Unit 5, Part 1: The DOTS Strategy For Controlling TB: Objectives

Return to the contents
Unit 5, part 1: The DOTS strategy for

controlling TB
___________________________________________________________
Objectives
___________________________________________________________
By the end of this subunit, participants will be able:
1) to describe the DOTS strategy (the WHO- recommended
strategy for controlling TB); and
2) to discuss the implications of the strategy for
implementing collaborative TB/HIV activities.
___________________________________________________________
Methods
___________________________________________________________
Plenary presentation: The DOTS strategy
Plenary discussion
___________________________________________________________
Materials
___________________________________________________________
Document 5.1: The DOTS strategy (slides)
___________________________________________________________
49
Document 5.1
The DOTS strategy for controlling TB Objectives of the sub-

sub-unit
Document No. 5.1
• To describe the DOTS strategy (the

WHO-recommended strategy for
controlling TB)
• To discuss the implications of the

TB/HIV course for managers at the national strategy for implementing
and subnational levels collaborative TB/HIV activities
Open
History of DOTS
1980s : Styblo defines International Union against Tuberculosis
and Lung Diseases model to control TB in the United Republic The DOTS strategy
of Tanzania
1991: World Health Assembly establishes the 70/85 targets for 2000
1993: WHO declares TB as a global emergency is a comprehensive strategy that ensures
1994: New TB control framework cure to most people with TB disease
1995: DOTS launched as a WHO strategy presenting to primary health care
1998: London Committee, StopTB Partnership launched services.
2000: Amsterdam Declaration; targets in 2005
2001: Six working groups and Global Drug Facility launched
2001: Global Fund to Fight AIDS, Tuberculosis and Malaria,
Millennium Development Goals and Washington Commitment Sources: Stop TB at the source. Geneva, World Health Organization, 1995.
2002: Expanded framework DOTS brand name Use DOTS more widely. Geneva, World Health Organization, 1997.
DOTS
• Government commitment to ensuring sustained, Aspects of DOTS
comprehensive TB control activities
• Case detection by sputum smear microscopy among
symptomatic patients self-reporting to health services
• Standardized short-course chemotherapy using regimens of
6–8 months for at least all confirmed smear-positive cases. • Technical
Good case management includes directly observed therapy
during the intensive phase for all new sputum-positive cases,
the continuation phase of rifampicin-containing regimens and • Logistical
the whole re-treatment regimen.
• A regular, uninterrupted supply of all essential anti-TB drugs • Operational
• A standardized recording and reporting system that allows
assessment of case-finding and treatment results for each
patient and of the TB control programme performance
• Political
overall
Source: World Health Organization, International Union against Tuberculosis and Lung Disease and Royal Netherlands
Tuberculosis Association. Revised international definitions in tuberculosis control. International Journal of Tuberculosis
and Lung Disease, 2001; 5:213–215.
50
Aspects of DOTS Justification for Directly
Observed Treatment (DOT)
Technical
About one third of patients do not take
• Case detection and diagnosis medications regularly as prescribed
• Standardized short-course chemotherapy
• Direct observation during the initial phase Perhaps one third of patients who do
of treatment (DOT)
take medications make errors in self-
• Recording and reporting of progress and
cure administration.
Source: Sbarbaro JA. The patient-physician relationship: compliance revisited. Annals of Allergy,
1990, 64:325–331.
Aspects of DOTS Aspects of DOTS

Logistical Operational
• Dependable drug and
diagnostic supply • Five basic core elements
• Laboratories for
microscopy
• Supervision and • Flexibility in implementation
training of health
workers
Aspects of DOTS Three phases to gradual DOTS

implementation
Political
1. A pilot project phase
• Government commitment
• Policy formulation 2. An expansion phase
• Resource mobilization 3. A maintenance phase
51
A strategy for quality DOTS is more than
DOTS Non-DOTS
Detection Passive, risk group Active, population screening
Diagnosis Three smear + limited X-ray Extensive X-ray or fluoroscopy • DOT
Category Smear-positive, smear-negative,
extrapulmonary, new, relapse, • Only five components (but: planning,
treatment after interruption, failure,
budgeting, financing, training, supervision,
transfer in
Weak mapping, staff management, data analysis and
Treatment Standardized, DOT Individual, inadequate, assessment)
decentralized, cheap centralized or specialized
Follow-up 2, 4, 6 or 2, 5, 8 smear Not systematic, X-ray • Strictly five components (but: flexible DOT in
Recording
and reporting Standard system No records, not done
low incidence, culture and drug susceptibility
Cure Reliable cohort Unreliable outcome testing, X-ray and DOTS Plus)
Result Success, cost-effective Multi-drug resistance, expensive
Treatment outcomes by WHO region:

DOTS versus non-
non-DOTS
Dynamics of pulmonary TB in Peru
2001 cohort
DOTS Non-DOTS
220
DOTS 1990
Pulmonary TB cases per 100 000
100
100
200
Pe rc e nta ge of c ohort
80
80 Case-finding
60
60 180
40
40
20
160
20
0 0 140
AFR AMR EMR EUR SEAR WPR AFR AMR EMR EUR SEAR WPR
Pulmonary TB
Treated Not treated 120
successfully successfully
Not evaluated declining 6% per year
AFR:African Region. AMR:Region of the Americas. EMR: Eastern Mediterranean Region. EUR: European 100
Region. SEAR: South-East Asia Region. WPR Western Pacific Region
1980 1985 1990 1995 2000
Source: Global tuberculosis control. WHO Report 2003. WHO/HTM/TB/2004.331
Progress towards the 70/85 targets WHO-

