1. Opportunistic Infections Dr. Robert Harrington, M.D. December 18, 2008
I’d like to welcome everyone to the I-TECH HIV/AIDS Clinical Seminar Series. We have with us today Dr. Robert Harrington. Dr. Harrington is currently an associate professor of medicine at the University of Washington and medical director of the Harborview Medical Center HIV clinic (the Madison Clinic).  His interests are in general infectious diseases, clinical HIV, and the development of laboratory assays of HIV infectivity.  He’s published over 40 manuscripts and book chapters on HIV and infectious diseases.
Today he will be presenting on HIV and opportunistic infections (OIs). He will review relevant facts, differential diagnoses, and treatment, as well as the timing of HAART initiation in the context of treating OIs.
Before we begin, I’d like to ask all the sites to type in how many participants are at their sites. If you are an individual, please type “1”.
If your site has not already provided a topic suggestion for next year’s series, please do so now. Site coordinators should solicit ideas from participants at this time During the session, Maureen will be privately chatting sites who have not responded. Your input is very important to the planning for next year’s Clinical Seminar Series.

2. MMWR 1981

3. HIV Infection: Pathogenesis
Anti-HIV
T-cell response
Sero-conversion
Antibody response
Typical Course
Intermediate Stage
AIDS
CD4 Cell Count
Plasma RNA Copies
Viral set point
1,000
CD4 Cells
500
4-8 Weeks
Up to 12 Years
2-3 Years
A lot of important stuff happens here

4. CD4 Count and Opportunistic Infections
CD4 Cell Count
Bacterial Pneumonia, TB,
HSV, Cryptosporidiosis
1,000
Thrush, lymphoma, KS
500
PCP
200
100
MAC, CMV, PML, PCNSL,
Cryptococcus, Microsporidia
Toxo
4-8 Weeks
Up to 12 Years
2-3 Years

5. Opportunistic Infections and Geography
North America
Common OIs
PCP
MAC
Candida
Regional Effects
Southwest:
Coccidiodomycosis
Midwest:
Histoplasmosis and Blastomycosis
South:
Blastomycosis and Toxoplasmosis

6. Opportunistic Infections and Geography
PCP, TB
Candida, MAC
Cryptococcus
Leishmaniasis
The World
PCP TB
Candida
Cryptococcus
Penicilliosis
Candida
PCP
MAC TB
Bacteria
Malaria
Cryptococcus
PCP TB
Cryptococcus
Isospora
Cryptosporidiosis
Microsporidia
Holmes, CID, 03
Putong, SEA Trop Med, 02
Margues, Med Mycol, 2000
Amornkul, CID, 03

7. Prophylaxis to Prevent Opportunistic Infections
Considerations for Prophylaxis
Infection should be common and/or predictable
Infection should be clinically significant
Treatment (prophylaxis) should be effective, non-toxic and affordable

8. Prophylaxis to Prevent Opportunistic Infections in the Developed World
Primary
PCP CD4 < 200
MTb PPD > 5mm
Toxo IgG+,CD4 < 100
MAC CD4 < 50
VZV Exposure with IgG- or no hstry
S. pneumoniae
HBV
HAV
Influenza
Secondary
PCP
Toxo
MAC
CMV
Cryptococcosis
Histoplasmosis
Coccidioidomycosis
Salmonella species bacteremia
Recurrent HSV
Recurrent Candidiasis

9. Prophylaxis to Prevent Opportunistic Infections in the Developing World
Primary prophylaxis:
Secondary prophylaxis: for PCP and Cryptococcus
WHO Guidelines on co-trimoxazole prophylaxis for HIV-related
infections among children, adolescents and adults. August, 2006

10. TB prevention WHO recommendation:
Treat tuberculin skin test positive HIV-infected persons without active TB with 6 month regimen isoniazid preventive therapy (IPT)
Difficulties:
Lack of tuberculin skin testing
People not screened
Screen positive do not receive INH
Screen positive started on INH do not complete regimen

