Lesson 1. Initial Evaluation

Background

Untreated HIV causes significant illness, beginning with an acute, self-limited viral syndrome and ultimately progressing to acquired immunodeficiency syndrome (AIDS), with the time between initial acquisition of HIV and development of AIDS varying widely from a few months to longer than 10 years (Figure 1).[1,2] Early diagnosis, linkage to care, antiretroviral therapy, and retention in care all play an important role in preserving the health of individuals with HIV as well as preventing transmission of HIV to others. The initial medical visit provides an opportunity to build trust, educate about HIV diseases and the benefits of antiretroviral treatment, and reinforce the importance of engagement in care. A similar evaluation can also occur at the time of transfer of care or with reengagement into care after a prolonged absence. At any of these initial encounters, the interaction between the individual with HIV and the medical provider may influence the patient’s likelihood of returning for further medical care. This review will explore the initial evaluation of persons who are newly diagnosed with HIV and/or newly entering care for HIV.

Goals of Initial Evaluation

The immediate goals of the initial evaluation are to confirm the diagnosis of HIV, obtain a complete medical history, perform a comprehensive physical examination, obtain appropriate laboratory studies, and initiate antiretroviral therapy.[3,4] If the individual is not already taking antiretroviral therapy, prioritize starting antiretroviral therapy as soon as possible, ideally on the same day as the initial visit.[5] As part of this process, it is important to address any concerns and barriers the patient may have related to starting antiretroviral therapy. During the initial encounter, it is important to establish a positive relationship with the patient. Further, since HIV can have a significant psychosocial impact on the individual with HIV, as well as on their partner, family, and community, the clinical care should be culturally sensitive, nonjudgmental, client-centered, and multidisciplinary.

The initial evaluation of a person diagnosed with HIV is an important time to determine the stage of the HIV disease. In the most recent 2014 case definition, a 5-stage system (0, 1, 2, 3, or unknown) is used (Table 1).[6]

• Stage 0 indicates early HIV infection, inferred from a negative or indeterminate HIV test result within 6 months of HIV diagnosis.
• Stage 1 is defined by a CD4 count equal to or greater than 500 cells/mm³, or a percentage equal to or greater than 26%, without the presence of an AIDS-defining clinical condition.
• Stage 2 is defined by a CD4 count equal to or greater than 200 cells/mm³ and less than 500 cells/mm³, or a percentage between 14 and 25%, without an AIDS-defining clinical condition.
• Stage 3 is defined by a CD4 count of less than 200 cells/mm³, or a percentage less than 14%, or the presence of an AIDS-defining illness. The absolute CD4 count takes precedence over the CD4 percentage, and the percentage is only considered if the corresponding CD4 count is unknown.
• Stage unknown refers to a person with laboratory confirmation of HIV infection but no information about CD4 cell count or percentage (and no information about the presence of AIDS-defining clinical conditions).

AIDS-Defining Clinical Conditions

In persons with laboratory-confirmed HIV infection, AIDS is defined based on a CD4 count below 200 cells/mm³, a CD4% less than 14%, or a specific clinical condition.[6] The list of AIDS-defining clinical conditions is extensive.[6](Table 2)

The initial evaluation and the focus of the first visit should take into account whether the client is newly diagnosed with HIV or has established HIV and is new to the clinic. For some initial visits, the client may have active HIV-related issues that need to be immediately addressed, and these issues may need to take priority. The initial encounter is an opportunity for the clinician to establish rapport with the patient, assess the client’s support network, assess readiness to start antiretroviral therapy (if they are not currently taking antiretroviral therapy), and inquire about any experience with HIV pre-exposure prophylaxis (PrEP) and HIV postexposure prophylaxis (PEP). Key elements of the medical history are listed below and are also outlined in detail in the HIVMA/IDSA Primary Care Guidance.[4]

