Chapter 18: AIDS, HIV Infection, and Related Conditions

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1

What is HIV?

human immunodeficiency virus

2

What is AIDS?

acquired immunodeficiency syndrome

3

What populations are at greatest risk for HIV in the US?

  1. 25 to 29 years
  2. males
  3. blacks
  4. homosexuals
4

What is HAART?

highly active antiretroviral therapy

5

What is the leading cause of death in men 25 to 44 years of age in the US?

AIDS

6

What causes AIDS?

HIV

7

What type of virus is HIV?

A nontransforming retrovirus of the lentivirus family.

8

What is lymphadenopathy-associated virus?

The name initially given to HIV when it was first discovered in 1983 by Francoise Barre-Sinoussi.

9

What explains the variation in disease patterns of HIV and difficulty in producing a vaccine?

Sequence differences among different strains of HIV.

10

What is the basic structure of HIV?

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It is an enveloped RNA retrovirus about 100 nM in diameter.

11

What covers the surface of the HIV envelope, serving to bind to human cells?

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glycoproteins (gp41 and gp120)

12

What surrounds the viral enzymes and RNA inner core within the HIV envelope?

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protein capsid (p24)

13

Which human cells are most commonly infected by HIV?

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Those with CD4+ receptors, including T helper lymphocytes and macrophages.

14

What three co-receptors allow HIV to infect human cells?

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  1. CCR5
  2. CXCR4 (fusin)
  3. CCR2
15

What are the six stages of HIV-1 infection?

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  1. entry of HIV virion into the host cell
  2. reverse transcription of RNA to DNA
  3. integration of DNA into host DNA
  4. transcription of viral DNA to mRNA
  5. translation of viral mRNA to proteins
  6. assembly and release of virions
16

What three viral proteins play important roles in regulating viral replication?

  1. tat
  2. rev
  3. nef
17

What is the V3 loop?

The carboxyl-terminal half of the gp120, identified as the source of HIV virulence.

18

How is HIV transmitted?

By exchange of infected bodily fluids from sexual contact and through blood and blood products.

19

What are the top three forms of HIV transmission in the US?

  1. homosexual transmission (MSM)
  2. heterosexual transmission
  3. sharing needles
20

What is the most common method of HIV transmission globally?

heterosexual transmission

21

What are the four main bodily fluids shown to be associated with transmission of HIV?

  1. blood
  2. semen
  3. breast milk
  4. vaginal secretions
22

What is it called when a virus is transmitted from mother to infant?

vertical transmission

23

What cells are selectively targeted by HIV once the virus gains access to the bloodstream?

T helper lymphocytes

24

Once HIV enters the bloodstream, how does it bind to CD4+ lymphocyte cells?

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By outer surface envelope gp120 proteins.

25

Once HIV enters cells, how is viral RNA converted to a double-stranded DNA provirus?

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It is catalyzed by the enzyme reverse transcriptase.

26

What happens to the DNA provirus produced by reverse transcriptase from viral RNA?

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It becomes incorporated into the host DNA.

27

Once the DNA provirus is incorporated into the host DNA, it may remain latent until activated. What happens when it is activated?

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The DNA is transcribed to produced new virions.

28

What does it mean that HIV is "lymphotropic"?

It selectively infects and destroys lymphocytes.

29

How does the ratio of CD4+ T helper cells to CD8+ T suppressor cells change in HIV infection?

The normal ratio of T4 to T8 lymphocytes is about 2:1; in AIDS this reverses to 1:2.

30

What explains the ineffective immune response and increase in malignant disease seen in patients with AIDS?

The marked reduction in T helper lymphocytes.

31

What are the three stages of HIV infection?

  1. acute seroconversion syndrome
  2. latent period/early symptomatic
  3. AIDS
32

What is the earliest laboratory finding for recent HIV infection?

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positive p24 antigen

33

What is particularly dangerous about the brief period after a patient has been infected with HIV, but before they begin to show symptoms?

The patient is unaware of their infection, but can transmit the infection by blood or sexual activity.

34

How soon after HIV infection do the symptoms of seroconversion syndrome occur?

