HIV - Microbiology - Medbullets Step 1

Snapshot
- A 27-year-old man presents to the urgent care clinic with a 2-week history of fever, macular rash, and generalized lymphadenopathy. He denies a sore throat, genital ulcers, or urethral discharge. Sexual history is remarkable for having unprotected sex with both male and female partners while inconsistently using condoms. His last sexual encounter was a month prior to the onset of illness. His fourth-generation combination HIV-1/2 immunoassay is positive, and an HIV-1/HIV-2 antibody differentiation immunoassay confirms the diagnosis.

Introduction
- Classification
  - a Lentivirus from the Retroviridae family
    
    an enveloped, single-stranded, positive-sense RNA retrovirus
- Epidemiology
  - incidence
    
    most commonly transmitted by sexual intercourse or sharing needles
  - HIV-2 is endemic to West Africa
- Transmission
  - sexual intercourse
  - sharing needles
  - vertical transmission from the mother to the fetus
- Microbiology
  - genes
    
    env gene leads to the production of gp160, which is cleaved to produce gp120 and gp41
    
    gp120 attaches to the patient's CD4+ T-cells
    
    gp41 leads to fusion and entry into the immune cell
    
    gag gene leads to the production of p24 and p17
    
    p24 - viral capsid
    
    p17 - viral matrix proteins
    
    pol gene leads to the production of
    
    reverse transcriptase
    
    aspartate protease
    
    integrase
- Pathogenesis
  - HIV attaches to the surface of CD4+ T-cells, along with either CXCR4 or CCR5 coreceptor binding
    
    HIV enters the cell, uncoats, and its RNA genome is reverse transcribed (by reverse transcriptase) into DNA
    
    it integrates into the host's genome, creating billions of viral particles, lysing the host cell, and releasing the viral particles into the bloodstream infecting other CD4+ T-cells
- Associated conditions
  - opportunistic infections
  - malignancy
  - cognitive decline
  - cardiovascular disease
- Prognosis
  - high mortality rate (> 90%) in untreated patients

Presentation
- Symptoms/physical exam
  - acute retroviral syndrome
    
    fever
    
    lymphadenopathy
    
    sore throat
    
    rash
    
    myalgia/arthralgia
    
    weight loss
    
    mucocutaneous ulcers

Studies
- HIV serology
  - fourth-generation combination HIV-1/2 immunoassay
    
    best initial test
    
    detects both
    
    HIV-1 and HIV-2 antibodies
    
    HIV p24 antigen
    
    approximate time frame for positive test post-infection: 15-20 days
    
    interpretation
    
    if negative
    
    the patient is HIV-negative and no further test is needed
    
    if positive
    
    perform an HIV-1/HIV-2 antibody differentiation immunoassay
    
    confirms the diagnosis
    
    determines if the patient is infected with HIV-1, HIV-2, or both viruses
    
    if the differentiation immunoassay is negative or indeterminate
    
    perform a viral load
- Viral load (qRT-PCR)
  - used to determine the
    
    amount of virus the patient has
    
    response to antiretroviral therapy
  - a high viral load is associated with a poor prognosis
  - approximate time frame for positive test post-infection: 10-15 days
- CD4+ T-cell count and percentage
  - used to determine
    
    need for prophylactic medication to prevent the development of opportunistic infections
    
    response to antiretroviral therapy
- HIV genotyping
  - used to determine HIV mutations that can lead to antiretroviral drug resistance