• HIV-Related History
  • Date of diagnosis of HIV and, if known, the approximate date of initial HIV acquisition
  • Information on prior HIV testing, including most recent known negative HIV test
  • Identified risk factors related to HIV acquisition
  • Prior use of antiretroviral therapy, HIV PrEP, and/or HIV PrEP
  • Prior HIV-associated complications and comorbidities, including opportunistic infections, malignancies, and other HIV-related conditions
  • Obtain and review past medical records, if possible, including all prior HIV drug genotype resistance testing results
• Past Medical, Surgical, and Psychiatric History
  • Past medical history, including chronic medical conditions
  • Prior history of tuberculosis exposure, testing, and/or treatment
  • Past immunization history
  • Past surgical history, including complications with or from surgery
  • Psychiatric history, especially any history of depression, bipolar disorder, post-traumatic stress disorder, and intimate partner or domestic violence
• Medication and Allergy History
  • Medication history (including prior and/or current antiretroviral therapy, prior medications used for HIV preexposure prophylaxis or postexposure prophylaxis, over-the-counter drugs, pain medications, and dietary or herbal supplements)
  • Allergies and intolerances to medications, including hypersensitivity reactions to antibiotics and antiretroviral medications
• Sexual History
  • Sexual practices, including exposure sites with sex, condom use, and contraceptive use (if applicable)
  • History of prior sexually transmitted infections and treatment for these infections
  • HIV status of their partners (if known), and whether the individual has disclosed their HIV status to their partners
  • Past or current use of doxycycline posteexposure prophylaxis (doxy PEP)
• Substance Use History
  • Assess for current or past tobacco, vaping, alcohol, and illicit drug use
  • If substance use is present, address the impact on daily activities and readiness to engage in treatment for their substance use
  • Review current and past treatment for any substance use disorders
• Social, Family, and Travel History
  • Social support, coping strategies (including how the individual is dealing with a new HIV diagnosis or established HIV), employment status and history, financial status, housing, marital status, and desires related to family planning/reproduction
  • Family history, including history of cardiovascular disease and/or cancer
  • Residence and travel history (to determine if a patient has lived in or traveled to regions endemic to certain diseases, such as histoplasmosis or coccidioidomycosis)
• Comprehensive Medical Review of Symptoms
  • Perform a general review of symptoms, with emphasis on oral, cutaneous, respiratory, gastrointestinal, and neurologic systems

A complete physical examination should be performed at the initial encounter, with particular attention given to the oral, integumentary, and lymph node examinations. Key components of the physical examination are listed below and outlined in detail in the HIVMA/IDSA Primary Care Guidance:[4]

• Vital signs and General Appearance: including height and weight, evidence of obesity, wasting, or lipodystrophy
• Skin: rashes, bruising, inflammatory dermatoses, cutaneous lesions, and cutaneous manifestations of systemic disease
• Lymph nodes: generalized or localized lymphadenopathy (cervical, axillary, inguinal)
• Eye: retinal exudates or cotton wool spots, hemorrhages, pallor, icterus
• Oropharynx: abnormalities of dentition, gingiva, or mucosa, including ulcers, candidiasis, and oral hairy leukoplakia
• Cardiovascular: peripheral pulses, auscultation, and presence/absence of edema
• Chest: auscultation for breath sounds, airway movement, and wheezing
• Breast: nodules, nipple discharge
• Abdomen: masses, tenderness, hepatosplenomegaly
• Genitourinary: ulcers, warts, discharge, and appearance of cervix on gynecologic examination
• Anorectal: ulcers, warts, fissures, hemorrhoids, masses
• Neuropsychiatric: speech problems, gait abnormalities, focal deficits (motor or sensory), headaches, seizures, signs of dementia or memory impairments, depression and anxiety inventory, signs of drug or alcohol intoxication

As part of the initial evaluation for persons with HIV, a number of routine laboratory studies are recommended.[3,7,8] Recommendations from the Adult and Adolescent ARV Guidelines, the Adult and Adolescent OI Guidelines, the HIVMA/IDSA Primary Care Guidance, and the 2021 STI Treatment Guidelines are outlined below.[3,7,8,9] In addition, screening for cervical cancer and anal cancer should be discussed and addressed soon after a person with HIV has established medical care.[10] 

