AH314-Pathophysiology
Case Study #1
HIV
M.L. is a 26-year-old homosexual man admitted to the hospital for progressive respiratory
distress, fever, weakness, and chronic diarrhea. He tested HIV positive about 3 years ago, but his
infection has remained asymptomatic until 2 months prior to admission. Pneumocystis jiroveci
(carinii) pneumonia was suspected and confirmed by culture. Laboratory analysis demonstrates a
low CD4+ count of 185 cells/ml. HAART treatment with the antiretrovirals azidothymidine
(AZT), efavirenz (Sustiva), and ritonavir (Norvir) was started 2 months ago.
A medical student wants to discuss the pathophysiology of HIV with you and asks you to explain
the mechanism of intracellular infection and the role of reverse transcriptase. What would you
explain about the process? (4 points; Describe the steps in the process of infection.)
HIV stands for human immunodeficiency virus, which is a disease that suppresses the immune
system. This means that the immune system both works against itself as well as decreases an
immune response from foreign pathogens. HIV is a bloodborne infection and it can be
transmitted through various methods, including IV drug use, sexual activity, blood, and
maternal-child transmission. Per Huether et al. (2020), HIV is a retrovirus that carries genetic
information as two identical copies of single-stranded RNA. This RNA is transmitted through a
capsid which also contains protease, integrase, and reverse transcriptase. The capsid is then
encased in an envelope which is labeled glycoprotein 120 (gp120), connected to transmembrane
glycoprotein 41 (gp41). HIV begins its infectious process by attaching to dendritic cells, which
carry the virus into the lymph nodes, where it infects the Th lymphocyte (Huether et al., 2020).
The virus will attach itself to the Th lymphocyte and the dendritic cells by the binding of gp120
and CD4 molecules, and to further attach itself, it will bind to chemokine coreceptors. On
dendritic cells and macrophages, the coreceptor is CCR5, and on T-helper cells, it is CCR4. To
enable the virus to bind to the cellular membrane, it is necessary that the bound gp120 and CD4
molecule change to allow gp41 to attach with the target cell. Now that the fusion of the viral
envelope and the cellular membrane is complete, the capsid containing the HIV RNA is released
into the target cell cytoplasm. Once released, the enzyme HIV reverse transcriptase will then
convert the HIV RNA into dsDNA. Along with the HIV integrase, the newly converted DNA is
inserted into the target cell’s genetic material. Next begins the step of transcription and
translation which produces a long strand of viral components, and HIV protease processes this.
Then the creation of the virion core follows (Huether et al., 2020). Finally, the HIV core will
form and release new virions. Per Huether et al. (2020), as the virus grows, it takes some host
cell membrane with it, thus making the virus less vulnerable to adaptive immune attack. These
new virions will go on to infect mature Th cells, bone marrow precursor cells, and lymphoid
cells in the GI tract. The immune system will then send T cytotoxic cells to target the infected
cells, which decreases the amount of Th cells in the body. Due to the virions also targeting the
bone marrow cells, the Th cells cannot be replaced by the bone marrow or thymus. Thus causing
immunosuppression. The HIV virus can also stay dormant in the body for prolonged periods if
the target cell is dormant. New virions can be made at a later time if the cell becomes active.
M.L.’s mother is concerned about the potential for catching HIV from her son. What can you tell
her about the risk factors and transmission of HIV, and how she might protect herself from
infection? (6 points; List 6 interventions to protect the mother.)
M.L.’s mother would need to be informed that HIV is only transmitted in certain ways. HIV is a
bloodborne infection so it can be transmitted through blood or blood products, IV drug abuse,
sexual activity, and maternal-child transmission before or during birth (Huether et al., 2020). She
should be advised to take special precautions to avoid contact with M.L’s blood. Cowgill et al.
(2008) report that families in their research set household rules and maintained a clean house.
