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Author: Laura Kogelman, M.D.

1. HIV Case 1 Answer

  • Yes, he has AIDS.
  • AIDS is defined as the following:
    • CD4<200 or <15%
    • OIs: PCP, cryptococcal meningitis, recurrent bacterial pneumonia, candidal esophagitis, CNS toxoplasmosis, TB, disseminated MAI or other atypical mycobacteria, CMV infections
    • Non-Hodgkin's Lymphoma
    • Less common infections: candidiasis of trachea, larynx, bronchi, lungs;disseminated/extrapulmonary coccidiomycosis or histoplasmosis; chronic intestinal cryptosporidiosis or isosporiasis; recurrent salmonella septicemia.
    • KS, LIP (lymphoid interstitial pneumonia/pulmonary lymphoid hyperplasia), PML
  • CD4 counts and disease states:
    • >500: generally similar to HIV negative, slight increase in risk of bacterial infections, herpes zoster, TB, skin conditions
    • 200-500: increased risk of bacterial infections, especially pneumococcal pneumonia, sinusitis; cutaneous KS, vaginal candidiasis, ITP
    • 100-200: Thrush, OHL, PCP, cryptococcal meningitis, toxoplasmosis
    • 50-100: PML, CNS lymphoma
    • <50: disseminated MAC, CMV retinitis, neuropathy, encephalopathy
  • Classes of anti-HIV medications:
    • NRTIs and NtRTIs (Nucleoside or Nucleotide Reverse Transcriptase Inhibitors)
    • NNRTIs (Non-Nucleoside Reverse Transcriptase Inhibitors)
    • PIs (Protease Inhibitors)
    • Fusion Inhibitors

Poor adherence or compliance with ART (anti-retroviral therapy) can lead to poor control of the HIV virus, i.e. increase in HIV viral load, decrease in CD4 counts and subsequent development of drug resistance.

Never having had an "undetectable" viral load suggests that he is likely not completely adherent to his regimen and thus is not able to achieve control of viral replication. It also suggests that there is likely resistance to his current ART (and likely to prior regimens)--the virus is able to replicate itself despite the presence of the drug. Since he has been exposed to many anti-HIV drugs he may have a lot of resistance mutations.

The weight loss is concerning. It may be because of his advanced HIV infection alone or it may be because he has an underlying infection causing weight loss.

It is important to know what his HIV virus is resistant to and what it is sensitive to, so that we can come up with a regimen of medications that will be effective.

No. 1996-1999: number of deaths rapidly decreased by 50%. Since 1998, number of AIDS cases and deaths stabilized, while the prevalence of AIDS rose. Linear increase between 1984-1994, sharp decrease after the max. of 16deaths/100,000 pop. in 1995. The rate in 1998: 5 deaths /100,000 pop. The decrease after 1995: due to HAART and use of prophylactic medications against OIs. In Africa and other third world nations where ART is not available, the number of deaths continues to increase.

2. HIV Case 2 Answers

  • UTI with pyelonephritis
  • Urethritis secondary to an STD such as gonorrhea or chlamydia
  • Prostatitis
  • Nephrolithiasis

Indinavir (Crixivan) is known to cause crystalluria and nephrolithiasis. Good hydration can diminish this side effect.

Lipodytrophy syndrome involves a constellation of features of physical changes such as loss of subcutaneous fat especially in the limbs and face and increase in central abdominal adiposity. Increased fat deposition on the neck may occur, causing what is called "a buffalo hump."

The PI's have been implicated in this syndrome as have the "d" drugs-ddI and d4T. Other NRTIs and NNRTIs may cause some metabolic changes but less so than the classes listed above.

In addition to physical changes patients may also develop dyslipidemia: increase in total cholesterol, increase in triglycerides, increase in LDL and decrease in HDL. Insulin resistance and diabetes may also develop.

3. HIV Case 3 Answers

Ritonavir inhibits the cytochrome P450 system leading to decrease in metabolism of the other protease inhibitors, thus leading to higher levels of the other PIs. Use of ritonavir in combination with other PIs is known as boosting. Lopinavir/ritonavir is a fixed drug combination known as Kaletra.

You need to know other co-morbid conditions as it can help you to tailor a patient's ART regimen to avoid additional toxicity. For example, in a patient with Hepatitis C you would try to choose anti-retrovirals with less hepatotoxicity if possible. You would also need to think about the fact that the patient may need to be treated for the Hep C and you need to consider which HIV medications might interact with his Hepatitis C medications. In this patient another comorbidity to consider is his underlying peripheral neuropathy. Both d4T and ddI can cause peripheral neuropathy, the combination can be quite toxic in terms of this condition. We rarely (almost never) prescribe these two drugs in combination anymore. At the time this patient was treated, options were more limited and we did not know the full extent of this toxicity.

Hepatotoxicity and pancreatitis. Hepatotoxicity most likely secondary to lopinavir/ritonavir in the setting of underlying hepatitis C infection. Pancreatitis secondary to ddI and d4T toxicity. Lactic acidosis may also be playing a role (increased LFTs) and is most likely secondary to mitochondrial toxicity induced by d4T and ddI. Lactic acidosis typically presents with general malaise, low grade fevers, myalgias, i.e., flu-like symptoms. Hepatitis, decreased bicarb levels and increase lactate levels are seen on lab-work.