Baseline HIV-Related Tests

• Laboratory Confirmation of HIV Diagnosis: This test is not routinely needed since most individuals seen for an initial HIV evaluation have laboratory documentation of their HIV diagnosis. If, however, documentation of the HIV diagnosis is not available, appropriate confirmatory HIV diagnostic testing should be performed, with the logic that individuals may have undergone referral based only on a preliminary positive HIV test, or, in rare cases, individuals have factitiously claimed to have HIV.[7,11]
• CD4 Cell Count with Percentage: This test is recommended at baseline for all persons diagnosed with HIV, since the CD4 cell count and percentage are excellent indicators of immune function in persons with HIV. Further, the CD4 count and percentage help to estimate the individual’s risk for specific HIV-associated complications and to determine the need for prophylaxis against opportunistic infections. The absolute cell count is the number most often used in clinical practice, but the percentage can also be used to assess immune function and is somewhat less variable than the absolute count. The absolute CD4 count can be falsely low during an acute illness and in patients with cirrhosis or other causes of portal hypertension (due to splenomegaly and splenic sequestration).[12] In contrast, falsely elevated CD4 counts may occur in persons with anatomical or functional asplenia.[13]
• Quantitative Plasma HIV RNA Level (viral load): A quantitative plasma HIV RNA should be performed in all persons with HIV at entry into care.[7,14] The plasma HIV RNA level defines a baseline viral load, which can predict the pace of disease progression, with higher HIV RNA levels clearly correlating with more rapid disease progression and greater risk of developing AIDS (Figure 2).[15,16] In addition, the HIV RNA level is the most important marker to follow to assess treatment efficacy, so a baseline value is critical for monitoring subsequent treatment responses. Most of the commonly used quantitative HIV-1 RNA assays have a lower limit of detection threshold of 20 to 50 copies/mL.
• HIV Genotypic Drug-Resistance Testing: For all persons entering HIV care, a baseline standard genotypic resistance test is recommended to detect mutations in the reverse transcriptase and protease genes.[17] Results from the test provide information on the likely activity of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), and protease inhibitors (PIs). Routine baseline resistance testing of the integrase gene, which requires ordering a separate drug resistance test, is not routinely recommended in antiretroviral-naïve individuals, unless there is concern for transmitted integrase strand transfer (INSTI) drug resistance, such as in a person who has taken injectable cabotegravir for HIV preexposure prophylaxis (PrEP) or they have a sex partner with HIV who has known integrase resistance.[7,17,18]

• HLA-B*5701: Routine baseline screening for HLA-B*5701 is not recommended at the initial visit, since abacavir no longer a component the preferred antiretroviral initial treatment regimens.[7,19] When ordered, the HLA-B*5701 is used to identify individuals at high risk for an abacavir hypersensitivity reaction.[20] A negative test does not rule out the possibility of a hypersensitivity reaction but makes it extremely unlikely.
• Pregnancy Test: For women who have the potential to become pregnant, pregnancy testing should be performed at initiation or modification of antiretroviral therapy, since certain medications may be teratogenic.
• Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency Screening: Routine baseline screening for G6PD deficiency is not recommended, but is indicated before using oxidant drugs, such as dapsone, nitrofurantoin, or primaquine, in persons with a predisposing racial or ethnic background. Individuals with a higher genetic predisposition for G6PD include Black men and women, as well as men from the Mediterranean, Middle East, India, and Southeast Asia.[21] Persons with G6PD deficiency who have exposure to oxidant drugs have an increased risk of developing acute hemolysis.

Baseline Routine Medical Laboratory Tests

• Complete Blood Count (CBC) with Differential: Obtaining a baseline CBC is recommended since anemia, leukopenia, and thrombocytopenia are common among persons with HIV infection.
• Basic Chemistry Panel and Calculated Creatinine Clearance: A basic chemistry panel is recommended. As part of the basic chemistry panel, the test should determine the creatinine-based estimated glomerular filtration rate, which may affect the choice of antiretroviral therapy and the need for additional evaluation and monitoring.
• Hepatic Aminotransferase Levels: Baseline evaluation of hepatic aminotransferase levels is recommended, and testing should include alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Elevated levels may indicate a need for evaluation of medical comorbidities, including viral hepatitis.
• Urinalysis: A baseline urinalysis is recommended because individuals with HIV have an increased risk of developing HIV-associated nephropathy and chronic kidney disease. This risk is disproportionately higher among African Americans. The presence of proteinuria may be an early marker of disease in patients with normal renal function.
• Lipid Profile (Total cholesterol, HDL, LDL, triglycerides): A baseline lipid panel is recommended because antiretroviral drugs, HIV itself, and host factors are all associated with an increased risk of cardiovascular disease and dyslipidemia. If the initial lipid profile obtained is non-fasting and the results are abnormal, then a fasting lipid profile should be obtained.
• Random or Fasting Glucose: Baseline evaluation of blood glucose is recommended. If a random glucose is obtained, and it is abnormal, then a fasting glucose should be ordered. Screening for diabetes is important since it is more prevalent in people with HIV.

