Acquired Immuno-Deficiency Syndrome (HIV infection stage 3, AIDS)
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Introduction
Classifiction:
- reclassified as HIV infection stage 3[23]
Etiology
Epidemiology
- leading cause of death in USA for all persons 25-40 years of age
- leading cause of death for men 25-40
- 3rd leading cause of death for women 25-40
- 90% of cases in developing countries
- rapidly progressive, multidrug-resitant cases emerging ?
Clinical manifestations
- symptoms generally begin with CD4 counts < 500/uL
- general: weight loss, night sweats, fever/chills, fatigue/ malaise, general wasting (wasting syndrome), pain
- oral lesions & ulcers: hairy leukoplakia, oral candidiasis, periodontal disease, oral herpes, aphthous ulcers
- generalized lymphadenopathy
- cervical, axillary & inguinal nodes commonly involved
- loss of lymphadenopathy is generally a sign of disease progression
- thoracic or abdominal lymphadenopathy generally indicates opportunistic infection
- cardiopulmonary: cough, shortness of breath
- gastrointestinal: hepatosplenomegaly, diarrhea
- skin lesions: skin rashes, tinea infections, folliculitis/ acne, seborrheic dermatitis, Kaposi's sarcoma
- genital lesions
- musculoskeletal: myalgias, arthralgias,
- neurologic: encephalitis, meningitis, myopathy, neuropathy, paresthesias, ataxia, depression, cognitive impairment, personality changes (also see neurologic complications of AIDS)
- recurrent Herpes: simplex & zoster (shingles)
- recurrent respiratory tract infections
Diagnostic criteria
- HIV infection plus
- CD4 count < 200/mm3, or
- AIDS-defining condition
Laboratory
- Diagnosis
- screening with ELISA for antibody to HIV
- confirmatory Western blot for antibodies to virus- specific proteins: a positive western blot consists of the presence of bands for:
- gp24; b) gp41 & c) gp120 or gp160
- seronegative HIV1 infections are rare, but potentially lethal 16]
- CD4 count: (< 200/mm3 defines AIDS)
- CD8 count & CD4/CD8 ratio
- complete blood count
- serum chemistries
- hepatitis B serology
- stool examination: ova & parasites, routine culture, fecal leukocytes, Clostridium difficile toxin, colon biopsy if negative
- purified protein derivative (PPD)
- pap smears in women
- serologic test for syphilis yearly
- biopsy of skin & mucous membrane lesions
- induced sputum for
- cerebrospinal fluid (CSF)
- antinuclear antibody
- erythrocyte sedimentation rate (ESR)
- HIV-1 RNA (viral load) monitoring
- prior to initiating anti-retroviral therapy
- obtain 2 measurements within a 2 week period
- 3-4 weeks after starting new anti-retroviral regimen to assess response
- at 3-4 months intervals during anti-retroviral therapy
- prior to initiating anti-retroviral therapy
- monitor lipid levels in patients on protease inhibitors
- Toxoplasma IgG baseline, then again when CD4 count drops below 100/mm3
- laboratory monitoring for prior to & after initiation of antiretroviral therapy (see table 3, ref[16])
Diagnostic procedures
- bronchoscopy if induced sputum inadequate
Radiology
Complications
- see complications in patients with HIV disease
- AIDS-defining illnesses in 2% of patients with CD4 counts < 200 cells/uL vs 0.4% for those with CD4 counts > 1000 cells/uL[20]
Differential diagnosis
- lymphoma
- leukemia
- other cancers
- tuberculosis
- malabsorbtion syndromes
- fungal infections
- other viral infections including Epstein Barr/mononucleosis
- pneumonia
- lupus erythematosus
- other rheumatologic disorders
- subacute bacterial endocarditis
Management
antiretroviral agents
- see HIV1 infection
- older recommendations
- start antiretroviral therapy if symptomatic, regardless of CD4 cell count
- start antiretroviral therapy if pregnant, regardless of CD4 cell count[3]
- asymptomatic patients should start at CD4 counts of <= 500/mm3[3]
- CD4 count < 200/mm3[11] (200-350/mm3[6], 350/mm3[21])
- post-seroconversion HIV RNA load of > 5000 copies/mL (10,000-100,000 copies/mL[6])
