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Pamela R Hughes, MD, Candace A Adedokun, MD and Lauren Whitney Norman, B.S in Biomedical Science, M.D. Reviewed 05/2023



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Subject: HIV/AIDS

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  • HIV is a retrovirus (subgroup lentivirus) that integrates into CD4 T lymphocytes, altering cell-mediated immunity and causing cell death, severe immunodeficiency, opportunistic infections, and malignancies if not treated.

  • The natural history of untreated HIV infection includes viral transmission, acute retroviral syndrome, recovery and seroconversion, asymptomatic chronic HIV infection, and symptomatic HIV infection or AIDS.

  • Without treatment, the average patient progresses to AIDS ~10 years after acquiring HIV. Without treatment, people living with full-blown AIDS typically survive about 3 years.



  • ~30,000 people over the age of 13 years were diagnosed with HIV in the U.S. during 2020. The incidence decreased by 8% from 2016 to 2019.

  • There were approximately 1.5 million new cases of HIV worldwide in 2020 (1).


  • As of 2019, ~1.2 million persons in the United States have HIV, ~13% are not aware they are infected (1).

  • As of 2020, ~38 million people are living with HIV worldwide. ~45% of new diagnoses are in Eastern and Southern Africa (1).

  • In 2020, ~680,000 people died from AIDS-related illnesses (1).


  • HIV primarily infects CD4+ cells. HIV is a single-stranded, positive-sense, enveloped RNA virus. After entering target cells, viral RNA is transcribed to DNA (through reverse transcription), imported to the host cell nucleus and incorporated into host DNA. The virus can become latent or produce new viral RNA with proteins that are released to infect other CD4+ cells. Host CD8+ cells are activated as part of the seroconversion response.

  • There are two types of HIV. HIV-1 causes the majority of HIV infections. HIV-2 is less infectious and seen primarily in West Africa.


  • Sexual activity (>90% of transmission): Receptive anal sex is highest risk. Ulcerative urogenital lesions promote transmission (1).

  • Injection drug use

  • Children of HIV-infected women: Maternal HIV-1 RNA level predicts transmission.

    • HIV can also be transmitted in breast milk. HIV+ women should not breastfeed unless there is no alternative. In this case, consider antiretroviral therapy (ART).

  • Recipients of blood products prior to 1985

  • Occupational exposure (health care workers)


  • Avoid unprotected, high-risk sex, and injection drug use, especially shared needles.

  • Preexposure prophylaxis (PrEP) is recommended by WHO and USPSTF for persons at high risk of acquiring HIV.

    • General guidelines for PrEP: (i) exclude acute or chronic HIV infection before initiating therapy, (ii) repeat HIV testing every 3 months during therapy, (iii) renal and liver function testing at baseline, 2-8 weeks after initiating PrEP, and every 6 months.

  • Postexposure prophylaxis (PEP) should be started within 72 hours of exposure and continued for 28 days with a three-drug regimen  (2)[A].

  • For HIV+ patients using ART, maintaining HIV RNA levels <200 copies/mL prevents risk of transmission to sexual partners (treatment as prevention) (3)[A].

  • CDC recommends screening for HIV at least once in patients ages 13 to 64.

  • Pregnant women should be tested at the initial prenatal visit and again during the third trimester (4).

  • At least annual screening is recommended for patients at higher risk (4).


  • Syphilis is more aggressive in HIV-infected persons.

  • Tuberculosis (TB) is co-epidemic with HIV; test all patients for TB when newly diagnosed and annually if they have high risk factors for TB. Dually infected patients (TB and HIV) have 100 times greater risk of developing active TB.

  • Patients coinfected with hepatitis B or C have a more rapid progression to cirrhosis.

  • Increased risk for cervical cancer, lymphoma, and skin malignancies.


  • Acute retroviral syndrome: CD4 lymphocyte count declines with increase in viral load 1 to 4 weeks after transmission; confirmed by high-HIV RNA in the absence of HIV antibody.

