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