They state, “precautions were also taken when someone was cut; children were taught to avoid
parents when they were bleeding until the injury was properly cleaned and dressed”. Another
tool that the researchers identified was that children in the family were taught “…not to use their
parents' toothbrushes or razors and not to share food or drink from the parent's cup” (Cowgill et
al. 2008). M.L’s mother could use these rules of keeping her items completely separate from
M.Ls to avoid any issue. She also can be informed that HIV cannot be transmitted through
hugging or kissing, and so she does not need to limit these behaviors. To summarize,
interventions she can take are keeping a clean house, not sharing razors, not sharing
toothbrushes, not sharing food or drink with the same utensils, not assisting with bleeding
injuries, and allowing M.L. to clean the blood following the injury as to avoid incidence.
What is the significance of the CD4+ count? (2 points; Discuss the meaning of various ranges of
CD4 counts.)
In the early stages of infection, the acute phase, the virus infects CD4+/Th cells, bone marrow
precursor cells, and lymphoid cells. The immune system will then send T cytotoxic cells to target
the infected cells. This attack decreases the amount of CD4+/Th cells in the body. The patient
may have mild, flu-like symptoms in this stage, but they usually resolve. In the clinical latency
phase, the virus will continue replicating and destroying the T cells, but the HIV-infected
individual will remain asymptomatic. Per Schneider et al. (2008), at the first stage, the CD4+
count is at least 500 cells/ microliter. Equally so, the percentage of CD4+ cells at this stage is
29% of lymphocytes. At this initial stage, the patient may develop acute symptoms of a mild
viral infection, but nothing severe. At stage 2 of the infection, the CD4+ levels have continued to
decrease. Schneider et al. attest, the CD4+ cell count is 200-499 or the percentage is 14-28% of
lymphocytes. The patient is still unlikely to be exhibiting any malignancies or severe infections.
At stage 3, this is typically when the CD4+ cell count is critically suppressed and HIV transitions
to AIDS. The patient is at risk for opportunistic infections and cancers and their CD4+ levels are
<200, and the percentage is less than 14% of lymphocytes. The average time for progression of
AIDS without treatment is ~10 years.
P. jiroveci pneumonia is an opportunistic infection to which immunocompetent people are
immune. What other opportunistic infections are commonly seen in AIDS patients? Are there
any data to suggest that M.L. may have one of these? (6 points; List 5 opportunistic infections
AND describe data to suggest whether or not M.L. has such an infection.)
Due to M.L.’s low CD4+ count of 185, he would have progressed to the AIDS stage of HIV
infection. He is now in a severely immunocompromised state, exposing him to potential
opportunistic infections. With his current symptoms, M.L. could be experiencing a wide variety
of illnesses.
● Mycobacterium Avium Complex (MAC): This infection is caused by different
mycobacterium. MAC typically affects the lungs but may be disseminated throughout the
body. Per Genetic and Rare Diseases Information Center (GARD), (2018), the common
symptoms of this illness include fever, fatigue, diarrhea, shortness of breath, and
abdominal pain. As M.L. has presented with respiratory distress, weakness, fever, and
diarrhea, his symptoms fall in line with this illness. MAC typically affects the lungs, but
may be disseminated throughout the body.
● Cystoisosporiasis: This infection is caused by a parasite Cystoisospora belli, which is
able to enter the body through contaminated food or water. The symptoms of this
infection is mainly watery diarrhea, although patients can also have abdominal pain,
fatigue, and fever, per the CDC (2020). Those with AIDS can potentially have prolonged
illness with this infection. As M.L. has the symptoms of chronic diarrhea, weakness, and
fever, this infection could be a likely cause.
● Cryptococcis: This infection is caused by a fungus called Cryptococcus neoformans. This
fungus usually comes into the body through the lungs and causes pneumonia. Typically,
this illness will only affect the lungs, but with the immunocompromised, this infection
can be diffuse and affect many body systems. Per NORD (2007), those with HIV can
experience fevers, GI issues, fatigue, and more. Due to M.L.’s symptoms, he could
potentially be infected with this infection.