Because both ritonavir and the other PIs are metabolized by the P450 system, drugs that are also metabolized by this system can lead to significant drug interactions. You would generally try to avoid Dilantin in this patient for this reason.

4. HIV Case 4 Answers

HIV can be transmitted via blood, semen, breast milk and fluids such as vaginal secretions, CSF, synovial fluid, peritoneal fluid, pleural fluid, amniotic fluid, etc. It is not thought to be transmitted via tears, saliva, sputum, vomitus, urine, or feces unless there is visible blood in these fluids.

Main routes for transmission of HIV are through the following:

  • Unprotected sexual intercourse (anal receptive intercourse is highest risk, followed by vaginal receptive; anal/vaginal insertive and oral sex are lower risk; presence of open sores or lesions, traumatic tears, etc., increase likelihood of transmission).
  • Sharing needles
  • Blood transfusion before 1985. From 1985-1995, the risk in the United States of HIV-1 transmission per unit transfused was estimated to be between 1 in 450,000 and 1 in 660,000. By 2003, this estimated risk had decreased to between 1 in 1.4 million and 1 in 1.8 million units.
  • Human bite, if there is blood in the mouth of the biter and the bite breaks the skin.
  • Occupational exposure: needlestick (hollow bore greater risk than solid bore, risk ~0.3%); splash of infectious fluids onto mucous membrane (eyes, mouth, etc) risk ~0.09%; splash onto non-intact skin, risk <0.09%.
  • Maternal-fetal transmission (~30% without ART, ~2% with ART)

Baseline testing:

  • Toxoplasma Serology, CMV Serology
  • HAV serology; HBV serology, include HBVCoreAb if high risk; HCV serology
  • RPR
  • PPD
  • PAP smear or ? Anal Pap
  • Ophthalmologic exam

Current guidelines recommend starting treatment if CD4 count <350 cells/mm, Viral Load is >60,000 or patient is symptomatic from HIV, regardless of “numbers.” Symptoms of HIV include constitutional symptoms such as fevers, night sweats and weight loss as well as presence of any AIDS defining illnesses which are described in the answers to case #1.

Vaccinations: Aim for CD4>200 before vaccinating

  • Flu shot: everyone, every year
  • Pneumovax: everyone, every 5 years??
  • HAV: HCV+, gay men, travelers
  • HBV: everyone, but esp. HCV+, high risk
  • Measles, mumps, rubella: may need booster, check specific recommendations; may be contraindicated in patients with CD4<200
  • H. influenza: not recommended, 60% of H. flu infections are caused by non-type B
  • Travel vaccines: all considered safe except oral polio, yellow fever and live oral typhoid

Prophylaxis:

  • CD4 count <200 (15%): PCP prophylaxis, first choice is Bactrim 1 DS qd or qod or 1 SS qd
  • CD4 count <100: Toxoplasmosis prophylaxis, first choice is Bactrim 1 DS qd
  • CD4 count <50: MAC (Mycobacterium Avium Intracellulare Complex) prophylaxis, first choice azithromycin 1200mg once a week
  • Any CD4 count: Latent TB infection--positive PPD (â?¥5 mm induration) negative chest x-ray, INH (isoniazid) 300mg qd x 9 months, with vitamin B6 25-50mg qd to prevent neuropathy

5. Table 1. Nucleoside/Nucleotide Reverse Transcriptase Inhibitors (NRTIs)

Brand Name Generic Name Abbreviation
Combivir® zidovudine + lamivudine AZT + 3TC
Emtriva® emtricitabine FTC
Epivir® lamivudine 3TC
Epzicom™ abacavir + lamivudine ABC + 3TC
Hivid® zalcitabine ddC
Retrovir® zidovudine AZT or ZDV
Trizivir® abacavir + zidovudine + lamivudine ABC + AZT + 3TC
Truvada™ tenofovir DF + emtricitabine TDF + FTC
Videx® didanosine: buffered versions ddI
Videx® EC didanosine: delayed-release capsules ddI
Viread® tenofovir disoproxil fumarate (DF) TDF or Bis(POC) PMPA
Zerit® stavudine d4T
Ziagen® abacavir ABC

6. Table 2. Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs)

Brand Name Generic Name Abbreviation
Rescriptor® delavirdine DLV
Sustiva® efavirenz EFV
Viramune® nevirapine NVP

7. Table 3. Protease Inhibitors (PIs)

Brand Name Generic Name Abbreviation
Agenerase® amprenavir APV
Crixivan® indinavir IDV
Fortovase® saquinavir (Soft Gel Cap) SQV (SGC)
Invirase® saquinavir (Hard Gel Cap) SQV (HGC)
Kaletra® lopinavir + ritonavir LPV
Lexiva® fosamprenavir FPV
Norvir® ritonavir RTV
Reyataz® atazanavir ATZ
Viracept® nelfinavir NFV