17:I[462708,["/_next/static/chunks/3yo3kiro3bmlp.js","/_next/static/chunks/3vr2wvd8f2efb.js","/_next/static/chunks/2vtmb68_vu-9t.js","/_next/static/chunks/2s8mt6_8wrpfo.js","/_next/static/chunks/3vkulz2i3l61y.js","/_next/static/chunks/1cqw2i1silz0i.js","/_next/static/chunks/14dbm3lm_t629.js","/_next/static/chunks/335_v2mb569ld.js","/_next/static/chunks/3ykn5ops9bft5.js","/_next/static/chunks/3cmavum774kjt.js","/_next/static/chunks/3th-0-a2xf9qs.js","/_next/static/chunks/0p0xpwde6kzmv.js","/_next/static/chunks/401-sxxnzbtf_.js","/_next/static/chunks/0wywtv698a1v0.js","/_next/static/chunks/2botzqwpnrzyj.js"],"ArticleReader"] 18:T5653,## Summary Human immunodeficiency virus (HIV) is a chronic retroviral infection that causes progressive immune dysfunction unless viral replication is durably suppressed. **Antiretroviral therapy (ART) is recommended for every person with HIV and should begin immediately or as soon as possible after diagnosis.** Draw essential baseline safety, virologic and resistance samples first, but in most patients do not wait for all results before starting treatment.[1,2] For laboratory diagnosis in the United States, begin with a laboratory HIV-1/HIV-2 antigen/antibody assay. A reactive result is followed by an HIV-1/HIV-2 antibody differentiation assay; if that assay is negative or indeterminate, perform HIV-1 nucleic-acid testing. When acute HIV is strongly suspected despite nonreactive serology, obtain HIV RNA because antibody and antigen/antibody tests may still be negative early after acquisition.[3] At entry to care obtain HIV RNA, CD4 count, resistance testing, CBC, renal and hepatic chemistry, hepatitis B and C testing, urinalysis when appropriate, glucose, lipids, and pregnancy testing when relevant. Assess tuberculosis, sexually transmitted infections, immunization status, prior pre-exposure or post-exposure antiretroviral use, all medications and supplements, mental health, substance use, housing, food access, insurance/pharmacy access and other barriers to uninterrupted treatment.[2,8] For most adults without suspected integrase resistance, current U.S. guidance favors a second-generation integrase inhibitor with an appropriate nucleoside backbone: bictegravir/tenofovir alafenamide/emtricitabine or dolutegravir plus tenofovir alafenamide or tenofovir disoproxil fumarate plus emtricitabine or lamivudine. Dolutegravir/lamivudine is an option only in selected patients and should not be used for rapid start while hepatitis B or reverse-transcriptase genotype results are unknown, in hepatitis B coinfection, or when baseline HIV RNA is >500,000 copies/mL.[1,2] Measure HIV RNA 4–8 weeks after ART initiation and every 4–8 weeks until suppressed, then every 3–4 months; the interval may extend to 6 months in adherent, clinically stable patients suppressed for more than a year. Virologic failure is inability to achieve or maintain HIV RNA <200 copies/mL.[4] Advanced immunosuppression requires parallel evaluation for opportunistic infection (OI). Primary Pneumocystis prophylaxis is indicated for CD4 <200 cells/mm³ in people not receiving ART or beginning ART; in people already receiving ART, initiate prophylaxis at CD4 <100 regardless of HIV RNA, or at CD4 100–200 with persistent detectable HIV RNA. Toxoplasma prophylaxis is indicated when Toxoplasma IgG is positive and CD4 is <100 cells/mm³.[5,6] > **Caution:** Rapid ART is standard, but central nervous system cryptococcosis is an important exception; current NIH OI guidance generally defers ART for about 4–6 weeks after antifungal therapy begins because earlier ART can increase mortality through inflammatory complications.[9] ## Transmission, virology and natural history HIV-1 accounts for most infections worldwide. HIV-2 is concentrated in West Africa and epidemiologically linked regions and differs in drug susceptibility and viral-load monitoring; suspected HIV-2 requires specific confirmatory testing and specialist regimen selection. HIV infects CD4-expressing cells through receptor and coreceptor binding, reverse transcription, integration of viral DNA into the host genome and production of new virions. Current drug classes block entry, reverse transcriptase, integrase, protease, capsid function or other stages of viral replication. ART suppresses ongoing replication but does not eradicate integrated latent provirus, so treatment is lifelong with current standard therapies. Transmission occurs through sexual exposure, blood exposure including shared injection equipment, and vertical transmission. Effective ART that achieves and maintains an undetectable viral load prevents sexual transmission of HIV. Prevention care also includes partner testing, pre-exposure prophylaxis for HIV-negative partners when appropriate, sterile injection equipment, sexually transmitted infection care and reproductive counseling. ## Clinical presentation ### Acute HIV Acute retroviral syndrome often occurs 2–4 weeks after acquisition but may be mild or absent. Features can include: - fever; - pharyngitis; - diffuse rash; - lymphadenopathy; - myalgia or arthralgia; - headache or aseptic meningitis; - diarrhea; - oral or genital ulceration; - transient cytopenias. The syndrome overlaps with Epstein–Barr virus, cytomegalovirus, influenza, acute viral hepatitis, secondary syphilis and other febrile illnesses. A negative antibody-only test does not exclude acute infection. ### Chronic untreated infection Many