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Understanding HIV and AIDS Progression

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Understanding HIV and AIDS Progression

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© All Rights Reserved
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Available Formats
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CHAPTER 25 Acquired Immunodeficiency Syndrome 343

Results of blood donors and patients is usually by serologic


• One donor should be negative for HIV. The color change methods. In patients with signs and symptoms of AIDS,
should be similar to that of the negative control. both the assessment of cellular concentrations and function
• One donor should be shown positive for HIV. The color and the diagnosis and treatment of opportunistic infections
change should be similar to that of the positive control. become important.
• Antibodies to HIV-1 are usually detected by EIA and
confirmed by Western blot, currently the standard for
CHAPTER HIGHLIGHTS
confirming HIV-1 seropositivity. If positive for band p41
• H IV-1 is the predominant virus responsible for AIDS. In or p24 with a positive EIA, the test is confirmatory.
addition to the original HIV-1, a second AIDS-causing
virus, HIV-2, was identified in 1985.
• The HIV virus is composed of structural proteins and REVIEW QUESTIONS
glycoproteins that occupy the core and envelope regions of
1. Th
 e major structural protein (core) of the HIV-1 virus is:
the particle.
a. gp41
• Retroviruses contain a single, positive-stranded RNA with
b. p24
the genetic information of the virus and a special enzyme,
c. gp34
reverse transcriptase, in their core. Reverse transcriptase
d. gp140
enables the virus to convert viral RNA into DNA.
• HIV has a marked preference for the CD4+ subset of 2. Th
 e infectious process of AIDS begins when the gp120
lymphocytes. Macrophages, as many as 40% of the protein on the viral envelope bends to the protein
peripheral blood monocytes, and cells in the lymph nodes, receptor, _______, on the surface of a target cell.
skin, and other organs also express measurable amounts of a. CD8
CD4 and can be infected by HIV. In addition, about 5% of b. CD4
B lymphocytes may express CD4 and be susceptible to c. p24
HIV infection. d. p26
• Transmission of HIV is believed to be restricted to
3. H
 IV can infect all of the following cells except:
intimate contact with body fluids from an infected person;
a. CD4+ subset of lymphocytes
casual contact with infected persons has not been docu-
b. Macrophages
mented as a mode of transmission.
c. Monocytes
• The early phase of HIV-1 infection may last months to
d. Polymorphonuclear leukocytes
years after initial infection. Typically, patients in the early
stages of HIV-1 infection are completely asymptomatic or 4. Th
 e most rapidly growing segment of the HIV-infected
show mild, chronic lymphadenopathy. HIV-1 causes a population is:
predictable progressive derangement of immune function; a. Homosexual males
AIDS is one late manifestation of that process. b. Lesbians
• Two to 10 years after HIV infection, replication of the c. Health care workers
virus flares again and the infection enters its final stage. An d. IV drug users and their sexual partners
average of 8 or 9 years may pass before AIDS is fully
5. I n HIV infections, a window period of seronegativity
developed. The virus behaves differently depending on the
extends from the time of initial infection up to:
host cell and its level of mitotic activity. The end stage of
a. 2 weeks
AIDS is characterized by neoplasms and opportunistic
b. 2 to 6 weeks or longer
infections.
c. 6 to 12 weeks or longer
• Immunologic activities associated with HIV-1 infection
d. 4 to 8 months or longer
include the production of different types of antibodies
against HIV-1. Some antibodies neutralize it, others 6 and 7. H
 IV antibodies are usually detected by (6)
prevent it from binding to cells, and others stimulate ___________
B and confirmed by (7) ___________.
C
cytotoxic cells to attack HIV-infected cells.
Possible answers for question 6:
• A window period of seronegativity exists from the time of
a. Latex agglutination
initial infection to 6 or 12 weeks or longer. Using EIA
b. Enzyme immunoassay
methods based on defined HIV-1 proteins produced by
c. Enzyme inhibition
recombinant DNA methods, antibodies specific for gp41
d. Radioimmunoassay
are detectable for weeks or months before assays specific
for p24. The appearance of antibodies specific for p24 Possible answers for question 7:
precedes that of anti-gp41 in Western blot serum a. Southern blot
specimens. b. Northern blot
• Laboratory evaluation of HIV-infected patients consists of c. Western blot
assessment of cellular and humoral components. Screening d. DNA hybridization
344 PART III Immunologic Manifestations of Infectious Diseases

