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Infectious Diseases Review Session Hail M. Al-Abdely Consultant Infectious Diseases KFSH&RC Clinical, Virological and Immunological Course of HIV Infection 1000 800 600 400 Symptoms 200 Infection Virus in Plasma 0 Death Detectable Time 0 VIRUS IN PLASMA Detectable 12 Years Clinical, Virological and Immunological Course of HIV Infection 1000 CD4 Cell Count 800 600 400 Symptoms Virus in Plasma 200 Infection0 Time 0 Death Detectable VIRUS IN PLASMA Detectable > 500 cells CD4 COUNTS < 200 cells 12 Years Clinical, Virological and Immunological Course of HIV Infection 1000 CD4 Cell Count 800 600 400 Symptoms Virus in Plasma 200 Infection0 Death Detectable VIRUS IN PLASMA Detectable > 500 cells CD4 COUNTS < 200 cells Time 0 12 Years Seroconversion Asymptomatic AIDS Clinical, Virological and Immunological Course of HIV Infection 1000 CD4 Cell Count 800 600 RNA in Plasma 400 Symptoms Virus in Plasma 200 Infection0 Death Detectable VIRUS IN PLASMA Detectable > 500 cells CD4 COUNTS < 200 cells Time 0 12 Years Seroconversion Asymptomatic AIDS Development of AIDS is like an impending train wreck Viral Load = Speed of the train CD4 count = Distance from cliff HIV infection J. Coffin, XI International Conf. on AIDS, Vancouver, 1996 Viral Dynamics of HIV-1 Infection Latently infected CD4 lymphocytes Productively infected CD4 lymphocytes <1% T 1/2 ~1.6d 99% Uninfected CD4 lymphocytes 2.6 days per generation T1/2 ~5.7 hrs HIV <1% Uninfected activated CD4 lymphocytes Long-lived cell populations Perelson et.al. Science 271:1582 (1996) CD4 lymphocytes infected with defective virus Viral dynamics It takes 2.6 days to produce a new generation of viral particles Estimated total HIV production is 10.3 x 109 virions per day 99% of the virus pool is produced by recently infected cells Retroviral therapy should be able to reduce viral load within a few days GOALS OF THERAPY Clinical goals: Prolongation of life and improved quality of life Virologic goals: Reduction in viral load as much as possible for as long as possible to: 1) halt disease progression, and 2) prevent/reduce resistant variants Immunologic goals: Achieve immune reconstitution that is quantitative (CD4 to normal range) and qualitative (pathogen-specific immune response) Therapeutic goals: Rational sequencing of drugs in a fashion that achieves virologic goals, but also: 1) maintains therapeutic options; 2) is relatively free of side effects; and 3) is realistic in terms of probability of adherence Epidemiologic goals: Reduce HIV transmission Antiretroviral Drugs Approved by FDA for HIV Generic Name Class FDA Approval Date Zidovudine, AZT NRTI March 87 Didanosine, ddI NRTI October 91 Zalcitabine, ddC NRTI June 92 Stavudine, d4T NRTI June 94 Lamivudine, 3TC NRTI November 95 Saquinavir, SQV, hgc PI December 95 Ritonavir, RTV PI March 96 Indinavir, IDV PI March 96 Nevirapine, NVP NNRTI June 96 Nelfinavir, NFV PI March 97 Delavirdine, DLV NNRTI April 97 Combivir (AZT+3TC) NRTI September 97 Saquinavir, SQV, sgc PI November 97 Efavirenz, EFV NNRTI September 98 Abacavir, ABC NRTI February 99 Amprenavir (AMP) PI April 99 Lopinavir (LPV) PI September 00 EC Didanosine(EC DDI) NRTI September 00 Trizivir (AZT+3TC+ABC) NRTI September 00 Viral Suppression with Monotherapy versus Multiple Drugs 90 90 100 80 80 80 70 70 60 60 60 40 50 50 20 Monotherapy Dual therapy Triple therapy *Using the age distribution of the projected year 2000 US population as the standard. **Preliminary 1998 data Good News Highly active antiretroviral therapy has Changed our view toward HIV from inevitably fatal to a manageable disease over several decades Bad News 1. 