Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome

Care for patients with human immunodeficiency virus (HIV) has transformed dramatically since acquired immunodeficiency syndrome (AIDS) was first observed in 1981. Early detection and initiation of antiretroviral therapy (ART) has led to significant improvement in morbidity and mortality, but barriers remain. Approximately 15% of HIV-infected people in the United States are unaware of their infection and account for 40% of transmissions. In this section, we will cover:

• Screening

• Diagnosis

• Treatment

• Prevention and Prophylaxis

Screening

The Centers for Disease Control and Prevention (CDC) recommends routine screening for patients aged 13 to 64 years on an opt-out basis in all health care settings unless the incidence of undiagnosed HIV infection is <0.1%. The following populations should be screened regularly:

• all patients seeking treatment for sexually transmitted infections or starting treatment for tuberculosis

• all pregnant women as part of prenatal screening

• patients at high risk for HIV infection (who require at least annual testing)

  • people who inject drugs (PWID)

  • men who have sex with men (MSM)

  • people who exchange sex for drugs or money

  • people with new sexual partners

  • sexual partners of PWID or people with HIV

Screening and its frequency should ultimately be based on an individualized assessment of risks, and anyone who wants to be tested should be tested.

Diagnosis

Sensitivity of newer immunoassays has improved early diagnosis of HIV. Testing should include:

• a fourth-generation combination antigen/antibody immunoassay

• an HIV viral-load test when the above diagnostic test is indeterminate or when evaluating a patient in whom you are considering acute HIV infection

(Source: Quick Reference Guide: Laboratory Testing for the Diagnosis of HIV Infection. Centers for Disease Control 2018.)

A Western blot test to confirm an HIV diagnosis is no longer recommended because the antibody/antigen assay is more reliable and provides rapid results. Viral RNA can be used in cases of acute infection. However, within the first 10 days of the infection, an eclipse phase occurs (see figure below), when testing is negative followed by a “window” phase when certain tests may still remain negative. Therefore, repeat tests may be necessary if clinical suspicion is high.

(Source: Acute HIV-1 Infection. N Engl J Med 2011.)

Note: Some patients may be first diagnosed with HIV after presenting with an opportunistic infection (OI). It is important to look for signs of an OI after making the diagnosis. See Opportunistic Infections in this rotation guide for more information.

HIVinfo, a resource from the National Institutes of Health (NIH), provides a comprehensive table of laboratory testing for monitoring patients with HIV before and after initiation of antiretroviral therapy (ART). Some tests to obtain following diagnosis and prior to initiation of ART include:

• CD4-cell count

• HIV viral load

• genotype and resistance testing

• HLA-B*5701 testing (only if considering the use of abacavir; patients who are positive for HLA-B*5701 can develop a hypersensitivity reaction to abacavir)

• basic chemistry, aspartate aminotransferase (AST), alanine aminotransferase (ALT), bilirubin

• complete blood count (CBC) with differential

• fasting lipid profile

• fasting glucose or glycated hemoglobin

• urinalysis

• hepatitis B and C testing

• screening for coinfection: tuberculosis, syphilis, chlamydia, gonorrhea

• pregnancy

• consider serum cryptococcal antigen in patients with CD4-cell count <100/mm³

Treatment

Antiretroviral Therapy

Previous guidelines recommended waiting until a patient’s CD4-cell count was below a certain threshold to initiate ART. However, current U.S. and World Health Organization (WHO) guidelines recommend early initiation of ART for all patients, regardless of CD4-cell count, due to clear evidence of benefit (e.g., the INSIGHT START trial). Preventing the emergence of resistance to antiretroviral medications is crucial. Every patient should be counseled on adherence and strategies to optimize adherence. Test for resistance at the start of treatment and tailor therapy accordingly.

In general, ART includes a combination of drugs with different mechanisms of action (see figure below). The NIH treatment guidelines recommend the following regimens for most treatment-naive patients:

• bictegravir-tenofovir alafenamide-emtricitabine

• dolutegravir-abacavir-lamivudine—only for patients who are HLA-B*5701 negative and are not coinfected with chronic hepatitis B virus

• dolutegravir plus emtricitabine OR lamivudine plus tenofovir alafenamide or tenofovir disoproxil fumarate

• dolutegravir-lamivudine—except for individuals with HIV RNA >500,000 copies/mL, hepatitis B coinfection, or when ART is started before the results of HIV genotypic resistance testing or HBV testing are available

HIVinfo provides a list of HIV medicines approved by the U.S. Food and Drug Administration (FDA) with information about their use. Many factors can change an individual’s regimen, including CD4-cell count, HIV viral load, and comorbidities (e.g., chronic kidney disease, cirrhosis, osteoporosis, psychiatric illnesses, cardiac disease, hepatitis B or C virus, tuberculosis). Several complete regimens are coformulated into a once-daily pill that can improve adherence. An additional option is a long-acting injectable treatment (cabotegravir plus rilpivirine) given every 1 or 2 months, which may be more acceptable for some patients who cannot or do not wish to take pills.

