AIDS-defining Diseases – Human Immunodeficiency Virus (HIV)

by Sean Elliott, MD

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    00:01 So, what are those opportunistic infections? And those are called, variably, opportunistic infections, AIDS-defining infections, or in this case, AIDS indicator diseases, and they are many.

    00:13 And they correlate with how immunosuppressed the patient is from the attack on the CD4 count.

    00:19 We'll start with bacterial infection, and these can be bacterial infections which normally have limited virulence, limited pathogenicity.

    00:29 For example, a nontuberculous or an atypical mycobacterium avium-intracellulare complex.

    00:37 This is known frequently as MAI or MAC -- Mycobacterium Avium Complex.

    00:43 Normally, this causes only rare disease occasionally in children causing chronic lymph nodes.

    00:49 But in patients with HIV, it can cause disseminated disease causing lung disease, pneumonia, enteric disease with exaggerated enteric lymph nodes.

    00:59 And it is typically seen when the patient is very immunosuppressed.

    01:02 Their CD4 count, not percentage, but number of CD4 cells per milliliter of < 50.

    01:09 Similarly, these patients can develop normal mycobacterium.

    01:13 Tuberculosis, extra pulmonary tuberculosis.

    01:16 They develop pneumococcal sepsis, salmonella sepsis, name the bacteria, and they can develop overwhelming disease from any of those.

    01:25 Viral infections especially are known to be cytomegalovirus and chronic or disseminated herpes simplex virus.

    01:33 So, too, as immune discovery wanes, they can be at risk for escalation or activation of JC virus causing progressive multi-focal leukoencephalopathy.

    01:44 Fungal infections, anything and everything.

    01:47 So, candidiasis, a very simple yeast.

    01:50 Candida which exists everywhere causes thrush in children who are nursing from perhaps a slightly infected breast.

    01:59 The candidiasis can be overwhelming, and it goes not just from the mouth, it's not just thrush in a patient with HIV, but it travels all the way down through the GI collecting system.

    02:09 Not just the esophagus, but including even intestine to where it can limit absorption.

    02:15 There can be pulmonary candidiasis.

    02:17 There can be anything and everything.

    02:20 Cryptococcal meningitis, that's a classic one.

    02:23 Cryptococcus is an environmental mold, which in most immunocompetent people doesn't do anything because we have enough enough immune discovery to limit that, and it's typically addressed by macrophages.

    02:37 But in an HIV patient with a CD4 count < 200, the ability to stimulate macrophages by interferon -- alpha and interferon gamma is limited, as we just talked about.

    02:48 Thus these patients are at risk for cryptococcal meningitis.

    02:51 Similarly, histoplasmosis, another fungal mold, pneumocystis jiroveci, which used to be known as pneumocystis carinii, PCP. It's now PJP.

    03:01 It is also unclear if it's a bacteria or a fungus, but it causes a diffuse interstitial pneumonia.

    03:08 All these are seen in patients who are starting to lose their CD4 count.

    03:13 Protozoal infections such as cryptosporidiosis, cerebral toxoplasmosis as the patient gets to a CD4 count < 100.

    03:22 And then they also can, develop due to lack of immune -- actually increased, I'm sorry -- immunotolerance, lack of immune discovery, they can develop cancers because the proliferating cells don't have any control due to an absence of natural killer cell function, CD8 cellular or cytotoxic function.

    03:42 And then, unrelated necessarily to the opportunistic infections, but still certainly quite common is HIV wasting syndrome.

    03:51 And there is a massive weight of research, pardon the pun, which has been aimed at trying to identify why patients with progressive HIV infection lose so much weight.

    04:02 And it's not just fat, but it's fat, muscle, you name it.

    04:06 So, how do we diagnose HIV infection? Well, there are many screening tests including fourth generation screening tests, basically all looking for evidence of specific antigens to HIV.

    04:19 And those are enough to at least get that first screening positive, but they need to be confirmed either by Western blot or far more commonly now, by PCR.

    04:29 Western blot is able to detect presence of antigens or even proteins specifically expressed by HIV, including the envelope proteins and some others, the specific ones that we've mentioned are produced by HIV.

    04:43 However, once the diagnosis is made, or to confirm the diagnosis, use of a reverse transcriptase PCR to give a quantitative estimate of how many RNA copies exist in the bloodstream is absolutely how we follow these patients.

    04:59 So, too, we'll look at the number and the percentage of CD4-positive T lymphocytes in the peripheral blood.

    05:05 Here's an important factor for use clinically Patients may have a low CD4 number if their total number of circulating white blood cells is low as well.

    05:16 It kind of makes sense.