  • Acute retroviral syndrome presents as an influenza-like syndrome: fever, lymphadenopathy, pharyngitis, rash, myalgias/arthralgias.

  • Clinical latency (asymptomatic): variable duration (average is 8 to 10 years) accompanied by a gradual decline in CD4 cell counts and relatively stable HIV RNA levels (the viral “set point”). Patients often develop persistent generalized lymphadenopathy and may develop fever, weight loss, myalgias, and gastrointestinal problems if unrecognized.

  • AIDS is defined by a CD4 cell count <200, a CD4 cell percentage of total lymphocytes <14%, or an AIDS-related opportunistic infection: Pneumocystis jiroveci (carinii) pneumonia, cryptococcal meningitis, recurrent bacterial pneumonia, candida esophagitis, CNS toxoplasmosis, TB, non-Hodgkin lymphoma (NHL), progressive multifocal encephalopathy, HIV nephropathy, Kaposi sarcoma, Hodgkin lymphoma, and invasive cervical cancer

  • Advanced HIV disease: CD4 cell count <50. Most AIDS-related deaths occur at this time.


  • Complete medical history, including risk exposures, sexual, social and occupational histories, injection drug use, receipt of blood products (prior to 1985), prior use of PrEP or PEP, and medications

  • Comprehensive review of systems

  • Review immunizations record


  • No physical examination findings are specific to HIV.

  • Focus on weight, skin exam, fundoscopic (retinal) exam, oropharynx, lymph nodes, lung, liver, spleen, mental status, neurologic, genital, and rectal examinations.


Burkitt lymphoma, candidiasis, CMV, coccidioidomycosis, cryptococcus, EBV, herpes simplex, influenza, lymphoma, mononucleosis, TB, toxoplasmosis 


Initial Tests (lab, imaging)

  • HIV testing combines antibody/antigen immunoassay for HIV-1/HIV-2 (3)[A].

    • Can be positive within 2 to 3 weeks of exposure

  • Obtain HIV RNA if acute HIV infection is suspected using quantitative PCR; detects infection within 12 days of exposure

  • CD4 cell count and percentage (3)[A]

  • Plasma HIV RNA viral load (3)[A]​​

  • CBC with differential, lipid levels, fasting blood glucose, creatinine (Cr), blood urea nitrogen (BUN), chemistry, transaminase levels, total bilirubin

  • Screen for hepatitis A/B/C and STIs (chlamydia, gonorrhea, syphilis)

  • Cervical cytology and HPV testing if 30 years or older

  • PPD or interferon-γ release assay (IGRA) to screen for latent TB infection; chest x-ray (CXR) if pulmonary symptoms or positive PPD

  • HLAB*5701 testing if abacavir planned for treatment (3)[A]

  • Genotypic tests for resistance to antiretrovirals for patients with pretreatment HIV RNA level <1,000 copies/mL; transmitted resistance to at least one drug seen in 6–16% of patients (3)[A]

Follow-Up Tests & Special Considerations

Postexposure prophylaxis 
  • Nonoccupational postexposure prophylaxis (nPEP) is recommended if care sought within 72 hours of possible exposure and substantial risk of exposure (2)[A]:

    • Source known to be HIV +, exposure to blood, semen, vaginal or rectal secretions, breast milk

  • 28 days of a three-drug regimen should be started if nPEP indicated (2)[A].

    • Tenofovir disoproxil fumarate 300 mg + emtricitabine 200 mg daily plus:

      • Raltegravir 400 mg BID OR dolutegravir 50 mg daily

  • Counsel patients with more than one course of nPEP on prevention and consider PrEP (2)[A].

  • For nPEP: complete HIV, hepatitis B, and hepatitis C testing at baseline, 4 to 6 weeks, 3 months, and 6 months after exposure (2)[A].