- rapid rate of CD4 count decline, HIV viral load of > 100,000 copies/mL, hepatitis B or hepatitis Ccoinfection, HIV-associated neuropathy or cardiovascular risk factors even if CD4 count is > 350/mm3[22]
- early treatment of asymptomatic patients (48 weeksof therapy) associated with higher CD4 counts at 4 years
- older recommendations
- initial therapy should consist of a 3-drug combination, individualized according to the results of HIV1 resistance testing
- multiple agents are used to prevent emergence of viral resistance (at least 3 agents)
- QUAD HIV therapy (4 drugs, once a day) non-inferior to standard of care regimens
- 3 one pill once a day regimens
- reverse transcriptase inhibitors
- nucleoside reverse transcriptase inhibitors (NRTI)*
- zidovudine (AZT, Retrovir) 200 mg PO TID (do NOT use with stavudine)
- didanosine (ddI, Videx)
- zalcitabine (ddC, Hivid)
- lamivudine (3TC)
- stavudine (d4T)
- 40 mg PO BID, or
- 30 mg PO BID if < 60 kg
- do NOT use with zidovudine
- abacavir: 300 mg PO BID
- HLA-B*5701-positive patients should not be prescribed abacavir due to risk of hypersensitivity
- tenofovir (Viread) 300 mg QD
- emtricitabine (FTC, Emtriva) 200 mg QD
- tenofovir/FTC (emtricitabine) combination (Truvada)
- all NRTIs except didanosine can be taken without food restrictions
- tenofovir associated with fewer cardiovascular deaths than avacavir[17]
- non-nucleoside reverse transcriptase inhibitors
- nevirapine 200 mg PO QD (x 14 days), then 200 mg PO BID
- delavirdine: 400 mg PO TID
- efavirenz: 600 mg PO QD
- etravirine (Intelence)
- nucleoside reverse transcriptase inhibitors (NRTI)*
- retroviral protease inhibitors
- saquinavir: 600 mg PO TID (with food)
- ritonavir: 600 mg PO BID (with food)
- indinavir: 800 mg PO every 8 hours (without food)
- nelfinavir: 750 mg PO TID
- amprenavir: 1200 mg PO BID & fosamprenavir
- Kaletra: lopinavir/ritonavir
- atazanavir 300 mg QD with ritonavir 100 mg QD
- darunavir 800 mg QD with ritonavir 100 mg QD
- tipranavir 500 mg BID with ritonavir 100 mg QD
- cross resistance may develop: do NOT use suboptimal doses that may result in partially resistant virus
- viral fusion inhibitors, enfuvirtide (Fuzeon)
- HIV co-receptor antagonists, maraviroc (Selzentry)
- HIV integrase inhibitors, raltegravir (Isentress)
- multidrug regimens[16]
- 2 NRTI* + (non-NRTI or retroviral protease inhibitor)[3]
- also see HAART
- preferred DHHS-recommended components for initial ART
- tenofovir/FTC + efavirenz + atazanavir + ritonavir
- tenofovir/FTC + efavirenz + darunavir + ritonavir
- tenofovir/FTC + efavirenz + fosamprenavir + ritonavir
- tenofovir/FTC + efavirenz + lopinavir/ritonavir
- once daily regimens
- tenofovir/FTC & lopinavir/ritonavir are coformulated
- ritonavir 100 mg QD is used in combination with atazanavir, darunavir or fosamprenavir
- elvitegravir/emtricitabine/cobicistat/tenofovir (Quad) once a day for treatment-naive adults
- efavirenz/FTC/tenofovir (Atripla) (once a day)
- lopinavir/ritonavir plus lamivudine not inferor to lopinavir/ritonavir plus two NRTI[21]
- abacavir/dolutegravir/lamivudine better than Atripla[22]
- alternative DHHS-recommended components for initial ART
- abacavir/3TC + nevirapine + atazanavir (HLA-B*5701 negative)
- ddI + 3TC or FTC + fosamprenvir
- AZT/3TC + saquinavir + ritonavir
- Combinations Not to Use or to Use with Caution:
- unboosted atazanavir + didanosine + emtricitabine (or lamivudine); efficacy concerns
- combination of nevirapine + tenofovir + emtricitabine (or lamivudine); reports of early virologic failure
- ritonavir 100mg per day must be given when tenofovir or efavirenz is used with atazanavir
- other (older) contraindicated regimens
- all monotherapies
- stavudine (d4T) + zidovudine (AZT)
- zalcitabine (ddC) + stavudine (d4T), didanosine (ddI) or lamivudine (3TC)
- treatment failure
- evaluate potential causes of treatment failure
- see HIV treatment failure