    05:17 So it's far more sensitive look at the percentage of the lymphocytes which are CD4-positive or the percentage which are not When the percentage drops below 15%, 15%, that is when one is in trouble and can expect to have a specific targeting action on the CD4-positive T lymphocytes.

    05:37 Another way which is also quite sensitive is to look at the ratio between CD4-positive and CD8- positive T lymphocytes.

    05:45 Normally, in healthy individuals, that ratio is 2 -- 2:1.

    05:51 In somebody with active HIV infection or active retroviral attack on the CD4 cell, that ratio typically drops to 0.5 -- 1:2.

    06:01 It's a significant difference and it's quite sensitive.

    06:05 Treatment.

    06:06 Treatment, historically, was initiated only when the patient developed AIDS-defining illnesses or opportunistic infections.

    06:15 However, now due to a wealth of research, it's far more expedient, far more successful to start treatment as soon as the diagnosis is made.

    06:25 So, at the very least, we will start treatment with the patient, you know, strongly advise them to start treatment when their CD4 count drops below 500, which is the indication of first trouble.

    06:37 And you see here that one can start with AZT, a reverse transcriptase inhibitor in combination with lamivudine or a non- nucleoside reverse transcriptase inhibitor.

    06:49 Those are 2 possible ways to prevent transmission from an infected mother to the baby.

    06:55 However, those 2 drugs by themselves will not be sufficient to treat HIV anymore.

    07:00 Although, historically, we started with just that; AZT and another NRTI -- nucleoside reverse transcriptase inhibitor.

    07:08 Instead, now, we start with highly active antiretroviral therapy, which can be several of the different types of retroviral medications in combination, typically including 1-2 protease inhibitors, and 1-2 nucleotide or non-nucleotide reverse transcriptase inhibitors in combination, many times, with integrase or sometimes some other anti-envelope proteins.

    07:36 So, the ideal combination remains to be completely described, but there are many which are exactly perfect.

    07:45 That is what we know.

    07:46 There's actually a lot more, but not time in this session to talk about for HIV infection.

    07:51 But let's look briefly at human T lymphotropic virus type 1, or HTLV type 1.

    07:58 The primary target, just as it was for HIV, is the CD4 T lymphocyte and secondarily, neurons when they become inflamed.

    08:06 This virus also carries a protein which can upregulate both interleukin-2 production and interleukin-2 receptors, which is a way to further stimulate the CD4 T lymphocyte production.

    08:20 So, it increases and actually in an uncontrolled fashion, proliferation of the T lymphocytes.

    08:28 Those proliferating T lymphocytes then develop chromosomal aberrations because normal mutations occur, unfortunately, quite frequently in human body.

    08:37 And when one gets the proper accumulation of chromosomal aberrations, those cells become leukemic.

    08:44 So we are talking a pre-malignant virus by doing its targeting action on CD4 cells and then upregulating their function.

    08:53 So, adult T cell leukemia/lymphoma which is a direct result of this process will generate cells such as you see in front of you, which looks as a flower or a violet, as has been suggested.

    09:06 And it's a circulating malignant cell, which can be found anywhere: bone lesions, lymph nodes, in the skin, etc., and is typically associated with hypercalcemia as a sign of increased cell turnover, or proliferation.

    09:21 Acutely, this illness is lethal within 1 year, as would be many other hematologic malignancies without intervention.

    09:29 Even in chronic form, it's similar to a non-Hodgkin lymphoma, which means a long array of chemotherapy agents and support.

    09:38 So, this is a very concerning section.

    09:42 The retroviruses have significant morbidity and mortality associated with them because they target a critical part of human immune architecture And they do so in a very difficult, challenging, hard-to-treat way.

    09:55 So, look for more information on this subject coming.

    09:58 We have a long ways to go to try and end the intervention or end the impact of the retroviruses.

    About the Lecture

    The lecture AIDS-defining Diseases – Human Immunodeficiency Virus (HIV) by Sean Elliott, MD is from the course Viruses.

    Included Quiz Questions

    1. ...50.
    2. ...100.
    3. ...200.
    4. ...150.
    5. ...250.
    1. 100
    2. 500
    3. 300
    4. 200
    5. 50
    1. RT-PCR
    2. ELISA
    3. Western blot
    4. CD4 T cells in peripheral blood
    5. CD4/CD8 T cell ratio
    1. When CD4 count falls below 500
    2. When CD4 count falls below 800
    3. When CD4 count falls below 700
    4. When CD4 count falls below 600
    5. When CD4 count falls below 1000
    1. Hypercalcemia
    2. Hypocalcemia
    3. Hyperkalemia
    4. Hypokalemia
    5. Hypomagnesemia

    Author of lecture AIDS-defining Diseases – Human Immunodeficiency Virus (HIV)

     Sean Elliott, MD

    Sean Elliott, MD

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