HIV Infection and AIDS

Basics

Description

HIV is a retrovirus that integrates into CD4 T lymphocytes (a critical component of cell-mediated immunity), causing cell death and resulting in severe immunodeficiency, opportunistic infections (OI), and malignancies:

  • Due to treatment advances, HIV is now 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 antiretroviral treatment, the average patient develops AIDS ∼10 years after transmission.
  • All HIV-infected persons with CD4 <200 cells/mm3 or having AIDS defining illnesses are categorized as having AIDS.

Epidemiology

Incidence

  • At end of 2008, 33.4 million people were estimated to be living with HIV/AIDS worldwide per UNAIDS and WHO. 2.7 million new HIV infections yearly and 2.0 million deaths attributable to AIDS (1)
  • US: 56,300 new cases; estimated 17,197 deaths of persons with AIDS in 2007 (2)

Prevalence

  • Estimated 1.1 million persons in US are living with HIV/AIDS, 25% of them were unaware of their status (1)
  • HIV/AIDS cases are disproportionately high among racial/ethnic minority populations (1).
  • Transmission of drug resistant virus is on the rise (1).
  • Younger women and girls are particularly vulnerable (1)

Risk Factors

  • Sexual activity (70% of world transmission). Viral load strongest predictor of heterosexual transmission with ulcerative urogenital lesions (3)[B].
  • 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. Male-to-male sexual contact accounts for 53% of newly diagnosed HIV/AIDS cases in 2007.
  • Injection drug use
  • Children of HIV-infected women:
    • Maternal HIV-1 RNA level is the best predictor of transmission risk.
    • HIV testing and use of antiretroviral drugs in pregnant women and their newborns has reduced the incidence of perinatal HIV transmission by >70% (from 25–29% without treatment to 8% with treatment) (4)[B].
    • Pregnant women should be treated until viral load is undetectable.
    • Can be transmitted through breastfeeding
  • Recipients of blood products between 1975 and March 1985
  • Occupational exposure

Genetics

People who lack CCR5, a cell-surface chemokine coreceptor used by HIV to infect cells, are highly resistant to HIV infection (5)[B].

General Prevention

Avoid unprotected sexual intercourse, injection drug abuse.

Etiology

HIV, a retrovirus

Commonly Associated Conditions

  • Syphilis may be more aggressive in HIV-infected persons.
  • Tuberculosis (TB) is coepidemic with HIV; test all persons with HIV for TB. Dually infected patients: 100× greater risk of developing active TB disease (compared with non-HIV) and higher rates of multidrug-resistant TB
  • Hepatitis C–coinfected patients have more rapid progression to cirrhosis.

Diagnosis

  • Acute retroviral syndrome: Precipitous decline in CD4 lymphocyte count and increased viremia, about 1–4 weeks after transmission. Confirmed by demonstrating a high HIV RNA in the absence of HIV antibody.
  • Mononucleosis-like syndrome, including:
    • Fever (97%)
    • Adenopathy
    • Pharyngitis (73%)
    • Rash (77%)
    • Myalgias/Arthralgia (58%)
    • Less commonly: Headache, diarrhea, nausea, vomiting, hepatosplenomegaly, weight loss, thrush, and neurologic symptoms (12%)
    • Seroconversion: Development of a positive HIV antibody test usually occurs within 4 weeks of acute infection and invariably by 6 months.
    • Asymptomatic infection: Variable duration (average 8–10 years) and is accompanied by a gradual decline in CD4 cell counts and a relatively stable HIV RNA levels (the viral “set point”). Persistent lymphadenopathy: >1 cm in ≥2 extrainguinal sites, persists >3 months
  • Symptomatic conditions:Without antiretroviral treatment, the average patient develops AIDS ∼10 years after transmission.
    • 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, tuberculosis and NHL, progressive multifocal encephalopathy. HIV nephropathy, Kaposi’s sarcoma, NHL, Hodgkin’s, invasive cervical cancer.
  • Advanced HIV disease: CD4 cell count of <50. Most AIDS related deaths occur at this time. Common late opportunistic infections: CMV disease (retinitis, colitis) or disseminated Mycobacterium avium complex. Also HIV wasting syndrome (>10% wt loss) and HIV encephalopathy/dementia/minor cognitive-motor disorder.

History

  • Past medical history, including sexually transmitted diseases and TB
  • Review of systems: Fever, chills, night sweats, diarrhea, weight loss, fatigue, adenopathy, oral sores, odynophagia (esophageal candidiasis), cough, shortness of breath and dyspnea on exertion (early P. carinii pneumonia), visual changes (cytomegalovirus [CMV] retinitis <200 CD4), skin rash, neurologic symptoms (central nervous system [CNS] infection, malignancy, or dementia), sinusitis
  • Social history, transmission risks, adherence
  • Immunization review

Physical Exam

All HIV-infected persons with CD4 <200 cells/mm3 or having AIDS defining illnesses are categorized as having AIDS.


Focus on weight, skin, retinal exam, oropharynx; lymph nodes; liver, spleen, mental status, sensation, genital and rectal examinations.