WHO-recommended global strategy to stop TB
100 and reach the Millennium Development Goals for 2015
China
Cambodia
Treatment success (%)
Pursuing expansion and enhancement of high-quality DOTS

90 Indonesia
Philippines Viet Nam
Afghanistan India • Political commitment
Kenya
Myanmar • Case detection through bacteriology
Bangladesh
80 Nigeria Mozambique • Standardized treatment, with supervision and patient support
United Republic
of Tanzania • Effective drug supply system
Democratic Republic of Congo
Pakistan Ethiopia
Thailand
• Monitoring system and evaluation of impact
70
Zimbabwe Additional components
Russian Federation South Africa
60 Brazil 1. Addressing TB/HIV and multi-drug-resistant TB

Uganda 2. Contributing to strengthening health systems
50
3. Engaging all care providers
4. Empowering patients and communities

40
0 20 40 60 80 100 5. Enabling and promoting research
DOTS detection rate (%) 18
52
The anchor of the WHO-
WHO-recommended global strategy:
pursue expansion and enhancement of high-
high-quality DOTS
9 Political commitment with long-term planning, adequate human
resources and expanded and sustainable financing to reach the
targets set by the World Health Assembly and the Millennium
Development Goals
9 Case detection through bacteriology (microscopy first and then
culture and drug susceptibility testing) and strengthening the
laboratory network to facilitate detection of TB cases that are sputum
smear–positive and –negative, drug-resistant and multi-drug-resistant
9 Standardized treatment, under proper case management conditions,

including DOT to reduce the risk of acquiring drug resistance, and
patient support to increase adherence and the chance of cure
9 An effective and regular drug supply system, including improving drug
management capacity
9 An efficient monitoring system for supervising and evaluating

programmes, including measuring impact
19
The other five components of the

WHO-
WHO-recommended global strategy
2. Addressing TB/HIV, multi-drug-resistant TB and other special

challenges by scaling up TB/HIV joint activities, DOTS Plus and other relevant
approaches
3. Contributing to strengthening health systems by collaborating

with other health programmes and general services in, for example, mobilizing the
necessary human and financial resources for implementation and evaluating
impact and by sharing and applying the achievements of TB control
4. Engaging all care providers, public, nongovernmental and private, by

scaling up public-private mix approaches to ensure adherence to the international
standards of TB care, with a focus on the providers for the poorest people
5. Empowering patients and communities by scaling up community TB

care and creating demand through context-specific advocacy, communication and
social mobilization
6. Enabling and promoting research to improve programme performance

and for developing new drugs, diagnostics and vaccines
20
Quality TB care for all: ensure a high standard

• Patient care to cure and prevent TB is the ultimate goal of
DOTS.
• The foundation of DOTS is effective patient care that alleviates

suffering and controls and prevents TB in a community.
• A standard of care for TB exists already, and is evidence-

based, but needs to be further promoted among all care
providers.
• Simply, each care provider, public or private, should:

• Diagnose TB quickly (bacteriological confirmation)
• Treat TB properly (short-course chemotherapy and treatment
support)
• Report TB cases and treatment outcomes
• If all providers did the right thing, TB would be controlled.
53
Unit 5, part 2: Clinical management

of TB
___________________________________________________________
Objectives
___________________________________________________________
1) to describe how the clinical management of TB is
organized;
2) to state the principles of diagnosis, treatment and case
management related to controlling TB; and
3) to discuss the implications of these principles for
___________________________________________________________
Methods
___________________________________________________________
Plenary presentation: Clinical management of TB
Exercise
Plenary discussion
___________________________________________________________
Materials
___________________________________________________________
Document 5.2: Clinical management of TB (slides)
Document 5.3: Introduction to the exercise for Unit 5
___________________________________________________________
54
Document 5.2
Clinical management of TB Objectives of the subunit

Document No. 5.2
• To describe how the clinical management

of TB is organized
• To state the principles of diagnosis,
treatment and case management of TB
TB/HIV course for managers at the national • To discuss the implications for
and subnational levels
collaborative TB/HIV activities
1 2
Open
Organization of clinical management:
Organization of clinical factors
management: objective • Patient’s access
– distance, time, cost, acceptability
• Regular drug supply
• Duration and periodicity of treatment
• To ensure that the drug regimen is – daily, intermittent
regularly taken until cure • Direct observation of treatment (DOT)
• Drug presentation
– blister pack, fixed-dose combination, patient kit
3 4
Diagnosis versus case detection Diagnosis versus case detection

• Diagnosis: health care activity performed on people
• Case detection: control programme activity, mainly to find
consulting for symptoms or signs
sources of infection: smear-positive pulmonary cases
• Main objective: curing the patient
• Mainly by sputum smear examination in people with cough of
• Uses all methods available, and covers all ages, sites long duration
and forms of the disease • To shorten infectivity, reduce the risk of infection to the
• Is followed by information to the patient and community, mortality and morbidity (contacts and high-risk
prescription of treatment groups)
• Must be followed by information to the person with TB and
• Treatment is patient’s responsibility
treatment (programme responsibility)
5 6
55
Case detection Case detection
Sputum smear examination
• Active and passive are obsolete terms
• Rapid results
• All diagnosis is passive (patient demand)
• Correlates with infectivity
• All case detection is active
• Detects the main sources
– contacts
– High-risk groups • Without HIV, correlates with severity
– suspects with cough in health facilities • Technique allows decentralization
• The key is correct selection of the target population • Less costly than culture
and the method
7 8