2. 3. 4. 5. Incomplete response Complexity of treatment Short and long term side effects Resistance Drug-drug interactions Bad News Incomplete response 1. • • 2. 3. 4. 5. Complete RNA suppression and sustained CD4 increase happens only in 60-80%. Effectiveness is even lower in patients with high replication rates and extensive antiretroviral experience. Complexity of treatment Short and long term side effects Resistance Drug-drug interactions Viral Suppression with Monotherapy versus Multiple Drugs 90 90 100 80 80 80 70 70 60 60 60 40 Monot herapy 20 Monot herapy 50 50 Monot herapy Monotherapy Dual therapy Triple therapy Bad News 1. Incomplete response 2. Complexity of treatment • • • Too many tablets. Difficult schedule. Food factor 3. Short and long term side effects 4. Resistance 5. Drug-drug interactions Bad News 1. Incomplete response 2. Complexity of treatment 3. Short and long term side effects 4. Drug-drug interactions 5. Resistance Side Effects of NRTIs Drug Common Side effects Zidovudine (azt, zdv) Initial nausea, headache, fatigue, anemia, neutropenia, neuropathy, myopathy. Lamivudine (3TC) GI side effects. Didanosine (ddl) GI side effects. Peripheral neuropathy in 15%, pancreatitis. Zalcitabine (ddC) Peripheral neuropathy in 17-31% of trial participants; oral ulcers. Stavudine (d4T) Peripheral neuropathy (1-4% in early studies; 24% in expanded access patients with CD4+ counts < 50) Abacavir (ABC) About 3%-5% hypersensitivity reaction: malaise, fever, possible rash, GI. Resolves within 2 days after discontinuation. Side Effects of NNRTIs Drug Common Side effects Delavirdine Transient rash. P450 3A4 inhibitor Nevirapine Transient rash, hepatitis. P450 3A4 inducer. Efavirenz Initial dizziness, insomnia, transient rash, P450 3A4 inducer. Side Effects of PIs Drug Common Side effects Amprenavir Rash (20%), diarrhea, nausea Indinavir Kidney stones in 6 to 8%: good hydration essential. Occasional nausea and GI upset. Nelfinavir Diarrhea common; occasional nausea Ritonavir Nausea, diarrhea, numb lips for up to 5 weeks; occasional hepatitis. Saquinavir Nausea, diarrhea. Metabolic Complications of PIs Hyperbilirubinemia Hyperlipidemia Coronary artery disease Insulin resistance Abnormal fat distribution. Lipodystrophy Lactic acidosis Bad News 1. Incomplete response 2. Complexity of treatment 3. Short and long term side effects 4. Drug-drug interactions 5. Resistance Drugs That Should Not Be Used With Antiretrovirals Drug Category Indinavir Ritonavir* Saquinavir Nelfinavir Amprenavir Nevirapine Delavirdine Efavirenz Ca++ channel blocker (none) bepridil (none) (none) bepridil (none) (none) (none) Cardiac (none) amioderone flecainide propafenone quinidine (none) (none) (none) (none) (none) (none) Lipid Lowering Agents simvastatin lovastatin simvastatin lovastatin simvastatin lovastatin simvastatin lovastatin simvastatin lovastatin (none) simvastatin lovastatin (none) AntiMycobacterial rifampin none rifampin rifabutin rifampin rifampin (none) rifampin rifabutin (none) Antihistamine astemizole terfenadine astemizole terfenadine astemizole terfenadine astemizole terfenadine astemizole terfenadine (none) astemizole terfenadine astemizole terfenadine cisapride cisapride cisapride cisapride cisapride (none) cisapride H-2 blockers Proton pump inhibitors cisapride Neuroleptic (none) clozapine pimozide (none) (none) (none) (none) (none) (none) Psychotropic midazolam triazolam midazolam triazolam midazolam triazolam midazolam triazolam midazolam triazolam (none) midazolam triazolam midazolam triazolam Gastrointestinal Drugs Bad News 1. Incomplete response 2. Complexity of treatment 