Transcript HIV-Associated Opportunistic Infections 2003

Welcome to I-TECH HIV/AIDS Clinical Seminar Series
Opportunistic Infections
Dr. Robert Harrington, M.D.
December 18, 2008
MMWR 1981
HIV Infection: Pathogenesis
Anti-HIV
T-cell response
10,000,000
Sero-conversion
Antibody response
AIDS
Plasma HIV RNA
1,000,000
100,000
Plasma RNA Copies
10,000
Viral set point
1,000
CD4 Cell Count
Intermediate Stage
Typical Course
1,000
100
CD4 Cells
500
10
1
4-8 Weeks
Up to 12 Years
A lot of important stuff happens here
2-3 Years
CD4 Count and
Opportunistic Infections
CD4 Cell Count
10,000,000
Plasma HIV RNA
1,000,000
100,000
10,000
1,000
Bacterial Pneumonia, TB,
HSV, Cryptosporidiosis
Thrush, lymphoma, KS
1,000
100
500
200
PCP
MAC, CMV, PML, PCNSL,
Cryptococcus, Microsporidia
Toxo
10
1
4-8 Weeks
Up to 12 Years
2-3 Years
100
Opportunistic Infections and Geography
North America
Common OIs
• PCP
• MAC
• Candida
Regional Effects
• Southwest:
– Coccidiodomycosis
• Midwest:
– Histoplasmosis and
Blastomycosis
• South:
– Blastomycosis and
Toxoplasmosis
Opportunistic Infections and Geography
The World
Candida
PCP
MAC
PCP
TB
Cryptococcus
Isospora
Cryptosporidiosis
Microsporidia
PCP, TB
Candida, MAC
Cryptococcus
Leishmaniasis
PCP
TB
Candida
Cryptococcus
Penicilliosis
TB
Bacteria
Malaria
Cryptococcus
Holmes, CID, 03
Putong, SEA Trop Med, 02
Margues, Med Mycol, 2000
Amornkul, CID, 03
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
Prophylaxis to Prevent Opportunistic
Infections in the Developed World
Secondary
Primary
PCP
MTb
Toxo
MAC
VZV
S. pneumoniae
HBV
HAV
Influenza
CD4 < 200
PPD > 5mm
IgG+,CD4 < 100
CD4 < 50
Exposure with
IgG- or no hstry
PCP
Toxo
MAC
CMV
Cryptococcosis
Histoplasmosis
Coccidioidomycosis
Salmonella species bacteremia
Recurrent HSV
Recurrent Candidiasis
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
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
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
HIV ASSOCIATED MALIGNANCIES
•
•
•
•
AIDS Defining Malignancies
Kaposi’s sarcoma
Primary CNS lymphoma (PCNSL)
Non-Hodgkin’s lymphoma (NHL)
Invasive cervical cancer
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
EFFECTS OF HAART ON
OPPORTUNISTIC INFECTIONS
• Declining incidence
• Reduced need for prophylaxis (primary and
secondary)
• Spontaneous improvements and cure
• Immune reconstitution effects
EFFECT OF HAART ON INCIDENCE
OF OPPORTUNISTIC INFECTIONS
J.E. Kaplan et al. CID 2000;30:S5-S14
(Kovacks, NEJM, 2000)
Effect of HAART on Opportunistic Infections:
Reduced Need for Prophylaxis
PCP
MAC
Toxo
Primary Prophylaxis
When CD4 > 200 for 3 months
When CD4 > 100 for 3 months
When CD4 > 200 for 3 months
Effect of HAART on Opportunistic Infections:
Reduced Need for Prophylaxis
Secondary Prophylaxis or Maintenance Therapy
PCP
CMV
MAC
Toxo
Cryptococcus
When CD4 > 200 for 3 months
When CD4 > 100-150 for 6 months
When CD4 > 100 for 6 months, no
symptoms of MAC and after 12 months
of MAC Rx
When CD4 > 200 for 6 months and
completed initial Toxo Rx
When CD4 > 100-200 for 6 months and
completed initial Crypto Rx
Opportunistic Infections Treatable with
HAART alone
•
•
•
•
•
Progressive Multifocal Leukoencephalopathy (PML)
Cryptosporidiosis
Microsporidiosis
Kaposi’s sarcoma
Mycobacterium avium complex (sometimes)
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.