Coinfection and Comorbidity Screening

• Cryptococcal Screening: Baseline screening for cryptococcal antigen in individuals newly diagnosed with HIV who have a CD4 count of less than 200 cells/mm³ (and particularly when the CD4 count is less than 50 cells/mm³). A positive serum cryptococcal antigen required further evaluation.[22]
• Cytomegalovirus (CMV): Routine serologic testing (anti-CMV antibody) for evidence of established CMV infection is not recommended for men who have sex with men or persons who inject drugs, since these individuals can be assumed to be CMV seropositive. Checking anti-CMV can be considered for persons with HIV who have a lower risk of having acquired CMV infection and who currently have a CD4 count less than 50 cells/mm³.[23] All patients with a CD4 count of less than 50 cells/mm³ should receive counseling about common symptoms of CMV retinitis (floaters, flashes, field cuts), and ideally have a referral to an ophthalmologist for a dilated ophthalmologic examination to screen for CMV retinitis.[23]
• Hepatitis A Virus (HAV): Screen with hepatitis A antibody to evaluate for evidence of prior HAV infection or immunity.
• Hepatitis B Virus (HBV): All persons diagnosed with HIV should undergo testing for HBV with a triple screen of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), and total hepatitis B core antibody (total anti-HBc).[24]
• Hepatitis C Virus (HCV): At entry into care, all persons with HIV infection should undergo routine screening for HCV infection with HCV antibody, with all reactive results reflexed to HCV RNA testing.[25] Due to possible seronegative HCV infection among individuals with HIV infection, HCV RNA testing should be considered in some individuals who have a negative HCV antibody, particularly those with a history of injection drug use, a CD4 less than 200 cells/mm³, or an abnormal ALT.[26] Persons with prior natural clearance of HCV or clearance with HCV treatment should have screening with an HCV RNA test.
• Mycobacterium avium Complex (MAC) Screening: Routine screening for MAC infection is not recommended. Obtaining a blood culture for acid-fast bacilli (AFB) to screen for disseminated MAC infection may be considered in persons with a CD4 count of less than 50 cells/mm³ if they are initiating MAC prophylaxis.[27] Individuals with a CD4 count less than 50 cells/mm³ should have screening for symptoms of MAC disease (e.g., weight loss, fever, diarrhea, and lymphadenopathy); if these are present, a blood culture for AFB is indicated to test for MAC infection.[27]
• Mycobacterium tuberculosis: All individuals with HIV entering care should undergo screening for tuberculosis with tuberculin skin testing (TST) or interferon-gamma release assay (IGRA).[28] Individuals with a positive tuberculosis test result should receive treatment for latent M. tuberculosis infection after active tuberculosis has been excluded by a thorough history and chest radiographic imaging. Repeat TST or IGRA testing is recommended in persons with advanced HIV disease who initially had negative (or indeterminate) results but subsequently experienced an increase in the CD4 cell count to greater than 200 cells/mm³ after receiving antiretroviral therapy; in this situation, these individuals may have developed sufficient immune reconstitution to mount a positive TST or IGRA reaction.
• Toxoplasma gondii: Individuals with a CD4 count less than 200 cells/mm³ should have baseline screening for toxoplasmosis with anti-Toxoplasma IgG to detect latent infection.[29] If Toxoplasma serology is negative, patients should be counseled about methods to avoid exposure.[29] To minimize exposure risk, individuals with HIV who are Toxoplasma-seronegative should avoid eating raw or undercooked meat and shellfish; they should wash their hands after handling raw meat or after gardening or contact with soil; and if they own cats, they should not change the litter box and should be encouraged to keep their cats inside.[29] If a person with HIV has a positive Toxoplasma serology at baseline and a CD4 count decline less than 100 cells/mm³, they should receive prophylaxis for Toxoplasma encephalitis.

Screening for Sexually Transmitted Infections

• Syphilis: All persons with HIV should undergo screening for syphilis at the initial visit and periodically thereafter if ongoing risk exists for exposure to syphilis. In recent years, there have been high rates of syphilis in persons with HIV, especially among men with HIV who have sex with men.[9] Screening for syphilis is performed with either the reverse sequence algorithm, which starts with a treponemal test (EIA or CIA), or the traditional algorithm, which starts with a nontreponemal test (RPR or VDRL).[30] Persons with a prior history of syphilis should have screening with a nontreponemal test (RPR or VDRL).
• Herpes Simplex Virus (HSV): Routine serologic screening for past herpes infection with type-specific (HSV-1 and HSV-2) antibody tests is not recommended.[31] Type-specific herpes serologic screening can be considered for individuals with a history of genital ulcer disease, a history of atypical genital lesions that were not confirmed as HSV by PCR or culture, and/or when they have a sexual partner with HSV-2 infection.[9,31] In addition, type-specific HSV serologic screening should generally be limited to situations where the results will change clinical management or counseling.
• Routine STI Screening in Women: All women should be screened for Neisseria gonorrhoeae, Chlamydia trachomatis, and Trichomonas vaginalis at baseline and periodically thereafter, depending on risk and the prevalence of sexually transmitted infections in the community. Retesting in 3 months is indicated for women found to have any of these infections on initial screening because of high reinfection rates. Nucleic acid testing (NAT) or polymerase chain reaction (PCR) testing of urine is the preferred method of screening, but for clinics that do not have urine PCR testing for trichomoniasis, screening should utilize a wet mount or culture for T. vaginalis.
• Routine STI Screening in Men: All men should be screened for gonorrhea and chlamydia at baseline and at least annually thereafter, depending on risk and the prevalence of sexually transmitted infections in the community. Retesting in 3 months is indicated for men found to have gonorrhea or chlamydia infection because of high reinfection rates. Further, all men who have sex with men should have testing for urethral and rectal gonorrhea and chlamydia, as well as testing for oral gonorrhea—if they report receptive sex at these sites.[9] The NAT is the preferred method for these screening tests at urethral, rectal, and pharyngeal sites.[9,32] Routine screening for oropharyngeal chlamydia is not recommended. When testing for urethral infection, testing of a urine sample (not a urethral swab) with a NAT is the preferred approach and is FDA-approved. There are no guidelines for screening men for T. vaginalis.