- HIV genotype resistance testing
- AT LEAST 2, preferably 3 new drugs should be used[16]
- pregnancy
- efavirenz should not be used in pregnant women (especially during the first trimester) or in women of childbearing potential[3][16]
- nevirapine may be used as an alternative to efavirenz for the initial NNRTI-based regimen in women with pretreatment CD4 counts <250 cells/mm3
- all drugs category C except ddI (category B)
- treat pregnant woman per standard care guidelines
- consider postponing or discontinuing therapy until 10-14 weeks of gestation
- continue AZT even with failed regimen (AZT is the only agent found to reduce the risk of perinatal HIV infection
- referrals may be directed to
Antiviral Pregnancy Registry PO Box 13398 Research Park Triangle, NC 27709-3398 (919) 483-9437, (800) 722-9292 x 38465
prophylaxis for AIDS patients
- Pneumocystis carinii pneumonia (PCP)
- indications: CD4 count < 200 uL
- prophylaxis:
- Bactrim/Septra DS QD or 3x/week (drug of choice)
- dapsone 100 mg QD
- atovaquone 750 mg BID with food
- pentamidine, aerosolized 300 mg (Respiguard II nebulizer)
- toxoplasmosis
- indications: CD4 count < 100/uL & positive IgG toxoplasmosis serology
- prophylaxis:
- Mycobacterium avium complex
- indications: CD4 count < 50/uL
- prophylaxis:
- azithromycin 1200 mg weekly (most cost-effective)
- clarithromycin 200 mg BID
- rifabutin 300 mg QD
- tuberculosis (see below)
- influenza: influenza virus vaccine annually
- pneumococcal pneumonia: Pneumovax every 5-10 years
- viral hepatitis:
- hepatitis A vaccine
- hepatitis B vaccine (series)
- one-time vaccination
- discontinue prophylaxis when HAART results in CD4 counts of > 200/uL for at least 6 months[3]
other
- tuberculosis
- skin testing & prophylaxis
- tuberculin skin testing annually unless PPD+ or with active tuberculosis
- indications for prophylaxis:
- PPD+ with negative chest X-ray
- anergic patients in high risk areas
- isoniazid (INH) 300 mg QD or 900 mg 2 x/week for 12 months
- active tuberculosis
- treat as extrapulmonary tuberculosis
- increased incidence of multidrug resistant TB
- indinavir or nelfinavir are protease inhibitors of choice
- rifabutin 150 mg/day should be subsituted forrifampin (with protease inhibitor)
- skin testing & prophylaxis
- oral Candidiasis (thrush)
- diarrhea
- Imodium 4 mg PO, then 2 mg PO every 6 hours or PRN
- Lomotil 2.5-5 mg PO 3-6 x/day, then TID PRN
- Paregoric (0.4 mg morphine/mg) 5-10 mL PO QID PRN
- octreotide (Sandostatin) 100 ug SQ TID, then increase to a maximum of 500 ug SQ QID
- soluble fiber (oats, rice psyllium) may diminish AIDS- associated diarrhea[3]
- insoluble fiber (wheat brain, fruit skins) may exacerbate AIDS-associated diarrhea[3]
- parenteral nutrition may be required for severe, intractable diarrhea
- weight loss
- megestrol (Megace) 80 mg PO TID (max 800 mg/day)
- dronabinol (tetrahydrocannabinol, Marinol) 2.5-5.0 mg PO BID before meals
- referral to clinical nutritionist[3]
- recombinant growth hormone & anabolic steroids are used by some clinicians, but clinical utility has not been demonstrated
- enteral nutrition is preferred over parenteral nutrition
- no restriction of activity: increased activity is not associated with accelerated HIV progression
- regular oral, funduscopic, dental, physical & pelvic examination
- treatment of opportunistic infections in patients with advanced HIV disease
- coexisting opportunistic infections is common
- relapse without maintenance therapy is common
- lifelong maintenance therapy for opportunistic infection may be indicated
- patient education
- use latex condoms with each episode of sexual intercourse
- avoid sexual practices that result in oral exposure tofeces
- pai n management in terminally ill patients
- alternative therapies with possible benefit
- hypericin or Essiac
- dinitrochlorobenzene, a contact sensitizer that may boost immune function
- case reporting required in California (local health department)[9]