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1 to 3 weeks

35

What are the signs and symptoms of stage 1 HIV infection (seroconversion syndrome)? (5)

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  1. fever, fatigue
  2. nausea, vomiting, diarrhea
  3. myalgia, headache, weight loss
  4. skin rashes
  5. lymphadenopathy
36

How long does it take for the symptoms of seroconversion syndrome to clear?

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1 to 2 weeks

37

What are the laboratory findings for the following in stage 1 HIV infection?

  1. HIV antibodies
  2. CD4+ count
  3. Western blot/ELISA
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  1. HIV antibodies (−) initially, then (+)
  2. CD4+ ↓, but >500 cells/µL
  3. Western blot/ELISA (+)
38

How soon after HIV exposure do infected patients develop develop antibodies?

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6 and 12 weeks

39

What three important antibodies are produced in response to HIV infection?

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  1. anti-gag
  2. anti-gp120
  3. anti-p24
40

How long from the time of initial infection does the latent period of stage 2 HIV infection last?

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8 to 10 years

41

What are the laboratory findings for the following in the latent period of stage 2 HIV infection?

  1. Western blot/ELISA
  2. viral load
  3. CD4+ count
  4. CD4+/CD8+ ratio
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  1. Western blot/ELISA (+)
  2. viral load steadily ↑
  3. CD4+ count steadily ↓
  4. CD4+/CD8+ ratio ↓ (close to 1)
42

Fewer than 1% of HIV patients are "nonprogressors." What does this mean?

These patients have a low viral load and do not show a decline in CD4+ cells during the latent period.

43

What are the signs and symptoms of the early symptomatic period of stage 2 HIV infection? (9)

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  1. fever, fatigue
  2. night sweats
  3. diarrhea
  4. weight loss
  5. persistent generalized lymphadenopathy (PGL)
  6. fungal infections
  7. oral hairy leukoplakia
  8. herpes infections
  9. retinopathy
44

How long does the early symptomatic period of stage 2 HIV infection last without treatment?

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1 to 3 years

45

What are the laboratory findings for the following in the symptomatic period of stage 2 HIV infection?

  1. Western blot/ELISA
  2. HIV antigen test
  3. CD4+ count
  4. viral load
  5. platelet count
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  1. Western blot/ELISA (+)
  2. HIV antigen test (+)
  3. CD4+ ↓, but >200 cells/µL
  4. viral load ↑
  5. platelet count ↓ (about 10%)
46

What are the signs and symptoms of stage 3 HIV infection (AIDS)?

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  1. opportunistic infections
  2. malignancies
47

What opportunistic infections are associated with stage 3 HIV infection (AIDS)? (5)

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  1. Pneumocystis jiroveci pneumonia
  2. cryptococcosis
  3. tuberculosis
  4. toxoplasmosis
  5. histoplasmosis
48

What malignancies are associated with stage 3 HIV infection (AIDS)? (5)

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  1. Kaposi sarcoma
  2. Burkitt lymphoma
  3. non-Hodgkin lymphoma
  4. primary CNS lymphoma
  5. slim (wasting) disease
49

What are the laboratory findings for the following in the stage 3 HIV infection (AIDS)?

  1. viral load
  2. CD4+ count
  3. platelet count
  4. neutrophil count
  5. Western blot/ELISA
  6. HIV antigen test
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  1. viral load ↑
  2. CD4+ <200 cells/µL
  3. platelet count ↓
  4. neutrophil count ↓
  5. Western blot/ELISA (+)
  6. HIV antigen test (+)
50

What are the neurological complications of AIDS?

HIV infection of cells in the CNS leads to rapidly progressive dementia.

51

What are the cardiovascular complications of AIDS?

HIV infection leads to dysregulated lipid metabolism, resulting in hyperlipidemia and hypertension.

52

What is the median time from primary HIV infection to the development of AIDS?

10 years

53

How does the median time from primary HIV infection to the development of AIDS vary between genders?

Progression to AIDS is faster in infected women.

54

What is the significance of the severity of the initial acute infection with HIV?

It is predictive of the prognosis of the infection.

55

According to the CDC, what are the criteria for stage 1 HIV infection?

  1. laboratory confirmation of HIV infection
  2. no AIDS-defining conditions
  3. CD4+ count of ≥500 cells/µL, or;
  4. CD4+ percentage ≥29%
56

According to the CDC, what are the criteria for stage 2 HIV infection?