3. Short and long term side effects 4. Drug-drug interactions 5. Resistance Resistance Genotypic Mutations Associated With Resistance to NRTI & NNRTIs Agent ZDV 41 67 69* 3TC 69* ddI 65 ddC 65 d4T 70 Resistance mutations 151 69 50 ABC 151 184 69* 74 151 184 69* 74 151 184 69* 65 210 75 69* 74 Agent 151 115 215 219 333 333 178 151 184 Resistance mutations DLV 103 EFV 100 103 NV 100 103 181 108 106 108 179 236 181 188 190 181 188 190 225 Resistance Genotypic Mutations Associated With Resistance to PIs Agent APV 10 IDV 10 NFV 10 RTV 10 20 SQV 10 20 LPV 10 20 24 32 30 32 24 30 32 33 36 Resistance mutations 46 47 48 50 54 63 71 36 46 48 63 71 36 46 48 36 46 36 46 46 54 48 47 50 82 84 82 84 71 82 84 82 84 90 82 84 90 54 63 71 54 63 71 73 73 84 90 88 90 Percentage of patients with plasma HIV-RNA below 200 copies/ml in the VIRADAPT study % <200 copies/ml Randomized Study 35 30 25 Control Genotypic 20 15 10 5 0 0 3 6 9 Months (Adapted from Clevenbergh et al. Antiviral Therapy 2000; 5:65–70) 12 Percentage of patients with plasma HIV-RNA below 200 copies/ml in the VIRADAPT study % <200 copies/ml Open Study Randomized Study 35 30 25 Control Genotypic 20 15 10 5 0 0 3 6 9 Months (Adapted from Clevenbergh et al. Antiviral Therapy 2000; 5:65–70) 12 Barriers to the Development of an Effective AIDS Vaccine Sequence variation Protective immunity in natural infection not clearly established Lack of adequate animal model to study vaccine protection with HIV Latency and integration of HIV into host genome Limited knowledge about mucosal transmission and immune responses Financial disincentives Ethical issues MCQs HAART Opportunistic Infections A patient with HIV infection, treated with HAART, and a CD4 count of 240/mm3 has the findings shown in the photograph on retinal (funduscopic) exam. The most appropriate therapy is: 1. 2. 3. 4. 5. Pyrimethamine plus sulfamethoxazole Intravenous ganciclovir Intravenous cidofovir Amphotericin B No treatment A 30-year-old man with HIV infection with a CD4 count of 680/mm3 is referred for evaluation of refractory sinusitis. He reports headaches, purulent nasal drainage and nasal stuffiness for 2 weeks. There has been no documented fever. Prior treatment consisted of amoxicillin x 5 days, then TMP-SMX, one DS bid x 3 days; epinephrine nasal spray and ibuprofen has been given for 2 to 3 weeks. Diagnostic studies included the following: CT scan--bilateral air fluid levels in maxillary sinuses Nasal drainage--PMNs and eosinophils Culture--moderate S. aureus sensitive to methicillin WBC--7,800 with 62% PMNs, 4% bands, 20% lymphocytes, 9% monocytes, 5% eosinophils. The treatment that is likely to be most effective is: 1. 2. 3. 4. 5. Dicloxacillin Decongestant nasal spray Cortisone nasal spray Ipratropium bromide nasal spray Cough syrup containing dextromethorphan A pregnant woman has a CD4 count of 550/mm3 and viral load of 860 c/ml with no antiretroviral therapy. Which of the following has demonstrated benefit in preventing perinatal transmission in this setting? 1. 2. 3. 4. 5. AZT monotherapy Nevirapine HAART C-section None of the above The frequency of HIV perinatal transmission is low when the viral load is <1,000 c/ml, but a review of seven prospective studies of perinatal transmission in the U.S. and Europe showed that there was a significant reduction even further when AZT was given (JID 2001;183:539). A 30-year-old woman presents with watery diarrhea with 6-8 stools/day for nearly 2 months. She is discovered to have HIV infection with a CD4 count of 22/mm3. A stool AFB smear is shown. Which of the following treatments is most likely to eradicate the pathogen? 1. 2. 3. 4. 