Sputum smear examination
• Three smears detect >60% of pulmonary TB
Sputum culture
>95% of the most infectious cases
• One smear detects ~75% of smear-positive, the second adds ~20%
and the third ~5% • Allows confirmation of M. tuberculosis
• Spot/overnight/spot maximizes results • Detects lower concentration (100 bacteria/ml)
• Reduces the number of visits (patient cost) • One culture detects ~80% of culture (+)
– spot is immediately available • Does not identify most infectious cases
– overnight is the best quality
• Long delay until results available
• Error (disagreement) <5%
• More complex than smears (central laboratory)
9 10

Radiology Radiology
• As a case detection method
• As a diagnostic tool
– useful for differential diagnosis and site – does not identify most infectious sources
– rapid – ~12% of positive cases missed, ~37% unconfirmed
– requires expert interpretation
– under-reading 20–30%, over-reading 1–20% • In mass examination (MMR)
– does not confirm diagnosis – most cases detected through symptoms
– less useful for TB among people living with HIV/AIDS – does not detect incidence (75% of cases in Kolin District)
• As a monitoring tool
– smear and culture (+) develop in <1 year
– inter- and intrareader disagreement >20% – costly
– shadows (scars) do not mean active disease – leads to over-diagnosis
– patients not motivated for treatment
11 12
56
Smear (+) infect ~10 times more than (–)
Screening for cough in outpatient department)
Where to find sources (actively)?
• Cough is a common outpatient symptom
• In the community
• Screening is rapid and inexpensive
– Prevalence is low (1–2 per 1000)
• 3–10% of general adult outpatients may have cough of
– Does not detect the true incidence
over two weeks’ duration
– Is costly and complex
– Patients detected are not motivated for treatment • 1–10% are smear-positive for TB
• In high-risk groups • Many attend for other reasons (including child

– Rationale if abnormal X-ray, contacts, prisons vaccination)
– If high prevalence (1–10%) • People with TB disease visit health facilities several times
– They are usually a small number before diagnosis
13 14
Case detection Case detection: definitions

• The best indicator of case detection is the number
of people with cough examined for diagnosis • TB suspected: with symptoms or signs of TB
(district level).
• The positivity of smears and bacillary load are • Case of TB: a person bacteriologically
operational (during expansion) and then confirmed or diagnosed by a clinician
epidemiological indicators.
• In health facilities, the percentage of outpatients • Definite case of TB: culture-positive or with
examined is an indicator of detection. two positive sputum smears
• The denominator can be easily studied.
15 16
Standardized TB treatment regimens

Case detection: conclusions
Diagnostic People with TB Initial phase Continuation
category disease Daily or 3 times Daily or 3 times
• Smear examination: rapid detection of sources to reduce risk of weekly weekly
New sputum smear positive Isoniazid + Rifampicin + Isoniazid + Rifampicin for 4
infection (treatment monitoring) 1 New sputum smear negative pyrazinamide + ethambutol months (4 HR)
(extensive) for 2 months (2 HRZE) or
Severe HIV disease or severe Isoniazid+ ethambutol daily
forms of extrapulmonary TB for 6 months (6 HE)
• Culture: confirms TB disease (+ treatment monitoring) Previously treated sputum smear Isoniazid + rifampicin + Isoniazid + rifampicin +
2 positive: relapse pyrazinamide + ethambutol + ethambutol for 5 months
streptomycin for 2 months
Re-medication after failure (5 HRE)
(2 HRZES) followed by Isoniazid
Re-medication after interruption
• Radiology: helps clinical diagnosis (+ screening high-risk group) + rifampicin + pyrazinamide +
ethambutol for 1month (1 HRZE)
Diagnosis of adult pulmonary TB should include smear results 3 New sputum smear negative
(other than category 1)
Isoniazid + rifampicin +
pyrazinamide + ethambutol
Isoniazid + rifampicin for 4
months (4 HR)
(positive or negative) Less severe extrapulmonary TB for 2 months (2 HRZE) or isoniazid + ethambutol
daily for 6 months (6 HE)
Chronic and multi-drug-resistant Specially designed standardized or individualized
4 TB (still sputum smear positive regimens
17 after supervised re-medication) 18
57
Organization of treatment (1) Organization of treatment (2)
Initial phase alternatives Initial phase alternatives
• Hospitalization (daily treatment) • 3 or 4 drugs
• Costly, helps patient but not family – severity, load of bacilli, HIV, resistance
• Food, rest, specialists not critical

• Fixed-dose combinations
• Allows direct observation of intake – ensures all-or-none intake
• Ambulatory (daily or three times weekly) – practical to define dosage by weight
• Accessible, acceptable, allows work

• Patient kits
• Requires well-organized supplies, staff – ensures full supply
• Requires organization of DOT – facilitates ordering and distribution
19 20
Organization of treatment (3) Treatment delivery process
Continuation phase alternatives • Integrated activity including:

• Isoniazid + rifampicin 6 months (observed) or isoniazid +
ethambutol 8 months - Appropriate regimen (quality proven, properly
– Isoniazid + rifampicin more effective, mainly in HIV-positive selected, right dose, given at the right time …)
people - This involves the drug management cycle, the
• “Daily” or three times per week
training and capacity-building component of the
– Three times is better for observed treatment, less costly for
patient, allows time for retrieval programme and the health education (to the
• Fixed-dose combinations, blister packs and patient kits patient) component
- The DOT component
21 22
58
Document 5.3
Introduction to the exercise for Unit 5

