One-half of the estimated 1.1 million people in the United States with HIV infection are not receiving antiretroviral therapy (ART) or are receiving ART that is not sufficiently effective to achieve key clinical outcomes. Key outcomes include preventing clinical progression to advanced HIV disease, allowing near-normal life expectancy, and reducing transmission risk (i.e., treatment as prevention).^1–8 HIV disproportionately affects people of color and people with limited access to continuous, comprehensive health care.^9,10 Family physicians are uniquely positioned to diagnose HIV early and ensure long-term quality care for patients.

Diagnosis

HIV screening and diagnostic testing are essential for timely ART initiation and transmission prevention because approximately 38% of new transmissions are from people with HIV who are unaware of their HIV status.² Testing with the fourth-generation combination HIV antigen-antibody immunoassay is widely available and is recommended for screening people 15 to 65 years of age and for testing people with risk factors^11–14 (Table 1). In addition to HIV-specific immunoglobulin M and immunoglobulin G antibodies, which typically develop three or more weeks following infection, the fourth-generation HIV test detects the p24 antigen that appears as early as two weeks after infection. Inclusion of the p24 antigen shortens the time frame for detecting HIV, increasing the likelihood of identifying people with HIV who recently acquired the infection (i.e., within the previous one to two months).

The risk of HIV transmission from untreated people with acute or early HIV infection is much higher than from people with established chronic infection who are receiving suppressive ART. Therefore, improved identification of acute infection allows for earlier intervention, including ART initiation and education about transmission prevention (i.e., pre- and postexposure prophylaxis for partners who are seronegative).^15–18 Acute symptomatic HIV is often unrecognized, and fewer than 50% of people will have an identifiable acute illness.¹⁹ Many respiratory illnesses, including those caused by SARS-CoV-2 or influenza, are more common; therefore, a careful assessment of recent risk behaviors and exposures may be a factor that prompts HIV testing.

Evaluation

HISTORY AND PHYSICAL EXAMINATION

After a diagnosis of HIV, the initial history should document details about other chronic health conditions, hospitalizations, medications and allergies, mental and behavioral health, substance use, sexual health history, and experience with HIV pre- or postexposure prophylaxis. For people with advanced HIV, which is generally indicated by a CD4 lymphocyte count of less than 200 cells per μL (0.20 × 10⁹ per L), a full review of systems to assess for opportunistic infections or conditions associated with significant immunosuppression such as Pneumocystis jiroveci pneumonia, oropharyngeal candidiasis, tuberculosis, HIV-associated central nervous system and gastrointestinal disorders, and disseminated fungal or viral infections is recommended. When patients with chronic HIV infection reengage in care, clinicians should obtain a comprehensive history of previous ART regimens and treatment responses, including previous laboratory results. The initial examination generally shows no specific HIV-related manifestations unless symptomatic acute infection or advanced HIV disease is present.

LABORATORY TESTING

The diagnosis of HIV should be established with documented laboratory test results. Abnormal results from home-based, point-of-care, or rapid tests should be followed with standard, instrument-based laboratory assays. After the diagnosis is confirmed, comprehensive testing should be ordered (Table 2).^4,20 Testing should include primary care screening and HIV-specific baseline laboratory testing with a CD4 count, quantitative plasma HIV RNA (viral load), and HIV drug-resistance assessment. The CD4 count reflects the degree of immune system impairment and helps determine if opportunistic infection prophylaxis is indicated. The HIV viral load indicates how much active viral replication is occurring. Regular viral load monitoring during treatment is the most important indicator of a response to ART. HIV drug-resistance testing guides the initial selection of the ART regimen by identifying clinically significant mutations in the genes (reverse transcriptase, protease, integrase) targeted by commonly used antiretroviral drugs. Commercially available resistance tests are generally highly sensitive and accurate. Studies have established the clinical and cost-effectiveness of baseline resistance testing.²¹