This episode of CRACKCast covers Rosen’s Chapter 124 (9th Ed.), HIV/AIDS. Next time you look after an HIV/AIDS patient on shift, this episode will have you covered!
Shownotes – PDF Here[bg_faq_start]
Rosen’s In Perspective
Box 124.2: Dermatologic and Mucocutaneous Manifestations of WHO Stage 4 HIV Disease
- Chronic herpes simplex virus ulcers
- Extrapulmonary tuberculosis
- Kaposi’s sarcoma
- Extrapulmonary cryptococcosis
- Disseminated mycosis
- Atypical disseminated leishmaniasis
- Disseminated nontuberculous mycobacterial infection
- Extrapulmonary cryptococcosis including meningitis
Box 124.3: Cutaneous Findings Highly Suggestive of HIV Disease
- Any WHO criteria for stage 4 HIV disease
- Facial molluscum in an adult
- Proximal subungual onychomycosis
- Herpes zoster scarring
- Oral hairy leukoplakia
- Bacillary angiomatosis
- Widespread dermatophytosis
- Severe seborrheic dermatitis
See Figure 124.4 for a graphic representation of the natural history of untreated HIV.
 Define AIDS
CDC definition: “a CD4+ cell count below 200 cells/μL or the presence of an AIDS-defining condition.”
At this level, immune dysfunction is severe and, without ART, survival is short. Those with a CD4+ cell count below 50 cells/μL have advanced AIDS and are at much higher risk for death and development of opportunistic infections. Some infections are so common in patients with AIDS that primary prophylaxis is indicated and is cost-effective. Prophylaxis is started for PCP when CD4+ counts are less than 200 cells/μL, for toxoplasmosis, when CD4+ counts are less than 100 cells/μL and, for Mycobacterium avium complex (MAC) infection, when CD4+ counts are less than 50 cells/μL (Table 124.2).
 List 5 risk factors for HIV / AIDS
- Contact with semen, blood, vaginal secretions, and breast milk of viremic individuals
- These fluids must come into contact with damaged tissue / mucous membrane / entry into bloodstream.
- HIV-positive blood transfusion MOST COMMON
- exposure to serum with a high viral load
- lack of male circumcision
- presence of an ulcerative, sexually transmitted infection.
- Type of sexual contact:
- 1% to 30% for receptive anal intercourse
- 0.1% to 10% for receptive vaginal and insertive anal intercourse
- 0.1% to 1% for insertive vaginal intercourse.
After transmission, the virus replicates in the mucosal surface or lymphoid tissue at the site of entry in lymphocytes and macrophages. If enough cells are infected, the virus spreads to draining lymph nodes and infection is established, usually within 48 to 72 hours.
 List 10 AIDS defining conditions
Box 124.1 – AIDS-Defining Conditions
- Bacterial infections, multiple or recurrent
- Candidiasis of bronchi, trachea, or lungs
- Candidiasis of esophagus
- Cervical cancer, invasive
- Coccidioidomycosis, disseminated or extrapulmonary
- Cryptococcosis, extrapulmonary
- Cryptosporidiosis, chronic intestinal (>1 mo duration)
- Cytomegalovirus disease (other than liver, spleen, or nodes), onset at age >1 mo
- Cytomegalovirus retinitis (with loss of vision)
- Encephalopathy, HIV related
- Herpes simplex: chronic ulcers (>1 mo duration) or bronchitis, pneumonitis, or esophagitis (onset at age >1 mo)
- Histoplasmosis, disseminated or extrapulmonary
- Isosporiasis, chronic intestinal (>1 mo duration)
- Lymphoma, Burkitt’s (or equivalent term)
- Kaposi’s sarcoma
- Lymphoma, immunoblastic (or equivalent term)
- Lymphoma, primary, of brain
- Mycobacterium avium complex or Mycobacterium kansasii,disseminated or extrapulmonary
- Mycobacterium tuberculosis of any site, pulmonary, disseminated, or extrapulmonary
- Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
- Pneumocystis jiroveci pneumonia
- Pneumonia, recurrent
- Progressive multifocal leukoencephalopathy
- Salmonella septicemia, recurrent
- Toxoplasmosis of brain, onset at age >1 mo
- Wasting syndrome attributed to HIV
Think head to toe and start listing conditions
 Describe 3 serum tests for HIV
- HIV Serology. A screening CBC and CD4 count are the place to start, but you still need to send for serology!!!