Case 1
CXR of Case 1
(www.learningradiology.com)
Case 1
• What diagnostic studies do you want?
(www.tulane.edu)
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
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?
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
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
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)
50
Immediate
45
Delayed
40
35 P=0.035
30
25
20
15
10
5
0
Death or New
OI
VL > 50
VL < 50
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
Case 2
• How common is chronic Hepatitis B
infection and why do you suppose he has it?
• What about co-infection with HIV?
100
100
80
80
60
60
Chronic Infection
40
40
20
20
Symptomatic Infection
0
Birth
1-6 months
7-12 months
Age at Infection
1-4 years
0
Older Children
and Adults
Symptomatic Infection (%)
Chronic Infection (%)
Outcome of Hepatitis B by Age of Acquisition
Natural History: Acute HBV Infection with
Progression to Chronic Infection
Acute
(6 months)
Chronic
(Years)
HBeAg
anti-HBe
HBsAg
Total antiHBc
Titer
IgM anti-HBc
0 4 8 12 16 20 24 28 32 36
Weeks after Exposure
52
Years
Natural History: Chronic HBV
Definitions: NIH Workshop
Perinatal
Transmission
Immune
Tolerant
Horizontal
Transmission
Immune
Active
(Clearance)
60-80%
Inactive
Chronic
Carrier
20-40%
(Hoofnagle, Hepatology 2007;45:1056-1075)
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;45:1056-1075)
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 HBVrelated chronic liver disease
Hepatitis B: Epidemiology
HBsAg Prevalence
8% - High
2-7% - Intermediate
<2% - Low
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
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?
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;61:1942-66
McMahon. Ann Intern Med 2001;135:759-768
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
Chen, Chen
C.-J. et
al. JAMA
2006;295:65-73.
JAMA
2006;295:65-73
*Funded by Bristol Myers Squib
APPLIES TO ADULTS > 40
WITH GENOTYPES B&C
Cumulative Incidence of Hepatocellular Carcinoma by Serum
HBV DNA Level at Study Entry
Chen, C.-J. et al. JAMA 2006;295:65-73.
Natural History: Chronic HBV:
Factors Associated with Progression
• HBV
–
–
–
–
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
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
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
AASLD Practice Guidelines, 2007*
HBsAg +
HBeAg
Positive
ALT < 1 X ULN
Q 6 mo ALT
Q 12 mo HBeAg
ALT 1-2 X ULN
Q 3 mo ALT
Q 6 mo HBeAg
Liver bx if persistent or
age > 40, Rx as needed
* HCC surveillance if indicated
ALT >2 X ULN
Q 1-3 mo ALT, HBeAg
If persistent, Liver bx & Rx;
Immediate Rx if jaundice or
decompensated
Lok & McMahon. Hepatology 2007;45:507-539.
Available at aasld.org
AASLD Practice Guidelines, 2007*
HBsAg +
HBeAg
Negative
ALT > 2X ULN
DNA > 20,000 IU/mL
Liver bx & Rx
* HCC surveillance if indicated
ALT 1-2X ULN
DNA 2,000-20,000 IU/ml
ALT < 1X ULN
DNA < 2,000 IU/mL
Q 3 mo ALT & DNA
Q 3 mo ALT X 3,
If results persist,
Then Q 6-12 mo
liver bx, treat as needed If ALT still WNL
Lok & McMahon. Hepatology 2007;45:507-539.
Available at aasld.org
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
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.
Case 3
What diagnostic testing do you want?
• HIV test is + and Sputum smear stains 3+ for AFB
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?
