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Am Fam Physician. 2021;103(7):407-416

Related letter to the Editor: Management of Syphilis in People with HIV Infection

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

The HIV epidemic is an important public health priority. Transmissions continue to occur despite effective therapies that make HIV preventable and treatable. Approximately one-half of people with HIV are not receiving suppressive antiretroviral therapy (ART). Starting ART early, followed by continuous lifetime treatment, most effectively achieves durable virologic suppression and restoration of immune function that can improve clinical outcomes and prevent transmission to partners who are seronegative. National treatment guidelines include ART options that can be offered immediately after diagnosis, even before the results of baseline HIV drug-resistance testing are available. Initial ART selection should be guided by co-occurring conditions, including viral hepatitis, medications, and other factors such as pregnancy. Identifying and addressing psychosocial barriers to care is a key element of ensuring long-term adherence to treatment. The initial physical examination typically reveals no clinical manifestations of HIV in the absence of advanced disease. A comprehensive laboratory evaluation, including HIV viral load and CD4 lymphocyte monitoring, is necessary to guide decision-making for treatment, opportunistic infection prophylaxis, and vaccinations. The initial management of people with HIV presents a unique opportunity for family physicians to improve patients' long-term health care and reduce HIV transmissions.

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).18 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.

Clinical recommendationEvidence ratingComments
All people 15 to 65 years of age should be screened for HIV at least once; all people who are pregnant should be screened for HIV.12 AU.S. Preventive Services Task Force recommendations based on systematic review of high-quality patient-oriented evidence
Combination antiretroviral therapy should be initiated as soon as possible after HIV diagnosis.4,20 CDepartment of Health and Human Services guidelines based on epidemiologic and modeling studies; consensus guidelines from the International Antiviral Society–USA Panel
Combination antiretroviral therapy with durable viral load suppression is recommended for people with HIV to reduce the risk of sexual transmission to seronegative partners.48,20 CDepartment of Health and Human Services guidelines based on randomized controlled trials of serodiscordant couples; consensus guidelines from the International Antiviral Society-USA Panel
If the CD4 count is less than 200 cells per μL, prophylaxis against Pneumocystis jiroveci should be initiated.23 CDepartment of Health and Human Services guidelines based on retrospective studies
If the CD4 count is less than 100 cells per μL and Toxoplasma antibodies are positive, prophylaxis against Toxoplasma gondii should be initiated.23 CDepartment of Health and Human Services guidelines based on retrospective studies
Most vaccinations can be administered according to standard adult vaccination schedules; live vaccines should be avoided in people with a CD4 count less than 200 cells per μL.23,24 CDepartment of Health and Human Services guidelines based on expert opinion
RecommendationSponsoring organization
Do not routinely test for cytomegalovirus immunoglobulin G in patients with HIV infection who have a high likelihood of being infected with cytomegalovirus.HIV Medicine Association


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 factors1114 (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).

Screen all people 15 to 65 years of age at least once; younger adolescents and older adults at increased risk should also be screened.* Retest people who are at increased risk of infection.
Screen all pregnant people, including those who present in labor or at delivery whose HIV status is unknown.
Screen all patients being considered for pre- and postexposure prophylaxis according to established guidelines.
Test when acute HIV infection is suspected in people with recent exposure history (i.e., within the previous two months) and symptoms of recent viral infection, including fever, chills, night sweats, fatigue, myalgia, lymphadenopathy, headache, sore throat, and diarrhea.
Test when chronic HIV infection is suspected, based on clinical presentation and risk or exposure history. Symptoms of chronic untreated HIV include fever, lymphadenopathy, malaise or fatigue, weight loss, and symptoms from undiagnosed opportunistic infections.

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).1518 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.



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.


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

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