  1. laboratory confirmation of HIV infection
  2. no AIDS-defining conditions
  3. CD4+ count of 200–499 cells/µL, or;
  4. CD4+ percentage 14–28%
57

According to the CDC, what are the criteria for stage 3 HIV infection?

  1. laboratory confirmation of HIV infection
  2. presence of an AIDS-defining condition, or;
  3. CD4+ count of <200 cells/µL, or;
  4. CD4+ percentage <14%
58

Patient with HIV infection show delayed allergic reactions to skin testing. What is this called?

cutaneous anergy

59

Following HIV diagnosis, how often should CD4+ and CD8+ cell counts be performed?

every 3 to 4 months

60

What test is used to screen for antibodies to HIV?

enzyme-linked immunosorbent assay (ELISA)

61

What is the disadvantage of ELISA for HIV?

It is 90% sensitive but has a high rate of false-positive results.

62

What is the current three-test protocol used in screening for HIV?

  1. ELISA, if positive;
  2. ELISA, if positive;
  3. Western blot

(this procedure is accurate 99% of the time)

63

What do positive ELISA and Western blot tests for HIV indicate?

Positive results indicate exposure to HIV, they do not indicate the status of infection.

64

What test can be used to detect both HIV antigens (p24) and antibodies to HIV?

ARCHITECT HIV Ag/Ab Combo assay

65

When is the ARCHITECT HIV Combo assay most useful in the diagnosis of HIV?

This test is useful in the acute phase of the disease when antibodies are not yet present.

66

What type of tests detect viral RNA to determine the viral load of HIV in the blood?

polymerase chain reaction (PCR)

67

When are viral loads highest during the course of HIV?

During the first 3 months after initial infection and during late stages of the disease.

68

What are the four main treatment goals of medical management of the HIV-infected patient?

  1. reduce morbidity and prolong survival
  2. to restore and preserve immune function
  3. to maximally suppress plasma viral load
  4. prevent viral transmission
69

What are the three major areas of treatment for HIV?

  1. antiretroviral therapy (ART)
  2. prophylaxis for opportunistic infections
  3. treatment of HIV-related complications
70

Both ART and HAART involve use of combinations of antiretroviral drugs. What is the difference between them?

Strictly speaking, HAART is defined as the use of at least three active antiretroviral medications.

71

What is the major goal of ART?

To inhibit HIV replication completely such that the viral load is undetectable at 4 to 6 months.

72

What are the two conditions under which ART is indicated?

  1. CD4+ count <350 cells/µL
  2. HIV RNA >55,000 copies/mL
73

What are the five categories of antiretroviral agents?

  1. protease inhibitors (PIs)
  2. nucleoside reverse transcriptase inhibitors (NRTIs)
  3. non-NRTIs (NNRTIs)
  4. nucleotides
  5. entry inhibitors
74

What class do the following drugs belong to?

  1. atazanavir
  2. darunavir
  3. lopinavir
  4. ritonavir

protease inhibitors (PIs)

75

What is the mechanism of action of protease inhibitors (PIs) such as indinavir or tipranavir?

They bind to HIV-1 protease, preventing cleavage of viral polyprotein precursors into individual functional proteins required for infectious HIV.

76

What class do the following drugs belong to?

  1. abacavir
  2. didanosine
  3. stavudine
  4. zidovudine

nucleoside reverse transcriptase inhibitors (NRTIs)

77

What is the mechanism of action of NRTIs such as emtricitabine or lamivudine?

They are are structural nucleoside analogues, which inhibit polymerisation when incorporated into the DNA provirus by reverse transcriptase.

78

Why is zalcitabine not commonly used in ART?

Because of its narrow therapeutic window.

79

What is the most commonly used NTRI?

stavudine

80

What class do the following drugs belong to?

  1. delavirdine
  2. efavirenz
  3. etravirine
  4. nevirapine

non-nucleoside reverse transcriptase inhibitors (NNRTIs)

81

What is the mechanism of action of NNRTIs such as efavirenz or nevirapine?

They inhibit HIV reverse transcriptase, preventing conversion of viral RNA into the DNA provirus, thereby preventing viral replication.