people remain asymptomatic for years. Possible clues include persistent generalized lymphadenopathy, herpes zoster, oral candidiasis, recurrent bacterial infection, chronic constitutional symptoms, thrombocytopenia, unexplained weight loss or chronic diarrhea. ### Advanced HIV Urgently consider OI or malignancy with: - progressive dyspnea or hypoxemia; - subacute headache, confusion, focal neurologic deficit or meningismus; - visual loss or floaters; - odynophagia; - persistent fever or night sweats; - chronic diarrhea or wasting; - severe cytopenias; - focal lymphadenopathy or mass lesions; - oral thrush with systemic symptoms. See [Pneumocystis jirovecii Pneumonia in Adults](pneumocystis-jirovecii-pneumonia-in-adults.md) and [Tuberculosis Infection and Active Disease](tuberculosis.md). ## Diagnosis ### Laboratory algorithm | Sequence | Test | Interpretation and next action | |---|---|---| | 1 | Laboratory HIV-1/HIV-2 antigen/antibody assay | If nonreactive, established infection is unlikely unless exposure is recent. If reactive, proceed to differentiation testing.[3] | | 2 | HIV-1/HIV-2 antibody differentiation assay | Positive result identifies HIV type in the standard laboratory algorithm.[3] | | 3 | HIV-1 NAT/RNA if differentiation result is negative or indeterminate | Detects acute HIV-1 and resolves discordant serology.[3] | CDC describes approximate detection windows in people not taking antiretrovirals: venous laboratory antigen/antibody tests often detect infection **18–45 days** after exposure; antibody tests generally **23–90 days**; NAT generally **10–33 days**.[3] When recent exposure plus compatible symptoms creates high suspicion, obtain both an antigen/antibody assay and HIV RNA rather than waiting for seroconversion. ### New diagnosis: immediate questions Determine: - whether infection is confirmed; - whether acute HIV is possible; - whether there are symptoms of active OI; - prior ART, pre-exposure prophylaxis or post-exposure prophylaxis exposure; - whether long-acting cabotegravir was previously used for prevention; - pregnancy status when relevant; - hepatitis B status; - renal and hepatic function; - interacting medicines and supplements; - immediate barriers to treatment access and adherence. ## Baseline investigations | Domain | Baseline test | Clinical implication | |---|---|---| | HIV activity | Plasma HIV RNA | Establishes pretreatment viral burden and response baseline | | Immune status | CD4 count | Determines OI risk and prophylaxis needs | | Resistance | Genotype for reverse transcriptase/protease; integrase genotype when indicated | Guides regimen selection; draw before ART but do not usually delay rapid start | | Blood count | CBC with differential | Detects cytopenias and establishes treatment baseline | | Renal/metabolic | Creatinine/eGFR, electrolytes, glucose; urinalysis when indicated | Guides tenofovir selection and identifies kidney/metabolic disease | | Liver | AST, ALT, bilirubin and related chemistry | Detects liver disease and provides toxicity baseline | | Hepatitis | HBsAg, anti-HBs, total anti-HBc; HCV antibody ± RNA | Determines vaccination, HBV-active ART and HCV treatment needs | | Lipids | Lipid profile | Cardiovascular risk and treatment planning | | Pharmacogenetics | HLA-B*5701 if abacavir is being considered | Prevents abacavir hypersensitivity | | Coinfection | TB risk/testing; syphilis; gonorrhea/chlamydia by exposed site | Identifies common treatable coinfection | | Reproductive | Pregnancy test when relevant | Regimen and perinatal planning | Current NIH guidance also recommends integrase resistance testing when transmitted integrase resistance is suspected or there is prior long-acting cabotegravir use for prevention.[2] ## Starting antiretroviral therapy ### Rapid-start principle Start ART on the day of diagnosis or as soon as feasible in most patients.[1] Essential samples can be drawn immediately. Do not require complete social stabilization before treatment; instead, start treatment while simultaneously addressing medication access, adherence barriers and follow-up. Rapid start requires special thought when there is suspected central nervous system OI because timing may change, particularly with cryptococcal meningitis and some forms of tuberculosis. ### Preferred initial approaches for most adults Current U.S. guidance recommends the following general strategies for most treatment-naive adults:[2] | Regimen | Standard adult dosing | Key constraints | |---|---|---| | Bictegravir/tenofovir alafenamide/emtricitabine | 50/25/200 mg orally once daily | Check renal function and interactions; avoid if regimen is compromised by resistance | | Dolutegravir + tenofovir alafenamide/emtricitabine | Dolutegravir 50 mg once daily + TAF/FTC 25/200 mg once daily | Check interactions, renal/hepatic context and HBV status | | Dolutegravir + tenofovir disoproxil fumarate/emtricitabine | Dolutegravir 50 mg once daily + TDF/FTC 300/200 mg once daily | Consider kidney and bone risk | | Dolutegravir/lamivudine | 50/300 mg orally once daily | Do not use for HBV coinfection, HIV RNA >500,000 copies/mL, or rapid start before HBV/genotype results are available | These are common U.S. adult formulations; local licensing, available combinations and renal thresholds vary by jurisdiction. ### Prior long-acting cabotegravir exposure Acquisition of HIV during or after long-acting cabotegravir prevention can select integrase resistance and may delay standard serologic diagnosis. Obtain HIV RNA and integrase resistance testing. If integrase susceptibility is not yet known, current NIH guidance recommends a boosted darunavir-based regimen with two appropriate nucleoside agents while results are pending.