Transcript the 2014 HIV/STD Update

Overview
• Background
• HIV and tuberculosis syndemic
• Pathophysiology, clinical manifestations
• Epidemiology
• Diagnosis
• Management
• What drugs to use
• When to start ART
• IRIS and drug interactions
• Prevention of TB & HIV Advances
• IPT
• ART
• Infection Control
• Unmet Needs & Recommendations
What is a Syndemic?
“A set of linked health problems involving two or more
afflictions, interacting synergistically, contributing to
excess burden of disease in a population.”
Linked epidemics, interacting epidemics, connected
epidemics, co-occurring epidemics, co-morbidities, and
clusters of health-related crises

http://www.medterms.com/script/main/art.asp?articlekey=22591
TB Pathophysiology &
Clinical Manifestations
TB Pathophysiology
Etiology: Mycobacterium tuberculosis complex
Airborne
droplets
(1-5 μ)
~10%
lifetime
risk
~36-50% lifetime risk
Small PM, Fujiwara PI. N Engl J Med 2001;345:189-200
Clinical Sites of TB
TB Cases by Site, 2012*
• Pulmonary (PTB)
68.5
• Both PTB and EPTB
10.2
• Extrapulmorary (EPTB) 21.1
• Miliary
78.7%
3.5
* CDC. Reported Tuberculosis in the United States, 2012. Atlanta, GA. Dept HHS Oct 2013
Goals of Anti-TB Chemotherapy
• Individual benefits
– Prevent morbidity and mortality
• Kill bacilli rapidly (rifamycins play key role)
• Prevent drug resistance (multidrug therapy)
• Eliminate persistent bacilli  relapse
• Public health benefits
– Prevent transmission (identify contacts in
need of treatment for LTBI or active TB)
– Protect effective drug regimens
Epidemiology (TB and HIV-associated
associated TB) in U.S. and Globe
No. of Cases
Reported TB Cases
United States, 1982–2013*
2013 Data
9,588 Cases
Rate
3.0/100,000
1985-1992
Resurgence
• HIV
• MDR TB
• Immigration
• Institutional
transmission
• Weak
infrastructure
Year
* MMWR 2013;63:229-33
HIV-Associated MDR TB Outbreaks,
1988-1995 and 2006
Evidence of institutional MDR TB transmission
Hospital KZN, South Africa, 2006
53
100
98
2
Wells CD, et al. J Infect Dis 2007;196:S86-S107; Gandhi NR et al. Lancet 2006;368:1575-80
Reporting of HIV Test Results
in Persons with TB by Age Group,
United States, 1993 – 2012*
% with Test Results
100
80
60
40
20
0
All Ages
Aged 25 - 44
*Updated as of June 10, 2013.
Note: Includes persons with positive, negative, or indeterminate HIV test results and persons from
California with co-diagnosis of TB and AIDS. Rhode Island did not report HIV test results for years
1993–1997. HIV test results for Vermont are not included for years 2007–2010. HIV test results for
California are not included for years 2005 - 2010
Estimated HIV Coinfection in Persons
Reported with TB, U.S., 1993 – 2012*
70
% Coinfection
60
50
40
30
20
10
0
Aged 25-44
All Ages
Note: Minimum estimates based on reported HIV-positive status among all TB cases in the age group
CDC. Reported Tuberculosis in the United States, 2012. Atlanta, GA. Dept HHS Oct 2013
TB Case Rates by Race/Ethnicity,*
United States, 2003–2012**
35.0
Cases per 100,000
30.0
25.0
20.0
15.0
10.0
5.0
0.0
2003
2004
2005
2006
2007
Hispanic or Latino
Asian
Native Hawaiian or Other Pacific Islander
*All races are non-Hispanic.
**Updated as of June 10, 2013.
2008
2009
2010
2011
American Indian or Alaska Native
Black or African American
White
2012
TB Case Rates in U.S.-born vs. Foreignborn Persons, United States,* 1993 – 2012**
Cases per 100,000
100.0
10.0
1.0
U.S. Overall
* TB case-rates presented on a logarithmic scale.
**Updated as of June 10, 2013.
U.S.-born
Foreign-born
HIV Prevalence and Incidence
United States, 1980-2010
Number of people living with HIV has grown because
incidence is relatively stable and survival has increased
Hall HI et al. JAMA 2008 Aug 6;300(5):520-9; Prejean J et al PLoS One 2011;6(8):e17502; MMWR 2012 Mar 2;61(8):133-8.
Estimated Number of Adults and Adolescents
Living with HIV Infection and Percent
Undiagnosed, U.S., 1985-2008
Estimated HIV prevalence among new
TB cases, 2012
Adults and children estimated to be living
with HIV, 2012
Eastern Europe
& Central Asia
Western &
1.3 million
Central Europe [1.0 million
– 1.7 million]
North America
860 000
1.3 million
[800 000 – 930 000]
East Asia
[980 000 – 1.9 million]
880 000
[650 000 – 1.2 million]
Middle East & North Africa
260 000
Caribbean
[200 000 – 380 000]
250 000
South & South-East Asia
[220 000 – 280 000]
3.9 million
[2.9 million – 5.2 million]
Sub-Saharan Africa
Latin America
25.0 million
1.5 million
[23.5 million – 26.6 million]
Oceania
[1.2 million – 1.9 million]
51 000
[43 000 – 59 000]
Total: 35.3 million [32.2 million – 38.8 million]
Estimated HIV-associated TB incidence
and mortality globally, 1990-2012
In 2012: 8.6 million TB cases (1.3 million deaths )