11. HIV-Associated and Opportunistic Infections
PCP
MAC
Cryptosporidiosis
Microsporidiosis
Bacterial respiratory infections
Bacterial enteric infections
Bartonellosis
Coccidiodomycosis
Paracoccidiomycosis
Histoplasmosis
Cryptococcus
Toxoplasmosis
Candida TB
Aspergillosis
CMV
HSV
VZV
PML (JCV)
HHV-8
HPV
Penicilliosis
Leshmaniasis

12. HIV ASSOCIATED MALIGNANCIES
AIDS Defining Malignancies
Kaposi’s sarcoma
Primary CNS lymphoma (PCNSL)
Non-Hodgkin’s lymphoma (NHL)
Invasive cervical cancer

13. HIV ASSOCIATED MALIGNANCIES
Increased Rates of Other Cancers in HIV
Hodgkin’s disease
Anal cancer
Multiple myeloma
Leukemia
Lung cancer
Head and neck tumors
GI malignancies
Genital cancers
Hypernephroma
Soft tissue tumors

14. EFFECTS OF HAART ON OPPORTUNISTIC INFECTIONS
Declining incidence
Reduced need for prophylaxis (primary and secondary)
Spontaneous improvements and cure
Immune reconstitution effects

15. EFFECT OF HAART ON INCIDENCE OF OPPORTUNISTIC INFECTIONS
J.E. Kaplan et al. CID 2000;30:S5-S14
(Kovacks, NEJM, 2000)

16. Effect of HAART on Opportunistic Infections: Reduced Need for Prophylaxis
Primary Prophylaxis
PCP When CD4 > 200 for 3 months
MAC When CD4 > 100 for 3 months
Toxo When CD4 > 200 for 3 months

17. Secondary Prophylaxis or Maintenance Therapy
Effect of HAART on Opportunistic Infections: Reduced Need for Prophylaxis
Secondary Prophylaxis or Maintenance Therapy
PCP When CD4 > 200 for 3 months
CMV When CD4 > for 6 months
MAC When CD4 > 100 for 6 months, no symptoms of MAC and after 12 months of MAC Rx
Toxo When CD4 > 200 for 6 months and completed initial Toxo Rx
Cryptococcus When CD4 > for 6 months and completed initial Crypto Rx

18. Opportunistic Infections Treatable with HAART alone
Progressive Multifocal Leukoencephalopathy (PML)
Cryptosporidiosis
Microsporidiosis
Kaposi’s sarcoma
Mycobacterium avium complex (sometimes)

19. Case 1
A 40 yo male with severe bipolar disease presents with cough, weight loss, dyspnea and low grade fever.
His PMH is notable for recurrent bacterial pneumonia, methamphetamine and alcohol abuse. He has refused all medications.
On exam he is thin and in mild respiratory distress. T 38C, BP 100/70, HR 100, RR 18, O2 saturation 89% at rest. Lung exam reveals fine rales at lung bases.

20. Case 1
CXR of Case 1 (

21. Case 1
What diagnostic studies do you want? (

22. Case 1 How would you treat this patient? Treatment:
TMP-SMX, pentamidine
Timethoprim-dapsone, clindamycin and primaquine, atovoqone
Trimetrexate and leucovorin
Severe disease (paO2 < 70 or Aa gradient > 35): add steroids
How would you treat this patient?

23. Case 1 Over the next 10 days the patient slowly improves.
His CD4 T-cell count returns at 60 cells/uL.
Should he receive HAART and, if so, when should he start?