For this exercise, your facilitator will divide the participants into groups of three. The
purpose of the exercise is to analyse the implementation of the DOTS strategy in
“Fictitia”, identify gaps and propose activities to address the gaps.
• Read pages 140-148 in the report from Fictitia in Annex 1
• Analyse what the national TB control programme has done so far for
implementing the DOTS strategy in the country in relation to WHO
recommendations for a public health approach, with special focus on:
1) organization of the TB diagnosis and treatment services;
2) standardization of TB treatment regimens;
3) provision of isoniazid preventive therapy; and
4) collaboration between the TB and HIV/AIDS programmes.
• Identify immediate gaps in the programme (especially in terms of

strengthening the capacity of the health system) and propose priorities for your
planning.
• Prepare to present the group work in the plenary session.
Tell a facilitator when you are ready for the plenary discussion.
59
Unit 6, part 1: Universal access to

antiretroviral therapy
___________________________________________________________
Objectives
___________________________________________________________
1) to describe universal access to antiretroviral therapy
(rationale, core premises and principles, targets,
objectives, and components of its strategic framework);
and
2) to discuss the implications of universal access to
antiretroviral therapy for implementing collaborative
TB/HIV activities.
___________________________________________________________
Methods
___________________________________________________________
Plenary presentation: Universal access to antiretroviral therapy
Plenary discussion
___________________________________________________________
Materials
___________________________________________________________
Document 6.1: Universal access to antiretroviral therapy (slides)
Document 6.2: UNAIDS/WHO policy statement on HIV testing (1)
___________________________________________________________
60
Document 6.1
Universal access to antiretroviral Objectives of the subunit

therapy
Document No. 6.1 • To describe universal access to antiretroviral
therapy (rationale, core premises and
principles, targets, objectives, and
components of its strategic framework)
• To discuss the implications of universal

TB/HIV course for managers at the national access for implementing collaborative
and subnational levels TB/HIV activities
1 2
Open
Myths about antiretroviral therapy Why now?
• Six million people need antiretroviral therapy
• Developing countries are too poor to afford • Only 1 million were receiving it by mid-2005
antiretroviral drugs.
• Antiretroviral therapy offers hope
• Antiretroviral drugs are too complicated. – Has decreased death rates by up to 80% in Europe and the
Americas
• Infrastructure to support antiretroviral therapy is – Drug prices continue to fall
insufficient: • Unprecedented global political commitment
¾ Poor drug procurement and distribution systems
¾ No laboratories to monitor resistance • New sources of financing – US$ 20 billion on the table:
- Multilateral sources: World Bank, Global Fund to Fight AIDS,
• Inadequate human resources Tuberculosis and Malaria
¾ To prescribe and monitor antiretroviral therapy use - Bilateral funding: United States President's Emergency Plan
for AIDS Relief, United Kingdom Department for
• Everything must be in place before any action. International Development, GTZ and Sweden
3 4
Antiretroviral therapy coverage in low- and middle-income

countries, June 2005
Estimated
Geographical region Number of people

Coverage
need
receiving antiretroviral
therapy
(low estimate –
high estimate)
Sub-Saharan Africa 500 000 (425 000–575 000) 4 700 000 11%
Latin America and the Caribbean 290 000 (270 000–310 000) 465 000 62%
East, South and South-East Asia 155 000 (125 000–185 000) 1 100 000 14%
Europe and central Asia 20 000 (18 000– 22 000) 160 000 13%
North Africa and the Middle East 4 000 (2 000–6 000) 75 000 5%
Total 970 000 (840 000–1 100 000) 6.5 million 15%
5 6
61
Number of people receiving antiretroviral (ARV) therapy in
low- and middle income countries, end 2002 to mid-2005
1000 North Africa and the Middle East

Europe and Central Asia
East, South and South-East Asia
People receiving ARV therapy (thousands)

900
Latin America and the Caribbean
Sub-Saharan Africa
800
700
600
500
400
300
200
100
0
End Mid- End Mid- End Mid-
7 2002 2003 2003 2004 2004 2005 8
10
62
Mortality and use of antiretroviral therapy, 1995–2001
40 100
Widening gap in HIV/AIDS treatment
Percentage of patient-days on antiretroviral therapy

35
Deaths per 100 person-years
30 75
Use of antiretroviral therapy
AIDS deaths in Africa
25
Yearly deaths as a proportion of 1995 values

Deaths
2.0
20 50
15
1.5
10 25 1.0
5 Death s per 100 P er so n-Y ears
0.5 Introduction of highly active antiretroviral therapy

0 0 AIDS deaths in western Europe
0.0
1995 1996 1997 1998 1999 2000 2001
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001
Source: Palella FJ Jr et al. Survivial benefit of initiating antiretroviral therapy in HIV-infected
persons in different CD4+ cell strata. Annals of Internal Medicine, 2003, 138:620–626.
11 12
Prices (US$ per year) of a first-line antiretroviral Guiding principles

regimen in Uganda, 1998–2001
• Respect of ethical standards
AI
ck
eA
er
a
th
M
nd
• Universal and equitable access

in
d
ga
an
th
U
wi
14 000
S
to
I
BM
AA
a
m
pl
n
12 000 Paying attention to vulnerable groups

ti o
•
by
ar
Ci
of
Ph
uc
ith
ns
ch
ed
10 000
Price in US$
io
nw
un
R&
er
ct
La
Involving people living with HIV/AIDS

io
u
•
ric
ed
th
8 000
ss
fp
wi
er
cu
ro
n
ic
6 000
dis
tio
pr
fe
• Country in the driving seat

tia
of
er
er
4 000
go
rth
rth
a
pl
Ne
Fu
Fu
Ci
2 000
• Intensive partnership (countries, multilateral partners,
0
Jun Jul Aug Apr Oct Nov Dec Jan Feb Mar Apr May Jun Jul Aug bilateral partners, communities and the private sector)
1998 1998 1998 2000 2000 2000 2000 2001 2001 2001 2001 2001 2001 2001 2001
• Innovation, learning and sharing