82

What class do the following drugs belong to?

  1. adefovir
  2. tenofovir

nucleotides

83

What is the mechanism of action of nucleotides such as adefovir and tenofovir?

Similar to NRTIs, they nucleotide analogues, which inhibit polymerisation when incorporated into the DNA provirus by reverse transcriptase.

84

Why is adefovir not commonly used in ART?

Because of its GI and renal toxicity.

85

When is tenofovir indicated in ART?

In patients on multiple-drug therapy who are not responding.

86

What class do the following drugs belong to?

  1. enfuvirtide
  2. maraviroc

entry inhibitors

87

What is the mechanism of action of the entry inhibitor enfuvirtide?

It binds to the gp41 of the viral envelope glycoprotein, inhibiting fusion of HIV-1 with CD4+ cells.

88

What is the mechanism of action of the entry inhibitor maraviroc?

It bind to CCR5 receptors on human CD4 cells, preventing interaction with the gp120 subunit of the viral envelope glycoprotein, inhibiting fusion of HIV-1.

89

What is the life expectancy of an HIV-infected individual appropriately treated with ART compared to the general population?

It is estimated to be nearly equal to the general population.

90

How many drugs are used in typical ART regimens?

A two-drug regimen is effective, but three drugs are preferred.

91

How long are ART regimens recommended to last?

28 days

92

What is the preferred regimen for an ART-naive, HIV-positive patient?

  1. efavirenz + tenofovir + emtricitabine, or;
  2. ritonavir-boosted atazanavir–darunavir + tenofovir–emtricitabine, or;
  3. raltegravir + tenofovir + emtricitabine
93

What improvements in CD4+ count and viral load are expected in patients who respond to ART?

  1. CD4+ ↑ by 50-150 cells/µL/year
  2. viral load <75 copies/mL
94

What is the definition of "virologic suppression" in context of ART?

viral load <48 copies/mL

95

What is the definition of "virologic failure" in context of ART?

viral load >200 copies/mL

96

What are the important toxicities of ART medications? (5)

  1. hyperlactemia
  2. mitochondrial dysfunction
  3. peripheral neuropathy
  4. hepatotoxicity
  5. lipodystrophy
97

What is one of the biggest challanges during ART?

compliance

98

About 25% of patients expereince an exacerbation of preexisting opportunistic infections after initiation of ART. What is this called?

immune reconstitution inflammatory syndrome (IRIS)

99

Why does IRIS occur following iniation of ART?

It probably results from elicitation of an inflammatory response in association with the antiviral drugs.

100

When are chemoprophylaxis regimens for opportunistic diseases indicated in patients with HIV?

When CD4+ counts drop to levels insufficient to prevent initial episode of a disease or to suppress a developing opportunistic infection.

101

Why might it be more complicated for a dentist to obtain a health history from patients with HIV or AIDS?

Patients who are seropositive and those at high risk may not answer questions honestly on account of the stigma or concern for privacy.

102

What is the recommended course of action for dental patients found to be at high risk for AIDS or HIV?

Refer to a physician for testing and medical evaluation.

103

Can patients with HIV or AIDS receive dental treatment?

Yes, they should be treated with standard precautions just like any other patient.

104

Can a dentist refuse to treat a patient that is suspected to have HIV, but refuses testing?

No, the dentist may just assume that the patient is a potential carrier of HIV and should treat the person using standard precautions, just as for any other patient.

105

Can a dentist refuse to treat a patient with AIDS?

No, there is no medical or scientific reason to justify why patients with AIDS who seek dental care may be declined treatment by the dentist.

106

Should a dentist infected with HIV inform their patients of their serostatus?

Yes, and they should receive consent or refrain from performing invasive procedures.

107

What are the two major considerations in dental treatment of the patient with HIV infection/AIDS ?

  1. CD4+ count and level of immunosuppression of the patient
  2. viral load and susceptibility to opportunistic infections
108

How must dental treatment be altered for HIV-infected patients without symptoms?

It is no different than any other patient; standard precautions must be used for all patients.

109

What tests should be ordered before any surgical procedure is undertaken in HIV-infected patients?

  1. WBC counts
  2. platelet count
110

Why should acetaminophen be avoided in patients taking zidovudine?

