What is the current approach to diagnosing and treating Human Immunodeficiency Virus (HIV)?

Current Diagnosis of HIV

Screen all persons aged 15-65 years at least once using a fourth-generation HIV antigen/antibody combination assay, followed by HIV-1/HIV-2 antibody differentiation testing if reactive, and confirm with nucleic acid testing if the differentiation assay is negative. 1, 2

Screening Recommendations

Universal screening is recommended for all adolescents and adults aged 15-65 years regardless of perceived risk, using routine opt-out testing in primary care, emergency departments, and for all pregnant women. 2 Younger adolescents and adults over 65 should be screened if they have ongoing risk factors such as new sexual partners. 3

High-Risk Populations Requiring Annual Screening

• Men who have sex with men and active injection drug users are at very high risk and should be rescreened at least annually. 3
• Persons with unprotected vaginal or anal intercourse, sex partners who are HIV-infected or injection drug users, those exchanging sex for drugs or money, and anyone requesting testing for sexually transmitted infections should be screened annually. 3
• Patients in high-prevalence settings (≥1% HIV seroprevalence) including STD clinics, correctional facilities, homeless shelters, tuberculosis clinics, and adolescent health clinics with high STI prevalence require more frequent screening. 3

Modern Diagnostic Testing Algorithm

The CDC-recommended algorithm begins with a fourth-generation HIV antigen/antibody combination assay that detects both HIV antibodies and p24 antigen, allowing detection of acute infection approximately 2 weeks earlier than antibody-only tests. 1, 2, 4

Step-by-Step Testing Protocol

1. Initial screening: Fourth-generation antigen/antibody combination assay 1, 2

   • If non-reactive: Patient is HIV-negative (unless tested during window period)
   • If reactive: Proceed to step 2

2. Confirmatory testing: HIV-1/HIV-2 antibody differentiation immunoassay 1

   • If positive: HIV infection confirmed; proceed to post-diagnosis evaluation
   • If negative: Proceed to step 3

3. Nucleic acid amplification test (NAAT/HIV RNA qualitative or quantitative) 1

   • If positive: Acute HIV-1 infection confirmed
   • If negative: False-positive screening result; patient is HIV-negative

Alternative Traditional Algorithm (Still Valid)

The traditional approach uses enzyme immunoassay (ELISA) for initial screening, followed by Western blot confirmation if repeatedly reactive. 3, 1 A positive Western blot confirms HIV infection, while a negative Western blot indicates the person is uninfected unless acute infection is suspected. 1 Indeterminate Western blot results require follow-up testing at 4-6 weeks and consideration of HIV RNA testing. 1, 5

Critical Window Period Considerations

Standard antibody tests cannot definitively rule out infection that occurred less than 6 months before testing, as at least 95% of infected individuals develop detectable antibodies within 6 months of infection. 3, 4

• Fourth-generation tests detect HIV 18-45 days post-infection 4
• For suspected acute infection (within the first few weeks), nucleic acid testing should be performed rather than relying solely on antibody tests, as NAT can detect HIV 10-14 days after exposure 4
• Post-exposure testing should occur at 4-6 weeks, 3 months, and in rare cases at 6 months 4

Post-Diagnosis Evaluation

All persons with confirmed HIV infection must receive comprehensive baseline testing before initiating antiretroviral therapy, including: 3, 2

• HIV RNA viral load level 3, 2
• CD4 cell count with percentage (obtain 2 baseline measurements before therapy decisions due to substantial variation) 3
• Genotypic resistance testing (all patients should be assessed for transmitted drug resistance upon diagnosis) 3, 2
• HLA-B*5701 testing (required prior to prescribing abacavir) 3, 2
• Coreceptor tropism assay (if CCR5 entry inhibitor considered) 3
• Complete blood count, comprehensive metabolic panel, fasting lipid profile, fasting glucose, hepatic function tests, urinalysis 3
• Screening for coinfections: hepatitis B and C, tuberculosis, sexually transmitted infections 3

Special Population Considerations

For infants <15-18 months born to HIV-positive mothers, standard antibody tests are unreliable due to maternal antibody transfer; definitive diagnosis requires two positive HIV RNA PCR or viral culture tests on separate specimens. 1

HIV-2 testing should be considered in persons from endemic regions (West Africa), their sexual partners, or when clinical evidence suggests HIV disease but HIV-1 tests are negative. 3, 1

Immediate Treatment Initiation

All persons diagnosed with HIV should be offered antiretroviral therapy immediately upon diagnosis, regardless of CD4 count or viral load. 2 Preferred regimens include an integrase strand transfer inhibitor (INSTI) such as dolutegravir plus two nucleoside reverse transcriptase inhibitors (NRTIs). 2, 6

Common Pitfalls to Avoid

Never disclose a positive HIV diagnosis based on screening test alone without confirmatory testing, as false positives can occur with devastating psychological and social consequences. 1

Do not use oral fluid-based rapid HIV tests in post-exposure prophylaxis contexts, as they are less sensitive for acute or recent infection detection than blood-based tests. 4

For individuals on antiretrovirals (PrEP or PEP), both laboratory-based antigen/antibody test AND diagnostic NAT are required for follow-up testing due to potential viral suppression. 4

Recognize that CD4 cell counts have substantial variation, especially during acute illness; some experts recommend obtaining 2 baseline measurements before therapy decisions. 3