24. Timing of HAART
#142: Immediate Vs Delayed ART in Setting of Acute OI, Zolopa, Powderly, et.al. (ACTG 5164)
Randomized study of ARV given within 14 days of Rx for OI Vs delayed (at least 4 wks)
Patients with TB excluded
Primary endpoint: 48 week combination of 3 categorical variables
1. Death or alive with new AIDS diagnosis
2. Alive with HIV RNA > 50 and no new AIDS diagnosis
3. Alive with HIV RNA < 50 and no new AIDS diagnosis

25. Timing of HAART
#142: Immediate Vs Delayed ART in Setting of Acute OI, Zolopa, Powderly, et.al. (ACTG 5164)
Patients (N=282)
Median age 38
Median CD4 = 29 and log10 HIV RNA level = 5.07
OIs
PCP 63%
Cryptococcal meningitis 13%
Pneumonia 10%
Median time to starting ART 12 Vs 45 days

26. Timing of HAART ACTG 5164: Results
No significant difference between immediate Vs delayed for the composite endpoint
Immediate arm had fewer deaths/new AIDS diagnosis
Immediate arm had longer time to death/new AIDS diagnosis (HR 0.53)
P=0.035

27. Case 2
RT is an asymptomatic 47 yo Asian male with newly diagnosed HIV who presents for care.
His PMH is notable for multiple STDs and “hepatitis”
PE is notable only for thrush, mild cervical adenopathy and seborrheic dermatitis.
CD4 is 380, HIVRNA is 80K, ALT is 240, HepAAB+, HepCAB and RNA negative, HepBsAG+, cAB+, eAG+ and HBV DNA 40 million

28. Case 2
How common is chronic Hepatitis B infection and why do you suppose he has it?
What about co-infection with HIV?

29. Outcome of Hepatitis B by Age of Acquisition
100
100 80 80 60 60
Chronic Infection (%)
Chronic Infection
Symptomatic Infection (%) 40 40 20 20
Symptomatic Infection
Birth
1-6 months
7-12 months
1-4 years
Older Children
and Adults
Age at Infection

30. Natural History: Acute HBV Infection with Progression to Chronic Infection
(6 months)
Chronic
(Years)
HBeAg
anti-HBe
HBsAg
Total anti-HBc
Titer
IgM anti-HBc
Weeks after Exposure 4 8 12 16 20 24 28 32 36 52
Years

31. Natural History: Chronic HBV Definitions: NIH Workshop
Perinatal
Transmission
Horizontal
Transmission
60-80%
Immune
Active
(Clearance)
Inactive
Chronic
Carrier
Immune
Tolerant
20-40%
(Hoofnagle, Hepatology 2007;45: )

32. Natural History: Chronic HBV Definitions: NIH Workshop
HBsAg-positive for at least 6 months
Phases of Chronic hepatitis B
Immune Tolerant Phase: HBeAg+, normal ALT, HBV DNA > 200,000 IU/ml (>1 million copies)
Immune Active or Clearance Phase: elevated ALT, HBV DNA > 2,000 IU/ml, HBeAg or anti-HBe
Inactive Hepatitis B carrier: anti-HBe, ALT WNL, HBV DNA < 2,000 IU/ml
Reactivation of hepatitis
Clearance of HBsAg
(Hoofnagle, Hepatology 2007;45: )

33. Hepatitis B: Epidemiology
2 billion people have evidence of HBV infection
1/3 of world’s populations
350 million people chronically infected
15% to 25% will develop HBV-related chronic liver disease (cirrhosis, hepatocellular carcinoma) and die without intervention
Up to 1 million deaths worldwide each year from HBV-related chronic liver disease
Worldwide Burden of Disease
Worldwide, approximately 2,000 million individuals, or X% of the world’s population, have serologic evidence of current or past HBV infection. Over 200 million individuals are chronically infected with HBV, and are at risk of developing and dying from HBV-related chronic liver disease, including cirrhosis and primary hepatocellular carcinoma. Each year 1 million people die from HBV-related chronic liver disease making it one of the major causes of mortality worldwide. (Kane M. Global status of HB Immjnization, Acta Gastro-Enterologica Belgica, LXI, April-June 1998)

