Human immunodeficiency virus (HIV) infection has evolved from a disease that was predictably fatal to a chronic disease that can be effectively managed with contemporary antiretroviral therapy (ART) regimens. As a result of improved HIV care, the life expectancy in persons with HIV infection is similar to that in the general population. [1, 2] HIV treatment guidelines now recommend ART in all HIV-infected individuals, regardless of CD4 cell count. 
Diagnosis of HIV infection soon after infection and early initiation of ART are highly important, as both have been associated with improved CD4 count gains during ART, a reduced risk of acquired immunodeficiency syndrome (AIDS) development, reduced T-cell activation, and greater vaccine responsiveness. [4, 5]
Primary care providers (PCPs) are experiencing new challenges and opportunities in the current era of HIV infection. Understanding HIV risk factors and groups at highest risk is important, as targeted testing by PCPs plays an important role in diagnosing new HIV cases and preventing transmission to others.
In 2011, an estimated 49,273 new HIV infections occurred in the United States.  Most (65%) of these occurred in gay and bisexual men. Black/African American men and women were also strongly affected and were estimated to have an HIV incidence rate that was nearly 10 times higher than the incidence rate among whites. 
In addition to being on the front line for both HIV diagnosis and prevention, PCPs are increasingly involved in the co-management of HIV-infected patients with an HIV specialist.  PCPs provide expertise in preventive care and management of chronic conditions, such as cardiovascular disease, osteoporosis, and renal disease, which have become increasingly important for aging individuals with HIV infection.
Components of HIV Care
Caring for patients with HIV is challenging, and PCPs need to be mindful of special issues that encompass this population, like medical, psychological, and social challenges involved, along with the stigma associated with the disease. The most important aspect of patient care is education, which should include empowering patients with basic knowledge about HIV infection, methods of transmission, progression, prognosis, and prevention. A multidisciplinary approach that uses the special skills of nurses, pharmacists, nutritionists, social workers, and case managers is desirable. [8, 9]
Presenting Signs and Symptoms
HIV infection manifests in 3 main ways:
- An acute viral illness seen in the initial weeks of infection
- Immunologically mediated processes related to host responses to chronic viral infection
- Opportunistic diseases
Acute Retroviral Syndrome
Acute retroviral syndrome was first described in 1985 by Cooper and colleagues as an acute mononucleosislike syndrome. 
The incidence is not precisely known. A prospective study of homosexual men showed a 55% incidence in 22 subjects who became antibody-positive compared with 21% in 44 nonconverting control subjects.  The onset of illness is between 2 and 6 weeks after viral transmission and is believed to correlate with peak viremia, often in excess of 1 million viral copies/mL. Symptoms and associated frequency are as follows:
Chronic Viral Infection
In some cases, HIV infection is initially diagnosed when the patient presents with an AIDS-defining illness. These include the following: 
Bacterial infections, multiple or recurrent
Cervical cancer, invasive
Coccidioidomycosis, disseminated or extrapulmonary
Cryptosporidiosis, chronic intestinal
Herpes simplex virus (HSV) - Chronic ulcers or bronchitis, pneumonitis, or esophagitis
Histoplasmosis, disseminated or extrapulmonary
Isosporiasis, chronic intestinal
Lymphoid interstitial pneumonia or pulmonary lymphoid hyperplasia complex
Lymphoma - Burkitt (or equivalent term), immunoblastic (or equivalent term), or primary
Mycobacterium avium complex (MAC) or Mycobacterium kansasii, disseminated or extrapulmonary
Mycobacterium tuberculosis of any site, pulmonary, disseminated, or extrapulmonary
Mycobacterium, other species or unidentified species, disseminated or extrapulmonary
Pneumocystis jiroveci pneumonia (PJP)
Salmonella septicemia, recurrent
Wasting syndrome attributed to HIV
History and Physical Examination
A detailed review of symptoms and a complete physical examination should be performed. 
Specific information to gather should include the date of the first positive HIV test, as well as the date of the most recent HIV care visit.
The most important laboratory information for the PCP is the documentation of the patient’s most recent CD4 count and HIV viral load, as these serve as predictors of possible opportunistic infections upon presentation, or for which prophylaxis is needed.
Other information to gather includes medication history, including antiretrovirals (ARVs) and immunization status (reviewed below), and sexual history, including previous sexually transmitted infections (STIs).
Health-related behaviors such as tobacco abuse, alcohol use, drug use, and exercise and diet should be detailed and counseled appropriately.