Because the granulocytopenia and anemia associated with zidovudine may be intensified.

111

Why might aspirin have to be avoided in HIV-infected patients?

Due to the possibility of thrombocytopenia.

112

Why should meperidine be avoided in patients taking ritonavir?

Ritonavir increases metabolism of meperidine to normeperidine, which is associated with lethargy, agitation, and seizures.

113

Why should propoxyphene be avoided in patients taking ritonavir?

Ritonavir increases levels of propoxyphene, leading to lead to toxic effects such as drowsiness or incoordination.

114

Why should midazolam and triazolam be avoided in patients taking select protease inhibitors?

Because benzodiazepine metabolism may be inhibited, leading to excessive sedation or respiratory depression.

115

What is recommended following needlestick injury with exposure to HIV-infected blood?

postexposure prophylaxis (PEP)

116

When are two-drug HIV PEP regimens indicated?

For a minor needlestick injury from a source patient with a low viral load (<1500 copies/mL).

117

What is the standard two-drug regimen for HIV PEP?

  1. tenofovir + emtricitabine, or;
  2. zidovudine + lamivudine
118

When are three-drug HIV PEP regimens indicated?

For any major needlestick injury or when the patient is symptomatic or has AIDS or a high viral load.

119

What is the standard three-drug regimen for HIV PEP?

  1. tenofovir + emtricitabine, or;
  2. zidovudine + lamivudine, and;
  3. a protease inhibitor (e.g. lopinavir)
120

How long should HIV PEP be continued for?

4 weeks

121

When should tests for seroconversion be performed following possible exposure to HIV-infected blood?

  1. 3 months
  2. 6 months
  3. 12 months
122

What are one of the early signs of HIV infection and risk for progression to AIDS detectable by dentists?

oral lesions

123
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An HIV-infected patient presents with white lesions on the palate, mucosa, and tongue, which could be scraped off with a tongue blade to reveal underlying erythematous mucosa. What is the diagnosis?

pseudomembranous candidiasis

124
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An HIV-infected patient presents with a erythematous palatal lesion; smears taken from the lesion showed hyphae and spores. What is the diagnosis?

erythematous candidiasis

125
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An HIV-infected patient presents with crusty, red patches at the corners of their mouth which responded well to antifungal medication. What is the diagnosis?

angular cheilitis

126
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An HIV-infected patient presents with multiple erythematous lesions on the face. What is the diagnosis?

Kaposi sarcoma

127
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An HIV-infected patient presents with multiple large, erythematous lesions involving the palatal mucosa. What is the diagnosis?

Kaposi sarcoma

128
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An HIV-infected patient presents with erythematous gingival enlargement. What is the diagnosis?

Kaposi sarcoma

129
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An HIV-infected patient presents with a diffuse white lesion involving the borders of the tongue. What is the diagnosis?

hairy leukoplakia

130
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An HIV-infected patient presents with a band of linear redness involving the free gingival margin. What is the diagnosis?

linear gingival erythema

131
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An HIV-infected patient presents with ulceration and necrosis with attachment loss and does not respond to conventional periodontal therapy. What is the diagnosis?

necrotizing ulcerative periodontitis (NUP)

132
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An HIV-infected patient presents with multiple warty lesions of the gingivae. What is the diagnosis?

condyloma acuminatum (HPV)

133

What early sign of HIV infection can found in about 70% of infected patients during the latent stage of infection?

persistent generalized lymphadenopathy (PGL)

134

What are the treatment options for PGL in HIV-infected patients?

It is usually not treated directly; may need biopsy to rule out lymphoma or other conditions.

135

What is the most common intraoral manifestation of HIV infection?

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oral candidiasis

136

What is the prognostic significance of oral candidiasis in HIV-infected patients?

It indicates that AIDS will develop within 2 years in untreated patients.

137

What are the four different manifestations of oral candidiasis?

  1. pseudomembranous
  2. erythematous
  3. hyperplastic
  4. angular cheilitis
138

What are the treatment options for oral candidiasis in HIV-infected patients?

  1. nystatin
  2. fluconazole
  3. itraconazole
  4. IV amphotericin B

*systemic antifugals have more drug interactions and may result in drug-resistant candidiasis.