34. Hepatitis B: Epidemiology
Geographic Distribution of Chronic HBV Infection
The world can be divided into areas of high, intermediate, and low endemicity based on the prevalence of HBsAg in the population. Areas of high endemicity are those in which the prevalence of HBsAg >8%. Southeast Asia, East Asia, many of the Pacific Islands, and parts of South America and Africa are areas of high endemicity. Areas of intermediate endemicity are those in which the prevalence of HBsAg is 2%-7%, and include Eastern Europe, the Middle East, and central Asia. Areas of low endemicity, in which <2% of the population is HBsAg positive, include Australia, North America, and Western Europe.
HBsAg Prevalence
8% - High
2-7% - Intermediate
<2% - Low

35. Hepatitis B: Epidemiology
Among all the chronic hepatitis B carriers worldwide, 75% are Asians
While the overall incidence of chronic hepatitis B in the US population is less than 1 in 200, the incidence among Asian Americans is 1 in 10 (Source: Asian Liver Center of Stanford University)
9-16% of HIV infected patients in the US are co-infected with HBV

36. Case 2
….back to the case
He is not inclined to start HAART but wants to discuss it with you.
Should you be worried about his HBV infection and why?
Does it influence your decision to recommend HAART?

37. Natural History: Long-Term Outcome of Chronic HBV
Hepatocellular carcinoma (HCC)
25%-40% of males
10-15% females
Cirrhosis
10% to 20% of males and females
Beasley. Cancer 1988;61:
McMahon. Ann Intern Med 2001;135:

38. Elevated HBV DNA as Risk for HCC: R.E.V.E.A.L.-HBV Study*
23,820 residents 7 townships in Taiwan
4,155 HBsAg-positive
3,653 tested for HBV DNA at entry
Median age 46 years; follow-up 11.4 years
Findings: Risk factors for HCC at study entry using Regression analysis
HBV DNA > 104 copies/ml
Liver cirrhosis
Age
APPLIES TO ADULTS > 40
WITH GENOTYPES B&C
Chen, C.-J. et al. JAMA 2006;295:65-73.
Chen JAMA 2006;295:65-73
*Funded by Bristol Myers Squib

39. Cumulative Incidence of Hepatocellular Carcinoma by Serum HBV DNA Level at Study Entry
Chen, C.-J. et al. JAMA 2006;295:65-73.

40. Natural History: Chronic HBV: Factors Associated with Progression
HBV DNA level
Genotype
Pre-core mutant
Core Promoter mutations
Other viruses: HIV, DELTA, HCV
Demographic: Age, male sex
Environmental and Social
Alcohol
NAFLD
Aflatoxin

41. Natural History: Chronic HBV/HIV Co-infection
Co-infected patients have
Higher HBV DNA levels
Lower rates of spontaneous HBeAg clearance
More severe liver disease and higher liver-related mortality
May experience severe hepatitis flares due to immune reconstitution after HAART
May have “occult” HBV infection with high HBV DNA levels but with negative HBsAg.
Any HIV+ patient who tests + for either HBsAg or HBcAB should be tested for HBV DNA

42. Long-Term Goals of Antiviral Therapy
Decrease risk of development of cirrhosis
If cirrhosis is present, decrease risk of decompensation
If decompensated cirrhosis present, treat to revert patient to compensated cirrhosis
Decrease risk of development of hepatocellular carcinoma

43. AASLD Practice Guidelines, 2007*
HBsAg +
HBeAg
Positive
ALT < 1 X ULN
ALT 1-2 X ULN
ALT >2 X ULN
Q 6 mo ALT
Q 12 mo HBeAg
Q 3 mo ALT
Q 6 mo HBeAg
Liver bx if persistent or age > 40, Rx as needed
Q 1-3 mo ALT, HBeAg
If persistent, Liver bx & Rx;
Immediate Rx if jaundice or
decompensated
Lok & McMahon. Hepatology 2007;45: Available at aasld.org
* HCC surveillance if indicated

