What is the recommended diagnostic and treatment approach for a patient suspected of having Human Immunodeficiency Virus (HIV) infection?

HIV Diagnosis and Confirmation

All persons aged 15-65 years should undergo routine opt-out HIV screening at least once in their lifetime using fourth-generation HIV antigen/antibody combination assays, with reactive results confirmed by HIV-1/HIV-2 antibody differentiation immunoassay followed by HIV RNA testing if needed. 1, 2

Initial Screening Approach

Universal Screening Recommendations

• Screen all adolescents and adults aged 15-65 years regardless of perceived risk, as risk-based screening has failed to identify 10-25% of HIV-positive individuals who report no high-risk behaviors 2, 3
• Implement routine opt-out testing in primary care settings, emergency departments, and for all pregnant women 1, 3
• Screen younger adolescents (<15 years) and adults >65 years only if ongoing risk factors are present 2

High-Risk Populations Requiring Frequent Testing

• Test every 3 months for men who have sex with men, transgender women, people who inject drugs, and persons newly diagnosed with sexually transmitted infections or hepatitis C 4, 3
• Test annually for persons with unprotected vaginal or anal intercourse, sex partners who are HIV-infected or inject drugs, those exchanging sex for drugs or money, and anyone requesting STI testing 2

Diagnostic Testing Algorithm

Step 1: Initial Screening

• Use fourth-generation HIV antigen/antibody combination assay as the initial screening test, which detects both HIV antibodies and p24 antigen, allowing detection of acute infection approximately 2 weeks earlier than antibody-only tests 1, 2, 3
• This test can detect HIV infection in >95% of patients within 6 months of exposure 4

Step 2: Confirmatory Testing

• If initial screening is reactive, perform HIV-1/HIV-2 antibody differentiation immunoassay to confirm infection and differentiate between HIV-1 and HIV-2 1, 2
• If antibody differentiation is negative or indeterminate, perform HIV RNA qualitative or quantitative testing to detect acute infection 2, 3
• 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 2

Step 3: Acute HIV Infection Detection

• For patients with signs or symptoms of acute retroviral syndrome (fever, malaise, lymphadenopathy, skin rash), perform HIV RNA testing immediately, as antibody tests may still be negative 4
• Persons with ongoing condomless sexual exposures or needle sharing require testing with assays that can detect HIV RNA or combination antibody + p24 antigen tests 4

Special Population Considerations

Infants Born to HIV-Positive Mothers

• Standard antibody tests are unreliable in infants <15-18 months due to transplacental passage of maternal HIV antibody 4, 2
• Definitive diagnosis requires two positive HIV RNA PCR or viral culture tests on separate specimens 2
• Passively acquired maternal HIV antibody falls to undetectable levels in most infants by 15 months of age 4

HIV-2 Testing

• Test for HIV-2 only in persons from endemic regions (West Africa, Angola, France, Mozambique, Portugal) or their sexual partners 4, 2
• Consider HIV-2 testing when clinical evidence suggests HIV disease but HIV-1 tests are negative 4, 2

Post-Diagnosis Baseline Evaluation

Mandatory Pre-Treatment Testing

Before initiating antiretroviral therapy, obtain the following baseline tests:

• HIV RNA viral load level to establish baseline viremia 1, 3
• CD4 cell count with percentage to assess immune function 1, 3
• HIV genotype resistance testing to assess transmitted NRTI and NNRTI resistance 4, 1
• HLA-B*5701 testing (only needed once) before use of abacavir to prevent hypersensitivity reactions 4, 1
• CCR5 tropism testing if considering maraviroc 4
• Screen for coinfections including hepatitis B and C, tuberculosis, and sexually transmitted infections 2

Additional Confirmatory Testing

• Perform HIV viral load testing before ART initiation to confirm diagnosis, as all available tests can have false-positive results 4
• Treatment may be started before viral load results are available if clinical suspicion is high 4

Immediate Treatment Initiation

All persons diagnosed with HIV should be offered antiretroviral therapy immediately upon diagnosis, regardless of CD4 count or viral load. 4, 1, 3

Preferred Initial Regimens

• Integrase strand transfer inhibitor (INSTI) plus two nucleoside reverse transcriptase inhibitors (NRTIs) is the preferred regimen 1, 3
• Dolutegravir-based regimens are specifically recommended as first-line therapy 4

Monitoring After Diagnosis

Early Monitoring

• Measure viral load 4-6 weeks after starting ART to assess initial response 4, 1, 3
• Monitor viral load every 3 months until HIV RNA <50 copies/mL for at least 1 year 4, 3
• After 1 year of viral suppression with consistent adherence, monitoring can be reduced to every 6 months 4

CD4 Monitoring

• Measure CD4 counts every 6 months until counts are >250/μL for at least 1 year with concomitant viral suppression 4, 1, 3
• CD4 monitoring can be discontinued once this threshold is maintained 3

Treatment Failure Management

• If viral load remains above 50 copies/mL, repeat measurement within 4 weeks and reassess medication adherence and tolerability 4
• If adherence appears sufficient but viral suppression is not achieved, perform genotypic resistance testing 4, 1

Critical Pitfalls to Avoid

Diagnostic Errors

• Never rely solely on patient-reported risk behaviors, as many infected individuals either don't recognize their risk or won't disclose behaviors 3
• Avoid using 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 2
• Do not delay testing in low-prevalence settings, as screening is cost-effective even at prevalence as low as 0.1-0.2% 3

Consent and Counseling Requirements

• Obtain informed consent before performing HIV testing (some states require written consent) 4
• Provide pretest and posttest counseling addressing behavioral, psychosocial, and medical implications 4

Psychosocial Support and Comprehensive Care

Immediate Post-Diagnosis Support

• Behavioral and psychosocial services are integral to HIV care and should be available on-site or through referral 1, 3
• Implement brief, strengths-based case management after HIV diagnosis to facilitate linkage to care 4, 3
• Screen routinely for depression and provide treatment as needed 4, 1, 3

Prevention Counseling

• Assess transmission risk to others at each visit and provide risk reduction counseling 3
• Offer pre-exposure prophylaxis (PrEP) to HIV-negative persons with ongoing high risk for HIV infection 3
• Offer post-exposure prophylaxis (PEP) to persons with high-risk exposure within the previous 72 hours 3