[2] ### Hepatitis B coinfection People with HIV and chronic hepatitis B should receive fully suppressive ART containing **two agents active against HBV**, usually tenofovir (TAF or TDF) plus emtricitabine or lamivudine.[7] Do not use lamivudine or emtricitabine as the only HBV-active drug because HBV resistance emerges readily. Stopping HBV-active therapy can precipitate hepatitis flare; when changing ART, maintain effective HBV treatment. Cross-links: [Chronic Hepatitis B](../hepatology/chronic-hepatitis-b.md), [Chronic Hepatitis C](../hepatology/chronic-hepatitis-c.md). ## Monitoring response ### HIV RNA - obtain at ART initiation; - repeat within **4–8 weeks**; - if still detectable, repeat every **4–8 weeks** until suppressed; - once stable and suppressed, measure every **3–4 months**; - extend to every **6 months** in adherent, clinically and immunologically stable patients with >1 year of sustained suppression.[4,8] ### CD4 count CD4 remains essential for initial staging and OI decisions. Once viral suppression is sustained and CD4 has recovered well above OI thresholds, monitoring can become less frequent; NIH guidance permits optional CD4 monitoring after 1–2 years of sustained suppression when CD4 remains >300 cells/mm³ unless clinically indicated.[4] ### Safety monitoring Repeat kidney, liver, metabolic and hematologic testing according to the regimen, comorbidity and baseline abnormalities. Current NIH laboratory guidance commonly uses a 4–8 week safety check after initiation in people with relevant preexisting disease or risk, followed by periodic monitoring.[4] ## Interpreting detectable HIV RNA A single low detectable value after prior suppression can be a transient “blip.” Confirm persistence before labeling failure unless the value or clinical context is clearly concerning. **Virologic failure** is inability to achieve or maintain HIV RNA **<200 copies/mL**.[4] For persistent HIV RNA ≥200 copies/mL: 1. confirm the result and trajectory; 2. assess adherence without blame; 3. verify pharmacy access and treatment interruptions; 4. review food requirements, absorption and drug interactions; 5. check multivalent-cation use with integrase inhibitors; 6. review all historical ART and resistance results; 7. obtain resistance testing while the patient is taking the failing regimen, when technically feasible; 8. construct a new regimen using current and archived resistance information rather than adding a single active drug to a failing regimen. > **Clinical pearl:** A detectable viral load often reflects access, adherence, interaction or tolerability problems before it reflects high-grade drug resistance. The evaluation should address all of these simultaneously. ## Opportunistic-infection prevention ### Pneumocystis jirovecii pneumonia Primary prophylaxis is recommended for:[5] - CD4 <200 cells/mm³ in people not receiving ART or beginning ART; - CD4 <100 cells/mm³ regardless of HIV RNA in people already receiving ART; - CD4 100–200 cells/mm³ with sustained detectable HIV RNA. Preferred prophylaxis: **trimethoprim-sulfamethoxazole one double-strength tablet (160 mg TMP/800 mg SMX) orally once daily**, or one single-strength tablet daily.[5] Discontinuation is generally appropriate after immune recovery to CD4 ≥200 cells/mm³ for at least 3 months due to ART; current NIH guidance also allows consideration at CD4 100–200 when HIV RNA remains below assay detection for 3–6 months.[5] ### Toxoplasma gondii encephalitis If Toxoplasma IgG is positive and CD4 is **<100 cells/mm³**, provide prophylaxis. Preferred prophylaxis is trimethoprim-sulfamethoxazole one double-strength tablet daily, which also covers Pneumocystis.[6] ### Mycobacterium avium complex Routine primary MAC prophylaxis is **not** needed when effective suppressive ART is started promptly. Consider it in advanced immunosuppression when CD4 is <50 cells/mm³ and the patient is not receiving fully suppressive ART or remains viremic without an immediately effective regimen; exclude disseminated MAC first. NIH-preferred prophylaxis includes azithromycin 1,200 mg orally once weekly in appropriate patients. ## OI symptoms that alter immediate management | Presentation | Concern | Immediate action | |---|---|---| | Subacute dyspnea, dry cough, exertional desaturation | Pneumocystis pneumonia | Chest imaging, oxygenation assessment, organism-directed testing; treat promptly | | Subacute headache, fever, raised intracranial pressure | Cryptococcal meningitis | Serum cryptococcal antigen and lumbar puncture when safe; measure opening pressure | | Focal neurologic deficit, seizure, ring-enhancing lesions | Toxoplasmosis or CNS lymphoma | Brain imaging and targeted infectious/oncologic evaluation | | Cough, fever, night sweats, weight loss | Tuberculosis | Airborne precautions when pulmonary TB is plausible; microbiologic testing | | Floaters or visual loss with very low CD4 | CMV retinitis | Urgent dilated ophthalmic assessment | ### ART timing during OI treatment Most OIs favor early ART once treatment begins, but timing depends on the pathogen and disease site. For Pneumocystis pneumonia, NIH guidance recommends starting ART within **2 weeks** when possible.