Cervical and Anal Cancer Screening

• Cervical Cancer Screening: All persons with HIV who have a cervix and are at least 21 years of age should undergo cervical cancer screening soon after entry to HIV care.[33] Although most clinicians do not perform this testing at the initial visit to clinic given other priorities and time limitations, it is a test that can be discussed at the first visit and should be completed as soon as feasible after the first visit, if indicated. The cervical cancer screening test method should be determined by the individual’s age.[33] For those younger than 30 years of age, Pap testing is the recommended screening test.[33] For individuals with a cervix who are 30 years of age or older, the initial testing should consist of either (1) Pap testing alone or (2) Pap testing plus simultaneous HPV co-testing.[33]
• Anal Cancer Screening: All people with HIV, regardless of anal intercourse history, should have screening for anal cancer at least annually, with assessment for anal symptoms and a digital anorectal examination (DARE).[10] Anal cancer screening with cytology and/or HPV testing should start at age 35 years for men who have sex with men with HIV, and at age 45 years for most other persons with HIV.[10] The screening methods are based on local availability of high-resolution anoscopy (HRA) and on the cytology and HPV results.[10] In addition, anyone under the routine cytology screening age who has concerning symptoms should be evaluated with standard anoscopy.[10]

Providing appropriate immunizations is an important component of comprehensive HIV clinical care and should be addressed starting at the first visit. In general, response to any vaccine will be greatest in patients with higher CD4 cell counts and in those receiving suppressive antiretroviral therapy. Some routine immunizations, such as hepatitis A and hepatitis B, require baseline serologic testing first to determine whether the patient has immunity. Many experts defer most if not all immunizations from the initial visit to subsequent visits, primarily due to the overall complexity and priorities of the initial visit. Seasonal vaccines, such as influenza, could be prioritized to give at this initial visit. Up-to-date and thorough immunization recommendations for people with HIV are available in the Adult and Adolescent OI Guidelines section Immunizations for Preventable Diseases in Adults and Adolescents Living with HIV.[34] In addition, for a discussion of immunizations for people with HIV in this curriculum, see the topic Immunizations in Adults in this same Module Basic HIV Primary Care.

• The goals of the initial evaluation are to confirm the HIV diagnosis, obtain a complete medical history and physical examination, obtain appropriate baseline and historical laboratory data, provide basic education regarding HIV and its transmission, and initiate antiretroviral therapy.
• Establishing rapport at the initial evaluation is critical for keeping the person with HIV engaged in clinical care. The interaction at the initial visit should be culturally sensitive, nonjudgmental, client-centered, and multidisciplinary.
• The 2014 CDC case definition for HIV is divided into 5 stages based on CD4 count (or percentage) and the presence or absence of AIDS-defining conditions.
• The initial history intake should be comprehensive and cover medical, surgical, past HIV treatment, and psychiatric history, as well as address sexual behaviors, substance use, financial issues, interpersonal/family issues, and cultural influences that may impact care.
• A complete physical examination should be performed at the first visit, with special attention given to the oral, skin, and lymph node examinations.
• Baseline laboratory evaluation includes HIV disease tests, antiretroviral-specific tests, basic blood counts and chemistry panels, comorbidity and coinfection tests, and screening for STIs.
• Completing or making a plan for cancer screening tests, including HIV-associated malignancies as well as general age-appropriate cancer screening, should also be a priority at entry into HIV care.
• Initiating a discussion about appropriate immunizations is an important component of comprehensive HIV clinical care and should be addressed at the first visit.