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HIV/Aids
Meera Shah, MD, MS, AAHIVS
image BASICS
DESCRIPTION
HIV is a retrovirus (subgroup lentivirus) that integrates into CD4 T-lymphocytes, altering cell-mediated immunity and causing cell death, severe immunodeficiency, opportunistic infections, and malignancies if untreated.
  • Because of treatment advances, HIV is now classified as a chronic disease.
  • The natural history of untreated HIV infection includes viral transmission, acute retroviral syndrome, recovery and seroconversion, asymptomatic chronic HIV infection, and symptomatic HIV infection or AIDS.
  • Without treatment, the average patient progresses to AIDS about 10 years after acquiring the virus.
  • All HIV-infected persons with CD4 <200 cells/mm3 or with AIDS-defining illnesses are categorized as living with AIDS.
EPIDEMIOLOGY
Incidence
In the United States, HIV incidence has remained relatively stable at about 50,000 infections per year since the mid-1990s.
Prevalence
  • Estimated 1.2 million persons in the United States are living with HIV/AIDS as of 2012; 12.8% are unaware of their status (1).
  • HIV/AIDS cases are disproportionately high among racial/ethnic minority populations.
  • Transmission of drug-resistant HIV is rising.
ETIOLOGY AND PATHOPHYSIOLOGY
  • HIV primarily infects CD4+ cells. HIV is a singlestranded, positive-sense, enveloped RNA virus. After entering target cells, through the process of reverse transcription, viral RNA is transcribed to DNA and imported to the host cell nucleus and encoded into the cellular DNA. The virus can become latent or produce new viral RNA and proteins that are released to infect other CD4+ cells. Host CD8+ cells are activated to produce the seroconversion response.
  • There are two types of HIV. HIV-1 is the virus that was first described and is more virulent. It causes the majority of HIV infections worldwide. HIV-2 is less infective and seen primarily in West Africa or countries with economic ties to West Africa.
Genetics
People who have a mutation in CCR5, a cell-surface chemokine coreceptor, are resistant to HIV infection.
RISK FACTORS
  • Sexual activity (70% of transmission): Ulcerative urogenital lesions promote transmission (2).
  • Male-to-male sexual contact accounts for most (63%) newly diagnosed HIV/AIDS cases (1).
  • Injection drug abuse (IDA)
  • Children of HIV-infected women
    • Maternal HIV-1 RNA level predicts transmission.
    • HIV testing and treatment in pregnancy: With ARV prophylaxis, scheduled C-section and avoiding breastfeeding, HIV transmission rates have declined to <2% in the US and Europe (3)[B].
    • HIV can also be transmitted in breastmilk. HIV+ women should not breastfeed their infants.
  • Recipients of blood products prior to 1985
  • Occupational exposure (health care workers)
GENERAL PREVENTION
  • Avoid unprotected, high-risk sexual intercourse and intravenous drug use, particularly with shared needles.
  • Preexposure prophylaxis (PrEP) is recommended for individuals at high risk for transmission (4)[A].
COMMONLY ASSOCIATED CONDITIONS
  • Syphilis may be more aggressive in HIV-infected.
  • Tuberculosis (TB) is coepidemic with HIV; test all persons with HIV for TB (and vice versa). Dually infected patients have 100 times greater risk of developing active TB.
  • Patients coinfected with hepatitis C or hepatitis B have a more rapid progression to cirrhosis.
image DIAGNOSIS
  • Acute retroviral syndrome: CD4 lymphocyte count declines with increase in viral load 1 to 4 weeks after transmission; confirmed by demonstrating a high-HIV RNA in the absence of HIV antibody
  • Acute retroviral syndrome presents as a mononucleosislike syndrome including:
    • Fever (97%)
    • Adenopathy
    • Pharyngitis (73%)
    • Rash (77%)
    • Myalgias/arthralgia (58%)
    • Less common symptoms include headache, diarrhea, nausea, vomiting, weight loss, thrush, and neurologic symptoms (12%).