WHO/DHHS: Treatment
HIV-TB
Pulmonary TB
Extrapulmonary TB
CD4 < 100
CD4 100-200
CD4 200-350
CD4 > 350
CD4 not
available
TB therapy
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)
Start TB therapy
HAART after intensive phase of TB Rx
(HAART earlier if severely immunocompromised)
Start TB therapy
Monitor CD4 count and start HAART when indicated
Improving, no OIs
HAART when TB Rx
complete
Treatment and Outcome
Survival
Thailand
• 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)
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
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
Immune Reconstitution Syndrome
• TB-associated IRS in
South Africa
TB-IRS and CD4 and HAART
– 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
(Lawn, AIDS 2007;21:335-41)
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
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
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
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)
Principles of Treatment
Drug Interactions: The P450 system
• NNRTIs (efavirenz and nevirapine)
– Induce CYP 3A
• Protease Inhibitors (many)
– Inhibit CYP 3A
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
Principles of Treatment
Drug Interactions: Rifamycins and PIs
PI
ATZ 400/d
AMP 1200 BID
IDV 1000 q8hr
LPV/r 3 caps BID
NLF 1250 BID
Rifabutin
Rifampin
150 QOD
150 QD (300 3x/wk)
150 QD (300 3x/wk)
150 QD (150 3x/wk)
150 QD (300 3x/wk)
No
No
No
600 QD +R*
No
(*Extra RTV 300 BID)
Principles of Treatment
Drug Interactions: Rifamycins and PIs
PI
Rifabutin
SQV/RTV 400/400 BID
IDV/RTV 800/200 BID
ATZ/RTV 300/100 QD
APV/RTV 600/100 BID
TPV/RTV 500/200 BID
DRV/RTV 600/100 BID
150 QOD (150 3x/wk)
150 QOD (150 3x/wk)
150 QOD (150 3x/wk)
150 QOD (150 3x/wk)
150 QOD (150 3x/wk)
150 QOD (150 3x/wk)
Rifampin
No
No
No data
No data
No data
No data
Principles of Treatment
Drug Interactions: Rifamycins and NNRTIs
NNRTI
EFV 600 QD
NVP 200 BID
DLV
Rifabutin
Rifampin
450 QD (600 3x/wk)
300 QD
No
600 QD
600 QD
No
Web site for more complete table showing dosages:
www.cdc.gov/nchstp/tb/TB_HIV_Drugs/TOC.htm
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
Case 3
What are you worried about and what are you going to do?
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 2005-06
• N=170; 43 had baseline and follow-up cultures; 23
developed MDR or XDR TB
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
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 +
Treatment and Outcome
MDR and XDR TB
(Raviglione, NEJM 2007;356:656-59)
Treatment and Outcome
• 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%
(1993-99) Vs 10% (2000-06)
Survival
(Gandhi, Lancet, 2006; 368: 1575-80)
(MMWR, 2007; 56(11): 250-53)
XDR TB
# 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
–Better
diagnosis
and
infection
control
procedures
– De-centralization
ofof
care
–De-centralization
care
– Better
integration
ofof
HIV
and
TBTB
care
–Better
integration
HIV
and
care
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.
Case 4
Skin lesions for Case 4
(www.dermatology.cdlib.org)
Case 4
• What is your differential diagnosis for this patient?
• What diagnostic tests will you perform?
Case 4
• Blood smear or buffy coat or BM of Leishmania
amastigotes
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
Leishmaniasis and HIV
Reported cases of Leishmania and HIV Co-infection - 1998
(www.who.int)
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
Leishmaniasis and HIV
Treatment: HAART +
• AmB 0.5 to 1.0mg/kg/d (to total dose of 1.5-2.0
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
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
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!
Thank you!
Next session: January 8th, 2009
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Welcome to I-TECH HIV/AIDS Clinical Seminar Series
Next session: January 8th, 2009
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Pediatric HIV