1.3 million (13%) with HIV – 75% in AFRO

450,000 with MDR TB (170,000 deaths)
Diagnosis & Management/ Rx Needs
Clinical Signs & Symptoms Pulmonary TB
Pulmonary Symptoms:
Systemic Symptoms:
• Productive, prolonged
cough of over 3 weeks
duration
• Chest pain
• Hemoptysis
•
•
•
•
•
•
Fever
Chills
Night sweats
Appetite loss
Weight loss
Easy fatigability
Armitige LY. U Texas HSC Tyler
Challenges of Diagnosing
HIV-related TB
• Frequency and broad spectrum of lung
disease among patients with HIV/AIDS
• Rapid progression of HIV-related TB and
possibility of transmission to others – need for
quick diagnosis
• Effects of immunodeficiency on clinical
symptoms and signs of TB
Burman WJ. 2008
Challenges in HIV-associated TB
Diagnosis
• Paucibacillary
• Atypical CXR
• Extrapulmonary*
Treatment
• Drug-drug
interactions between
rifamycins and ARV
• Inmune reconstitution
inflammatory
syndrome
* Lymphatic, meningeal, milliary,
disseminated (mycobacteremia)
Advanced
HIV
(CD4<200)
Pulmonary
TB
Early HIV
(CD4>350)
Clinical
Postprimary
Primary TB
Sputum
AFB
Positive
Negative
Chest
Radiograph
Cavitary
Infiltrates
Occasional
Common
With extrapulmonary
TB
Effect of HIV-induced Immunosuppression
on CXR Presentation of TB
• CD4 > 200
– Upper lobe, fibronodular
– Cavitation
• CD4 < 200
– Upper or lower lung field involvement
– Absence of scarring and cavitation
– Miliary or nodular infiltrates
– Intrathoracic adenopathy, with necrosis
– Pleural and pericardial involvement
% with extrapulmonary involvement
Extrapulmonary manifestations of TB,
by CD4+ T-lymphocyte count range
80
70
60
50
40
30
20
10
0
>300
201-300
101-200
Jones BE et al. Am Rev Respir Dis 1993;148:1292-7
0-100
Common Forms of Extrapulmonary TB in
HIV-infected Persons (Burman WJ. 2008)
• Nodal
– peripheral nodes: cervical > axillary > inguinal
– central nodes: mediastinal > hilar, intra-abdominal
• Disseminated disease
• Serosal - pleural, pericardial > ascites
• Central nervous system - meningitis,
tuberculoma
• Soft tissue abscesses
http://generalsurgeryclinics.blogspot.com/2013/02/clinical-pleomorphism-tuberculosis.html
Clinical Presentation
HIV-positive vs HIV-negative patients
• Influenced mostly by degree of immunity
• HIV-positive patients are more likely to have:
– Isolated extrapulmonary localization (53-63% in some studies)
–
–
–
–
–
–
Primary infection
Pulmonary basilar involvement
Tuberculous pneumonia
Hilar or mediastinal lymphadenopathies
Miliary or disseminated TB
Normal CXR (8-20% in some studies)
Aaron L et al. Clinical Microbiology and Infection 2004;10 (5): 388-98
When Should You Start ART in a
Patient with Active TB?
Options:
1. At time of TB treatment initiation
2. 2-8 weeks after TB medications are started
3. After TB treatment is completed
4. Not at all
N Engl J Med 2010;365:1471-81
N Engl J Med 2011;362:697-706
Early Timing of ART Therapy
in TB-HIV
PRO:
– High mortality without ART
– Beneficial effect of HAART on other OIs
– ART decreases risk of TB relapse
CON:
– Large pill burden for TB and HIV regimens
– Drug-drug interactions and toxicity