Opportunistic Infections

Opportunistic Infection Based on CD4+ T-Cell Count
CD4+ Count	Opportunistic Infection	Findings	Prophylactic Treatment
< 500mm3	Candida albicans	Oral thrush that is scrapable Pseudohyphae on microscopy	-
	Epstein-Barr virus	Oral hairy leukoplakia not scrapable
	HHV-8	Kaposi sarcoma a palpable, nonpruritic lesion that is brown, pink, red, or violaceous in color
	HPV	Squamous cell carcinoma anus (in men who have sex with men) cervix
< 200mm3	Histoplasma capsulatum	Nonspecific findings fevers, night sweats, chills, and weight loss dyspnea nausea and vomiting Macrophages contain oval yeast cells	-
	JC virus reactivation	Progressive multifocal leukoencephalopathy demyelinating disease of the central nervous system	-
	Pneumocystis jirovecii	Pneumonia ground-glass opacity on chest radiography	Trimethoprim-sulfamethoxazole if contraindicated, can give dapsone, atovaquone, or pentamidine
	Cryptosporidium parvum	Watery diarrhea	Nitazoxanide
< 100mm3	Aspergillus fumigatus	Hemoptysis Pleuritic chest pain	-
	Bartonella henselae	Bacillary angiomatosis angiomatous skin lesions	-
	Candida albicans	Esophagitis white plaques may appear on endoscopy	-
	Cytomegalovirus	Retinitis Esophagitis Colitis Pneumonitis Encephalitis Linear ulcers on endoscopy Fundoscopy may demonstrate cotton-wool spots Intranuclear inclusion bodies (owl eyes)	-
	Cryptosporidium spp.	Watery diarrhea Stool studies will show acid-fast oocysts	-
	Ebstein-Barr virus	B-cell lymphoma Central nervous system lymphoma	-
	Mycobacterium avium-intracellulare	Non-specific findings fever night sweats weight loss lymphadenitis	The goal is to initiate antiretroviral therapy as soon as possible Azithromycin
	Toxoplasma gondii	Ring-enhancing brain abscesses	Trimethoprim-sulfamethoxazole if contraindicated, give dapsone, pyrimethamine, and leucovorin in the presence of ring-enhancing lesions, treat with pyrimethamine

Differential
- Influenza infection and immunosuppression caused by medications
  - differentiating factor
    
    negative HIV screening tests
    
    few to no risk factors for developing HIV (e.g., having sex without the use of barrier contraception and sharing needles)

Treatment
- HIV-infected breastfeeding mothers
  - preferred to use replacement feedings due to high risk for transmission to the infant
- HIV-infected patients and vaccinations
  - HIV is an indication for obtaining the following vaccines
    
    pneumococcal
    
    hepatitis B (if not already immune)
    
    meningococcal
- Medical
  - antiretroviral therapy
    
    indication
    
    first-line treatment for patients with HIV infection
    
    drug regimen
    
    2 nucleoside reverse transcriptase inhibitors (e.g., tenofovir alafenamide and emtricitabine) and an integrase inhibitor (e.g., bictegravir)
    
    comments
    
    the choice of antiretroviral drugs is guided by drug resistance testing
    
    the most common cause of treatment failure is nonadherence
    
    HIV-2 intrinisic resistance
    
    non-nucleoside reverse transcriptase inhibitors (e.g., delavirdine efavirenz and nevirapine) and enfuvirtide (fusion inhibitor)
    
    regimen should utilize nucleoside reverse transcriptase inhibitors, integrase inhibitors, and protease inhibitors (e.g., lopinavir darunavir and saquinavir)
  - post-exposure prophylaxis
    
    indication
    
    first-line treatment given immediately after HIV exposure (such as in health care personnel)
    
    initiate within 72 hours
    
    drug regimen
    
    tenofovir, emtricitabine, and raltegravir
    
    tenofovir, emtricitabine, and dolutegravir
  - pre-exposure prophylaxis
    
    indication
    
    to prevent HIV infection in high-risk patients
    
    drug regimen
    
    tenofovir and emtricitabine
  - antiretroviral therapy in pregnancy
    
    indication
    
    first-line treatment for pregnant women
    
    comment
    
    women who are pregnant are treated the same as for nonpregnant patients; however, certain medications should be avoided
    
    dolutegravir
    
    elvitegravir
    
    tenofovir alafenamide
    
    intrapartum management
    
    HIV RNA ≤ 1000 copies/mL
    
    mode of delivery
    
    cesarean sections are not needed
    
    HIV RNA > 1000 copies/mL
    
    mode of delivery
    
    if < 38 weeks, plan to perform a cesarean section at 38 weeks in order to prevent HIV exposure to the baby via rupture of membranes
    
    drug regimen
    
    intravenous zidovudine
    
    postpartum management
    
    indication
    
    all infants born to HIV-infected mothers
    
    drug regimen
    
    mothers with HIV RNA ≤ 1000 copies/mL
    
    zidovudine in the infant for 4-6 weeks
    
    mothers with HIV RNA > 1000 copies/mL
    
    zidovudine, lamivudine, and nevirapine in the infant for 6 weeks

Complications
- Malignancy
- Cardiovascular and pulmonary disease
- AIDS

Action	Numeric Key	Letter Key	Function Key
Show Bullets		S	Enter (frontside only)
20%	1	N
40%	2	H
60%	3	F	Enter (backside only)
80%	4	E
100%	5	M
Toss	0	T