5. Paromomycin Trimethoprim-sulfamethoxazole Albendazole Nitrazoxanide Highly active antiretroviral therapy (HAART A lymph node biopsy from an HIV-positive patient currently residing in the state prison is submitted to the laboratory for acid-fast smear and culture. The acid-fast smear is reported as positive. Acid-fast organisms are recovered on solid medium after 3 days of incubation. This organism is likely to be: Mycobacterium xenopi 2. Mycobacterium kansasii 3. Mycobacterium fortuitum. 4. Mycobacterium tuberculosis 5. Mycobacterium avium 1. All of the following are poor prognostic factors in Cryptococcal meningitis except: 1. 2. 3. 4. 5. Cerebrospinal fluid (CSF) leukocytosis Serum of CSF cryptococcal antigen titer >1:32 Elevated CSF opening pressure Altered mental status Low CSF glucose A 32-year-old drug user is seen in an emergency department with abdominal pain and fever. He has known HIV infection and a recent CD4 count was 10/mm3. He reports that he has had intermittent diarrhea with 2 to 6 loose stools daily for about 2 weeks, and then noted nausea, vomiting, and right upper quadrant abdominal pain. Physical exam shows a temperature of 38.5 C and right upper quadrant tenderness. Medications include AZT, ddI, TMP- SMX, fluconazole, acyclovir, and megavitamins. Laboratory tests show the following: Hematocrit: 29% WBC: 3200 (72% PMNs, 8% bands, 10% lymphs, 5% monocytes, and 5% eosinophils) Platelet count: 88,000/mm3 Bilirubin: 1.4 mg/dL, AST: 121 U/L, ALT: 135 U/L Alkaline phosphatase: 860 U/L Chest x-ray: Negative Abdominal flat plate: Negative Ultrasound of abdomen: Dilated biliary ducts without stones Stool ova and parasite exam with AFB stain: Negative The most likely cause is: An adverse drug reaction Cryptosporidia 3. Cyclospora 4. Entamoeba histolytica 5. Mycobacterium avium 1. 2. The diagnosis of progressive multifocal leukoencephalopathy is supported by which of the following findings? 1. 2. 3. 4. 5. Cerebrospinal fluid pleocytosis Cerebrospinal fluid elevated protein Fever Rapid onset of symptoms Brain biopsy with positive stain for SV-40 virus Which of the following drugs is least likely to cause lactic acidosis? 1. 2. 3. 4. 5. AZT 3TC ddC ddI Tenofovir A 30-year-old man has been treated with AZT, 3TC, ritonavir, and indinavir for three years. His CD4 count increased from 230 to 550/mm3 with VL<50 c/ml for over two years. He decides to stop therapy. When should HIV become detectable? 1. 2. 3. 4. 5. One week Two weeks Four weeks Eight weeks Three months Which of the following decreases blood levels of indinavir? 1. 2. 3. 4. 5. Delavirdine Efavirenz Nelfinavir d4T Ketoconazole Efavirenz decreases the AUC of indinavir by 31%. The practical application is that the dose of indinavir when these two drugs are used together should be increased to 1,000 mg q8h. All of the other drugs that are listed increase the levels of indinavir. Which of the following drugs is most likely to increase the fasting blood glucose? 1. 2. 3. 4. 5. Tenofovir Hydroxyurea Nevirapine Indinavir IL-2 There is some substantial confusion about the agents and mechanisms of lipodystrophy, but this is not the case with insulin resistance resulting in elevated blood sugar. All protease inhibitors are associated with insulin resistance, which can be measured within days of administration. Thus, indinavir is the best option since this is the only PI on the list. Food should be given with: 1. 2. 3. 4. 