● Cytomegalovirus (CMV): This infection is viral in nature and is a common illness. In
those with typical immune systems, this illness will be taken care of easily. Those with
compromised immune systems like HIV, however, can experience a multitude of
symptoms. This virus can infect the lungs causing pneumonia, can affect GI causing
gastroenteritis, and can even affect the brain causing encephalitis. The symptoms that
M.L. has align with the issues this virus can cause and he could potentially be infected
with CMV.
● Cryptosporidiosis (Crypto): This infection is a diarrheal disease. It is caused by a parasite
called Cryptosporidium. This parasitic infection affects the GI tract and its main
symptom is chronic watery diarrhea. Although M.L. has additional symptoms than just
diarrhea, his chronic diarrhea and the infection, in addition to his immunosuppressed
state, could allow for additional symptoms of sepsis-like fever, weakness, and respiratory
distress. This could be true especially if this chronic diarrhea is not allowing him to keep
hydrated and depleting his nutrition.
M.L.’s sexual partner recently tested negative for HIV. What conclusions can be made about his
HIV status? (2 points; Discuss the 2 possible conclusions regarding the partner’s HIV status.)
With a negative test, M.L.’s partner has two potential scenarios that would have procured this
result. The first option would be that the partner’s HIV is still in its window period. This means
that he is currently in a period of time between his HIV exposure and when a test can detect HIV.
So if he is tested within this period, the test would be negative. His viral load is not high enough
for the test to pick up the virus in his system.
The second option is that he has not contracted HIV and has taken appropriate cautionary
measures to protect himself. Per CDC (2018), HIV is not necessarily transmitted with each
sexual encounter. Also, his partner could be taking precautions such as wearing a condom for
each sexual engagement, taking antiretroviral (ART) medications, or utilizing options like
preexposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP).
References
About Cytomegalovirus and Congenital CMV Infection | CDC. (n.d.). Centers for Disease
Control and Prevention. Retrieved March 25, 2022, from
https://www.cdc.gov/cmv/overview.html
Cowgill, B. O., Bogart, L. M., Corona, R., Ryan, G., & Schuster, M. A. (2008). Fears About HIV
Transmission in Families With an HIV-Infected Parent: A Qualitative Analysis. Pediatrics, 5,
e950–e958. https://doi.org/10.1542/peds.2008-0390
Cryptococcosis - NORD (National Organization for Rare Disorders). (n.d.). NORD (National
Organization for Rare Disorders). Retrieved March 25, 2022, from https://rarediseases.org/rarediseases/cryptococcosis/
Mycobacterium Avium Complex infections
| Genetic and Rare Diseases Information
Center (GARD) – an NCATS Program. (n.d.). Genetic and Rare Diseases Information Center
(GARD) – an NCATS Program | Providing Information about Rare or Genetic Diseases.
Retrieved March 25, 2022, from https://rarediseases.info.nih.gov/diseases/7123/mycobacteriumavium-complex-infections
Opportunistic Infections | Living with HIV | HIV Basics | HIV/AIDS | CDC. (n.d.). Centers for
Disease Control and Prevention. Retrieved March 25, 2022, from
https://www.cdc.gov/hiv/basics/livingwithhiv/opportunisticinfections.html
Revised Surveillance Case Definitions for HIV Infection Among Adults, Adolescents, and
Children Aged <18 Months and for HIV Infection and AIDS Among Children Aged 18 Months
to <13 Years --- United States, 2008</FONT>. (n.d.). Centers for Disease Control and
Prevention. Retrieved March 25, 2022, from
https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5710a1.htm
Understanding HIV Test Results | HIV.gov. (2018, May 14). HIV.Gov. https://www.hiv.gov/hivbasics/hiv-testing/learn-about-hiv-testing/understanding-hiv-test-results