Guideline sources The following summarized guidelines for the evaluation and management of human immunodeficiency virus infection (HIV) are prepared by our editorial team based on guidelines from the Center for Disease Control (CDC 2021), the International AIDS Society (IAS 2018), the Clinical Pharmacogenetics Implementation Consortium (CPIC 2014), and the U.S. Preventive Services Task Force (USPSTF 2013). 1 2 3 4 5 6 6 7 8 9 10 Definition HIV is a chronic viral disease that, if untreated, leads to progressive T cell depletion with resultant infectious and oncological complications. 6 Epidemiology Human immunodeficiency virus type 1 is responsible for the vast majority of infections, while human immunodeficiency type 2 is relatively uncommon and follows a more indolent course. 8 Pathophysiology https://web.pathway.md/diseases/recQ0DpI3qRwt7qOo 1/8 6/24/23, 12:45 PM Human immunodeficiency virus infection Pathway In the United States, the incidence and prevalence of human immunodeficiency virus are estimated at 18.0 cases per 100,000 person-years and 380.9 persons per 100,000 population, respectively. 7 Disease course Infection begins by invasion of the target cells in a mucosa, following which the infection spreads to the lymphoid system. In untreated patients, the destruction of human immunodeficiency virus- infected CD4 T cells results in immunodeficiency and chronic inflammation. CD4 T cell counts of < 350 cells/ L are associated with an increased risk of complications such as varicella-zoster, tuberculosis, and other severe bacterial infections. The risk of opportunistic infections, such as pneumocystis pneumonia and esophageal candidiasis, increases with CD4 T cell counts of < 250 cells/ L. CD4 T cells count < 100 cells/ L result in an increased risk of coccidioidomycosis, cryptococcosis, CMV infection, histoplasmosis, progressive multifocal leukoencephalopathy, disseminated mycobacterium avium complex, brain toxoplasmosis, human immunodeficiency virus- associated wasting syndrome, and finally death. 6 Prognosis and risk of recurrence The standardized mortality rate ratio of patients with HIV is estimated at 3.97 (95% CI 3.01-5.24) in patients who have never received antiretroviral therapy, and 2.76 (95% CI 2.25-3.39) in patients who have been treated with antiretroviral therapy. The 2-year and 10-year survival rates of patients diagnosed with AIDS are 82% and 26%, respectively. 9 10 Calculator Calculator CKD prediction in HIV patients Denver HIV risk score Guidelines 1. Screening and diagnosis Indications for screening: As per IAS 2018 guidelines, screen for HIV at least once in all individuals who have ever been sexually active. B Show 2 more As per USPSTF 2013 guidelines: Screen adolescents and adults 15 to 65 years of age for HIV. Screen younger adolescents and older adults who are at an increased risk. A https://web.pathway.md/diseases/recQ0DpI3qRwt7qOo 2/8 6/24/23, 12:45 PM Human immunodeficiency virus infection Pathway Screen all pregnant women for human immunodeficiency virus, including those who present in labor who are untested and whose human immunodeficiency virus status is unknown. A As per USPSTF 2013 guidelines: Screen for HIV in patients 15-65 years of age. A Screen for HIV in patients < 15 years of age and patients > 65 years of age who are at increased risk. A 2. Diagnostic investigations Initial and confirmatory testing: Use assays that can detect recent HIV (either an instrument-based combination antigen/antibody assay or a combination of a stand-alone antibody assay and nucleic acid testing) to screen for HIV. B Obtain confirmatory measurement of human immunodeficiency virus RNA levels in patients with positive screening results. A Baseline laboratory investigations: Obtain the following laboratory testing prior to initiating antiretroviral therapy: human immunodeficiency virus RNA level CD4 cell count reverse transcriptase and protease genotype complete blood cell count kidney and LFTs lipid levels, glucose level, and pregnancy status screening for hepatitis A, B, and C, tuberculosis, and STIs. A Testing for HLA-B5701: Obtain testing for HLA-B5701 allele before initiating abacavir. A Avoid abacavir in patients who test positive for HLA-B5701. D Bone mineral density testing: obtain baseline bone mineral density testing in postmenopausal women and in all patients > 50 years of age. B Evaluation for comorbidities: implement age- and risk-appropriate screening for STIs at various anatomical sites, anal or cervical dysplasia, tuberculosis, general health, and medication toxicity. B Show 2 more 3. Medical management General principles: initiate antiretroviral therapy as soon as possible after diagnosis, including immediately after diagnosis, unless the patient is not ready to commit to starting therapy. A https://web.pathway.md/diseases/recQ0DpI3qRwt7qOo 3/8 6/24/23, 12:45 PM Human immunodeficiency virus infection Pathway Initial ART regimens: Choose among the following initial regimens for the treatment of HIV: bictegravir/tenofovir alafenamide/emtricitabine A dolutegravir/abacavir/Lamivudine A dolutegravir plus tenofovir alafenamide/emtricitabine A Updated evidence: ATLAS-2M (152-week results) In adults living with human immunodeficiency virus-1 infection, every 8 weeks dosing was noninferior to every 4 weeks dosing with respect to a HIV-1 RNA 50 copies/mL at week 152. Edgar T Overton et al. Clin Infect Dis. 2023 Jan 20. ART initiation (rapid start): initiate antiretroviral therapy, including rapid start, for all infected ambulatory patients committed to starting antiretroviral therapy, unless the patient has symptoms that suggest an opportunistic infection for which immediate antiretroviral therapy is contraindicated, or for those with