HIV

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
< 500 mm3	Candida albicans	Oral thrush that is scrapablePseudohyphae on microscopy	–
Epstein-Barr virus	Oral hairy leukoplakianot scrapable
HHV-8	Kaposi sarcoma a palpable, nonpruritic lesion that is brown, pink, red, or violaceous in color
HPV	Squamous cell carcinomaanus (in men who have sex with men)cervix
< 200 mm3	Histoplasma capsulatum	Nonspecific findings fevers, night sweats, chills, and weight lossdyspneanausea and vomitingMacrophages contain oval yeast cells	–
JC virus reactivation	Progressive multifocal leukoencephalopathydemyelinating disease of the central nervous system
Pneumocystis jirovecii	Pneumoniaground-glass opacity on chest radiography	Trimethoprim-sulfamethoxazoleif contraindicated, can give dapsone, atovaquone, or pentamidine
Cryptosporidium parvum	Watery diarrhea	Nitazoxanide
< 100 mm3	Aspergillus fumigatus	HemoptysisPleuritic chest pain	–
Bartonella henselae	Bacillary angiomatosisangiomatous skin lesions	–
Candida albicans	Esophagitis white plaques may appear on endoscopy	–
Cytomegalovirus	RetinitisEsophagitisColitisPneumonitisEncephalitisLinear ulcers on endoscopyFundoscopy may demonstrate cotton-wool spotsIntranuclear inclusion bodies (owl eyes)	–
Cryptosporidium spp.	Watery diarrheaStool studies will show acid-fast oocysts	–
Ebstein-Barr virus	B-cell lymphomaCentral nervous system lymphoma	–
Mycobacterium avium-intracellulare	Non-specific findingsfevernight sweatsweight losslymphadenitis	The goal is to initiate antiretroviral therapy as soon as possibleAzithromycin
Toxoplasma gondii	Ring-enhancing brain abscesses	Trimethoprim-sulfamethoxazoleif 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

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