    • Seroconversion: Positive HIV antibody test occurs 4 weeks to 6 months after exposure.
  • Clinical latency (asymptomatic): variable duration (average is 8 to 10 years) accompanied by a gradual decline in CD4 cell counts and relatively stable HIV RNA levels (the viral “set point”). Patients often develop persistent generalized lymphadenopathy (>1 cm in ≥2 extrainguinal sites) and may develop fever, weight loss, myalgias, and gastrointestinal problems if the diagnosis is unrecognized.
  • Symptomatic conditions:
    • Fever or diarrhea >1 month, bacillary angiomatosis, thrush, persistent candidal vulvovaginitis, cervical dysplasia or carcinoma in situ, oral hairy leukoplakia, herpes zoster, idiopathic thrombocytopenic purpura, pelvic inflammatory disease, peripheral neuropathy or myelopathy
  • AIDS: defined by a CD4 cell count <200, a CD4 cell percentage of total lymphocytes <14%, or one of several AIDS-related opportunistic infections: Pneumocystis jiroveci (carinii) pneumonia, cryptococcal meningitis, recurrent bacterial pneumonia, candida esophagitis, CNS toxoplasmosis, TB and non-Hodgkin lymphoma (NHL), progressive multifocal encephalopathy, HIV nephropathy, Kaposi sarcoma, NHL, Hodgkin lymphoma, invasive cervical cancer
  • Advanced HIV disease: CD4 cell count <50. Most AIDS-related deaths occur at this time. Common late opportunistic infections: cytomegalovirus (CMV) disease (retinitis, colitis) or disseminated Mycobacterium avium complex as well as HIV wasting syndrome (>10% weight loss) and HIV encephalopathy/dementia/cognitive-motor disorder.
PHYSICAL EXAM
Focus on weight, skin, retinal exam, oropharynx, lymph nodes, liver, spleen, mental status, sensation, genital, and rectal examinations.
DIFFERENTIAL DIAGNOSIS
Burkitt lymphoma; candidiasis; coccidioidomycosis; cryptococcus; CMV; herpes simplex; lymphoma; toxoplasmosis, influenza
DIAGNOSTIC TESTS & INTERPRETATION
Initial Tests (lab, imaging)
  • Screening: Rapid oral test available and FDA approved. Two FDA-approved home testing kits are also available.
  • Obtain HIV RNA if acute HIV infection is suspected.
  • 4th-generation HIV testing combines antibody/antigen immunoassay for HIV-1, HIV-2 (5)
    • Can be positive within 2 to 3 weeks of exposure
    • Is considered a confirmatory test
  • CD4 cell count and percentage (5)[A]
  • HIV RNA viral load (5)[A]
  • CBC with differential
  • Serum chemistry
  • Serologies: hepatitis A, B, and C; syphilis
  • Urine screen for STIs (Neisseria gonorrhoeae, Chlamydia trachomatis)
  • Oral and anal screen for STIs (N. gonorrhoeae, C. trachomatis)
  • Cervical cytology at diagnosis, after 6 months and then annually in women with a cervix
  • Anal cytology in HIV-positive men who have sex with men and women with abnormal cervical cytology
  • Purified protein derivative (PPD) or QuantiFERON-TB Gold to screen for latent TB infection, chest x-ray if pulmonary symptoms or positive PPD
  • Glucose-6-phosphate levels
  • HLAB*5701 testing if abacavir is considered for treatment.
  • Lipids at baseline and during highly active antiretroviral therapy (HAART)
  • Genotypic tests for resistance to antiretrovirals for patients with pretreatment HIV RNA >1,000 copies/mL. Transmitted resistance to at least one drug can be seen in 6-16% of individuals (5)[A].
  • Tropism assay if considering CCR5 antagonist therapy
image TREATMENT
  • Initiate antiretroviral therapy in all patients with HIV to reduce risk of disease progression (AI to BIII) and to prevent the risk of transmission (AI to AIII) (5).