8. Th
 e AIDS-causing virus HIV has also been referred to as: 20. A
 s AIDS progresses, the quantity of _______ diminishes
a. Human T-lymphotropic virus type III and the risk of opportunistic infection increases.
b. HTLV-III a. HIV antigen
c. Lymphadenopathy-associated virus (LAV) b. HIV antibody
d. All of the above c. CD4+ T lymphocytes
d. CD8+ T lymphocytes
9. H
 TLV-III was unique when it was isolated because it:
a. Is a bovine infectious retrovirus 21. Th
 e clinical symptoms of the later phase of AIDS are:
b. Is a canine infectious retrovirus a. Weight loss and decreased polymorphonuclear
c. Was identified as the cause of AIDS leukocyte (PMN) cells
d. Is a DNA containing virus b. Extreme weight loss and fever
c. Multiple secondary (opportunistic) infections
10-12. F
 ill in the blanks in the following table with the
d. Both b and c
correct letter, choosing from the following answers:
a. Codes for p24 and for proteins such as p17, p9, and 22. Th
 e most frequent malignancy observed in AIDS
p7 patients is:
b. Codes for two glycoproteins, gp41 and gp120 a. Pneumocystis jiroveci (P. carinii)
c. Produces DNA polymerase; produces endonuclease b. Kaposi’s sarcoma
c. Toxoplasmosis
Viral Genome Structural Components d. Non-Hodgkin’s lymphoma
Component Product 23. S
 ources of error in the Western blot test include:
pol 10. _______
C a. Concentration of HIV antigen
b. Presence of other infectious agents
gag 11. _______
A
c. Technical skill and experience of the technologist
env 12. _______
B performing the test
d. Age of the blood specimen
13-17. Arrange the HIV-1 life cycle events in proper order.
24. A
 ll the following methods have been developed to detect
13. _______
D a. R
 everse transcriptase converts viral
HIV-1 antigen except:
RNA into proviral DNA.
a. Transcriptase method
A
14. _______ b. N
 ew virus particles are produced as the b. Synthetic peptide approach
result of normal cellular activities of c. Immunofluorescence assay
transcription and translation. d. Immunohistochemical staining
E
15. _______ c. N
 ew particles bud from the cell 25. A
 ll the following methods have been developed to detect
membrane. the presence of HIV-1 viral gene except:
16. _______
B d. V
 irus attaches to CD4 membrane a. Radioimmunoassay
receptor and sheds its protein coat, b. In situ hybridization
exposing its RNA core. c. Southern blot analysis
17. _______
C e. P
 roviral DNA is integrated into the d. DNA amplification
genome (genetic complement of cell).
BIBLIOGRAPHY
American Association for Clinical Chemistry: Routine HIV testing in the ED
18. Th
 e criteria for HIV infection for persons 13 years of age catches unidentified cases, 2007, [Link]
or older include: 2007/august/ Pages/newsbrief_0807.aspx#.
a. Repeatedly reactive screening test for HIV antibody Baeten JM, et al: Antiretroviral prophylaxis for HIV prevention in heterosex-
b. Specific HIV antibody identified by use of supple- ual men and women, N Eng J Med 367:399–410, 2012.
Bayer R, Oppenheimer GM: Pioneers in AIDS care: reflections on the epi-
mental tests demic’s early years, N Engl J Med 355:2273–2278, 2006.
c. Direct identification of the virus Bio-Rad Laboratories: GS HIV Combo Ab/Ab EIA, product insert, 2011,
d. All of the above [Link].
Centers for Disease Control and Prevention: HIV in the United States: at a
19. A
 fter the early period of primary HIV infection, the glance, August 31, 2012, [Link]/hiv/resources/factsheets/PDF/
patient enters a period of clinical latency that lasts a HIV_at_a_glance.pdf. retrieved.
Cohen JK, Klausner JD: HIV testing update, 2011, [Link]
median of _______ years. [Link]/ features/201111/clinical-issues/[Link].
a. 5 Cohen MS, et al: Acute HIV-1 infection, N Engl J Med 364:1943–1954, 2011.
b. 10 Cohen MS, et al: Prevention of HIV-1, N Engl J Med 365:493–505, 2011.
c. 15 El-Sadr WM, et al: CD4+ count–guided interruption of antiretroviral treat-
ment, N Engl J Med 355:2283–2294, 2006.
d. 20 Gallo RC, Montagnier L: AIDS in 1988, Sci Am 259:40–51, 1988.