- non-HIV related deaths becoming more common[14]
- aggressive cardiovascular risk reduction[3]
* best initial 3 drug regimen[6]
# better than *[12] (not yet new standard) addition of abacavir to AZT, 3TC, efavirenz does not improve outcome
More general terms
More specific terms
Additional terms
- AIDS dementia complex; AIDS encephalopathy; HIV-associated dementia (HAD)
- AIDS-defining condition
- complications in patients with HIV1 infection
- HIV treatment failure
- HIV1/AIDS-associated malignancy
- hospice guidelines for determining prognosis, HIV
- human immunodeficiency virus-1 (HIV-1)
- oral lesions of HIV & AIDS
- outpatient management of HIV related pneumonia
- safe sex (prevention of HIV1 & other STDs)
References
- ↑ Saunders Manual of Medical Practice, Rakel (ed), WB Saunders, Philadelphia, 1996, pg 720-26
- ↑ DeGowin & DeGowin's Diagnostic Examination, 6th edition, RL DeGowin (ed), McGraw Hill, NY 1994, pg 861
- ↑ 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 3.8 3.9 Medical Knowledge Self Assessment Program (MKSAP) 11, 14, 16 American College of Physicians, Philadelphia 1998, 2006, 2012
- ↑ Journal Watch 22(20):150, 2002 Yeni PG et al, JAMA 288:222, 2002 Dybul M et al, Ann Intern Med 137:381, 2002 MMWR Recomm Rep 51:1-64, 2002 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5107a1.htm Masur H et al, Ann Intern Med 137:435, 2002 http://www.cdc.gov/mmwr/preview/mmwrhtml/rr5108a1.htm
- ↑ http://www.dhs.ca.gov.aids Action Report, Medical Board of California, 85:9 (April) 2003
- ↑ 6.0 6.1 6.2 6.3 Journal Watch 24(3):24, 2004 Robbins GK et al, N Engl J Med 349:2293, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14668455 Shafer RW et al, 349:2304, 2003 PMID: https://www.ncbi.nlm.nih.gov/pubmed/14668456
- ↑ Journal Watch 24(11):89, 2004 van Leth F, Phanuphak P, Ruxrungtham K, Baraldi E, Miller S, Gazzard B, Cahn P, Lalloo UG, van der Westhuizen IP, Malan DR, Johnson MA, Santos BR, Mulcahy F, Wood R, Levi GC, Reboredo G, Squires K, Cassetti I, Petit D, Raffi F, Katlama C, Murphy RL, Horban A, Dam JP, Hassink E, van Leeuwen R, Robinson P, Wit FW, Lange JM; 2NN Study team. Comparison of first-line antiretroviral therapy with regimens including nevirapine, efavirenz, or both drugs, plus stavudine and lamivudine: a randomised open-label trial, the 2NN Study. Lancet. 2004 Apr 17;363(9417):1253-63. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15094269
Gulick RM, Ribaudo HJ, Shikuma CM, Lustgarten S, Squires KE, Meyer WA 3rd, Acosta EP, Schackman BR, Pilcher CD, Murphy RL, Maher WE, Witt MD, Reichman RC, Snyder S, Klingman KL, Kuritzkes DR; AIDS Clinical Trials Group Study A5095 Team. Triple-nucleoside regimens versus efavirenz-containing regimens for the initial treatment of HIV-1 infection. N Engl J Med. 2004 Apr 29;350(18):1850-61. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15115831 <Internet> http://www.thelancet.com/journal/vol363/iss9417/full/llan.363.9417.original_research.29309.1 - ↑ Journal Watch 24(17):136, 2004 Yeni PG, Hammer SM, Hirsch MS, Saag MS, Schechter M, Carpenter CC, Fischl MA, Gatell JM, Gazzard BG, Jacobsen DM, Katzenstein DA, Montaner JS, Richman DD, Schooley RT, Thompson MA, Vella S, Volberding PA. Treatment for adult HIV infection: 2004 recommendations of the International AIDS Society-USA Panel. JAMA. 2004 Jul 14;292(2):251-65. PMID: https://www.ncbi.nlm.nih.gov/pubmed/15249575
DHHS Panel on Clinical Practices for Treatment of HIV Infection. Guidelines for the use of antiretroviral agents in HIV-1 infected adults and adolescents. March 23, 2004 http://www.aidsinfo.nih.gov/guidelines/adult/AA_032304.pdf - ↑ 9.0 9.1 Journal Watch 25(10):84, 2005 Markowitz M, Mohri H, Mehandru S, Shet A, Berry L, Kalyanaraman R, Kim A, Chung C, Jean-Pierre P, Horowitz A, La Mar M, Wrin T, Parkin N, Poles M, Petropoulos C, Mullen M, Boden D, Ho DD. Infection with multidrug resistant, dual-tropic HIV-1 and rapid progression to AIDS: a case report. Lancet. 2005 Mar 16;365(9464):1031-8. <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/15781098 <Internet> http://www.nyc.gov/htmldoh/html/pr/pr16-05.shtml