Diagnostic Tests & Interpretation

Lab

  • Screening: Enzyme-linked immunoabsorbent assay (ELISA) reported as reactive or nonreactive; sensitivity and specificity >98%. Obtain HIV RNA if acute HIV infection is suspected.
    • New rapid and oral test available (Home test kit, OraSure, OraQuickAdvanced Rapid HIV test).
  • Confirmatory: Western blot:
    • Results positive, negative, or indeterminate
    • Per Centers for Disease Control (CDC): Positive test is reaction with 2 of these 3 bands: P24, gp 41, and gp 120/160. If indeterminate, repeat test in 3–6 months.
  • CD4 cell count and percentage (6)[A]
  • HIV-RNA viral load (6)[A]
  • Complete blood count (CBC) with differential
  • Serum chemistry
  • Serologies: Hepatitis A, B, C; syphilis.
  • Urine screen for sexually transmitted infections (N. gonorrhoeae, C. trachomatis)
  • Cervical cytology
  • PPD
  • Glucose-6-phosphate (G-6PD) levels
  • Lipids at baseline and during highly active antiretroviral therapy (HAART)
  • Genotypic tests for resistance to antiretrovirals for patients who have pretreatment HIV RNA >1000 copies/m regardless of whether therapy will be initiated immediately (6)[A].

Imaging

Chest X-ray (CXR) if pulmonary symptoms or positive PPD.

Differential Diagnosis

Order other tests/serologies if HIV RNA test is negative. Order throat cultures for bacterial/viral respiratory pathogens, EBV VCA IgM/IgG, CMV IgM/IgG, HHV-6 IgM/IgG, and hepatitis serologies as appropriate to establish a diagnosis for patient’s symptoms.

Treatment

  • Antiretroviral therapy should be initiated in all patients with a history of an AIDS-defining illness or with a CD4 count <350 (6)[A]
  • Antiretroviral therapy should be initiated regardless of CD4 count in patients with the following conditions: Pregnancy, HIV-associated nephropathy and HBV coinfections when treatment of HBV is indicated [A], rapidly declining CD4 counts (e.g., >100 cells/mm decrease per year, higher viral load (e.g., >100,000 copies/ml) (6)[B]
  • Antiretroviral therapy is recommended for all patients with CD4 count between 350 and 500 (6)[A].
  • Consider for patients with CD4 count >500 (6)[B].

Medication

  • Nucleoside reverse transcriptase inhibitors (NRTI):
    • Abacavir (ABC, Ziagen), didanosine (DDL, Videx), emtricitabine (FTC, Emtriva), lamivudine (3TC, Epivir), stavudine (d4T, Zerit), tenofovir (Viread), zalcitabine (ddC, Hivid), zidovudine (AZT, Retrovir), zidovudine + lamivudine (Combivir), zidovudine + lamivudine + abacavir (Trizivir), tenofovir + emtricitabine (Truvada)
  • Non-nucleoside reverse transcriptase inhibitors (NNRTI): Delavirdine (Rescriptor), efavirenz (Sustiva), nevirapine (Viramune)
  • Protease inhibitors (PI): Amprenavir (Agenerase), atazanavir (Reyataz), darunavir (Prezista), fosamprenavir (Lexiva), indinavir (Crixivan), lopinavir-ritonavir (Kaletra), nelfinavir (Viracept), ritonavir (Norvir), saquinavir (Fortovase, Invirase), tipranavir (Aptivus)
  • Fusion inhibitors: Enfuvirtide (Fuzeon)
  • Entry inhibitors: Maraviroc (Selzentry)
  • Integrase inhibitors: Raltegravir (Isentress)
  • Drug failure: Before selecting regimen, review clinical symptoms, history of HAART, and adherence. Perform resistance testing.
  • Protease inhibitors can cause metabolic syndrome (lipodystrophy, decreased high-density lipoprotein [HDL], increased triglycerides, high blood pressure [BP], and hyperglycemia).
  • HAART, especially the protease inhibitors, have potentially life-threatening interactions.

First Line

  • NNRTI + 2NNRTI (6)[A]
  • PI (preferably boosted with ritonavir) + 2 NRTI (6)[A]
  • Integrase inhibitor + 2 NRTI (6)[A]

