Acquired Immuno-Deficiency Syndrome (HIV infection stage 3, AIDS)

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Introduction

Classifiction:

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

Diagnostic criteria

Laboratory

Diagnostic procedures

Radiology

Complications

Differential diagnosis

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
  • 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
      • efavirenz/FTC/tenofovir (Atripla)
      • elvitegravir/cobicistat/FTC/tenofovir (Stribild)
  • reverse transcriptase inhibitors
    • nucleoside reverse transcriptase inhibitors (NRTI)*
      • zidovudine (AZT, Retrovir) 200 mg PO TID (do NOT use with stavudine)
      • didanosine (ddI, Videx)
        • 100 mg PO BID < 60 kg
        • 200 mg PO BID > 60 kg
      • zalcitabine (ddC, Hivid)
        • 0.375 mg PO TID < 45 kg
        • 0.750 mg PO TID > 45 kg
      • lamivudine (3TC)
        • 150 mg PO BID (> 50 kg)
        • 2 mg/kg PO BID (< 50 kg)
      • 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)
  • 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
  • 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:
      • Bactrim/Septra DS QD (drug of choice)
      • dapsone 50 mg QD or 200 mg weekly
      • pyrimethimine 50-75 mg weekly
      • leucovorin 25 mg weekly
  • 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)
  • oral Candidiasis (thrush)
    • ketoconazole (Nizoral) 400 mg PO QD for 14 days, then 200 mg PO QD or for 7 consecutive days/month
    • fluconazole (Diflucan) 100-200 mg PO QD for 14 days, then 100-200 mg PO weekly or 50-100 mg QD
    • clotrimazole (Mycelex) troches 10 mg dissolved in mouth 5 x/day
    • nystatin swish & swallow 5 mL TID
  • 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, fundoscopic, 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

References

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