5. Amprenavir Indinavir AZT Nevirapine Lopinavir A 37-year-old man with AIDS is receiving AZT, ddI and nelfinavir. He has done well with a viral burden that decreased from 88,000 copies/dL to undetectable. At his last clinic visit he is noted to have a CBC showing an absolute neutrophil count of 400/mm3; neutropenia is confirmed. A review of prior CBCs shows all had ANC values >1800/mm3. The preferred regimen for this patient among the options given is: 1. 2. 3. 4. 5. ddI, d4T, and saquinavir (Fortovase) d4T, ddI and nelfinavir 3TC, ddI and indinavir ddC, ddI and ritonavir ddI, ritonavir and saquinavir A 40-year-old man with HIV infection and a CD4 count of 360/mm3 is taking INH due to a positive PPD skin test. After one month of treatment the ALT increased from 30 IU/dL at baseline to 90 IU/dL. The upper limit of normal is 35 IU/dL. The patient is asymptomatic. What treatment should be given? 1. 2. 3. 4. 5. The current recommendations Continue INH in same dose with INH and hepatic function Discontinue prophylaxis testing is that increases of 3 - 5Substitute rifampin fold for transaminase levels Substitute rifampin + ethambutol should lead to careful monitoring, but discontinuation Biopsy the liver and then continue INH if there is no of INH is not necessary unless evidence of drug-induced hepatitis the increase is 5 - 10-fold higher of the upper limits of normal. For the average patient, which of the following treatments gives the longest delay in relapse of CMV retinitis? The median times to progression with initial with CMV retinitis are: 1. 2. 3. 4. 5. IV ganciclovir IV foscarnet IV cidofovir Ganciclovir implant Oral ganciclovir ganciclovir IV of 47 - 104 days, foscarnet IV 53 - 93 days, ganciclovir plus foscarnet IV 129 days, oral ganciclovir 29 - 53 days, cidofovir IV 64 - 120 days, ganciclovir implant (Vitrasert) 216 - 226 days. Most patients in late-stage HIV infection develop toxoplasmosis from which of the following? 1. 2. 3. 4. 5. New infection following exposure to cat stool New infection following exposure to undercooked meat New infection from exposure to a patient with toxoplasmosis New infection from contaminated water Activation of latent infection The risk of which of the following HIV-associated complications is the least reduced by immune reconstitution with HAART? 1. 2. 3. 4. 5. Kaposis sarcoma HIV-associated dementia Non-Hodgkins lymphoma Thrush Pneumococal pneumonia A patient sees you complaining of a sore mouth for 2 days. There is a history of genital herpes, pneumococcal pneumonia,zoster, oral hairy leukoplakia and a positive PPD. The CD4 count is 205/mm3 and current medications include nevirapine, nelfinavir, ddI, hydroxyurea, trimethoprimsulfamethoxazole, and sertraline (Zoloft). Oral exam is shown in the figure. A Tzanck prep of the lesion is negative. Which of the following is most likely to provide relief? 1. 2. 3. 4. 5. Acyclovir therapy Thalidomide therapy Discontinue nevirapine Discontinue trimethoprim sulfamethoxazole Discontinue nelfinavir Human herpes virus 8 has been most convincingly implicated in which of the following: 1. 2. 3. 4. 5. Hepatocellular carcinoma CNS lymphoma Castleman's disease Acute myelocytic leukemia Hypernephroma Which of the following drugs shows the best penetration across the blood-brain barrier? 1. 2. 3. 4. 5. Zidovudine (AZT). Stavudine (d4T) Lamivudine (3TC) Didanosine (ddI) Zalcitabine (ddC) With the exception of abacavir, AZT shows the best penetration of the NRTIs across the bloodbrain barrier with CSF levels that are approximately 60% of serum levels (Lancet 1998; 351: 1547). A 25-year-old HIV-infected man presents to your office with severe herpes proctitis. The patient has been treated with acyclovir, 200 mg five times daily for six weeks without improvement in the lesions. On repeat culture of the rectum, herpes simplex virus 2 is again isolated and further testing reveals that this is a thymidine kinase-deficient strain. Which is the preferred treatment option for this condition? 