[5] For central nervous system cryptococcosis, defer ART approximately **4–6 weeks** after antifungal treatment begins.[9] Tuberculosis timing depends on CD4 count, site of disease and drug interactions; tuberculous meningitis is handled differently from pulmonary disease. ## Immunization and preventive care Use current HIV-specific and national immunization schedules. Key principles include: - annual influenza vaccination; - current COVID-19 vaccination according to jurisdictional guidance; - pneumococcal vaccination using current conjugate-vaccine strategies; - hepatitis A and B vaccination when nonimmune; - HPV vaccination according to age and shared decision-making recommendations; - meningococcal vaccination where indicated; - recombinant zoster vaccination in eligible adults; - mpox vaccination according to exposure risk and local guidance.[8] Live vaccines may be contraindicated or deferred in advanced immunosuppression; use pathogen- and CD4-specific guidance. ## Long-term primary care Durable viral suppression does not eliminate noninfectious morbidity. At least annually reassess:[8] - cardiovascular risk, blood pressure, diabetes and lipids; - kidney and liver disease; - bone health and fracture risk; - tobacco, alcohol and other substance use; - depression, anxiety, trauma and cognitive symptoms; - cancer screening based on age, anatomy and HIV-specific risk; - sexual health and sexually transmitted infections; - contraception and reproductive goals; - medication interactions and polypharmacy; - housing, food access and treatment affordability; - stigma, disclosure concerns and safety. The 2024 HIVMA/IDSA primary-care guidance recommends baseline bone-density testing in postmenopausal cisgender women and men aged ≥50 years and emphasizes proactive age-related comorbidity care.[8] ## Special situations ### Pregnancy ART is indicated during pregnancy both for maternal health and prevention of vertical transmission. Regimen selection, viral-load monitoring and delivery planning should follow current perinatal HIV guidance because preferred drugs and timing differ from general adult recommendations. ### Kidney disease Tenofovir formulation and dose depend on renal function and the complete regimen. TDF has greater renal tubular and bone toxicity risk than TAF. Severe kidney disease may require alternative nucleoside strategies and specialist review. ### Tuberculosis Rifamycins cause major interactions with many antiretrovirals. Do not substitute or dose-adjust casually; use current HIV/TB interaction tables. See [Tuberculosis Infection and Active Disease](tuberculosis.md). ### Chronic hepatitis HBV coinfection changes ART selection immediately. HCV should be treated with direct-acting antivirals after interaction review; HIV is not a reason to defer curative HCV therapy. ## Disposition and urgent referral Admit or urgently refer patients with suspected severe OI, hypoxemia, meningitis/encephalitis, focal neurologic deficits, hemodynamic instability, inability to take essential therapy, severe drug toxicity, or an unsafe outpatient plan. A stable new diagnosis can usually be managed as an outpatient if rapid ART, medication access, baseline investigations and prompt follow-up are secured. Linkage failure is a clinical risk; arrange the next contact before the patient leaves whenever possible. ## References 1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Initiation of Antiretroviral Therapy. *Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV*. U.S. Department of Health and Human Services; updated 2025. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/initiation-antiretroviral-therapy 2. Panel on Antiretroviral Guidelines for Adults and Adolescents. What to Start: Initial Combination Antiretroviral Regimens. U.S. Department of Health and Human Services. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/what-start-initial-combination-regimens-antiretroviral-naive 3. Centers for Disease Control and Prevention. HIV Testing / Clinical Testing Guidance. Updated 2025-2026. https://www.cdc.gov/hivnexus/hcp/diagnosis-testing/ and https://www.cdc.gov/hiv/testing/ 4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Laboratory Testing for Initial Assessment and Monitoring; Plasma HIV-1 RNA and CD4 Count Monitoring. U.S. Department of Health and Human Services. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/tests-initial-assessment-and-follow-up-full 5. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Pneumocystis Pneumonia. NIH/CDC/HIVMA; updated 2026. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/pneumocystis 6. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Toxoplasma gondii Encephalitis. NIH/CDC/HIVMA; updated 2026. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/toxoplasmosis 7. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Hepatitis B Virus Infection. NIH/CDC/HIVMA; updated 2026. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/hepatitis-b-virus 8. Horberg M, Thompson M, Agwu A, et al. Primary Care Guidance for Providers of Care for Persons With Human Immunodeficiency Virus: 2024 Update by the HIV Medicine Association of the Infectious Diseases Society of America. *Clin Infect Dis*. 2024. DOI: 10.1093/cid/ciae479. https://www.idsociety.org/practice-guideline/primary-care-management-of-people-with-hiv/ 9. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Cryptococcosis. NIH/CDC/HIVMA. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/cryptococcosis19:T5653,## Summary Human immunodeficiency virus (HIV) is a chronic retroviral infection that causes progressive immune dysfunction unless viral replication is durably suppressed. **Antiretroviral therapy (ART) is recommended for every person with HIV and should begin immediately or as soon as possible after diagnosis.** Draw essential baseline safety, virologic and resistance samples first, but in most patients do not wait for all results before starting treatment.[1,2] For laboratory diagnosis in the United States, begin with a laboratory HIV-1/HIV-2 antigen/antibody assay. A reactive result is followed by an HIV-1/HIV-2 antibody differentiation assay; if that assay is negative or indeterminate, perform HIV-1 nucleic-acid testing. When acute HIV is strongly suspected despite nonreactive serology, obtain HIV RNA because antibody and antigen/antibody tests may still be negative early after acquisition.[3] At entry to care obtain HIV RNA, CD4 count, resistance testing, CBC, renal and hepatic chemistry, hepatitis B and C testing, urinalysis when appropriate, glucose, lipids, and pregnancy testing when relevant. Assess tuberculosis, sexually transmitted infections, immunization status, prior pre-exposure or post-exposure antiretroviral use, all medications and supplements, mental health, substance use, housing, food access, insurance/pharmacy access and other barriers to uninterrupted treatment.[2,8] For most adults without suspected integrase resistance, current U.S. guidance favors a second-generation integrase inhibitor with an appropriate nucleoside backbone: bictegravir/tenofovir alafenamide/emtricitabine or dolutegravir plus tenofovir alafenamide or tenofovir disoproxil fumarate plus emtricitabine or lamivudine. Dolutegravir/lamivudine is an option only in selected patients and should not be used for rapid start while hepatitis B or reverse-transcriptase genotype results are unknown, in hepatitis B coinfection, or when baseline HIV RNA is >500,000 copies/mL.[1,2] Measure HIV RNA 4–8 weeks after ART initiation and every 4–8 weeks until suppressed, then every 3–4 months; the interval may extend to 6 months in adherent, clinically stable patients suppressed for more than a year. Virologic failure is inability to achieve or maintain HIV RNA <200 copies/mL.[4] Advanced immunosuppression requires parallel evaluation for opportunistic infection (OI). Primary Pneumocystis prophylaxis is indicated for CD4 <200 cells/mm³ in people not receiving ART or beginning ART; in people already receiving ART, initiate prophylaxis at CD4 <100 regardless of HIV RNA, or at CD4 100–200 with persistent detectable HIV RNA. Toxoplasma prophylaxis is indicated when Toxoplasma IgG is positive and CD4 is <100 cells/mm³.[5,6] > **Caution:** Rapid ART is standard, but central nervous system cryptococcosis is an important exception; current NIH OI guidance generally defers ART for about 4–6 weeks after antifungal therapy begins because earlier ART can increase mortality through inflammatory complications.[9] ## Transmission, virology and natural history HIV-1 accounts for most infections worldwide. HIV-2 is concentrated in West Africa and epidemiologically linked regions and differs in drug susceptibility and viral-load monitoring; suspected HIV-2 requires specific confirmatory testing and specialist regimen selection. HIV infects CD4-expressing cells through receptor and coreceptor binding, reverse transcription, integration of viral DNA into the host genome and production of new virions. Current drug classes block entry, reverse transcriptase, integrase, protease, capsid function or other stages of viral replication. ART suppresses ongoing replication but does not eradicate integrated latent provirus, so treatment is lifelong with current standard therapies. Transmission occurs through sexual exposure, blood exposure including shared injection equipment, and vertical transmission. Effective ART that achieves and maintains an undetectable viral load prevents sexual transmission of HIV. Prevention care also includes partner testing, pre-exposure prophylaxis for HIV-negative partners when appropriate, sterile injection equipment, sexually transmitted infection care and reproductive counseling. ## Clinical presentation ### Acute HIV Acute retroviral syndrome often occurs 2–4 weeks after acquisition but may be mild or absent. Features can include: - fever; - pharyngitis; - diffuse rash; - lymphadenopathy; - myalgia or arthralgia; - headache or aseptic meningitis; - diarrhea; - oral or genital ulceration; - transient cytopenias. The syndrome overlaps with Epstein–Barr virus, cytomegalovirus, influenza, acute viral hepatitis, secondary syphilis and other febrile illnesses. A negative antibody-only test does not exclude acute infection. ### Chronic untreated infection Many people remain asymptomatic for years. Possible clues include persistent generalized lymphadenopathy, herpes zoster, oral candidiasis, recurrent bacterial infection, chronic constitutional symptoms, thrombocytopenia, unexplained weight loss or chronic diarrhea. ### Advanced HIV Urgently consider OI or malignancy with: - progressive dyspnea or hypoxemia; - subacute headache, confusion, focal neurologic deficit or meningismus; - visual loss or floaters; - odynophagia; - persistent fever or night sweats; - chronic diarrhea or wasting; - severe cytopenias; - focal lymphadenopathy or mass lesions; - oral thrush with systemic symptoms. See [Pneumocystis jirovecii Pneumonia in Adults](pneumocystis-jirovecii-pneumonia-in-adults.md) and [Tuberculosis Infection and Active Disease](tuberculosis.md). ## Diagnosis ### Laboratory algorithm | Sequence | Test | Interpretation and next action | |---|---|---| | 1 | Laboratory HIV-1/HIV-2 antigen/antibody assay | If nonreactive, established infection is unlikely unless exposure is recent. If reactive, proceed to differentiation testing.