Laboratory Evaluation and Other Studies
According to the Department of Health and Human Services (DHHS) HIV treatment guidelines  and the HIV Medicine Association of the Infectious Diseases Society of America guidelines for primary care of HIV infection,  the laboratory tests listed below are useful in monitoring and maintaining the health of patients with HIV infection.
This is important for HIV staging and prognosis. It helps guide initiation of ART and indicates risk of opportunistic infections and guides initiation of prophylaxis.
DHHS guidelines  recommend checking the CD4 count upon entry into care and repeating every 3-6 months in patients who have not initiated ART. In patients on ART, CD4 count monitoring should also be performed every 3-6 months during the first 2 years of ART or if viremia develops while the patient is on ART or if the CD4 count is below 300 cells/µL.
After 2 years on ART with consistently suppressed viral load, the CD4 count can be tested every 12 months in those with a CD4 count between 300 and 500 cells/µL; CD4 count monitoring is optional in those with CD4 count over 500 cells/µL.
HIV viral load
This is used to monitor efficacy of ART. Viral load has a high sensitivity in the setting of acute HIV infection when antibody results may still be negative. The goal of ART is to suppress virus to undetectable levels, usually less than 20 or 50 copies/mL.
DHHS guidelines  recommend evaluating viral load upon entry into care and upon ART initiation or modification.
In patients on ART, the viral load typically is measured every 3-4 months. However, in adherent patients with consistently suppressed viral load and stable immunologic status for more than 2 years, monitoring can be extended to every 6 months.
Complete blood cell count
Perform a complete blood cell (CBC) count upon entry into care and monitor every 3-6 months and upon ART initiation or modification.
Complete metabolic profile
Perform a complete metabolic profile upon entry into care and monitor every 3-6 months and upon ART initiation or modification.
Perform a urine analysis upon entry into care and at ART initiation or modification and monitor every 12 months (or every 6 months in patients on tenofovir). More frequent monitoring may be indicated in patients with evidence of kidney disease.
Perform a lipid profile upon entry into care, at ART initiation or modification, and every 6-12 months if the prior measurement was abnormal or normal, respectively.
Glucose or glycated hemoglobin A1C
Perform glucose (preferably fasting) or glycated hemoglobin A1C (HbA1C) upon entry into care, upon ART initiation or modification, and every 6-12 months if the prior measurement was abnormal or normal, respectively.
Hepatitis A virus antibody
If a hepatitis A virus (HAV) immunoglobulin G (IgG) antibody test is negative, offer the patient vaccination (see section below).
Hepatitis B virus infection status
The patient’s hepatitis B virus (HBV) infection status should be tested upon entry to care, including measurement of hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb), and antibody to hepatitis B total core antigen (anti-HBc or HBcAb). Those who are susceptible to infection should be vaccinated against HBV (see section below).
Hepatitis C virus antibody
Testing for hepatitis C virus (HCV) antibody should be performed upon entry to care and annually thereafter in those at risk. If positive, confirm result with HCV RNA. 
If T gondii IgG results are negative, repeat if the patient becomes symptomatic or when the CD4 count is below 100 cells/µL. If the result is positive, initiate prophylaxis when the CD4 count is below 100 cells/µL.
Test for tuberculosis (TB) upon entry into care via either a tuberculin skin test (TST) or an interferon-gamma release assay (IGRA). Patients with positive test results should be treated for latent M tuberculosis infection after acute TB has been excluded. Patients who are close contacts of persons with infectious TB should be treated for latent M tuberculosis infection regardless of their TST results, age, or prior courses of TB treatment after the diagnosis of active TB has been excluded.
Baseline chest radiographs should be obtained in all patients with a positive TST result to rule out active disease.
Cervical cancer screening in women: If a cervical Papanicolaou test yields normal findings, repeat after 6 months and then annually thereafter. If the findings are abnormal, further evaluation should be performed as indicated.
Anal cancer screening: HIV-infected men and women with human papillomavirus (HPV) infection are at increased risk for anal dysplasia and cancer, particularly men who have sex with men (MSM). Anal cancer is the fourth most common cause of cancer in patients with HIV infection or AIDS. [14, 14] Anal cytologic screening (anal Papanicolaou test) is recommended in MSM, women with a history of receptive anal intercourse or abnormal cervical Papanicolaou test results, and all HIV-infected persons with genital warts. 
Anal cytology is a reasonable predictor of anal intraepithelial neoplasia (AIN), but there is poor correlation between cytology and histologic grade.  Unfortunately, no randomized controlled trials have documented the value of AIN screening to date. Thus, the recommendation to perform anal Papanicolaou tests relies mostly on the histologic similarity between the cervix and the anus and the significant benefits of cervical cytology screening in reducing the incidence of cervical cancer.