  • For persons exposed via sexual contact: test for syphilis, gonorrhea, and chlamydia at time of presentation and 4 to 6 weeks after exposure. Syphilis serology 6 months postexposure (2)[A]


  • Initiate antiretroviral therapy (ART) then select/change regimens based on resistance testing.

  • Consider dosing frequency, pill burden, adverse toxic effect profiles, comorbidities, and drug interactions (including OTC supplements).

  • Pregnancy, AIDS-defining conditions, acute opportunistic infections, CD4 count <200, HIV-associated nephropathy, acute/early infection, Hepatitis B or C coinfection, rapidly declining CD4 counts (>100 cells/mm3 per year), and high viral loads (>100,000 copies/mL) increase urgency for immediate therapy  (3)[A].


  • The goal of ART is to reduce viral load (below limits of detection: HIV RNA <200) and delay immune suppression. Viral load is the most important indicator of response to ART.

  • Assess drug resistance and recommend genotypic testing to guide therapy. (3)

  • Assess substance abuse, economic factors (unstable housing, food insecurity), social support, mental illness, comorbidities, and high-risk behaviors.

  • In women of childbearing age, use ART regimen that decreases viral load with minimal teratogenicity.


First Line

  • Recommended regimens for most people with HIV (3)[A]

    • Integrase strand transfer inhibitor plus 2 nucleoside reverse transcriptase inhibitors:

      • Bictegravir /tenofovir alafenamide /emtricitabine (50 mg/25 mg/200 mg PO daily)

      • Dolutegravir /abacavir /lamivudine (50 mg/600 mg/300 mg PO daily)—only for patients who are HLA-B*5701 negative

      • Dolutegravir (50 mg PO daily) plus tenofovir disoproxil fumarate (300 mg PO daily) or tenofovir alafenamide (25 mg po daily) plus emtricitabine (200 mg PO daily) or lamivudine (300 mg PO daily)

    • Integrase strand transfer inhibitor plus 1 nucleoside reverse transcriptase inhibitors

      • Dolutegravir /lamivudine (50 mg/300 mg PO daily) except if HIV RNA >500,000, Hepatitis B coinfection or genotypic resistance testing results not available

      • Dolutegravir is the preferred treatment for women who are pregnant or trying to conceive (3)[A].

  • Tenofovir/emtricitabine (Truvada) 300 mg/200 mg PO daily is FDA-approved for PrEP in adults at high risk  (2)[A].


  • Prophylactic antimicrobials and vaccines:

    • P. jiroveci prophylaxis: trimethoprim /sulfamethoxazole (TMP-SMX) if CD4 <200 cells/mm3, prior P. jiroveci, thrush, or unexplained fever for >2 weeks

    • Mycobacterium tuberculosis: Treat for latent TB if positive PPD or positive IGRA if no prior prophylaxis or treatment, negative CXR, no recent TB contact, and no history of inadequately treated TB.

    • Toxoplasma gondii prophylaxis: 33% per year risk of infection in untreated patients with CD4 <100 cells/mm3; prophylaxis: TMP-SMX 1 DS tab daily

    • M. avium complex prophylaxis: 20–40% risk with CD4 <50 and no ART. Azithromycin 1,200 mg PO weekly is preferred.

    • Streptococcus pneumoniae: 50 to 100 times increased risk of invasive infection compared with general population; Prevnar and Pneumovax at least 8 weeks apart, repeat every 5 years

    • Influenza vaccine annually (no live vaccine), hepatitis A and B vaccines, human papillomavirus vaccine, at least three Tdap vaccines in lifetime and Td vaccination every 10 years



Patient Monitoring

  • Monitor HIV RNA viral load 2 to 8 weeks after starting therapy; if detectable, repeat testing every 4 to 8 weeks until viral load is suppressed to <200 copies/mL. Then, repeat testing every 3 to 6 months (3).

    • A 3-fold decrease in HIV RNA viral load is considered a significant response.

  • Monitor HIV RNA viral load, CD4, and CBC every 3 to 4 months for first 2 years of ART or if the CD4 count is <300 cells/mm (3)​​​​.