13 14
Strategic framework Accelerating prevention

1. Global leadership, strong partnership, advocacy • Treatment and prevention must be scaled up
together or the epidemic will continue
2. Urgent, sustained country support
• Availability of treatment can reduce stigma
3. Simplified standardized tools to deliver antiretroviral and facilitate prevention
therapy • Routine testing increases the numbers of
people who know their HIV status
4. Effective, reliable supply of medicines and diagnostics
• Treatment has the power to mobilize funds to
5. Rapid identification and reapplication of new knowledge scale up prevention
and successes
15 16
63
Influence of TB lessons Treatment scale-up: countries that
requested assistance as of March 2004
• Target-driven
• Public health approach
• Integrate prevention with treatment
• Brand name
• Partnerships
• Standardization and harmonization
• Link people with TB disease to drug flow
• and many more ……..
17 18
Technical assistance needs identified Conclusions

Field of technical assistance % of countries
• Capacity-building (tools and training) 60%
• Medicines and diagnostics 56% • The most challenging public health intervention
(procurement, supply chain management, etc.)
• Monitoring and evaulation (patient-tracking system) 48%
• Antiretroviral therapy (policy and equity issues) 44%
• Human resources planning 32% • Considerable additional opportunities for developing
• Testing and counselling 28% health systems
• Laboratory 20%
• Program communication and advocacy 16%
• Coordination and management (understated) 15%
• Fundraising 8% • Monitoring and evaluation systems need to be
• Community involvement 5%
• Partnership 5%
reinforced and tailored to country needs
19 20
64
Unit 6, part 2: Clinical management

of HIV/AIDS
__________________________________________________________
Objectives
___________________________________________________________
1) to describe how the clinical management of HIV/AIDS

is organized;
2) to review the clinical and laboratory eligibility criteria
for antiretroviral therapy, antiretroviral drug regimens
and side-effects; and
3) to discuss the implications of these principles for
___________________________________________________________
Methods
___________________________________________________________
Plenary presentation: Clinical management of HIV/AIDS
Exercise
Plenary discussion
___________________________________________________________
Materials
___________________________________________________________
Document 6.3: Clinical management of HIV/AIDS (slides)
Document 6.4: Exercise
Document 6.5: Scaling up antiretroviral therapy in resource-limited
settings: treatment guidelines for a public health approach – 2003
revision (2)
Document 6.6: TB/HIV: a clinical manual (3)
Document 6.7: IMAI interim guidelines for first-level facility health
workers (4)
Document 6.8: Participant manual for the WHO basic ART clinical
training course (5)
___________________________________________________________
65
Document 6.3
Clinical management of HIV/AIDS Objectives of the subunit

Document No. 6.3
• Describe the organization of clinical management
of HIV/AIDS based on the WHO publication
Scaling up antiretroviral therapy in resource-limited
settings: treatment guidelines for a public health
approach
• Review the clinical and laboratory eligibility

criteria for antiretroviral therapy and the side
TB/HIV course for managers at the national effects
and subnational levels
• Discuss the implications for collaborative TB/HIV
activities
Open
Principles of the revised guidelines Scaling up antiretroviral therapy in resource-
limited settings - Key elements (1)
• Review and update of 2002 guidelines
• Standardization and simplification of antiretroviral regimens
• Simplified and standardized antiretroviral and monitoring tools (facilitate initial treatment)
therapy guidelines for WHO’s “3 by 5”
strategy to allow rapid scale-up of treatment • Better definiton of first- and second-line regimens
• First line: regimens based on non-nucleoside reverse
• Targets resource-limited settings transcriptase inhibitors (five drugs and four possibilities)
• Second line: regimens based on protease inhibitors
(preferentially protease inhibitor boosted)
• For use by national AIDS control programmes
and other policy-makers • Fixed-drug combinations and co-blister packs to improve
adherence, limit emergence of drug resistance and facilitate
logistics
Scaling up antiretroviral therapy in Assessing eligibility for

resource-limited settings- Key elements (2) antiretroviral therapy
• Laboratory-confirmed HIV infection
• Stavudine, lamivudine and nevirapine (d4T/3TC/NVP) is the
most suitable first-line option for immediate start in very- • Clinical assessment of HIV infection and HIV
low-resource settings (no laboratory, low cost, fixed-drug disease (WHO staging system)
combinations available, suitable for different patient groups)
• Assessment of CD4 cell count
• Body weight, total lymphocyte count, haemoglobin colour
• Total lymphocyte count as a substitute indication
scale, objective monitoring parameters (CD4 desirable, viral
for treatment (symptomatic HIV disease stage II)
load not recommended)
• Assessment of viral load not considered necessary
• Symptom-directed laboratory evaluation of toxicity to start therapy
66
WHO staging system for HIV infection WHO staging system for HIV infection
and disease in adults and adolescents (1) and disease in adults and adolescents (2)
WHO clinical stage 1: asymptomatic WHO clinical stage 3: moderate disease
• No weight loss
• No symptoms or only persistent generalized • Weight loss >10%
lymphadenopathy
• Performance scale 1: asymptomatic, normal activity
• Unexplained chronic diarrhoea or unexplained
prolonged fever >1 month, oral candidiasis
WHO clinical stage 2: mild disease (thrush),oral hairy leukoplakia, pulmonary TB within
• Weight loss 5-10%
last year, severe bacterial infections (such as
pneumonia or pyomyositis)
• Minor mucocutaneous manifestations, herpes zoster
within past five years, recurrent upper respiratory
infections (bacterial sinusitis or otitis) • Performance scale 3: bedridden <50% of the day
• Performance scale 2: symptomatic, normal activity
during past month
WHO staging system for HIV infection Recommendations for initiating antiretroviral
and disease in adults and adolescents (3) therapy among adults and adolescents with
WHO clinical stage 4: severe disease (AIDS) documented HIV infection (1)
• HIV wasting syndrome
• Pneumocystis carinii pneumonia, toxoplasmosis of the brain,
Cryptosporidium diarrhoea >1 month, extrapulmonary If CD4 assay available:
cryptosporidosis, cytomegalovirus disease other than liver,
spleen or lymph node (that is, retinitis), mucocutaneous or • WHO stage IV disease, irrespective of CD4 count
visceral herpes simplex virus infection, progressive • WHO stage III disease, considera using CD4 count
multifocal leukoencephalopathy, any disseminated endemic <350 to assist decision-making
mycosis, candidiasis of esophagus, trachea, bronchi, atypical
Mycobacterium tuberculosis TB (disseminated or lungs), non-
• WHO stage I or II if CD4 count <200
typhoid Salmonella septicaemia, extrapulmonary TB,
lymphoma, Kaposi’s sarcoma, HIV encephalopathy aIn this situation, the decision to start or defer antiretroviral therapy
• Performance scale 4: bedridden > 50% of the day during should take in consideration not only the CD4 cell count and its
past month evolution, but also concomitant clinical conditions.
Recommendations for initiating antiretroviral