HIV-infected men are at risk for hypogonadism. In male patients who experience fatigue, weight loss, loss of libido, erectile dysfunction or depression or who have evidence of reduced bone mineral density, consider obtaining morning serum total testosterone measurements.
Perform syphilis screening upon entry into care and at least annually in sexually active HIV-infected persons and frequent screening (every 3-6 months) in those considered high risk. A lumbar puncture should always be performed in patients with a reactive syphilis serology who have neurologic or ocular symptoms or signs (irrespective of past syphilis treatment) and in those who experience serologic treatment failure.
Screening for STIs
All women should be screened for trichomoniasis, and women aged 25 years or younger should be screened for chlamydial infection. Men and women should be screened for gonorrhea and chlamydia infection at initial presentation and then annually if at risk for infection. Retesting in 3 months is indicated in men and women found to be positive for gonorrhea and chlamydial infections and women found to be positive for trichomoniasis on initial screening owing to high reinfection rates. STIs should be screened for periodically thereafter, depending on the population, reported behaviors, the presence of other STIs the patient or his/her partner(s), and the prevalence of STIs in the community.
Patients at lower risk of CMV infection should be tested for latent CMV infection with an anti-CMV IgG test upon initiation of care. Patients who do not have evidence of immunity to varicella should receive postexposure prophylaxis with VariZIG as soon as possible (but within 96 hours) after exposure to a person with varicella or shingles. Varicella primary vaccination may be considered in HIV-infected, VZV-seronegative persons aged 18 years with CD4 cell counts at or above 200 cells/µL. 
Minimizing the risk of vaccine-preventable illnesses is an important component of primary care in HIV-infected individuals. Immunization recommendations in the setting of HIV infection are summarized below.
Administer to asplenic patients and those with history of recurrent Haemophilus infections.
Administer to susceptible MSM, as well as others with indications for hepatitis A virus vaccine. Revaccinate in 6-12 months for Havrix or 6-18 months for Vaqta. Vaccine is also available in combination with hepatitis B vaccine as Twinrix, administered as 3 or 4 doses. Serologic response should be checked 1 month after completion of series, and nonresponders should be revaccinated.
Administer to patients without evidence of past or present hepatitis B infection. Engerix-B or Recombivax HB is given at 0, 1, and 6 months. Vaccine is also available in combination with hepatitis A vaccine as Twinrix administered as 3 or 4 doses. Anti-HBV surface Ab titers should be checked 1 month after completion of vaccine series; if titer is 10 IU/mL or less, then revaccinate. Higher-dose booster or series may be considered in nonresponders.
The quadrivalent HPV vaccination should be given to all HIV-infected males and females in a 3-dose series at age 11 or 12 years and in those aged 13-26 years if not previously vaccinated.
This is administered yearly. Inactivated influenza vaccine is recommended; do not use live attenuated intranasal vaccine.
All patients with CD4 count above 200 cells/µL should receive a dose of PCV13 (Prevnar 13), followed by a dose of PPV23 (Pneumovax) at least 8 weeks later. If previously vaccinated with PPV23, give PCV13 at least 1 year after PPV23. A second PPV23 dose is recommended 5 years after the first PPV23 dose.
Oral polio vaccine (OPV) is contraindicated. Inactivated polio vaccine (IPV) should be given only if indicated. Administer 3 doses over 6-12 months for primary immunization.
Indications are same as for patients without HIV infection. Dose is Td, 0.5 mL IM; Tdap, 0.5-0.75 mL IM as per package insert. Substitute 1-time dose of Tdap vaccine at time of next booster, then Td every 10 years. Precautions should be observed with pregnancy. Td may be administered during second or third trimester or defer Td during pregnancy and administer Tdap postpartum.
Live vaccine is contraindicated for use in patients with severe immunosuppression (CD4 count < 200 cells/µL). Administer to all nonimmune persons with CD4 counts of 200 cells/µL or more.
Varicella zoster vaccine (VZV)
Live vaccine is contraindicated in patients with severe immunosuppression (CD4 count < 200 cells/µL). Consider for HIV-infected, VZV-seronegative persons with CD4 counts of 200 cells/µL or more. If vaccination results in infection with attenuated virus, treat with acyclovir. Susceptible household contacts of susceptible HIV-infected individuals should be vaccinated. Avoid exposure to VZV. If someone without immunity to VZV is exposed to VZV, administer varicella-zoster immune globulin (VZIG) as soon as possible (but within 96 hours).