1. 2. 3. 4. 5. Foscarnet Vidarabine Ganciclovir Valacyclovir Famciclovir A 43-year-old man with AIDS presents with a four-week history of ataxia, progressive right hand weakness, and tremor. Physical examination confirms his symptoms. His CD4 cell count is 56/mm3, and serum antitoxoplasma IgG antibody titer was negative one year ago. An MRI of the head reveals a solitary 2 x 4 cm lesion in the left cerebellar hemisphere which gives a high signal intensity on T2-weighted images but does not enhance with gadolinium. No mass effect is demonstrated. The most likely diagnosis is: 1. 2. 3. 4. 5. Toxoplasmosis A fungal abscess Primary CNS lymphoma Progressive multifocal leukoencephalopathy (PML) A mycobacterial abscess Which of the following best predicts long-term HIV suppression? 1. The nadir of plasma HIV RNA levels following treatment 2. Treatment in relatively early stage disease as indicated by a CD4 count >200/mm3 3. A relatively low plasma HIV RNA level at the time antiretroviral therapy is initiated 4. Absence of an AIDS-defining opportunistic infection 5. Use of a regimen that contains 2 protease inhibitors Which of the following is least likely to cause peripheral neuropathy? 1. 2. 3. 4. 5. Lamivudine (3TC) Stavudine (d4T) Didanosine (ddI) Zalcitabine (ddC) Zidovdine (AZT) Which of the following may cause a deceptively high CD4 cell count? 1. 2. 3. 4. 5. HTLV II co-infection Splenectomy Major surgery Pregnancy Acute administration of corticosteroids Which of the following vaccines is contraindicated in patients with HIV infection due to the potential to cause infection? 1. 2. 3. 4. 5. Tetanus Influenza Varicella Haemophilus influenzae type B Hepatitis A virus Which of the following microbes is most likely to cause a cerebrospinal fluid showing elevated protein and a polymorphonuclear pleocytosis in late-stage HIV infection? 1. 2. 3. 4. 5. Toxoplasma gondii Cytomegalovirus Treponema pallidum JC virus (Progressive multifocal leukoencephalopathy) Herpes simplex The most common cause of fever of unknown origin with no focal symptoms in a previously untreated patient with a CD4 count of 10/mm3 is: 1. 2. 3. 4. 5. Disseminated M. avium infection Disseminated cytomegalovirus Pneumocystis carinii pneumonia Toxoplasmosis Lymphoma A 45-year-old woman donated blood prior to elective surgery for urinary incontinence. The blood bank reports that the unit is repeatedly reactive in a HIV-1 enzyme immunoassay (EIA), with a negative HIV-1 Western blot. A test done 1 year previously showed the same results. She has no history of blood transfusion or injection drug use, and has been sexually monogamous for ten years with a single partner who has no known HIV risk factors. Your advice is: 1. 2. 3. 4. 5. Defer surgery until repeat HIV testing can be done at three months Advise the patient that she has early HIV infection Perform testing on her sexual partner to determine if he is the source of the infection Test the patient's sexual partner for HIV Inform the patient that HIV infection is unlikely given the absence of risk factors and the negative Western blot result For which of the following exposures would the use of HIV PEP be recommended? 1. A housekeeper sustains a percutaneous injury while emptying a needle box on a pediatric ward with no known cases of HIV infection. 2. A nurse has a urine splash to the eye while emptying an AIDS patient’s urinal. 