[3] | | 2 | HIV-1/HIV-2 antibody differentiation assay | Positive result identifies HIV type in the standard laboratory algorithm.[3] | | 3 | HIV-1 NAT/RNA if differentiation result is negative or indeterminate | Detects acute HIV-1 and resolves discordant serology.[3] | CDC describes approximate detection windows in people not taking antiretrovirals: venous laboratory antigen/antibody tests often detect infection **18–45 days** after exposure; antibody tests generally **23–90 days**; NAT generally **10–33 days**.[3] When recent exposure plus compatible symptoms creates high suspicion, obtain both an antigen/antibody assay and HIV RNA rather than waiting for seroconversion. ### New diagnosis: immediate questions Determine: - whether infection is confirmed; - whether acute HIV is possible; - whether there are symptoms of active OI; - prior ART, pre-exposure prophylaxis or post-exposure prophylaxis exposure; - whether long-acting cabotegravir was previously used for prevention; - pregnancy status when relevant; - hepatitis B status; - renal and hepatic function; - interacting medicines and supplements; - immediate barriers to treatment access and adherence. ## Baseline investigations | Domain | Baseline test | Clinical implication | |---|---|---| | HIV activity | Plasma HIV RNA | Establishes pretreatment viral burden and response baseline | | Immune status | CD4 count | Determines OI risk and prophylaxis needs | | Resistance | Genotype for reverse transcriptase/protease; integrase genotype when indicated | Guides regimen selection; draw before ART but do not usually delay rapid start | | Blood count | CBC with differential | Detects cytopenias and establishes treatment baseline | | Renal/metabolic | Creatinine/eGFR, electrolytes, glucose; urinalysis when indicated | Guides tenofovir selection and identifies kidney/metabolic disease | | Liver | AST, ALT, bilirubin and related chemistry | Detects liver disease and provides toxicity baseline | | Hepatitis | HBsAg, anti-HBs, total anti-HBc; HCV antibody ± RNA | Determines vaccination, HBV-active ART and HCV treatment needs | | Lipids | Lipid profile | Cardiovascular risk and treatment planning | | Pharmacogenetics | HLA-B*5701 if abacavir is being considered | Prevents abacavir hypersensitivity | | Coinfection | TB risk/testing; syphilis; gonorrhea/chlamydia by exposed site | Identifies common treatable coinfection | | Reproductive | Pregnancy test when relevant | Regimen and perinatal planning | Current NIH guidance also recommends integrase resistance testing when transmitted integrase resistance is suspected or there is prior long-acting cabotegravir use for prevention.[2] ## Starting antiretroviral therapy ### Rapid-start principle Start ART on the day of diagnosis or as soon as feasible in most patients.[1] Essential samples can be drawn immediately. Do not require complete social stabilization before treatment; instead, start treatment while simultaneously addressing medication access, adherence barriers and follow-up. Rapid start requires special thought when there is suspected central nervous system OI because timing may change, particularly with cryptococcal meningitis and some forms of tuberculosis. ### Preferred initial approaches for most adults Current U.S. guidance recommends the following general strategies for most treatment-naive adults:[2] | Regimen | Standard adult dosing | Key constraints | |---|---|---| | Bictegravir/tenofovir alafenamide/emtricitabine | 50/25/200 mg orally once daily | Check renal function and interactions; avoid if regimen is compromised by resistance | | Dolutegravir + tenofovir alafenamide/emtricitabine | Dolutegravir 50 mg once daily + TAF/FTC 25/200 mg once daily | Check interactions, renal/hepatic context and HBV status | | Dolutegravir + tenofovir disoproxil fumarate/emtricitabine | Dolutegravir 50 mg once daily + TDF/FTC 300/200 mg once daily | Consider kidney and bone risk | | Dolutegravir/lamivudine | 50/300 mg orally once daily | Do not use for HBV coinfection, HIV RNA >500,000 copies/mL, or rapid start before HBV/genotype results are available | These are common U.S. adult formulations; local licensing, available combinations and renal thresholds vary by jurisdiction. ### Prior long-acting cabotegravir exposure Acquisition of HIV during or after long-acting cabotegravir prevention can select integrase resistance and may delay standard serologic diagnosis. Obtain HIV RNA and integrase resistance testing. If integrase susceptibility is not yet known, current NIH guidance recommends a boosted darunavir-based regimen with two appropriate nucleoside agents while results are pending.[2] ### Hepatitis B coinfection People with HIV and chronic hepatitis B should receive fully suppressive ART containing **two agents active against HBV**, usually tenofovir (TAF or TDF) plus emtricitabine or lamivudine.