Additional Treatment

General Measures

  • Main goal of HAART: reduce the viral load, ideally to <50 HIV1 RNA copies/mL), and delay immune suppression. Viral load is the most important indicator of response to HAART.
  • An adequate CD4 response for most patients on therapy is defined as an increase in CD4 count in range of 50–150 cells/mm per year with an accelerated response in the first 3 months (6).
  • Prevent HIV-associated complications, short- and long-term adverse drug reactions, HIV transmission, HIV drug resistance, and preservation of HIV treatment options.
  • Assess substance abuse, economic factors (e.g., unstable housing), social support, mental illness, co-morbidities, high-risk behaviors, and other factors that are known to impair the ability to adhere to treatment and to promote HIV transmission.
  • With prolonged use of HAART, virus may mutate; medication will be less effective, but resistant strains have more difficulty reproducing. (Medication less effective than in a nonresistant patient.)
  • Occupational exposure: Postexposure treatment in conjunction with expert consultation
  • Prophylactic antimicrobial agents and vaccines:
    • P. jiroveci (former Pneumocystis carinii): TMP-SMX 1 DS/d or 1 SS/d indicated if CD4 <200/mm3, prior PCP, thrush, or unexplained fever for >2 weeks
    • M. tuberculosis: Treat if PPD >5 mm induration without prior prophylaxis or treatment, recent TB contact, or history of inadequately treated TB that healed. Confirmed by culture. Treatment is based on susceptibility.
    • Toxoplasma gondii: 33% per year risk of infection in untreated patients with CD4 <100/mm3. Prophylaxis: TMP-SMX DS/d.
    • M. avium complex (MAC): 20–40% risk with CD4 <50 and no HAART. Preferred prophylaxis is clarithromycin, 500 mg p.o. b.i.d., or azithromycin, 1,200 mg p.o. weekly.
    • Varicella (VZV): Seronegative and unexposed are at risk if exposed to chickenpox or shingles. Preferred regimen is VZIG 5 vials within 96 hours, preferably within 48 hours.
    • S. pneumoniae: 50–100× increased risk of invasive infection compared with general population; Pneumovax every 5 years
    • Influenza vaccine each fall
    • Hepatitis A and B vaccines for at-risk patients
    • Tetanus: dT vaccine in adults
    • Polio: Use IPV, not OPV in children.

Ongoing Care

Follow-Up Recommendations

Patient Monitoring

  • If HIV RNA is detectable at 2–8 weeks, repeat q 4–8 weeks until suppression to less than level of detection, then q 3–6 months (6)
  • Monitor HIV RNA, CD4 and CBC q 3–4 months (6).
  • Fasting lipids and fasting glucose annually if normal. Basic chemistry, AST, ALT, T/D bili q 6–12 months (6)
  • HLA-B 5701 if considering ABC (6)
  • Pregnancy test if starting EFV (6)

Diet

  • Encourage good nutrition, multivitamins.
  • Avoid raw eggs, unpasteurized milk. Severely immunocompromised should boil tap water to prevent Cryptosporidium.

Patient Education

  • Provide nonjudgmental prevention counseling, reviewing routes and behaviors leading to transmission to others and acquisition of super infection with resistant strains.
  • Counsel on importance of adherence to HAART and prevention of 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)
  • Information available at: http://www.aidsinfo.nih.gov/

Prognosis

  • When untreated HIV infection leads to AIDS, the life expectancy is 3.7 years.
  • AIDS-defining opportunistic infections usually do not develop until CD4 <200.
  • In HIV-untreated infection, CD4 counts decline at a rate of 50–80/yr, with more rapid decline as counts drop <200.
  • Drug resistance is not the most common cause of treatment failure, its adherence failure (7)[B].

Complications

  • Immunodeficiency
  • Opportunistic infections
  • Malignancy, including cervical or anal cancer

References

1. Centers for Disease Control and Prevention (CDC). HIV prevalence estimates–United States, 2006. MMWR Morb Mortal Wkly Rep. 2008;57:1073–6.

2. Centers for Disease Control and Prevention: Diagnoses of HIV infection and AIDS in the United States and Dependent Areas, 2008 HIV Surveillance Report, Volume 2 http://www.cdc.gov/hiv/surveillance/resources/reports/2008report/ Page last updated: June 14, 2010

3. 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;342:921–9.

4. US Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1 Infected Women for Maternal Health Interventions to Reduce Perinatal HIV-1 Transmission in the US. MMWR. 2002;51:1–38.

5. Lama J, Planelles V. Host factors influencing susceptibility to HIV infection and AIDS progression. Retrovirology. 2007;4:52.

6. US Department of Health and Human Services. Guide for the Use of Antiretroviral Agents in HIV-1 Infected Adults and Adolescents. Available at: http://aidsinfo.nih.gov/guidelines/adult/AA_040705.

7. Simon V, Ho DD, Abdool Karim Q. HIV/AIDS epidemiology, pathogenesis, prevention, and treatment. Lancet. 2006;368:489–504.

Codes

ICD9

042 Human immunodeficiency virus (HIV) disease

Snomed

  • 86406008 Human immunodeficiency virus infection (disorder)
  • 62479008 Acquired immune deficiency syndrome (AIDS) (disorder)

Clinical Pearls

  • The symptoms of HIV acute infection include fever, sore throat, adenopathy, myalgias, and rash.
  • Treatment guidelines are evolving to include earlier initiation of HAART in the course of the illness.
  • The most common complications of HIV/AIDS are immunodeficiency, opportunistic infections, and malignancy.
  • The prophylactic measures strongly recommended for HIV-infected patients are vaccination and prophylactic antibiotics based on history and CD4 count.

Jean-Paul Marat

Many tips are based on recent research, while others were known in ancient times. But they have all been proven to be effective. So keep this website close at hand and make the advice it offers a part of your daily life.

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