  • P.489

  • Several conditions increase the urgency for therapy including pregnancy (AI), AIDS-defining conditions (AI), acute opportunistic infections, CD4 <200 (AI), HIV-associated nephropathy (AII), acute/early infection (BII), HIV/HBV coinfection (AII), HIV/HCV coinfection (BII), rapidly declining CD4 counts (>100 cells/mm3 per year) (AIII), and high viral loads (> 100,000 copies/mL) (BII) (5)
  • Genotypic testing is recommended to guide therapy in patients who are naïve to antiretroviral therapy.
  • Tenofovir/emtricitabine or Truvada (300 mg/200 mg PO daily) FDA-approved for PrEP in adults at high risk (4)
GENERAL MEASURES
  • The main goal of HAART is to reduce viral load (ideally below limits of assay detection) and delay immune suppression. Viral load is the most important indicator of response to HAART.
  • Check for transmitted drug resistance before starting HAART (5)[A].
  • Prevent HIV-associated complications, short- and long-term adverse drug reactions, HIV transmission and drug resistance, and preservation of HIV treatment options.
  • Assess substance abuse, economic factors (unstable housing, food insecurity), social support, mental illness, comorbidities, high-risk behaviors, and factors known to impair adherence and promote transmission.
  • Prophylactic antimicrobial agents and vaccines:
    • P. jiroveci prophylaxis: trimethoprim/sulfamethoxazole (TMP-SMX) 1 DS (160 mg/800 mg) tab PO daily indicated if CD4 <200 cells/mm3, prior P. jiroveci, thrush, or unexplained fever for >2 weeks
    • Mycobacterium tuberculosis: Treat for latent TB if positive PPD or QuantiFERON-Gold without prior prophylaxis or treatment, with negative CXR, recent TB contact, or history of inadequately treated TB that healed.
    • Toxoplasma gondii prophylaxis: 33% per year risk of infection in untreated patients with CD4 <100 cells/mm3; prophylaxis: TMP-SMX 1 DS tab daily
    • M. avium complex prophylaxis: 20-40% risk with CD4 <50 and no HAART. Preferred prophylaxis is azithromycin 1,200 mg PO weekly.
    • Streptococcus pneumoniae: 50 to 100 times increased risk of invasive infection compared with general population; Prevnar and Pneumovax at least 8 weeks apart, every 5 years
    • Influenza vaccine annually
    • Hepatitis A and B vaccines
    • Tdap vaccination every 10 years. Substitute onetime dose of Tdap vaccine at time of next booster.
MEDICATION
  • Recommended regimens for ARV-naïve (5):
    • Integrase strand transfer inhibitor-based regimens:
      • Dolutegravir/abacavir/lamivudine (50 mg/600 mg/300 mg PO daily)—only for patients who are HLA-B*5701 negative (AI)
      • Dolutegravir (50mg PO daily) plus tenofovir disoproxil fumarate/emtricitabine (300 mg/200 mg PO daily) (AI)
      • Elvitegravir/cobicistat/tenofovir/emtricitabine (150 mg/150 mg/300 mg/200 mg PO daily)—only for patients with preantiretroviral therapy CrCl >70 mL/min (AI)
      • Raltegravir (400 mg PO BID) plus tenofovir/emtricitabine (300 mg/200 mg PO daily) (AI)
    • Protease inhibitor-based regimen:
      • Darunavir and ritonavir (800 mg PO daily and 100 mg PO daily) plus tenofovir/emtricitabine (300 mg/200 mg PO daily) (AI)
  • Alternative regimens
    • Based on a patient's individual needs and genotype, an alternative regimen may be chosen, which have been outlined in the DHHS guidelines.
  • Drug failure: Before selecting regimen, review clinical symptoms, history of HAART, and adherence. Perform resistance testing.
  • Protease inhibitors (PI) can cause metabolic syndrome.