[7] Do not use lamivudine or emtricitabine as the only HBV-active drug because HBV resistance emerges readily. Stopping HBV-active therapy can precipitate hepatitis flare; when changing ART, maintain effective HBV treatment. Cross-links: [Chronic Hepatitis B](../hepatology/chronic-hepatitis-b.md), [Chronic Hepatitis C](../hepatology/chronic-hepatitis-c.md). ## Monitoring response ### HIV RNA - obtain at ART initiation; - repeat within **4–8 weeks**; - if still detectable, repeat every **4–8 weeks** until suppressed; - once stable and suppressed, measure every **3–4 months**; - extend to every **6 months** in adherent, clinically and immunologically stable patients with >1 year of sustained suppression.[4,8] ### CD4 count CD4 remains essential for initial staging and OI decisions. Once viral suppression is sustained and CD4 has recovered well above OI thresholds, monitoring can become less frequent; NIH guidance permits optional CD4 monitoring after 1–2 years of sustained suppression when CD4 remains >300 cells/mm³ unless clinically indicated.[4] ### Safety monitoring Repeat kidney, liver, metabolic and hematologic testing according to the regimen, comorbidity and baseline abnormalities. Current NIH laboratory guidance commonly uses a 4–8 week safety check after initiation in people with relevant preexisting disease or risk, followed by periodic monitoring.[4] ## Interpreting detectable HIV RNA A single low detectable value after prior suppression can be a transient “blip.” Confirm persistence before labeling failure unless the value or clinical context is clearly concerning. **Virologic failure** is inability to achieve or maintain HIV RNA **<200 copies/mL**.[4] For persistent HIV RNA ≥200 copies/mL: 1. confirm the result and trajectory; 2. assess adherence without blame; 3. verify pharmacy access and treatment interruptions; 4. review food requirements, absorption and drug interactions; 5. check multivalent-cation use with integrase inhibitors; 6. review all historical ART and resistance results; 7. obtain resistance testing while the patient is taking the failing regimen, when technically feasible; 8. construct a new regimen using current and archived resistance information rather than adding a single active drug to a failing regimen. > **Clinical pearl:** A detectable viral load often reflects access, adherence, interaction or tolerability problems before it reflects high-grade drug resistance. The evaluation should address all of these simultaneously. ## Opportunistic-infection prevention ### Pneumocystis jirovecii pneumonia Primary prophylaxis is recommended for:[5] - CD4 <200 cells/mm³ in people not receiving ART or beginning ART; - CD4 <100 cells/mm³ regardless of HIV RNA in people already receiving ART; - CD4 100–200 cells/mm³ with sustained detectable HIV RNA. Preferred prophylaxis: **trimethoprim-sulfamethoxazole one double-strength tablet (160 mg TMP/800 mg SMX) orally once daily**, or one single-strength tablet daily.[5] Discontinuation is generally appropriate after immune recovery to CD4 ≥200 cells/mm³ for at least 3 months due to ART; current NIH guidance also allows consideration at CD4 100–200 when HIV RNA remains below assay detection for 3–6 months.[5] ### Toxoplasma gondii encephalitis If Toxoplasma IgG is positive and CD4 is **<100 cells/mm³**, provide prophylaxis. Preferred prophylaxis is trimethoprim-sulfamethoxazole one double-strength tablet daily, which also covers Pneumocystis.[6] ### Mycobacterium avium complex Routine primary MAC prophylaxis is **not** needed when effective suppressive ART is started promptly. Consider it in advanced immunosuppression when CD4 is <50 cells/mm³ and the patient is not receiving fully suppressive ART or remains viremic without an immediately effective regimen; exclude disseminated MAC first. NIH-preferred prophylaxis includes azithromycin 1,200 mg orally once weekly in appropriate patients. ## OI symptoms that alter immediate management | Presentation | Concern | Immediate action | |---|---|---| | Subacute dyspnea, dry cough, exertional desaturation | Pneumocystis pneumonia | Chest imaging, oxygenation assessment, organism-directed testing; treat promptly | | Subacute headache, fever, raised intracranial pressure | Cryptococcal meningitis | Serum cryptococcal antigen and lumbar puncture when safe; measure opening pressure | | Focal neurologic deficit, seizure, ring-enhancing lesions | Toxoplasmosis or CNS lymphoma | Brain imaging and targeted infectious/oncologic evaluation | | Cough, fever, night sweats, weight loss | Tuberculosis | Airborne precautions when pulmonary TB is plausible; microbiologic testing | | Floaters or visual loss with very low CD4 | CMV retinitis | Urgent dilated ophthalmic assessment | ### ART timing during OI treatment Most OIs favor early ART once treatment begins, but timing depends on the pathogen and disease site. For Pneumocystis pneumonia, NIH guidance recommends starting ART within **2 weeks** when possible.[5] For central nervous system cryptococcosis, defer ART approximately **4–6 weeks** after antifungal treatment begins.[9] Tuberculosis timing depends on CD4 count, site of disease and drug interactions; tuberculous meningitis is handled differently from pulmonary disease. ## Immunization and preventive care Use current HIV-specific and national immunization schedules. Key principles include: - annual influenza vaccination; - current COVID-19 vaccination according to jurisdictional guidance; - pneumococcal vaccination using current conjugate-vaccine strategies; - hepatitis A and B vaccination when nonimmune; - HPV vaccination according to age and shared decision-making recommendations; - meningococcal vaccination where indicated; - recombinant zoster vaccination in eligible adults; - mpox vaccination according to exposure risk and local guidance.