therapy among adults and adolescents with Antiretroviral regimens and
documented HIV infection (2) monitoring
If CD4 assay not available:a
• WHO-recommended first- and second-line
• WHO stage IV disease, regardless of total
lymphocyte count antiretroviral regimens and issues considered
• WHO stage III disease, regardless of total for selection
lymphocyte count
• WHO stage II or I disease with total lymphocyte
count <1200 • Steps recommended for clinical and
laboratory monitoring of antiretroviral
aTotal lymphocyte count is only useful for people with symptoms. In the therapy
absence of a CD4 assay, one would not treat a stage I asymptomatic adult.
67
Considerations that informed the
Current antiretroviral targets
choice of first-line antiretroviral
regimens
• Potency EFV (T20) Fusion
Viral protease
• Side-effect profile
• Maintenance of future options saquinavir(SQV)
RNA RNA ritonavir (RTV)
• Predicted adherence Proteins indinavir (IDV)
nelfinavir (NFV)
• Availability of fixed-dose combinations (FDCs) of Reverse RT amprenavir (APV)
antiretroviral drugs transcriptase
RNA
lopinavir (LPV)
fosamprenavir
• Coexistent medical conditions (TB and pregnancy zidovudine (ZDV) RNA (FOS)
didanosine (ddI)
or a risk thereof) stavudine (d4T) RT
DNA
• Concomitant medications lamivudine (3TC)

abacavir (ABC)
Integrase
DNA
• Presence of a resistant viral strain tenofovir (TDF)
emtricitabine (FTC)
DNA
• Cost and availability nevirapine (NVP) Provirus
efavirenz (EFV)
• Limited infrastructure
• Rural delivery
Recommended ARVs WHO-recommended first and second-line

Nucleoside Reverse Nucleotide Reverse Non-Nucleoside Protease antiretroviral therapy regimens for children
Transcriptase Transcriptase Reverse Inhibitors
Inhibitors Inhibitors Transcriptase (PIs) First-line regimen Second-line regimen
(NsRTIs) (NtRTI) Inhibitors (NNRTIs)
Zidovudine Tenofovir Nevirapine Saquinavir stavudine (d4T) or abacavir (ABC)a

ZDV TDF NVP SQV zidovudine (ZDV) +
+ didanosine (ddI)
Didanosine Efavirenz Ritonavir +
lamivudine (3TC)
ddI EFZ RTV protease inhibitor: lopinavir with a
Lamivudine Lopinavir
+ ritonavir boost (LPV/r) or
3TC LPV nevirapine (NVP) or nelfinavir (NFV), or
Stavudine Nelfinavir Efavirenz (EFZ) saquinavir with a ritonavir boost
d4T NFV (SQV/r) if weight >25 kg
Abacavir
aInsufficient pharmacokinetic data on tenofovir in children to recommend it as
ABC an alternative nucleotide reverse transcriptase inhibitor, and there are
15 concerns about the bone toxicity of tenofovir
Problems with second-line First-line antiretroviral regimens

antiretroviral regimens Regimen Fixed-drug
combination
Usage in TB/HIV Lab
monitoring
Price (LDC)
US$/year
• Multiple resistance mutations Stavudine + lamivudine

+ nevirapine
Yes Alternative regimen –
preferably not due to
No 281–358
30–40/150/200 mg rifampicin-nevirapine
• High pill burden Twice dailya

Zidovudine + lamivudine Yes
interaction
Alternative regimen – Yes 383–418

+ nevirapine preferably not due to
• Limited experience 300/150/200 mg rifampicin-nevirapine
interaction
Twice dailya
• Availability of tenofovir (TDF) Stavudine + lamivudine +

efavirenz
No
stavudine +
Yes
rifampicin-efavirenz
No 350–1086
30–40/150 mg twice lamivudine interaction

• Hypersensitivity to abacavir (ABC) daily +
600–800 mg once
only
• Cold chain for ritonavir (RTV) Zidovudine + lamivudine

+ efavirenz
No
stavudine +
Yes
rifampicin-efavirenz
Yes 611–986
300/150 mg twice 600– lamivudine interaction