The following illustration depicts the reproductive life cycle of HIV-1. HIV-1 has a high replication and mutation rate. Therefore, multiple drugs with effects at different stages of the life cycle must be taken at the same time to suppress HIV-1.

(Source: Single-Pill Combination Regimens for Treatment of HIV-1 Infection. N Engl J Med 2014.)

Other considerations for ART

• Immune reconstitution inflammatory syndrome (IRIS) is a sudden inflammatory response that can occur after initiation of ART in patients with a concurrent OI as the recovering CD4 cells respond to the infection, leading to excessive inflammation and clinical worsening.

• Despite the risk of IRIS, starting ART as soon as possible in patients with OIs is recommended because effective therapies for some OIs do not exist, and outcomes associated with early treatment are generally better. An exception is cryptococcal meningitis, because studies have shown a reduction in mortality when ART initiation is delayed for a few weeks after initiation of antifungal therapy.

• Be aware of drug-drug interactions in patients taking other medications. For example, ritonavir (a protease inhibitor and booster) potently inhibits the cytochrome P-450 3A4 enzyme and can cause Cushing syndrome when given with glucocorticoids (even inhaled or intra-articular).

Prevention and Prophylaxis

Besides safe sexual and drug use practices, early initiation of ART can reduce transmission in serodiscordant couples. Sexual transmission is eliminated when a partner with HIV has sustained and consistent viral suppression (i.e., Undetectable equals Untransmissible or U = U).

Preexposure Prophylaxis (PrEP)

• Studies have shown that a daily antiretroviral can prevent HIV infection in a variety of settings.

• The CDC estimates that PrEP can reduce sexual transmission by 90% and transmission from injection-drug use (IDU) by 70%.

• Truvada (tenofovir disoproxil fumarate [TDF] plus emtricitabine [FTC]) was the only option for HIV PrEP until 2019, when Descovy (tenofovir alafenamide [TAF]-FTC) was approved by the FDA. TAF is associated with less renal and bone toxicity than TDF. However, TAF-FTC should not be used in patients who are most at risk of acquiring HIV through receptive vaginal intercourse because efficacy data are lacking in this group.

• On-demand PrEP with Truvada (TDF-FTC) has been shown to provide effective protection in men who have sex with men (MSM) using a double dose taken 2-24 hours prior to sex and followed by the normal dose continued daily for at least 48 hours from the last sexual encounter (i.e., 2-1-1 dosing)

• Injectable cabotegravir (Apretude) was approved by the FDA in 2021 as a single injection every 2 months and has been shown to be superior to oral PrEP (possibly related to increased adherence)

• Consider PrEP for the following populations:

  • MSM or heterosexual women or men who have the following risk factors: partner with HIV who is not suppressed, recent bacterial sexually transmitted infection (STI), multiple partners, inconsistent condom use, commercial sex work

  • people who inject drugs and have the following risk factors: injecting partner with HIV, sharing needles

• Prior to starting PrEP, make sure the patient has no evidence of acute HIV and test for HIV, hepatitis B, and renal function.

• Follow up every 3 months for adherence counseling and assess for medication adverse effects, HIV status (important to avoid treating active HIV with inappropriate regimen), STIs, and renal function.

Postexposure Prophylaxis (PEP)

• PEP is indicated for exposure to HIV-positive body fluids or high-risk exposures (e.g., victims of sexual assault).

• In the health care setting, transmission rate is typically low: 0.3% after percutaneous exposure and 0.09% after mucous membrane exposure.

• PEP should be given as soon as possible and is not recommended >72 hours after exposure. Do not delay PEP while waiting to determine HIV status of the source.

• Typical regimen includes 28 days of:

  • tenofovir-emtricitabine and raltegravir or dolutegravir OR

  • tenofovir-emtricitabine and darunavir-ritonavir