– IRIS risk increased
Ruling Out TB in HIV-infected
Before Isoniazid Preventive Therapy
151 (61%) of 249
TB cases had
two negative
AFB smears
Symptoms
% Sensitivity
Cough <3wks
33
Cough or fever or 3wkNS 93
• NPV 97%
Cain KP, et al. N Eng J Med 2010;362:707-16
12–dose Isoniazid and Rifapentine
Regimen for LTBI in PLWH
Sterling T, et al. CROI 2014. Abstract 817
Starting ART During TB Treatment
– Steps Required
1. Start TB therapy: deal with initial side
effects
2. Help patient deal with 2 new diagnoses
3. Begin PCP prophylaxis if CD4 < 200
4. Coordinate start of ART: usually 2 weeks
after TB treatment start
5. Use DOT visits to  adherence with ART
6. Anticipate and manage IRIS events
ART and TB Therapy
Approach to building a regimen:
1. Use a rifamycin
2. Use efavirenz and rifampin as preferred
regimen
3. Alternative: Use rifabutin with PI
EFV-based ART with
RIF-based TB therapy
• Modest reduction in EFV levels does
not appear to reduce EFV activity
• EFV-based ART (600 mg) with RIFbased TB therapy is regimen of choice
Rifabutin and TB Therapy
• Rifabutin is as active as rifampin
• No dose adjustments of ART needed for
commonly-used drugs (ATZ, lopinavir/R)
• Decrease RBT from 300 mg daily to 150
mg thrice-weekly for boosted PIs
*Caution – RBT dose would be inadequate if
patient stopped PI
Summary – Treatment of HIV TB
• How long should TB treatment be given?
– 6-9 months*
• Can intermittent therapy be used in someone with
advanced HIV disease?
– Daily preferred
– After the intensive phase, can use thrice-weekly
– Avoid highly-intermittent Rx if CD4 low
* Extend treatment to 9 months if culture-positive at 2
months or extensive bilateral cavitary pulmonary disease
Summary-Treatment of HIV TB
• Should antiretroviral therapy be used during TB
treatment?
– Yes
• What regimens can be used for co-treatment of
HIV and TB?
– Preferred: efavirenz-based ART + rifampinbased TB treatment
– Alternative: PI-based ART + rifabutin-based TB
treatment
• When should HAART be started?
– 2 weeks to 2 months after starting TB treatment
Side Effects & Drug-to Drug Interaction
Overlapping Side Effect Profiles of First-line
TB drugs and Antiretroviral (ART) Drugs
Possible causes
Side effect
TB drugs
ART drugs
Skin rash
PZA, RIF, INH
NVP, EFV, ABC
Nausea, vomiting
PZA, RIF, RBT, INH
AZT, PIs
Hepatitis
PZA, RIF, RBT, INH
NVP, PIs, IRIS
Leukopenia,
Anemia, platelet
decrease
RBT, RIF
AZT
Immune Reconstitution Inflammatory Syndrome (IRIS)
Paradoxical Worsening of TB following ART
How Common?
Immune Reconstitution Inflammatory Syndrome (IRIS)
Possible Risk Factors
Manosuthi W et al. Journal of Infection 2006;53:357-363
Diagnosing IRIS
Meintjes et al. Lancet Infect Dis 2008;8:516-23.
IRIS
Management
•
•
•
•
Exclude treatment failure or new OI
Continue anti-TB and ART
NSAIDS
For severe symptoms: steroids (40 to 80
mg/d) for 5 to 14 weeks
Furrer, Am J Med, 1999.
Mansouthi W
Mansouthi W
Mansouthi W
Mansouthi W
Prevention and Treatment Advances
1995-2012 Global TB Response
Initially DOTS, Later Global Plan