ACIP recommends routine immunization with meningococcal conjugate vaccine (serogroups A, C, W, and Y; Menactra or Menveo) for persons aged 2 months or older with HIV infection. HIV-infected children younger than 2 years should receive the vaccine in accordance with the age-appropriate, licensed, multidose schedule (ie, Menveo at age 2, 4, 6, and 12 months). Persons aged 2 years or more with HIV infection who have not been previously vaccinated should receive a 2-dose primary series of MenACWY conjugate vaccine (Menactra or Menveo). Persons aged 2 years or older with HIV infection who have been previously vaccinated with 1 dose of meningococcal conjugate vaccine should receive a booster dose at the earliest opportunity, provided at least 8 weeks have elapsed since the previous dose, and then continue to receive boosters at the appropriate interval throughout life. 
The system-specific infections listed below are of concern when treating patients with HIV.
Central nervous system
A common symptom is headache. Some infectious causes include but are not limited to cryptococcal meningitis, neurosyphilis, tuberculous meningitis, progressive multifocal leukoencephalopathy, toxoplasmic encephalitis, CMV meningoencephalitis, other encephalitis, other meningitis (bacterial, tuberculous, fungal, viral), coccidioidomycosis, and histoplasmosis.
Infections that can affect the eye include HSV, herpes zoster virus (HZV), syphilis, CMV retinitis (CD4 count < 100/µL), Toxoplasma retinochoroiditis, and cryptococcal chorioretinitis.
Unilateral and bilateral sensorineural hearing loss may be caused by HIV infection involving CNS and syphilis, among others.
Nose and sinus
Sinusitis, allergic rhinitis, nasal lesions, and nasal obstruction are common.
Most common is oral candidiasis (CD4 cell count < 200/µL). Other causes include angular cheilitis, oral hairy leukoplakia, Kaposi sarcoma, and HSV.
Some common symptoms are dysphagia and odynophagia, infectious causes of which include candidal esophagitis, CMV, HSV, Kaposi sarcoma, MAC, and histoplasmosis. Another presenting symptom is nausea and vomiting, which is a common side effect of many ARVs but can sometimes be a sign of opportunistic infections.
Diarrhea is also a common symptom. Noninfectious causes such as adverse effects of ARVs, specifically protease inhibitors (PIs), are common. Infectious causes of diarrhea (occurring at any CD4 count) include viruses such as Norwalk virus, viral hepatitis, herpes enteritis, Salmonella, Shigella, Campylobacter, E coli O157:H7, Giardia lamblia, E histolytica, and C difficile. Other infectious causes of chronic diarrhea (occurring at CD4 cell counts < 300 cells/µL) include microsporidia, cryptosporidia, Isospora, MAC, and CMV (at CD4 counts < 50 cells/µL).
Causes of lymphadenopathy include HIV infection, persistent generalized lymphadenopathy (PGL), mononucleosis, EBV, MAC, TB, CMV, secondary syphilis, toxoplasmosis, histoplasmosis, other fungal diseases, immune reconstitution inflammatory syndrome (IRIS) involving various infections, and others.
Infections occurring at any CD4 count include TB and influenza, among others. Infections occurring at CD4 500 cells/µL or less include recurrent bacterial pneumonia, pulmonary Mycobacterium pneumonia (nontuberculous). Those occurring at CD4 200 cells/µL or less include PJP, Cryptococcus neoformans pneumonia or pneumonitis, and disseminated or extrapulmonary TB. At CD4 100 cells/µL or less, pulmonary Kaposi sarcoma and toxoplasma pneumonitis can occur. At CD4 50 cells/µL or less, disseminated histoplasmosis, disseminated coccidioidomycosis, CMV pneumonitis, disseminated MAC, disseminated Mycobacterium (nontuberculous), Aspergillus pneumonia, and Candida pneumonia can occur.
Vaginitis is a common symptom. Infectious causes include bacterial vaginosis (BV), candidiasis, trichomoniasis, pelvic inflammatory disease (PID), urinary tract infection, condyloma, HSV, chlamydia, and gonorrhea.
Rash is probably the most common symptom. During routine workup, possible drug-induced rash should be excluded. The 2 main ARVs that cause rash are nevirapine and abacavir. Nevirapine can cause a mild rash; moderate to severe rash with or without hepatitis requires discontinuation. Rash due to abacavir may occur in isolation or as part of the abacavir hypersensitivity reaction. The risk of hypersensitivity is closely linked to HLA-B*5701. Therefore, before starting an abacavir-containing regimen, patients should be tested for HLA-B*5701.
The comorbidities listed below may require management.