44. AASLD Practice Guidelines, 2007*
HBsAg +
HBeAg
Negative
ALT > 2X ULN
DNA > 20,000 IU/mL
ALT 1-2X ULN
DNA 2,000-20,000 IU/ml
ALT < 1X ULN
DNA < 2,000 IU/mL
Q 3 mo ALT & DNA
If results persist,
liver bx, treat as needed
Q 3 mo ALT X 3,
Then Q 6-12 mo
If ALT still WNL
Liver bx & Rx
* HCC surveillance if indicated
Lok & McMahon. Hepatology 2007;45: Available at aasld.org

45. Treatment of HBV/HIV Co-infection
All HBV/HIV patients should be offered HAART
If treating HBV only can use IFN or adefovir
When treating both HIV and HBV - Rx with TDF and FTC is preferred
Patients already on HAART with agents not active against HBV can be treated with the addition of IFN, adefovir or entecavir
Patients with lamivudine resistant HBV can be treated with the addition of TDF
When altering HAART, consider the need to continue HBV therapy unless the patient has cleared HBeAg

46. Case 3
A 38 yo South African male presents with a 10 kg weight loss, 10 weeks of cough and intermittent fever. He has no past medical history.
On exam he is thin, T 38.8 C, BP 100/70, HR 104, RR 20. He has prominent cervical adenopathy, oral thrush and course breath sounds over his R upper and mid lung zones.

47. Case 3 HIV test is + and Sputum smear stains 3+ for AFB
What diagnostic testing do you want?
HIV test is + and Sputum smear stains 3+ for AFB

48. Case 3
He is admitted to a hospital ward with similar patients and started on “RIPE” therapy.
After a week his constitutional symptoms improve. His CD4 T-cell count measures 15 cells/uL.
Should he be offered HAART?
If so, when should HAART be started?
Are there TB and HIV drug interactions of concern?

49. WHO/DHHS: Treatment HIV-TB Pulmonary TB Extrapulmonary TB CD4 < 100
Start TB therapy, start HAART in 2 weeks
Start TB therapy
HAART as soon as TB Rx tolerated (b/n 2-8 wks)
Some experts would wait until 8 weeks (avoid IRIS) CD
Start TB therapy
HAART after intensive phase of TB Rx
(HAART earlier if severely immunocompromised) CD
Start TB therapy
Monitor CD4 count and start HAART when indicated
CD4 > 350
CD4 not
available
TB therapy
Improving, no OIs
HAART when TB Rx
complete

50. Treatment and Outcome Thailand Survival
Retrospective study of 1103 HIV+ patients with TB
411 received HAART
Risk factors for death
No HAART
Delay of HAART > 6 months
MDR TB
Gastrointestinal TB
(Manosuthi, J Acquir Immune Defic Syndr 2006;43:42-46)

51. Timing of HAART and TB
CROI 2007: Abst # 81: Early Mortality Among Patients with HIV and TB in Africa, Lawn, et, al.
Observational study of mortality before and during first 16 weeks of ART in patients with (n=213) and without (n=675) TB
MV analysis: mortality associated only with CD4 < 100 and WHO stage 4
Among 73 patients who had TB diagnosed prior to HAART there were 14 deaths
10 occurred among patients waiting for HAART
4 occurred after HAART - 2 due to IRS

52. COD in Patients with TB
CROI 2007: Abst # 82: Cause of Death in HIV + Patients with TB in Soweto, South Africa, Martinson, et.al.
Results of complete autopsies, N=47
Immediate Cause of Death
Pulmonary TB 19
Bacterial pneumonia 4
Disseminated TB 4*
CMV pneumonia 7
PCP 3
* Contributed to another 28

53. Immune Reconstitution Syndrome
TB-associated IRS in South Africa
160 patients receiving Rx for TB at the time HAART initiated
Median CD4 68
IRS in 12% overall, 32% in those who started HAART within 2 months of TB Rx
MV analysis: IRS risks
Low CD4
Early HAART – OR for starting HAART < 30 days = 69.5
2 IRS deaths (both had disseminated TB
TB-IRS and CD4 and HAART
(Lawn, AIDS 2007;21:335-41)

