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A graph with time on the X axis and two Y axes – CD4+ T  lymphocyte count (cells/mm cubed) and HIV RNA copies per ml plasma. The primary infection is set at time 0 when there is a high CD4 count (over 1000) and a low RNA count (near 0). During the first weeks -  macrophage infection, increase in virus production and HIV-1 reservoirs. At about 6 weeks – acute HIV syndrome, wide dissemination of virus, seeding of lymphoid organs. During this time the RNA count increases to about 10 to the 6 and the CD4 count decreases to about 500. From 9 weeks to about 12 weeks the CD4 count increases and the RNA count decreases. From 9 weeks to about 7 years is classic latency –  T-cell depletion/immune dysfunction and neurocognitive impairment.  During this time CD4 count steadily decreases to near 0 and RNA count steadily increases to over 10 to the 6.  Constitutional symptoms occur at about 8 years. After this, opportunistic diseases occur; HIV-D and HIVAN. Then death.
This graph shows the clinical progression of CD4 T cells (blue line), clinical symptoms, and viral RNA (red line) during an HIV infection. (credit: modification of work by Kogan M, and Rappaport J)

The initial diagnosis of HIV is performed using a serological test for antibody production against the pathogen. Positive test results are confirmed by Western blot or PCR tests. It can take weeks or months for the body to produce antibodies in response to an infection. There are fourth-generation tests that detect HIV antibodies and HIV antigens that are present even before the body begins producing antibodies. Nucleic acid tests (NATs) are a third type of test that is relatively expensive and uncommon; NAT can detect HIV in blood and determine the viral load.

As a consequence of provirus formation, it is currently not possible to eliminate HIV from an infected patient’s body. Elimination by specific antibodies is ineffective because the virus mutates rapidly—a result of the error-prone reverse transcriptase and the inability to correct errors. Antiviral treatments, however, can greatly extend life expectancy. To combat the problem of drug resistance, combinations of antiretroviral drugs called antiretroviral therapy (ART), sometimes called highly active ART or combined ART, are used. There are several different targets for antiviral drug action (and a growing list of drugs for each of these targets). One class of drugs inhibits HIV entry; other classes inhibit reverse transcriptase by blocking viral RNA-dependent and DNA-dependent DNA polymerase activity; and still others inhibit one of the three HIV enzymes needed to replicate inside human cells.

  • Why is it not yet possible to cure HIV infections?

Hiv, aids, and education

When the first outbreaks of AIDS in the US occurred in the early 1980s, very little was known about the disease or its origins. Erroneously, the disease quickly became stigmatized as one associated with what became identified as at-risk behaviors such as sexual promiscuity, homosexuality, and IV drug use, even though mounting evidence indicated the disease was also contracted through transfusion of blood and blood products or by fetuses of infected mothers. In the mid-1980s, scientists elucidated the identity of the virus, its mode of transmission, and mechanisms of pathogenesis. Campaigns were undertaken to educate the public about how HIV spreads to stem infection rates and encourage behavioral changes that reduced the risk for infection. Approaches to this campaign, however, emphasized very different strategies. Some groups favored educational programs that emphasized sexual abstinence, monogamy, heterosexuality, and “just say no to drugs.” Other groups placed an emphasis on “safe sex” in sex education programs and advocated social services programs that passed out free condoms to anyone, including sexually active minors, and provided needle exchange programs for IV drug users.

These are clear examples of the intersection between disease and cultural values. As a future health professional, what is your responsibility in terms of educating patients about behaviors that put them at risk for HIV or other diseases while possibly setting your own personal opinions aside? You will no doubt encounter patients whose cultural and moral values differ from your own. Is it ethical for you to promote your own moral agenda to your patients? How can you advocate for practical disease prevention while still respecting the personal views of your patients?

Viral diseases of the circulatory and lymphatic systems

Many viruses are able to cause systemic, difficult-to-treat infections because of their ability to replicate within the host. Some of the more common viruses that affect the circulatory system are summarized in [link] .

