HIV Infection and AIDS
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.
- 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)
- 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)
- Sexual activity (70% of world transmission). Viral load strongest predictor of heterosexual transmission with ulcerative urogenital lesions (3)[B].
- 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
People who lack CCR5, a cell-surface chemokine coreceptor used by HIV to infect cells, are highly resistant to HIV infection (5)[B].
Avoid unprotected sexual intercourse, injection drug abuse.
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.
- 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%)
- 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:
- 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.
- 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
Focus on weight, skin, retinal exam, oropharynx; lymph nodes; liver, spleen, mental status, sensation, genital and rectal examinations.
Diagnostic Tests & Interpretation
- 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
- 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].
Chest X-ray (CXR) if pulmonary symptoms or positive PPD.
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.
- 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].
- 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.
- NNRTI + 2NNRTI (6)[A]
- PI (preferably boosted with ritonavir) + 2 NRTI (6)[A]
- Integrase inhibitor + 2 NRTI (6)[A]
- 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.
- 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)
- Encourage good nutrition, multivitamins.
- Avoid raw eggs, unpasteurized milk. Severely immunocompromised should boil tap water to prevent Cryptosporidium.
- 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/
- 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].
- Opportunistic infections
- Malignancy, including cervical or anal cancer
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.
042 Human immunodeficiency virus (HIV) disease
- 86406008 Human immunodeficiency virus infection (disorder)
- 62479008 Acquired immune deficiency syndrome (AIDS) (disorder)
- 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.