical course of an untreated HIV-infected individual
Harrison’s. 18th Ed.

16. Diagnosis of HIV Infection
 The standard blood screening test for HIV infection is the
ELISA:
 Sensitivity of >99.5%, but not specific.
 Most diagnostic laboratories can detect both HIV-1 and HIV-2.
 The fourth-generation ELISA tests combine detection of
antibodies to HIV with detection of the p24 antigen of HIV.
 False-positive ELISA tests are antibodies to class II antigens
(such as may be seen following pregnancy, blood transfusion, or
transplantation), autoantibodies, hepatic disease, recent influenza
vaccination, and acute viral infections.
 For these reasons, anyone suspected of having HIV infection
based on a positive or inconclusive EIA result must have the
result confirmed with a more specific assay such as the Western
blot.
Harrison’s. 18th Ed.

17. Diagnosis of HIV Infection
 The confirmatory test is the Western Blot:
 All HIV antigens can be separated on the basis of
molecular weight
 A negative Western blot is one in which no bands are
present at molecular weights corresponding to HIV
gene products.
 Criteria established by the FDA for a positive Western
blot state that a result is considered positive if
antibodies exist to two of the three HIV proteins: p24,
gp41, and gp120/160
Harrison’s. 18th Ed.

18. Diagnosis of HIV Infection
Harrison’s. 18th Ed.

19. Diagnosis of HIV Infection
 Other tests (in case of Western Blot
inconclusive):
Harrison’s. 18th Ed.

20. CD4+ T Cell Counts
 CD4+ T Cell count is the best indicator of the
immediate state of immunologic competence
of the patient with HIV infection.
Harrison’s. 18th Ed.

21. HIV RNA Determinations
 The measurement of serum or plasma levels of HIV
RNA has become an essential component in the
monitoring of patients with HIV infection.
 The two most commonly used techniques are:
 RT-PCR assay and the bDNA assay
 In most instances of effective antiretroviral therapy
the plasma level of HIV RNA will drop to <50 copies
per milliliter within 6 months of the initiation of
treatment. During therapy, levels of HIV RNA should
be monitored every 3–4 months to evaluate the
continuing effectiveness of therapy.
Harrison’s. 18th Ed.

22. Clinical Manifestations
 The Acute HIV Syndrome:
 3–6 weeks after primary infection
Harrison’s. 18th Ed.

23. Prevention of Opportunistic
Infections
Sabatine. 4th Ed.

24. Complications
Sabatine. 4th Ed.

25. Antiretrovirals (ARVs)
Sabatine. 4th Ed.

26. Indications for initiation of ARVs
1.- AIDS-defining illness
2.- CD4 <500/ml
3.- Pregnancy
4.- Nephropathy
5.- HBV co-infxn
6.- HIV-assoc. sx (systemic, neurocognitive,
mucocutaneous, etc.)
7.- Acute infection syndrome
Sabatine. 4th Ed.

27. Regimens for treatment
Sabatine. 4th Ed.

28. Indications for Changing
Antiretroviral Therapy
1.- Less than a 1-log drop in plasma HIV RNA
by 4 weeks following the initiation of therapy
2.- Persistently declining CD4+ T cell numbers
3.- Clinical deterioration
4.- Side effects
Harrison’s. 18th Ed.