- Absolute lymphocyte count between 1000 and 2000 cells/µL appears to correlate with immunosuppression
- CD4 count below 200!
Table 124.1: HIV Testing by Laboratory Stage
|STAGE||LABORATORY MARKER||HIV STAGE|
|RNA||p24 Antigen||Third-Generation Antibody (EIA)||Western Blot|
|1||+||−||−||−||Acute HIV infection|
|2||+++||+||−||−||Acute HIV infection|
|6||+–+++||+/−||+||+||Chronic HIV infection (all Western blot bands are positive, older antibody tests react)|
|EIA, Enzyme immunoassay.|
 List 6 causes of respiratory infection in HIV?
TABLE124.3 Differential Diagnosis of Respiratory Infections in HIV-Infected Patients by CD4+ Count
|CD4+ COUNT AND STAGE||DIFFERENTIAL DIAGNOSIS|
|Present at any stage||Acute bronchitis|
|>500 cells/µL||Bacterial pneumoniaa|
|Early HIV infection||PCPa|
|HHV-8–related Kaposi’s sarcoma|
|200–500 cells/µL||Bacterial pneumoniaa|
|<200 cells/µL||Bacterial pneumoniaa (consider bacteremia)|
|Histoplasma capsulatum or Coccidioides immitispneumonia|
|Cryptococcus neoformans pneumonia|
|Extrapulmonary or disseminated tuberculosisa|
|≤50 cells/µL||Bacterial pneumoniaa|
|Advanced HIV infection||PCPa|
|Toxoplasma gondii pneumonia|
|Pulmonary Kaposi’s sarcoma|
|Histoplasma capsulatum or Coccidioides immitispneumonia|
|Mycobacterium avium complex pneumonia|
|HHV-8, Human herpesvirus 8; PCP, Pneumocystis jiroveci pneumonia.|
See Table 124.4 for the pulmonary manifestations of disease in HIV patients.
 Describe the presentation and treatment of PCP pneumonia
- Gradual onset non productive cough / dyspnea / fever >2weeks
- Typical CD4 < 200
- Hypoxia w/ exercise (walk test)
- Elevated LDH
- CXR – bilateral retic / intersitial pattern (aka bat wing)
- CT Chest – ground glass
See figures 124.5 and 124.6 for x-ray and CT images of Pneumocystis pneumonia.
TABLE124.5 Treatment of Pneumocystis jiroveci Pneumonia in Patients with HIV Infection
|SEVERITY OF ILLNESS||PREFERRED THERAPY||ALTERNATIVE THERAPY|
|Moderate to severe||TMP-SMX, IV; switch to oral administration after clinical improvement|
Primaquine + clindamycin
|Mild to moderate||TMP-SMX||Dapsone + trimethoprim|
Primaquine + clindamycin
 Describe an approach to diagnosis and management of CNS infection in AIDS
Any HIV/AIDS patient w/ headaches, abnormal neuro exam, change in mental status needs labs, cultures, imaging and CSF sampling.
Imaging: CT with Contrast
- cryptococcal meningitis
- primary central nervous system (CNS) lymphoma
- progressive multifocal leukoencephalopathy
- Cryptococcal meningitis
See Table 124.6 for an extended list of causes.
- ART is first line!
- Chemo for lymphoma
- amphotericin B and flucytosine for Crypto
- pyrimethamine and sulfadiazine for toxoplasma
- Careful with steroid use and false negatives for CNS lymphoma
 List 5 causes of odynophagia in HIV
Esophagitis is common in HIV/AIDS, think about it especially in patients with CD4 <100
- Herpes simplex virus
- Deep aphthous ulcers
- Kaposi Sarcoma
 List 6 causes of diarrhea in the HIV patient
- Clostridium difficile
- Yersinia spp
 Describe HAART therapy
Taken from UpToDate
“OVERVIEW OF HIV REPLICATION — The life cycle of HIV can be broken down into 6 steps: (1) entry (binding and fusion), (2) reverse transcription, (3) integration, (4) replication (transcription and translation), (5) assembly, and (6) budding and maturation. The identification and understanding of these processes have provided the basis for antiretroviral drug discovery.