  • Confirm CD4 count level has increased 50 to 150 cells/mm3 within the first year of ART.

  • HIV RNA monitoring can be spaced to every 6 months in patients adherent to ART with consistently suppressed viral load and immunologically stable for more than 2 years (3).

  • Monitor CBC with every CD4 count (3).

  • Space CD4 monitoring to 12 months if suppressed viral load and CD4>300 cells/mm3 (3).

  • Once viral load has been suppressed consistently for >2 years and CD4 cell counts are consistently >500/μL, monitoring CD4 cell counts is optional unless virologic failure occurs (or if immunosuppressive treatments or conditions arise).

  • Annual fasting lipids and fasting glucose if normal at baseline  (3)

  • Basic metabolic panel, AST/ALT, total bilirubin every 6 months  (3)

  • Annual cervical cytology (regardless of age) until three negative screens, then every 3 years (3)

  • Urinalysis every 6-12 months or as indicated  (3)

  • Beta-hCG in women of childbearing age at diagnosis then as clinically indicated (3)


Encourage good nutrition; avoid raw eggs and unpasteurized dairy products. 


Provide nonjudgmental, sex-positive prevention counseling, reviewing high-risk behaviors and viral transmission.  


  • Untreated HIV infection leading to the diagnosis of AIDS has an associated life expectancy of about 3 years. If the patient has an opportunistic infection, the life expectancy is about 1 year.

  • AIDS-defining opportunistic infections usually do not develop until CD4 <200.

  • Adherence failure is the most common cause of treatment failure.


Centers for Disease Control and Prevention. Statistics Overview. Accessed September 21, 2022.
Centers for Disease Control and Prevention. Updated guidelines for antiretroviral postexposure prophylaxis after sexual, injection drug use, or other nonoccupational exposure to HIV—United States, 2016. Accessed September 21, 2022.
U.S. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in adults and adolescents living with HIV. September 21, 2022.
Centers for Disease Control and Prevention. Sexually Transmitted Infections Treatment Guidelines, 2021. Accessed September 21, 2022.


  • Jones AJ, Mathad JS, Dooley KE, et al. Evidence for Implementation: Management of TB in HIV in Pregnancy. Curr HIV/AIDS Rep. 2022;1-16. doi: 10.1007s11904-022-00641-x.
  • Gibas KM, Kelly SG, Arribas JR, et al. Two-drug regimens for HIV treatment. Lancet HIV. 2022;S2352-3018(22)00249-1. doi: 10.1016/S232-3018(22)00249-1. PMID: 3609038.



  • Z21 Asymptomatic human immunodeficiency virus infection status

  • B20 Human immunodeficiency virus [HIV] disease

  • R75 Inconclusive laboratory evidence of human immunodef virus

  • Z20.6 Contact w and (suspected) exposure to human immunodef virus


  • 91947003 Asymptomatic human immunodeficiency virus infection (disorder)

  • 86406008 human immunodeficiency virus infection (disorder)

  • 62479008 acquired immune deficiency syndrome (AIDS) (disorder)

  • 165816005 Human immunodeficiency virus positive (finding)

  • 78466009 positive serological AND/OR viral culture findings for human immunodeficiency virus (disorder)

  • 81000119104 Symptomatic human immunodeficiency virus infection (disorder)


  • Acute HIV seroconversion illness mimics mononucleosis and is characterized by fever, sore throat, adenopathy, myalgias, and rash.

  • Transmitted drug resistance is increasing. Evaluate for resistance prior to initiating ART.

  • Provide necessary vaccinations and prophylactic antibiotics to HIV+ patients based on clinical history and CD4 count.

  • Discuss prevention strategies, including PrEP, with individuals who are at high risk of HIV infection.

  • Routine screening for HIV should be completed in adults and adolescents.

  • Consider HIV testing in at-risk patients reporting unintended weight loss, fatigue, night sweats, or rash.