[8] Live vaccines may be contraindicated or deferred in advanced immunosuppression; use pathogen- and CD4-specific guidance. ## Long-term primary care Durable viral suppression does not eliminate noninfectious morbidity. At least annually reassess:[8] - cardiovascular risk, blood pressure, diabetes and lipids; - kidney and liver disease; - bone health and fracture risk; - tobacco, alcohol and other substance use; - depression, anxiety, trauma and cognitive symptoms; - cancer screening based on age, anatomy and HIV-specific risk; - sexual health and sexually transmitted infections; - contraception and reproductive goals; - medication interactions and polypharmacy; - housing, food access and treatment affordability; - stigma, disclosure concerns and safety. The 2024 HIVMA/IDSA primary-care guidance recommends baseline bone-density testing in postmenopausal cisgender women and men aged ≥50 years and emphasizes proactive age-related comorbidity care.[8] ## Special situations ### Pregnancy ART is indicated during pregnancy both for maternal health and prevention of vertical transmission. Regimen selection, viral-load monitoring and delivery planning should follow current perinatal HIV guidance because preferred drugs and timing differ from general adult recommendations. ### Kidney disease Tenofovir formulation and dose depend on renal function and the complete regimen. TDF has greater renal tubular and bone toxicity risk than TAF. Severe kidney disease may require alternative nucleoside strategies and specialist review. ### Tuberculosis Rifamycins cause major interactions with many antiretrovirals. Do not substitute or dose-adjust casually; use current HIV/TB interaction tables. See [Tuberculosis Infection and Active Disease](tuberculosis.md). ### Chronic hepatitis HBV coinfection changes ART selection immediately. HCV should be treated with direct-acting antivirals after interaction review; HIV is not a reason to defer curative HCV therapy. ## Disposition and urgent referral Admit or urgently refer patients with suspected severe OI, hypoxemia, meningitis/encephalitis, focal neurologic deficits, hemodynamic instability, inability to take essential therapy, severe drug toxicity, or an unsafe outpatient plan. A stable new diagnosis can usually be managed as an outpatient if rapid ART, medication access, baseline investigations and prompt follow-up are secured. Linkage failure is a clinical risk; arrange the next contact before the patient leaves whenever possible. ## References 1. Panel on Antiretroviral Guidelines for Adults and Adolescents. Initiation of Antiretroviral Therapy. *Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents With HIV*. U.S. Department of Health and Human Services; updated 2025. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/initiation-antiretroviral-therapy 2. Panel on Antiretroviral Guidelines for Adults and Adolescents. What to Start: Initial Combination Antiretroviral Regimens. U.S. Department of Health and Human Services. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/what-start-initial-combination-regimens-antiretroviral-naive 3. Centers for Disease Control and Prevention. HIV Testing / Clinical Testing Guidance. Updated 2025-2026. https://www.cdc.gov/hivnexus/hcp/diagnosis-testing/ and https://www.cdc.gov/hiv/testing/ 4. Panel on Antiretroviral Guidelines for Adults and Adolescents. Laboratory Testing for Initial Assessment and Monitoring; Plasma HIV-1 RNA and CD4 Count Monitoring. U.S. Department of Health and Human Services. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-arv/tests-initial-assessment-and-follow-up-full 5. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Pneumocystis Pneumonia. NIH/CDC/HIVMA; updated 2026. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/pneumocystis 6. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Toxoplasma gondii Encephalitis. NIH/CDC/HIVMA; updated 2026. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/toxoplasmosis 7. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Hepatitis B Virus Infection. NIH/CDC/HIVMA; updated 2026. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/hepatitis-b-virus 8. Horberg M, Thompson M, Agwu A, et al. Primary Care Guidance for Providers of Care for Persons With Human Immunodeficiency Virus: 2024 Update by the HIV Medicine Association of the Infectious Diseases Society of America. *Clin Infect Dis*. 2024. DOI: 10.1093/cid/ciae479. https://www.idsociety.org/practice-guideline/primary-care-management-of-people-with-hiv/ 9. Panel on Guidelines for the Prevention and Treatment of Opportunistic Infections in Adults and Adolescents With HIV. Cryptococcosis. NIH/CDC/HIVMA. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/cryptococcosis7:["$","$L17",null,{"article":{"id":"medical-hiv-infection-in-adults","title":"HIV Infection in Adults","slug":"hiv-infection-in-adults","description":"Human immunodeficiency virus (HIV) is a chronic retroviral infection that causes progressive immune dysfunction unless viral replication is durably suppressed. 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