unclear human immunodeficiency virus diagnosis. B Show 2 more ART initiation (opportunistic infections): initiate antiretroviral therapy within the first 2 weeks after diagnosis for most opportunistic infections. A Show 2 more ART switching (virologic failure): obtain resistance testing in patients with virologic failure, while taking the failing antiretroviral therapy regimen or within 4 weeks of stopping. B Prophylaxis for opportunistic infections: initiate primary prophylaxis for Pneumocystis pneumonia should be initiated for patients with CD4 cell counts below 200/ L. A Show 2 more 4. Specific circumstances Pregnant patients: advise individuals with HIV who are pregnant to initiate antiretroviral therapy as soon as possible, for their own health and to reduce transmission to the infant. A Show 3 more Patients with HBV co-infection: treat patients who are co-infected with human immunodeficiency virus and HBV with a regimen that contains 2 drugs active against HBV, usually tenofovir alafenamide or tenofovir disoproxil fumarate plus lamivudine or emtricitabine, in addition to a third antiretroviral therapy drug. B Patients with HCV co-infection: treat patients with human immunodeficiency virus who are co- infected with HCV using antiretroviral regimens that have minimal drug interactions with HCV therapies, such as dolutegravir/abacavir/lamivudine, dolutegravir/tenofovir alafenamide/emtricitabine, bictegravir/tenofovir alafenamide/emtricitabine, or raltegravir plus tenofovir alafenamide/emtricitabine. B https://web.pathway.md/diseases/recQ0DpI3qRwt7qOo 4/8 6/24/23, 12:45 PM Human immunodeficiency virus infection Pathway Patients with osteoporosis: Avoid tenofovir disoproxil fumarate for patients with osteopenia or osteoporosis. D Switch proactively from tenofovir disoproxil fumarate to tenofovir alafenamide for patients at high risk of renal or bone toxicity. B Patients with kidney disease: avoid tenofovir disoproxil fumarate for individuals with or at risk for kidney disease. D Show 2 more Patients with tuberculosis: treat patients with human immunodeficiency infection taking rifamycin-basedd antituberculosis therapy with 2 NRTIs (excluding tenofovir alafenamide) plus one of the following: efavirenz (600 mg daily), raltegravir (800 mg BID), or dolutegravir (50 mg BID). A Patients with substance use disorders: initiate opioid substitution therapy in patients with human immunodeficiency virus who are opioid-dependent. A Patients who are carriers of HLA-B57:01: avoid abacavir in patients who are carriers of HLA- B57:01. D 5. Patient education Sexual behaviour counseling: remind HIV-seropositive and HIV-negative individuals that condoms are required to prevent acquisition of non-HIV STIs. B 6. Preventative measures Pre-exposure prophylaxis: As per CDC 2021 guidelines, inform all sexually active adult and adolescent individuals about human immunodeficiency virus pre-exposure prophylaxis. B Show 10 more As per IAS 2018 guidelines, offer pre-exposure prophylaxis for populations whose annual HIV incidence is at least 2%. B Landmark trials: ANRS IPERGAY In men who have unprotected anal sex with men and who are at high risk for HIV infection, truvada was superior to placebo with respect to the incidence of human immunodeficiency virus 1 infection. Molina JM et al. N Engl J Med. 2015 Dec 3. Post-exposure prophylaxis: provide access to pre-exposure prophylaxis in patients who have completed post-exposure prophylaxis for a recent exposure, and are at risk of ongoing exposure. https://web.pathway.md/diseases/recQ0DpI3qRwt7qOo 5/8 6/24/23, 12:45 PM Human immunodeficiency virus infection Pathway B 7. Follow-up and surveillance Follow-up STI screening: perform quarterly screening for asymptomatic STIs in patient populations with high rates of bacterial STIs and incomplete condom use. B Follow-up viral load monitoring: measure viral load at 4-6 weeks after starting a new antiretroviral therapy regimen. B Follow-up CD4 cell count monitoring: measure CD4 cell counts every 6 months until cell counts are > 250 cells/ L for at least 1 year with concomitant viral suppression. B Linkage to care and adherence monitoring: monitor time to care linkage, retention in care, reengagement in care, antiretroviral therapy adherence, and rates of viral suppression, in all care settings and at a population level. B Likelihood Ratios Pertinent positives The following findings increase the probability of human immunodeficiency virus infection in adults. -1 Finding LR+ Value History of genital ulcer 5.4 (2.5-12) History of weight loss 4.7 (2.1-7.2) History of vomiting 4.6 (2.5-8.0) History of swollen lymph nodes 4.6 (1.3-8.0) Show 15 more Pertinent negatives The following findings decrease the probability of human immunodeficiency virus infection in adults. -1 Finding LR- Value Absence of generalized lymphadenopathy 0.70 (0.49-0.92) No history of fever 0.74 (0.64-0.84) No history of myalgia or arthralgia 0.79 (0.57-0.92) Absence of inguinal lymphadenopathy 0.82 (0.69-0.92) Show 20 more References 1. Saag MS, Benson CA, Gandhi RT et al. 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Management of Hepatitis B Virus Infection and Prevention of Hepatitis B Virus Reactivation in Children With Acquired Immunodeficiencies or Undergoing Immune Suppressive, Cytotoxic, or Biological Modifier Therapies. J Pediatr Gastroenterol Nutr. 2020 Apr;70 4 527 538. Open 26. Naokatsu Ando, Daisuke Mizushima, Kazumi Omata et al. Combination of Amoxicillin 3,000 mg and Probenecid versus 1,500 mg Amoxicillin Monotherapy for Treating Syphilis in Patients with HIV an Open- Label, Randomized, Controlled, Non-Inferiority Trial. Clin Infect Dis. 2023 May 9;ciad278. Open https://web.pathway.md/diseases/recQ0DpI3qRwt7qOo 8/8