Abnormalities of body fat distribution
These are a recognized complication of ART. Lipohypertrophy has been variably associated with PIs and with nucleoside reverse transcriptase inhibitors (NRTIs). Lipoatrophy is most commonly associated with NRTIs, specifically stavudine, didanosine, and zidovudine. Once body shape changes occur, they cannot be reliably reversed, and switching to an NRTI-sparing regimen can slowly improve limb fat in patients with lipoatrophy but does not help patients with lipohypertrophy.
Treatment involves a multimodal approach, incorporating diet changes, exercise, lipid-modifying drug therapy, and, potentially, changes to ART. New lipid management guidelines were released by the American College of Cardiology/American Heart Association  in November 2013, which emphasize global risk assessment rather than treat-to-cholesterol targets.
If pharmacologic intervention is indicated for LDL reduction, HMG-CoA reductase inhibitors are the first-line treatment. Note that significant drug interactions occur between most statins and both PIs and NNRTIs. PIs increase serum levels of most statins and increase risk of side effects (eg, rhabdomyolysis). Of all statins, pravastatin is least affected. Atorvastatin, if used, should be started at a low dose and titrated upward. Lovastatin and simvastatin are contraindicated; rosuvastatin and fluvastatin have not been as well studied. Most NNRTIs decrease levels of statins and higher doses may be needed. The other classes of ARVs do not have recognized interactions with statins.
For treating hypertriglyceridemia, fibrates are the first-line drug option.
Other drugs such as niacin can worsen insulin resistance and cause hepatotoxicity; bile acid sequestrants should be avoided because they can interfere with the absorption of other drugs.
Patients taking ARVs, especially certain PIs and NRTIs, have an increased risk of hyperglycemia and diabetes mellitus. The incidence of newly onset hyperglycemia among HIV-infected patients on ART has been reported as about 5%, on average. Diagnosis of diabetes mellitus equating to a HbA1C value of 6.5% is defined by the American Diabetes Association.  However, a lower HbA1C threshold of 5.8% has also been suggested, as this cutoff has been associated with better sensitivity and specificity for patients on ART. 
Coronary heart disease risk
The incidence is increased up to 2- to 3-fold in HIV-infected individuals. A number of studies suggest that inflammation and immune activation due to uncontrolled HIV infection likely contributes to atherosclerosis. Clinicians should ask patients about coronary heart disease (CHD), CHD risk equivalents, and CHD risk factors and address these appropriately.
This can occur either as a primary or as a secondary disease. Some known risk factors include CD4 count less than 200 cells/µL; HIV viremia, particularly RNA levels greater than 4,000 copies/mL; African-American race; family history of kidney disease; and use of nephrotoxins.
Screening studies at initial HIV documentation should include urine analysis and serum creatinine. If abnormal values are detected, these should be evaluated further. Of note, selective drugs can cause acute or chronic kidney injury. These include tenofovir (can cause acute tubular necrosis, Fanconi syndrome), indinavir (acute interstitial nephritis [AIN] and crystalluria), atazanavir (AIN and nephrolithiasis), and abacavir (AIN). Special consideration regarding dosing of their ARVs should be given to patients who have chronic kidney disease or are undergoing hemodialysis.
Osteopenia and osteoporosis
HIV infection and use of ART, particularly regimens containing tenofovir, increase the risk of premature bone loss, thereby exacerbating the risk of osteopenia and osteoporosis. [9, 3] In addition, some evidence suggests that women with HIV infection develop premature physiologic menopause.  Baseline bone densitometry (DXA) screening for osteoporosis is recommended in HIV-infected postmenopausal women and men aged 50 years or older.  Other recommendations include counseling patients about risk factors of osteopenia and osteoporosis, such as cigarette smoking and excessive alcohol use, and the importance of regular exercise and adequate intake of calcium and vitamin D. 
Adverse Effects of ARVs and Drug-Drug Interactions
Drug-drug interactions are a common concern. The issues involved in evaluating drug interactions are complex. This complexity is increased because ARVs, specifically PIs, NNRTIs, and the CCR5 antagonist, can cause or be affected by alterations in the activity of the cytochrome P450 enzyme system in the liver.
Details on these interactions are available via the topic Common Drug Interactions with Protease Inhibitors and in published guidelines.  The physician's role is to educate patients that ARVs have a high potential for significant drug interactions. A complete medication list, including any herbal, nutritional, and dietary supplements, should be reviewed at every visit.
What would you like to print?
- Components of HIV Care
- Presenting Signs and Symptoms
- Acute Retroviral Syndrome
- Chronic Viral Infection
- History and Physical Examination
- Laboratory Evaluation and Other Studies
- System-Specific Infections
- Managing Comorbidities
- Adverse Effects of ARVs and Drug-Drug Interactions
- Show All