139

What periodontal condition in HIV-infected patients presents as redness of the gingival margin associated with candidiasis that does not respond to plaque control?

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linear gingival erythema (LGE)

140

What are the treatments for LGE in HIV-infected patients? (3)

  1. plaque removal
  2. improved oral hygiene
  3. chlorhexidine rinses
141

What periodontal condition in HIV-infected patients presents as ulceration and necrosis of interdental papillae with no loss of periodontal attachment?

necrotizing ulcerative gingivitis (NUG)

142

What periodontal condition in HIV-infected patients consists of gingival ulceration and necrosis with attachment loss that does not respond to conventional periodontal therapy?

necrotizing ulcerative periodontitis (NUP)

143

What periodontal condition in HIV-infected patients is a progression of NUP, involving ulceration and necrosis of the oral mucosa separate from the gingiva?

necrotizing stomatitis (NS)

144

What are treatments for NUG, NUP, and NS in HIV-infected patients? (4)

  1. debridement
  2. chlorhexidine rinses
  3. metronidazole
  4. long-term maintenance
145

What are the treatment options for herpes simplex virus (HSV) co-infection in HIV-infected patients?

  1. valacyclovir 1 g PO tid x 5d, or;
  2. famciclovir 500 mg PO tid x 5d, or;
  3. acyclovir 800 mg PO x 5d, and;
  4. diphenhydramine (pain control)
146

What are the treatment options for varicella-zoster virus (VZV) co-infection in HIV-infected patients?

  1. valacyclovir 1 g PO tid x 5d, or;
  2. famciclovir 500 mg PO tid x 5d, or;
  3. acyclovir 800 mg PO x 5d
147

What co-infection is associated with oral hairy leukoplakia (OHL) in HIV-infected patients?

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Epstein-Barr virus (EBV)

148

What is the prognostic significance of OHL in HIV-infected patients?

In an untreated patient with HIV infection, its finding indicates that AIDS will develop in the near future.

149

What is the treatment for OHL in HIV-infected patients?

Treatment often is not needed; acyclovir or desiclovir can result in rapid resolution, but recurrence is likely.

150

What co-infection is associated with Kaposi sarcoma (KS) in HIV-infected patients?

human herpesvirus-8 (HHV-8)

151

What is the prognostic significance of KS in HIV-infected patients?

The presence of this condition in an HIV-infected patient is diagnostic of AIDS.

152

What is the treatment for KS in HIV-infected patients?

It often regresses with HAART; treatment involves irradiation and local and systemic chemotherapy.

153

What population is most commonly affected by KS?

MSM who are HIV-infected

154

What uncommon variants of human papillomavirus (HPV) are found in oral lesions of HIV-infected patients?

HPV-7 and HPV-32

155

What is the treatment for HPV lesions in HIV-infected patients?

Treatment of choice is surgical removal of the lesion(s).

156

What is the most common endemic respiratory fungal infection in the United States, which HIV-infected patients are especially susceptible to?

histoplasmosis

157

What are the treatment options for disseminated histoplasmosis in HIV-infected patients? (2)

  1. IV amphotericin B
  2. itraconazole

*itraconazole has been found to be effective with fewer adverse effects and better patient compliance.

158

What condition characterized by small papular lesions with a central depressed crater is caused by poxvirus co-infection in HIV-infected patients?

molluscum contagiosum

159

What is the treatment for molluscum contagiosum in HIV-infected patients?

Resolution has been reported with HAART; curettage, cryosurgery, and cautery have been used, but they are painful, and recurrences are common.

160

Why might HIV-infected patients be at greater risk for developing dental caries?

Due to xerostomia from HIV-associated salivary gland disease.

161

Which salivary glands are most commonly affected by HIV-associated salivary gland disease?

parotid

162

Patients who develop HIV-associated salivary gland disease are at increased risk for what type of cancer?

B-cell lymphoma

163

What are three possible explanations for why hyperpigmentation may occur in HIV-infected patients?

  1. Some medications (ketoconazole, clofazimine, zidovudine) may cause pigmentation.
  2. Addison-like pigmentation also may occur because of destruction of the adrenal gland.
  3. The HIV infection itself may cause melanin pigmentation.