- ↑ Napravnik S, Edwards D, Stewart P, Stalzer B, Matteson E, Eron JJ Jr. HIV-1 drug resistance evolution among patients on potent combination antiretroviral therapy with detectable viremia. J Acquir Immune Defic Syndr. 2005 Sep 1;40(1):34-40. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16123679
- ↑ 11.0 11.1 Severe P et al, Antiretroviral therapy in a thousand patients with AIDS in Haiti N Engl J Med 353:2325, 2005 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16319381
- ↑ 12.0 12.1 Gallant JE, DeJesus E, Arribas JR, Pozniak AL, Gazzard B, Campo RE, Lu B, McColl D, Chuck S, Enejosa J, Toole JJ, Cheng AK; Study 934 Group. Tenofovir DF, emtricitabine, and efavirenz vs. zidovudine, lamivudine, and efavirenz for HIV. N Engl J Med. 2006 Jan 19;354(3):251-60. PMID: https://www.ncbi.nlm.nih.gov/pubmed/16421366
- ↑ Gulick RM et al, Three vs four-drug antiviral regimens for intital treatment of HIV-1 infection. A randomized controlled trial. JAMA 2006, 296:769 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16905783
- ↑ 14.0 14.1 Sackoff JE et al, Causes of death among persons with AIDS in the era of highly active antiretroviral therapy: New York City Ann Intern Med 2006, 145:397 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16983127
Aberg JA The changing face of HIV care: Common things really are common. Ann Intern Med 2006, 145:463 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16983135 - ↑ Molina J-M et al. Once-daily atazanavir/ritonavir versus twice-daily lopinavir/ritonavir, each in combination with tenofovir and emtricitabine, for management of antiretroviral-naive HIV-1-infected patients: 48 week efficacy and safety results of the CASTLE study. Lancet. 2008 Aug 23;372(9639):646-55. PMID: https://www.ncbi.nlm.nih.gov/pubmed/18722869
- ↑ 16.0 16.1 16.2 16.3 16.4 Bartolo I et al Rapid clinical progression to AIDS and death in a persistently seronegative HIV-1 infected heterosexual young man. AIDS 2009 Nov 13; 23:2359. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19809269
- ↑ 17.0 17.1 Martin A et al Simplification of antiretroviral therapy with t enofovir-emtricitabine or abacavir-lamivudine: A randomized, 96-week trial. Clin Infect Dis 2009 Nov 15; 49:1591. PMID: https://www.ncbi.nlm.nih.gov/pubmed/19842973
- ↑ Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Nov 3 , 2008. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
- ↑ Zolopa A et al. A randomized double-blind comparison of coformulated elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate versus efavirenz/emtricitabine/tenofovir disoproxil fumarate for initial treatment of HIV-1 infection: Analysis of week 96 results. J Acquir Immune Defic Syndr 2013 May 1; 63:96 PMID: https://www.ncbi.nlm.nih.gov/pubmed/23392460
- ↑ 20.0 20.1 Mocroft A et al. The incidence of AIDS-defining illnesses at a current CD4 count >= 200 cells/uL in the post-combination antiretroviral therapy era. Clin Infect Dis 2013 Aug 6 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/23921881 <Internet> http://cid.oxfordjournals.org/content/early/2013/08/06/cid.cit423
- ↑ 21.0 21.1 21.2 Physician's First Watch, October 28, 2013 David G. Fairchild, MD, MPH, Editor-in-Chief Massachusetts Medical Society http://www.jwatch.org
- ↑ 22.0 22.1 22.2 Walmsley SL et al Dolutegravir plus Abacavir-Lamivudine for the Treatment of HIV-1 Infection. N Engl J Med 2013; 369:1807-1818November 7, 2013 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/24195548 <Internet> http://www.nejm.org/doi/full/10.1056/NEJMoa1215541
- ↑ 23.0 23.1 Centers for Disease Control & Prevention (CDC) National Notifiable Diseases Surveillance System (NNDSS) http://wwwn.cdc.gov/nndss/conditions/search/
- ↑ AIDSinfo http://aidsinfo.nih.gov/guidelines/