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 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 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 detects both HIV-1 and HIV-2 antibodies HIV p24 antigen 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 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 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 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 Nucleoside reverse transcriptase inhibitors abacavir emtricitabine lamivudine tenofovir zidovudine Non-nucleoside reverse transcriptase inhibitors efavirenz nevirapine Integrase inhibitors bictegravir dolutegravir raltegravir Protease inhibitors indinavir ritonavir 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 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 < 50 copies/mL zidovudine in the infant for 4 weeks mothers with HIV RNA ≥ 50 copies/mL zidovudine, lamivudine, and nevirapine in the infant for 6 weeks 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