56 million people successfully
treated for TB
22 million lives saved
Improvements in TB/HIV prevention
and care



46% of TB patients tested for HIV in 2012,
74% in Africa
57% TB patients known to be living with
HIV enrolled on ARVs, 80% received CPT
Diagnosis and treatment of MDRTB doubled between 2011 and 2012
, with case rates falling in some
countries
WHO/HTM/TB/2013.11
The 2012 WHO Policy
53 | Collaborative TB/HIV activities, 2012
Number of TB patients with known HIV status
2004-2012
54 | Collaborative TB/HIV activities, 2012
Number of HIV-positive TB patients enrolled on
co-trimoxazole preventive therapy (CPT) and
antiretroviral therapy (ART), 2004-2012
55 | Collaborative TB/HIV activities, 2012
Provision of isoniazid preventive therapy (IPT) to
people living with HIV without active TB, 2005-2012
56 | Collaborative TB/HIV activities, 2012
Collaborative TB/HIV activities 2004-2012
Global
57 | Collaborative TB/HIV activities, 2012
Estimated number of lives saved globally by the
implementation of TB/HIV interventions, 2005-2011
Blue band represents the uncertainty interval
58 | Collaborative TB/HIV activities, 2012
Evolution of Global TB Strategy
Post–2015 Global TB Targets
Far more needs to be
done!
• Est. 3 million with TB
disease “missed” (nearly
1/3)
• 1.3 million died of TB in 2012
(320,000 with HIV)
• Almost ¾ of MDR TB not
diagnosed or treated
properly
• More than half of TB patients
unaware of HIV status
• 530,000 children ill with TB
WHO/HTM/TB/2013.13
Frieden TR. AJPH 2010;100:590-595
Convergence of Thought in HIV Continuum
of Care Initiative and Post –2015 TB
Element
HIV Continuum of Care
Strategy Post-2015 TB Strategy
Political Will
POTUS Executive Order
WHA 2012 call to action
Support Integration of
Prevention and Care
Yes
Yes (with attention to infection
control and LTBI)
Promote Expansion of Service
Delivery Models
Yes
Yes
Encourage Innovative
Approaches
Yes
Yes (new way of thinking beyond
DOTS strategy)
Attention to Health Disparities
Yes
Yes (bold policies for universal
coverage)
Research for Evidence-based
Interventions
Yes
Yes
Measurable Targets with
Monitoring of Outcomes
Yes
Yes
Treatment As Prevention
Yes
Yes
Ambitious
Yes
Yes (DOTS initially not)
Filling in the Gaps Along the HIV Care
Continuum
Support and Guidance for Health Departments & CBOs
100
Lab Reporting and Surveillance
90
Health
Prevention with Positives Guidelines
and Research Capacity Building Assistance for
80 Department
Prevention FOA
70
60
50
40
Testing
guidelines
Surveillance
MSM Testing
Initiative
CAPUS
30
20
10
0
MSM & High Risk Populations
Partner services
Social
marketing
campaigns
ARTAS
New FOA
with HRSA
for CHCs
Health
Services
Research
ART
guidelines
Health
Department
and CBO
support
ART Adherence
interventions
Unmet Needs & Recommendations
Unmet Needs

New, less toxic anti-TB drugs for PLWH on ART

Shorter treatment regimens

Treatment for presumed LTBI due to MDR

Safe and effective TB vaccine(s)
Recommendations








Manage both HIV and TB
Test all TB patients for HIV and link to care
• Start treatment on ARVs and treat for TB
• Be on alert for DDI and IRIS
Implement and monitor infection control in HIV
clinics
Screen PLWH for TB and treat LTBI
Utilize ARVs to reduce risk of TB
Advance Treatment as Prevention (TASP)
Promote and monitor adherence to treatment
Monitor outcomes
THANK YOU
Publications and Resources
Available by visiting CDC’s DHAP and DTBE websites:
http://www.cdc.gov/hiv/
http://www.cdc.gov/tb/
Or by calling:
1-800-CDC-INFO
National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention
Division of HIV/AIDS Prevention