3. A resident, after assisting with an emergency insertion of a central venous line into an HIV-infected patient, notices a small tear in his/her glove but does not observe any blood on his/her skin. 4. A phlebotomist sustains a percutaneous injury while performing phlebotomy on an HIV-infected patient with low viral load. 5. All of the above. All of the following are correct about hairy leukoplakia except: 1. 2. 3. 4. 5. It will respond to treatment with acyclovir It will respond to treatment with ganciclovir It is a rare complication of diseases other than HIV infection It is usually not treated Scrapings of it will show pseudomycelia A 27-year-old intravenous drug abuser is referred to you with positive HIV serology. He is asymptomatic but continues to practice high risk behavior. Past medical history indicates herpes zoster involving the right leg one year ago. Initial evaluation shows the following: WBC 3,400 with 72% PMNs, 5% bands, 15% lymphocytes, 3% monocytes; CD4 count 240/mm3; Chemistry panel normal; Hepatitis serology HBsAg neg and anti-HBs positive; VDRL negative; Chest x-ray negative; PPD negative. Treatment at this time should include which of the following? 1. 2. 3. 4. 5. Pneumovax Azithromycin prophylaxis PCP prophylaxis Hepatitis B vaccine Acyclovir Which of the following is correct about Stavudine (d4T)? 1. The major side effect is peripheral neuropathy. 2. High level resistance occurs early in treatment when it is given as monotherapy. 3. It penetrates the blood-brain barrier better than AZT 4. Tablets should be chewed or dissolved in fluids before swallowing 5. It commonly causes lactic acidosis Which of the following conditions in a person with HIV infection is suggestive of the greatest degree of immunosuppression? 1. 2. 3. 4. 5. Peripheral generalized lymphadenopathy Thrush Pneumonia due to S. pneumoniae Cavitary pulmonary tuberculosis Vaginal candidiasis A HIV-infected patient has cough, fever, and sputum production for 4 days. A chest x-ray shows a left lower lobe infiltrate, the WBC is 4,200/mm3 and a CD4 count is 150/mm3. He takes no medication. The most likely microbial pathogen is: 1. 2. 3. 4. 5. S. pneumoniae Mycobacterium tuberculosis Rhodococcus equii P. carinii Cryptococcosis A HIV-infected woman has headache, fever, and a seizure. The CD4 count is 56/mm3, WBC is 3,200/mm3, and a MRI shows two ring-enhancing lesions. She takes no medicines other than methadone. The most likely diagnosis is: 1. 2. 3. 4. 5. Lymphoma Toxoplasmosis Cryptococcosis PML Herpes simplex encephalitis Which of the following drugs has been associated with serious hypersensitivity reactions characterized by fever, GI distress, and rash? 1. 2. 3. 4. 5. Efavirenz Hydroxyurea Abacavir Saquinavir Nelfinavir The opportunistic organism most likely to infect the adrenal gland in patients with advanced HIV infection is: 1. 2. 3. 4. 5. M. avium Histoplasma capsulatum Candida albicans CMV Cryptococcus neoformans Which of the following is most likely to show no white blood cells in cerebrospinal fluid? 1. 2. 3. 4. 5. Toxoplasma encephalitis CNS lymphoma Progressive multifocal leukoencephalopathy Neurosyphilis CMV encephalitis A patient with HIV infection is receiving no medications and is seen for routine follow-up. At the previous visit 6 months ago, the CD4 count was 860/mm3 and the CD4 percentage was 46%. The viral burden at that time was 562 copies/ml. At this visit the CD4 count is 620/mm3 and the CD4 percentage is 40%. The viral burden is undetectable (less than 400 copies/ml). Which of the following would be most appropriate? a. b. c. d. Repeat the CD4-cell count in the same lab Repeat the CD4-cell count, but use a different lab Request a complete T-subset analysis Obtain additional studies for HIV staging