• High cost 800 mg once
aNevirapine
only
200 mg once daily for two-week lead-in. LDC: least developed countries.
68
Fixed-dose combinations of antiretroviral drugs for use among
Why fixed-drug combinations? HIV-positive adults and adolescents at the end of 2003
Stavudine (30 mg) + lamivudine (150 mg)
+ nevirapine (200 mg)a
• Significant reduction of daily tablet doses Three-drug fixed-
dose combinations + nevirapine (200 mg)a
• Improves adherence and reduces the risk of the Zidovudine (300 mg) + stavudine (150 mg)
emergence of resistance + nevirapine (200 mg)
Zidovudine (300 mg) + lamivudine (150 mg)
• Lower cost + abacavir (300 mg)a
• Facilitates logistics
Two-drug fixed-dose
• Facilitates use of supervised treatment combinations
(for use with a third Stavudine (40 mg) + lamivudine (150 mg)
strategies antiretroviral drug and
• Reduces the production process time, enabling for nevirapine lead-in
dosing) Zidovudine (300 mg) + lamivudine (150 mg)a
accelerated delivery .
aPresentations with WHO prequalified manufacturers.
Stavudine
+ Special considerations among people with TB
Lamivudine
+ • Rifampicin drug interactions with nevirapine and protease inhibitors
Nevirapine
• Pill burden and adherence
• Drug toxicity
• First-line recommendation: (zidovudine or stavudine) + lamivudine +
efavirenz (600 or 800 mg/day)
• Use of nevirapine questioned: increased liver toxicity? Poor efficacy due to
50% reduction in serum concentrations?
• Zidovudine + lamivudine + abacavir is another alternative, especially in
children
• The optimal time to start antiretroviral therapy among people with TB is
unknown, but based on expert consensus:
• CD4 <200: start TB therapy; recommend antiretroviral therapy as soon
Efavirenz
as TB therapy is tolerated (2–8 weeks)
• CD4 200–350: start TB therapy; consider antiretroviral therapy
Lamivudine • CD4 >350: start TB therapy; defer antiretroviral therapy
• If no CD4 available: start TB therapy; recommend antiretroviral
Didanosine (EC) therapy, timing based on other clinical signs of immunodeficiency
Clinical and laboratory assessment of Clinical and laboratory assessment of

adults and adolescents on antiretroviral therapy adults and adolescents on antiretroviral therapy
Evaluations at baseline: Evaluations while on therapy:

• HIV disease stage • Assessment for signs and symptoms of
• Concomitant health conditions (TB, pregnancy, potential drug toxicity

• Body weight
major mental disorder)
• Assessment of response to therapy
• Concomitant medication use (including
• Assessment of adherence
traditional therapies)
• Laboratory evaluation when clinically indicated
• Body weight (depends on the antiretroviral drug regimen in
• Patient readiness for therapy use)
69
Basic laboratory monitoring for first-line antiretroviral Recommended tiered laboratory capabilities to
regimens at community or district centre (levels 1 & 2) monitor antiretroviral therapy
Community health District hospital Regional referral
Regimen Laboratory test at baseline Laboratory test on therapya
centre (level 1) (level 2) hospital (level 3)
Stavudine + Not required Symptom directed: alanine
lamivudine + (CD4 desirable) aminotransferase (ALT) Rapid HIV test Rapid HIV test Rapid HIV test
nevirapine CD4 every 6–12 months available
Recommended: haemoglobin; Symptom directed: haemoglobin, Haemoglobin (for Second serological HIV Second serological HIV
Zidovudine + desirable but not required: white blood cells, ALT zidovudine) rapid test method rapid test method
lamivudine + complete blood count, CD4
nevirapine CD4 every 6–12 months if available Pregnancy test (for Complete blood count Complete blood count
efavirenz in women) and differential
Not required Symptom directed and differential
Stavudine +
lamivudine +
(CD4 and pregnancy test CD4 every 6–12 months if available CD4 count CD4 count
desirable)
efavirenz Sputum smear for TB ALT Full chemistries
(referral if microscopy
Recommended: haemoglobin Symptom directed: haemoglobin, Pregnancy test (for
Zidovudine/
white blood cells not available) Pregnancy test (for EFZ
lamivudine + Desirable but not required: efavirenz in women)
efavirenz complete blood count, CD4, CD4 every 6–12 months if available in women)
pregnancy test Sputum smear for TB
Sputum smear for TB
aObtain if symptoms of toxicity develop (not routine). Viral load testing
Haemoglobin colour scale: a simple, Mean viral load, CD4 and weight evolution
practical and inexpensive tool developed by after antiretroviral therapy in South Africa
WHO (MSF project)
6
5
Plasma HIV RNA
4
(log10) 65
3 64
2
63
1
62
0
61
Baseline 6 months 12 months 15 months 18 months
(n=40) (n=40) (n=39) (n=36) n=38) 60
59 Weight (kg)
400 58
350 57
300
250
56
200
T-CD4 + Baseline 6 months 12 months 15 months 18 months
150
(n=40) (n=40) (n=39) (n=36) n=38)
100 (cells/mm3)
50
0
Baseline 6 months 12 months 15 months 18 months
(n=40) (n=40) (n=39) (n=36) n=38)
Clinical and CD4 definition of treatment Immune reconstitution

failure in adults and adolescents
Clinical criteria CD4 criteria • Inflammatory response in first 1–2 months
• New opportunistic infection or • Return CD4 cell count to pre-
malignancy (must differentiate therapy baseline or below without
from immune reconstitution other cause • Clinical spectrum – fever, lymph node swelling,
syndrome)
lung and central nervous system involvement
• Recurrence of prior • ≥50% fall from peak CD4 count
opportunistic infection (such as on therapy without other cause
oral candidosis refractory to • With latent Mycobacterium tuberculosis
treatment)a
infection, can develop active TB
• Onset or recurrence of WHO
stage III conditions
• If active TB develops, it is not necessary to stop
aRecurrence of TB may not reflect progression as reinfection may occur;
clinical evaluation necessary.
antiretroviral therapy.
70
Correlation between adherence and
viral failure Darwinian Evolution
Reproduction
100
People with viral failure (%)
80 P = 0.00001, r = –0.55
60 Mutation
Survival of the Fittest
40
20
0
Natural Selection Genetic Diversity
>95 90–95 80–90 70–80 <70
Adherence (%)
Source: Paterson DL et al. Adherence to protease inhibitor therapy and outcomes in patients with HIV
32
infection. Annals of Internal Medicine, 2000, 133:21–30.
HIV drug resistance and