Table titled: Viral Diseases of the Circulatory and Lymphatic Systems. Columns: Disease, Pathogen, Signs and Symptoms, Transmission, Diagnostic Tests, Antimicrobial Drugs. AIDS/HIV infection; Human immunodeficiency virus (HIV); Flu-like symptoms during acute stage, followed by long period of clinical latency; final stage (AIDS) includes fever, weight loss, wasting syndrome, dementia, and opportunistic secondary infections leading to death; Contact with body fluids (e.g., sexual contact, use of contaminated needles); Serological tests for antibodies and/or HIV antigens; nucleic acid test (NAT) for presence of virus; Antiretroviral therapy (ART) using various combinations of drugs. Burkitt lymphoma; Epstein-Barr virus (human herpesvirus-4 [HHV-4]); Rapid formation of malignant B-cell tumors, oral hairy leukoplakia; fatal if not promptly treated; Contact with body fluids (e.g., saliva, blood, semen); primarily affects patients immunocompromised by HIV or malaria; CT scans, tumor biopsy; Intensive alternating chemotherapy regimen. Chikungunya fever; Chikungunya virus; Fever, rash, joint pain ; Transmitted between humans by Aedes aegypti and A. albopictus vectors; Viral culture, IFA, EIA, ELISA, PCR, RT-PCR; None. Cytomegalovirus infection; Cytomegalovirus (HHV-5); Usually asymptomatic but may cause non-Epstein-Barr mononucleosis in adults; may cause developmental issues in developing fetus; in transplant recipients, may cause fever, transplant rejection, death; Contact with body fluids, blood transfusions, organ transplants; infected mothers can transmit virus to fetus transplacentally or to newborn in breastmilk, saliva; Histology, culture, EIA, IFA, PCR; Ganciclovir, valganciclovir, foscarnet, cidofovir. Dengue fever (breakbone fever); Dengue fever viruses 1–4; Fever, headache, extreme bone and joint pain, abdominal pain, vomiting, hemorrhaging; can be fatal Transmitted between humans by A. aegypti and A. albopictus vectors; Serologic testing, ELISA, and RT-PCR; None. Ebola virus disease (EVD); Ebola virus; Fever, headache, joint pain, diarrhea, vomiting, hemorrhaging in gastrointestinal tract, organ failure; often fatal; Contact with body fluids (e.g., blood, saliva, sweat, urine, feces, vomit); highly contagious; ELISA, IgM ELISA, PCR, and virus isolation; None. Hantavirus pulmonary syndrome (HPS); Hantavirus; Initial flu-like symptoms followed by pulmonary edema and hypotension leading to pneumonia and shock; can be fatal; Inhalation of dried feces, urine from infected mouse or rat; ELISA, Western blot, RIBA, RT-PCR; None. Hemorrhagic fever with renal syndrome; Hantavirus; Fever, headache, nausea, rash, or eye inflammation, followed by hemorrhaging and kidney failure; can be fatal Inhalation of dried feces, urine from infected mouse or rat; ELISA, Western blot, RIBA, RT-PCR; None. Infectious mononucleosis; Epstein-Barr virus (HHV-4), cytomegalovirus (HHV-5); Pharyngitis, fever, extreme fatigue; swelling of lymph nodes, spleen, and liver; Contact with body fluids (e.g., saliva, blood, semen); Tests for antibodies to various EBV-associated antigens; None. Yellow fever; Yellow fever virus; Dizziness, fever, chills, headache, myalgia, nausea, vomiting, constipation, fatigue; moderate to severe cases may include jaundice, rash, mucosal, hemorrhaging, seizures, shock, and death; From monkeys to humans or between humans via Aedes or Haemagogus mosquito vectors; Culture, serology, PCR; None for treatment; preventive vaccine available.

Key concepts and summary

  • Human herpesviruses such Epstein-Barr virus (HHV-4) and cytomegalovirus (HHV-5) are widely distributed. The former is associated with infectious mononucleosis and Burkitt lymphoma, and the latter can cause serious congenital infections as well as serious disease in immunocompromised adults.
  • Arboviral diseases such as y ellow fever, dengue fever, and chikungunya fever are characterized by high fevers and vascular damage that can often be fatal. Ebola virus disease is a highly contagious and often fatal infection spread through contact with bodily fluids.
  • Although there is a vaccine available for yellow fever, treatments for patients with yellow fever, dengue, chikungunya fever, and Ebola virus disease are limited to supportive therapies.
  • Patients infected with human immunodeficiency virus (HIV) progress through three stages of disease, culminating in AIDS . Antiretroviral therapy (ART) uses various combinations of drugs to suppress viral loads, extending the period of latency and reducing the likelihood of transmission.
  • Vector control and animal reservoir control remain the best defenses against most viruses that cause diseases of the circulatory system.

Fill in the blank

________ is a cancer that forms in patients with HHV-4 and malaria coinfections.

Burkitt lymphoma

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________ are transmitted by vectors such as ticks or mosquitoes.

Arboviruses

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Infectious mononucleosis is caused by ________ infections.

Epstein-Barr virus

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Short answer

Describe the progression of an HIV infection over time with regard to the number of circulating viruses, host antibodies, and CD4 T cells.

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Describe the general types of diagnostic tests used to diagnose patients infected with HIV.

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Identify the general categories of drugs used in ART used to treat patients infected with HIV.

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Source:  OpenStax, Microbiology. OpenStax CNX. Nov 01, 2016 Download for free at http://cnx.org/content/col12087/1.4
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