including B2 microglobulin and neopterin e. Do nothing and see the patient in 3 months A 25-year-old man with advanced HIV infection is hospitalized with fever and diarrhea of 2-3 weeks duration. He has been treated with ddI, ritonavir, saquinavir, and trimethoprim-sulfamethoxazole. Exam shows thrush, wasting, and KS lesions on the face and arms. Admission laboratory studies show: Hematocrit of 28%, WBC 3,100/mm3; CD4 count of 2/mm3; ALT of 56 IU/L, alkaline phosphatase of 211 IU/L, amylase of 53 IU/L, a potassium of 3.1 MEQ/L, and an albumin of 2.3 gm/dL; Chest x-ray is negative; Blood culture at 48 hours yields S. epidermidis; Stool C. difficile toxin assay is negative, stool culture is negative, Stool O&P exam shows Blastocystis hominis. Treatment directed against which organism is most likely to produce defervescence? a. b. c. d. e. S. epidermidis Microsporidia Blastocystis hominis Cryptosporidia M. avium complex A 27-year-old gay man has negative HIV serology but continues to practice high risk behavior. He requests assurance that he does not have HIV infection. The most sensitive blood test to provide this assurance is: a. b. c. d. e. p24 antigen Routine serologic test HIV DNA assay HIV RNA level HIV culture The most common side-effect of nelfinavir is: a. b. c. d. e. Epigastric pain Diarrhea Headache Nephrolithiasis Neuropathy Albendazole is effective therapy for most patients infected by: a. Toxoplasma gondii b. Enterocytozoon bienusi c. Septata intestinalis d. Cryptosporidia e. Cyclospora The average efficiency of HIV transmission with a single episode of unprotected receptive vaginal intercourse with an untreated HIV infected source is approximately? a. b. c. d. e. 30% 3% 0.3% 0.03% 0.003% A 30-year old woman with HIV infection and a CD4 count of 180/mm3 has a platelet count of 40,000/mm3. She reports mild gum bleeding while brushing teeth, but denies other forms of bleeding and has not noted bruising. Her platelet count 3 months ago was 65,000/mm3. Medications do not appear to be the cause of her thrombocytopenia. What treatment is appropriate at this time? a. b. c. d. e. IVIG Prednisone Splenic irradiation Danazol No treatment A 28-year old gay man has progressive dyspnea and hypoxemia over 2-3 months. He is afebrile and has a CD4 count of 26/mm3. Chest x-ray shows alveolar infiltrates bilaterally, hilar adenopathy and a pleural effusion. Bronchscopy with BAL and a transbronchial biopsy is negative. A gallium scan negative. The most likely cause is: 1. Histoplasmosis 2. Coccidiodomycosis 3. Lymphocytic interstitial pneumonia 4. Lymphoma 5. Kaposi sarcoma Which of the following drugs is recommended for AIDS patients with bacillary angiomatosis? 1. 2. 3. 4. 5. Penicillin Ciprofloxacin Erythromycin Cephalosporin Vancomycin Which of the following drugs is the most potent inhibitor of the hepatic p450 metabolic pathway? a. b. c. d. e. Ritonavir Saquinavir Rifampin Nevirapine Abacavir A 40-year-old man with HIV infection complains of headache, fever, and blurred vision. He takes AZT, 3TC, nelfinavir, dapsone, and INH. Exam shows thrush and perirectal vesicles. A CD4 count is 86/mm3 and a head MRI is negative. The most likely diagnosis of his CNS infection is: a. b. c. d. e. T. pallidum Toxoplasma gondii Cryptococcus Progressive multifocal leukoencephalopathy H. simplex A 32-year-old woman with HIV infection complains of intermittent diarrhea without fever for 30 days and fatigue. She takes d4T, 3TC, nevirapine, dapsone, and fluconazole. A CD4 count is 70/mm3. The single most likely diagnosis is infection due to: a. b. c. d. e. Giardia E. histolytica C. difficile Salmonella Cryptosporidia