54. TB/HIV Co-infection: Principles of Treatment
Treatment generally the same as in HIV- patients (4 drugs for 2 months and 2 drugs for 4 months)
Sub-optimal response (culture + after 2 months) – give 9 months, skeletal TB – 6 to 9 months, CNS TB – 9 to 12 months
If using regimens without INH or a rifamycin - duration should be 12 to 15 months

55. Principles of Treatment: Importance of Rifamycin
Treatment with NON rifamycin-containing regimens is associated with:
• Higher relapse rates
• Higher mortality
Wallis, et al. (1996) Tuber Lung Dis 77:516-23
Hawken, et al. (1993) Lancet 342:332-38
Perriens, et al. (1991) AM Rev Resp Dis 144:750-55
Korwnromp, et al. (2003) CID 37:101-12

56. Principles of Treatment
Be wary of drug interactions between the rifamycins and HIV medications
Do not use TB treatment regimens that are dosed weekly (e.g. INH-rifapentine) or even twice weekly in patients with CD4 counts < 100
Consider measuring drugs levels if there is concern for malabsorption or increased elimination of TB therapies

57. Principles of Treatment
Drug Interactions: The P450 system
Isoform CYP 3A is affected and/or involved in the metabolism of rifamycins, NNRTI and PIs
Rifamycins: Induce CYP 3A
Rifampin > rifapentine > rifabutin
Rifampin is not metabolized by CYP 3A (level not affected by other drugs that influence CYP 3A)
Rifabutin is metabolized by CYP 3A (level is affected by other drugs that also affect CYP 3A)

58. Principles of Treatment
Drug Interactions: The P450 system
NNRTIs (efavirenz and nevirapine)
Induce CYP 3A
Protease Inhibitors (many)
Inhibit CYP 3A

59. Principles of Treatment
If using rifampin - avoid PI-based HAART - use NNRTIs instead
If using rifabutin - can use PIs or NNRTI - but will have to dose adjust the rifabutin in most cases

60. Principles of Treatment
Drug Interactions: Rifamycins and PIs
PI Rifabutin Rifampin
ATZ 400/d QOD No
AMP 1200 BID QD (300 3x/wk) No
IDV 1000 q8hr QD (300 3x/wk) No
LPV/r 3 caps BID QD (150 3x/wk) QD +R*
NLF 1250 BID QD (300 3x/wk) No
(*Extra RTV 300 BID)

61. Principles of Treatment
Drug Interactions: Rifamycins and PIs
PI Rifabutin Rifampin
SQV/RTV 400/400 BID 150 QOD (150 3x/wk) No
IDV/RTV 800/200 BID 150 QOD (150 3x/wk) No
ATZ/RTV 300/100 QD 150 QOD (150 3x/wk) No data
APV/RTV 600/100 BID 150 QOD (150 3x/wk) No data
TPV/RTV 500/200 BID 150 QOD (150 3x/wk) No data
DRV/RTV 600/100 BID 150 QOD (150 3x/wk) No data

62. Principles of Treatment
Drug Interactions: Rifamycins and NNRTIs
NNRTI Rifabutin Rifampin
EFV 600 QD QD (600 3x/wk) QD
NVP 200 BID QD QD
DLV No No
Web site for more complete table showing dosages:

63. Case 3
…back to the case
10 days into his TB therapy he is started on HAART.
3 weeks later his fever and cough return

64. Case 3
What are you worried about and what are you going to do?

65. XDR TB
# 143: Exogenous Re-infection with MDR and XDR TB Among TB/HIV Infected Patients in Rural South Africa, Andrews, et.al.
Case control study of patient with pulmonary TB at Church of Scotland Hospital, South Africa from
N=170; 43 had baseline and follow-up cultures; 23 developed MDR or XDR TB

66. XDR TB
# 143: Exogenous Re-infection with MDR and XDR TB Among TB/HIV Infected Patients in Rural South Africa, Andrews, et.al.
170 patients with TB
43 had both initial and
follow up cultures done
23 developed MDR or XDR TB
17 had paired spoligotypes performed
17/17 pairs were NOT matched

