Snapshot A 44-year-old man presents to his primary care physician for 1 week of worsening malaise, myalgias, sore throat, and chills. He denies any sick contacts or recent travel history. His past medical history is noncontributory. He drinks alcohol occasionally, denies smoking, and is sexually active with 2 men and inconsistently uses condoms. In the past, he has been treated for chlamydia and gonorrhea. He consents for a fourth-generation combination HIV-1/2 immunoassay, which returns positive. An HIV-1/HIV-2 antibody differentiation immunoassay confirms the diagnosis and he is started on tenofovir alafenamide, emtricitabine, and bictegravir. Introduction Definition a blood-borne virus that is transmitted via sexual intercourse sharing needles vertical transmission from the mother to the fetus Microbiology enveloped virus single-stranded positive-sense RNA retrovirus genes env gene leads to the production of gp160, which is cleaved to produce gp120 and gp41 login to view 2 more bullets gag gene leads to the production of p24 and p17 login to view 2 more bullets pol gene leads to the production of login to view 3 more bullets Associated conditions opportunistic infections malignancy cognitive decline cardiovascular disease Epidemiology Incidence most commonly transmitted by sexual intercourse or sharing needles ETIOLOGY 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 is reverse transcribed (by reverse transcriptase) into DNA, which 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 Opportunistic Infections CD4+ Count < 500 mm3 Opportunistic Infection Based on CD4+ T-Cell Count Opportunistic Infection Findings Prophylactic Treatment 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 of the: anus (in men who have sex with men) cervix -- CD4+ Count < 200 mm3 Opportunistic Infection Based on CD4+ T-Cell Count Opportunistic Infection Findings Prophylactic Treatment Histoplasma capsulatum Nonspecific findings such as: 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 CD4+ Count < 100 mm3 Opportunistic Infection Based on CD4+ T-Cell Count Opportunistic Infection Findings Prophylactic Treatment Aspergillus fumigatus Hemoptysis Pleuritic chest pain -- Bartonella henselae Bacillary angiomatosis angiomatous skin lesions -- Candida albicans Esophagitis white plaques may appear on endoscopy -- Cytomegalovirus Retinitis (can also be caused by HSV) 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 focal neurologic deficits ring enhancing lesion on brain MRI EBV+ in CSF PCR -- 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 Empiric pyrimethamine-sulfadiazine indicated in patients CD4 < 100 cells/µL, focal neurologic findings, and ring-enhancing lesions on head imaging treat for 10-14 days then obtain follow-up head imaging. Brain biopsy If the patient fails to improve clinically or the size of the lesion does not change after 10-14 days on pyrimethamine-sulfadiazine, the next step would be a biopsy of the lesion. 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 login to view 3 more bullets screening criteria <ol> <li>at least once for all patients age 15 to 65 regardless of risk factors</li> <li>men who have sex with men</li> <li>pregnant women</li> <li>IV drug users</li> <li>patients who engage in unprotected sex</li> <li>those diagnosed with another sexually transmitted disease (STD)</li> </ol> interpretation login to view 8 more bullets 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 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 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 A (if not already immune) hepatitis B (if not already immune) meningococcal Medical antiretroviral therapy indication login to view 1 more bullet drug regimen login to view 1 more bullet comments login to view 2 more bullets Nucleoside reverse transcriptase inhibitors login to view 5 more bullets Non-nucleoside reverse transcriptase inhibitors login to view 2 more bullets Integrase inhibitors login to view 3 more bullets Protease inhibitors login to view 2 more bullets post-exposure prophylaxis indication login to view 2 more bullets drug regimen login to view 2 more bullets pre-exposure prophylaxis indication login to view 1 more bullet drug regimen login to view 1 more bullet antiretroviral therapy in pregnancy indication login to view 1 more bullet comment login to view 1 more bullet intrapartum management login to view 8 more bullets postpartum management login to view 7 more bullets Complications Malignancy Cardiovascular and pulmonary disease HIV-associated dementia cognitive deficits, behavioral changes, and diminished motor skills not attributable to another cause cortical atrophy and symmetric, periventricular white matter lesions on T2-weighted MRI Immune reconstitution inflammatory syndrome results in paradoxical worsening of infectious symptoms due to immune recovery from antiretroviral therapy treatment involves continuing antiretroviral therapy and symptomatic treatment (e.g., acetaminophen and a short course of steroids) if acute infection, often will start treating infection before initiating antiretroviral therapy Prognosis High mortality rate (> 90%) in untreated patients