  • HAART, especially the protease inhibitors, have interactions with other medications, such as antacids, steroids, contraceptives
image ONGOING CARE
FOLLOW-UP RECOMMENDATIONS
Patient Monitoring
  • If HIV RNA is detectable at 2 to 8 weeks, repeat every 4 to 8 weeks until suppressed to less than level of detection, then follow every 3 to 6 months (5).
  • Monitor HIV RNA, CD4, CBC every 3 to 4 months (5). CD4 monitoring may be spaced out after long-term virologic control.
  • Test fasting lipids and fasting glucose annually; basic chemistry, aspartate aminotransferase, alanine aminotransferase, T/D bilirubin every 6 to 12 months (5)
  • HLA-B 5701 if considering abacavir (5)
  • Pregnancy test women of childbearing age (5)
  • Urinalysis every 6 to 12 months or as clinically indicated (5)
  • Hepatitis C as clinically indicated (5)
DIET
  • Encourage good nutrition.
  • Discuss unknown and potentially harmful effects of supplement use including drug-drug interactions.
  • Avoid raw eggs and unpasteurized milk. Severely immunocompromised patients should boil tap water to prevent Cryptosporidium.
PATIENT EDUCATION
  • Provide nonjudgmental, sex-positive prevention counseling, reviewing high-risk behaviors and viral transmission.
  • Emphasize importance of adherence to HAART to prevent resistance.
  • National AIDS Hotline: 800-342-2437 [Spanish 800-342-7432]
  • National Institute of Health AIDS Clinical Trials Group: 800-874-2572
  • American Foundation for AIDS Research: 212-719-0033 (new treatments and research) www.aidsinfo.nih.gov
PROGNOSIS
  • Untreated HIV infection leading to the diagnosis of AIDS has an associated life expectancy of about 3 years, and if the patient has an OI, the life expectancy is about 1 year.
  • AIDS-defining opportunistic infections usually do not develop until CD4 <200.
  • Adherence failure—not drug resistance—is the most common cause of treatment failure (1)[B].
REFERENCES
1. Centers for Disease Control and Prevention. HIV/AIDS Statistics Overview. http://www.cdc.gov/hiv/statistics/overview/index.html. Accessed 2015.
2. Quinn TC, Wawer MJ, Sewankambo N, et al. Viral load and heterosexual transmission of human immunodeficiency virus type 1. Rakai Project Study Group. N Engl J Med. 2000;342(13):921-929.
3. U.S. Department of Health and Human Services. Recommendations for the use of antiretroviral drugs in pregnant HIV-1-infected women for maternal health and interventions to reduce perinatal HIV transmission in the United States. https://aidsinfo.nih.gov/contentfiles/lvguidelines/perinatalgl.pdf. Accessed 2015.
4. Centers for Diease Control and Prevention. Preexposure prophylaxis for the prevention of HIV infection in the United States—2014. A clinical practice guideline. http://www.cdc.gov/hiv/guidelines/index.html. Accessed 2015.
5. U.S. Department of Health and Human Services. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. http://aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf. Accessed 2015.
Additional Reading
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Aberg JA, Gallant JE, Ghanem KG, et al. Primary care guidelines for the management of persons infected with HIV: 2013 update by the HIV medicine association of the Infectious Diseases Society of America. Clin Infect Dis. 2014;58(1):e1-e34.
Codes
&NA;
ICD10
  • Z21 Asymptomatic human immunodeficiency virus infection status
  • B20 Human immunodeficiency virus [HIV] disease
  • R75 Inconclusive laboratory evidence of human immunodef virus
Clinical Pearls
&NA;
  • Acute HIV seroconversion illness mimics mononucleosis and is characterized by fever, sore throat, adenopathy, myalgias, and rash.
  • Transmitted drug resistance is increasing. Evaluate patients for resistance before initiating HAART.
  • Appropriate vaccination and prophylactic antibiotics should be administered to HIV+ patients based on clinical history and CD4 count.
  • Discuss prevention strategies, including PrEP, with individuals who are at high risk of HIV infection.