67. XDR TB
# 143: Exogenous Re-infection with MDR and XDR TB Among TB/HIV Infected Patients in Rural South Africa, Andrews, et.al.
23 developed MDR or XDR TB
17 had paired spoligotypes performed
17/17 pairs were NOT matched
All 17 patients had been hospitalized
15/17 who were HIV tested were +

68. Treatment and Outcome MDR and XDR TB
(Raviglione, NEJM 2007;356:656-59)

69. Treatment and Outcome Survival XDR TB
Report of 53 cases in rural South Africa
55% had never been treated for TB
67% had recently been hospitalized
44 (100%)/44 tested for HIV were + (median CD4 63)
52 (98%)/53 died, median survival of 16 days
49 cases in USA: HIV+: 74% ( ) Vs 10% ( )
Survival
(Gandhi, Lancet, 2006; 368: )
(MMWR, 2007; 56(11): )

70. # 112: Confronting the Catastrophe of M/XDR TB, Gerald Friedland
Infection with resistant organisms acquired in healthcare settings is central to recent MDR/XDR outbreaks
Need
Better diagnosis and infection control procedures
De-centralization of care
Better integration of HIV and TB care
Better diagnosis and infection control procedures
De-centralization of care
Better integration of HIV and TB care

71. Case 4
A 46 yo Ethiopian male with untreated HIV and a CD4 T-cell count of 110 presents with mild dysphagia, weight loss, abdominal fullness and fatigue.
On exam he appears chronically ill. T 38 C, BP 110/60, HR 98, RR12. He has thrush, a palpable liver and spleen tip and several nodular skin lesions.
His Hct is 24, WBC 1800, plts 90. AST 110, ALT 123, AP 200, bili 2.3.

72. Case 4
Skin lesions for Case 4 (

73. Case 4 What is your differential diagnosis for this patient?
What diagnostic tests will you perform?

74. Case 4
Blood smear or buffy coat or BM of Leishmania amastigotes

75. Leishmaniasis and HIV An intracellular protozoa
Transmitted to humans by phlebotomine sand flies
Most cases reported in southern Europe (Spain, Italy, France), Ethiopia, central and south America

76. Leishmaniasis and HIV
Reported cases of Leishmania and HIV Co-infection (

77. Leishmaniasis and HIV Clinically
Cutaneous, mucosal or visceral disease
HIV patients:
Disseminated visceral disease
Cytopenias
Atypical locations: GI, lung, pleura and peritoneal spaces, unusual cutaneous lesions

78. Leishmaniasis and HIV Treatment: HAART +
AmB 0.5 to 1.0mg/kg/d (to total dose of gms)
Liposomal AmB 2-4mg/kg/d (to total dose of 20 to 60 mg/kg)
Pentavalent antimony 20 mg/kg/d for 3-4 weeks
Secondary prophylaxis q 3 to 4 weeks
Consider discontinuing if CD4 > 350

79. Opportunistic Infections - not discussed
MAC
Cryptosporidiosis
Microsporidiosis
Bacterial respiratory infections
Bacterial enteric infections
Bartonellosis
Coccidiodomycosis
Paracoccidiomycosis
Histoplasmosis
Cryptococcus
Toxoplasmosis
Candida
Aspergillosis
CMV
HSV
VZV
PML (JCV)
HHV-8
HPV
Penicilliosis
Malaria

80. Summary
Opportunistic infections are predictable based on a patients immune status and environment
Disseminated and atypical presentations are the rule with extreme immune suppression
Prophylaxis against certain OIs is indicated if the OI is common and the prophylaxis is affordable, effective and well tolerated
HAART alone is treatment enough for certain OIs and can eliminate the need for prophylaxis
The timing of HAART relative to OI therapy is controversial but should probably be early…..however, watch out for IRIS!

81. Next session: January 8th, 2009
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82. Next session: January 8th, 2009 Lisa Frenkel Pediatric HIV
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