Common questions

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Antibodies against HIV-1 perform various roles, such as neutralizing the virus, preventing it from binding to host cells, and stimulating cytotoxic cells to attack HIV-infected cells . These antibodies contribute to controlling the virus by limiting its ability to replicate and spread within the host . In diagnosis, their presence is detected using EIA as a screening method and confirmed by the Western blot test, affirming HIV infection . Different antibodies target various viral proteins, such as gp41 and p24, providing essential markers for an accurate and timely diagnosis .

The 'window period' in HIV infection refers to the time from initial infection to when antibodies specific to HIV can be detected by standard testing methods . This period can last from 6 to 12 weeks or longer, during which a person might test negative despite being infected because the body has not yet produced enough antibodies to be detectable . This poses a significant challenge for early diagnosis and presents a risk of unknowingly transmitting the virus during this period . Enhanced testing methods and awareness of this window period are crucial for accurate diagnosis and prevention of transmission .

The HIV virus is composed of structural proteins and glycoproteins that inhabit the core and envelope regions of the viral particle . The virus consists of a single strand of positive-sense RNA that carries genetic information along with reverse transcriptase, essential for converting RNA into DNA . Glycoproteins, such as gp41 and gp120, enable the virus to attach to CD4+ receptors on host cells, facilitating entry and infection . These structural components are vital in the virus's ability to replicate, integrate into the host genome, and avoid immune detection, contributing to its pathogenicity .

HIV targets and destroys CD4+ T lymphocytes, leading to their progressive decline and a corresponding decrease in immune function . This depletion makes the body increasingly susceptible to opportunistic infections and certain cancers, which are hallmark features of AIDS . The virus's ability to replicate within and kill CD4+ cells underlies the gradual progression from initial HIV infection through clinical latency to AIDS . The quantity of CD4+ T lymphocytes is inversely related to disease severity and progression .

Common opportunistic infections associated with the end stages of AIDS include Pneumocystis jiroveci pneumonia and Kaposi's sarcoma . These occur due to the severe immune suppression caused by the depletion of CD4+ T lymphocytes, leaving the body vulnerable to infections that a normally functioning immune system would prevent or control . Other infections often observed are candidiasis, cytomegalovirus infection, and Mycobacterium avium complex . The reduced immune competency also increases susceptibility to various neoplasms and malignancies .

Reverse transcriptase in HIV is a special enzyme that converts viral RNA into DNA. This process is crucial for the virus because it allows the viral RNA to integrate into the host's genome, effectively making the host's cellular machinery produce viral components. This integration is a key step in the viral replication process and the persistence of the virus within the host . The enzyme's activity is significant since it provides a target for antiretroviral drugs, which aim to inhibit the transcription process and thus halt the proliferation of the virus .

HIV is primarily transmitted through intimate contact with body fluids from an infected person, such as blood, semen, vaginal fluids, and breast milk . Key transmission routes include unprotected sexual intercourse, sharing needles, transfusions of contaminated blood, and from mother to child during childbirth or breastfeeding . Casual contact, such as hugging, shaking hands, or sharing dishes, is not considered a risk because the virus cannot survive long outside the human body and is not transmitted through air, water, or casual touch .

The detection of HIV-1 antibodies is usually conducted using an Enzyme Immunoassay (EIA), which is a primary screening method . If the EIA is positive, the result is confirmed using a Western blot test, which looks for specific protein bands, such as p41 or p24, associated with HIV-1 . The Western blot is considered the standard for confirming HIV-1 seropositivity . Detection involves initial screening, whereas confirmation requires specific identification of viral proteins, ensuring the reliability of the diagnosis .

The replication rate of HIV varies throughout the infection. After initial exposure, there is often an early phase where the patient is asymptomatic, and viral replication may be relatively controlled . Over approximately 2 to 10 years, replication surges again, leading to the ultimate depletion of CD4+ T cells and progression to AIDS . This renewed viral replication coincides with a collapse in immune defenses, resulting in opportunistic infections and neoplasms characteristic of AIDS . The fluctuation in replication rates directly influences how quickly the disease progresses to its terminal stages .

HIV shows a marked preference for the CD4+ subset of lymphocytes. It can also infect macrophages and other cells expressing measurable amounts of CD4, such as some B lymphocytes . This targeting of CD4+ T cells leads to their progressive depletion. The depletion causes a significant derangement of immune function, impairing the body's ability to fight off infections and diseases, which eventually progresses to AIDS . This process culminates in an increased risk of opportunistic infections and neoplasms as AIDS develops .

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