- Entry – Entry inhibitors: Maraviroc and enfuvirtide are antiretroviral agents that inhibit binding and fusion, respectively. However, these agents are not commonly used for the treatment of HIV infection.
- Reverse transcription – Nucleoside reverse transcriptase inhibitors (NRTIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) inhibit the process of reverse transcription. There are several agents in each of these classes that are widely used for the treatment of HIV.
- Integration – Integrase strand transfer inhibitors (INSTIs) inhibit the process of integration. In many countries, INSTIs are considered the preferred third agent (in combination with two nucleoside analogues) for treatment-naïve individuals.
- Replication – There are no antiretroviral agents that inhibit this step of the replication cycle.
- Assembly – There are no antiretroviral agents that inhibit this step of the replication cycle.
- Budding and maturation – Protease inhibitors are antiretroviral agents that inhibit the HIV protease enzyme, and therefore, prevent this final step in the replication cycle.
See figure 124.3 for a visual representation of the HIV replication cycle.
 Describe prophylaxis of opportunistic infections
|CD4 count||Opportunistic Infection||Treatment|
|<200||PCP / PJP||Trimethoprim-Sulfamethoxazole DS x 1 tab daily|
|<100||Toxoplasmosis||Trimethoprim-Sulfamethoxazole DS x 1 tab daily|
|<50||Mycobacterium Avium Complex||Azithromycin / other macrolides|
 Risk stratify exposure to healthcare associated HIV and non-healthcare associated HIV.
Healthcare Associated Exposures
Needle stick injuries less than 1/300 get HIV. No recorded cases from intact skin.
Look at MDCalc Needle Stick
Factors increasing risk for needlestick injuries:
- depth of injury
- injury from a device visibly contaminated with the patient’s blood
- needle stick into a vein or artery
Bodily fluids of concern include –
- Semen / vaginal secretion / any fluid contaminated with visible blood
- Potentially infectious body fluids include CSF / synovial / pleural / peritoneal / pericardial / amniotic
- NO CONCERN: vomitus, feces, nasal secretions, saliva, sputum, sweat, tears, and urine
- solid needles (eg, suture needles)
- Superficial injuries
- low-risk source patient or body fluid
- mucocutaneous exposures
High-risk injuries: include those involving
- hollow bore needles with visible blood
- percutaneous injury from a needle that was in an artery or vein of the source patient
- Mucocutaneous exposure involves large volumes of blood from a source patient with a plasma HIV viral load more than 1500 copies/µL,. Transmission is estimated to be as low as 0.09% (1/1000) for a splash of infectious body fluid to mucous membranes or broken skin.
Non-Healthcare Associated Exposures
Possible exposure include
- sexual contact
- injection drug use,
- body fluids contact through broken skin or mucous membranes.
High risk exposures:
- receptive anal intercourse
- presence of genital ulcerative disease
- receptive vaginal intercourse and insertive vaginal intercourse
- IVDU w/ contaminated needle
*See shownotes for additional notes on PEP (post-exposure prophylaxis)
 What is Coccidiomycosis?
- Valley Fever!!! Fungal infection usually causing respiratory illness, possible extra-pulmonary disease as well
- Think about in HIV/AIDS snowbirds (traveling patients) that visit the southwestern USA
 Name common ART agents and their adverse effects
|ART Drug Class||Adverse effects|
|local cutaneous reactions|
|NUCLEOSIDE/NUCLEOTIDE REVERSE TRANSCRIPTASE INHIBITORS (NRTIS)|
Eg Tenofovir disoproxil fumarate
|Mitochondrial toxicity: manifest as peripheral neuropathy, pancreatitis, lipoatrophy, and/or hepatic steatosis. “black box” warnings for lactic acidosis|
|NON-NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS (NNRTIS)||(efavirenz and rilpivirine) can result in neurologic and psychiatric side effects.|
|INTEGRASE STRAND TRANSFER INHIBITORS (INSTIS)|
|insomnia and dizziness / depression / suicide|
|PROTEASE INHIBITORS (PIS)|
|insulin resistance, hyperglycemia, diabetes, hyperlipidemia, lipodystrophy, hepatotoxicity, bleeding in patients with hemophilia, and PR interval prolongation|
This post was uploaded and copyedited by Owen Scheirer (@OwenGregg1)