HIV resistance: underlying concepts developing countries
• Genetic variants are continuously produced • The induction and spread of drug-resistant strains is an inevitable
consequence of the introduction of antiretroviral therapy.
as a result of high viral turnover and
inherent error rate of reverse transcriptase. • This is not a reason to delay the introduction of effective therapy
into developing countries.
– Mutations at each codon site occur daily.
o Survival depends on replication competence and • Strategies to prevent drug resistance should be introduced in
presence of drug or immune selective pressure. parallel with antiretroviral therapy programmes.
– Double mutations in same genome also occur, • Drug resistance monitoring should be an essential component of
but three or more mutations in the same antiretroviral therapy programmes.
genome is a rare event.
• Technical issues need to be faced
– Numerous natural polymorphisms exist. – Assay questions
– Technology transfer
Adverse effects of antiretroviral drugs: Specific drug side-effects

class-specific effects • Zidovudine: gastrointestinal intolerance, haematotoxicity
(anaemia), muscle pains, headache
NsRTI Lactic acidosis Mitochondrial toxicity

Lipodystrophy syndrome with long usage • Stavudine: peripheral neuropathy, pancreatitis, lipoatrophy
NtRTI Mitochondrial toxicity

• Nevirapine: cutaneous hypersensitivity, hepatotoxicity
NNRTI Skin rash
Hepatitis • Efavirenz: teratogenicitiy, mental disorder
PI Lipodystrophy syndrome
Hyperlipidaemia • Nelfinavir: gastrointestinal intolerance, skin rash
Hyperglycaemia •
• Lopinavir: gastrointestinal intolerance, hypercholesterolaemia

and triglyceridaemia
71
First-line antiretroviral regimens: major side Simplified guidelines for antiretroviral therapy
(HIV-1 infection)
effects DISTRICT/REGIONAL
LEVEL
LOCAL LEVEL
If neuropathy or
Regimen Major side effects pancreatitis If clinical
Replace
d4T with
First-line regimen hepatitis
Stavudine + Lipoatrophy and neuropathy; skin Replace NVP
lamivudine + and liver toxicity; cannot use ZDV d4T/3TC/NVP with EFV
nevirapine nevirapine with rifampicin
If neuropathy or If severe rash
pancreatitis and
Zidovudine + Anaemia; skin and liver toxicity; Therapeutic
lamivudine + cannot use nevirapine with severe anaemia Replace NVP
nevirapine rifampicin
failure
with NFV
Replace d4T
Stavudine + with ddI
lamivudine + Lipoatrophy and neuropathy; central Second-line If severe
nervous system symptoms and
efavirenz
teratogenicity
If renal regimen dislipidaemia
Replace LPV/r
Replace failure
Zidovudine + Anaemia; central nervous system TDF TDF + ddI + LPV/r with NFV
lamivudine + symptoms and teratogenicity
efavirenz with
TB/HIV
ABC Replace LPV/r If severe gastrointestinal intolerance
with SQV/r Replace ddI with ABC
Simplified guidelines for antiretroviral therapy Simplified guidelines for antiretroviral therapy
(HIV-1 infection) DISTRICT/REGIONAL
LEVEL
(HIV-1 infection) DISTRICT/REGIONAL
LEVEL
LOCAL LEVEL LOCAL LEVEL
If severe If neuropathy or
anaemia If clinical pancreatitis If severe CNS
Replace Replace
ZDV
First-line regimen hepatitis First-line regimen symptoms
Replace NVP d4T with Replace EFV
with d4T ZDV/3TC/NVP with EFV ZDV d4T/3TC + EFV with NVP
If severe anaemia If severe rash If neuropathy or If hepatitis or
and neuropathy or pancreatitis and severe rash
pancreatitis Therapeutic severe anaemia Therapeutic
Replace NVP Replace EFV
failure failure
with NFV with NFV
Replace ZDV Replace d4T
with ddI Second-line with ddI
If severe Second-line If severe
If renal regimen dislipidaemia If renal regimen dyslipidaemia
failure Replace LPV/r failure Replace LPV/r
Replace Replace
TDF + ddI + LPV/r with NFV TDF + ddI + LPV/r with NFV
TDF with TDF
ABC with
TB/HIV If severe gastrointestinal intolerance TB/HIV If severe gastrointestinal intolerance
ABC
Replace LPV/r Replace LPV/r
with SQV/r Replace ddI with ABC with SQV/r Replace ddI with ABC
Simplified guidelines for antiretroviral therapy Simplified guidelines for antiretroviral therapy
(HIV-1 infection) DISTRICT/REGIONAL (HIV-2 infection) DISTRICT/REGIONAL
LEVEL LEVEL
LOCAL LEVEL LOCAL LEVEL
If severe
If severe If neuropathy or
anaemia If severe CNS Replace pancreatitis gastrointestinal
Replace
First-line regimen symptoms d4T with
First-line regimen intolerance Replace
ZDV Replace EFV
ZDV d4T/3TC + NFV NFV
with d4T ZDV/3TC + EFV with NVP with
If hepatitis or If neuropathy or
If severe anaemia If TB/HIV LPV/r
and neuropathy or severe rash pancreatitis and
Therapeutic severe anaemia Therapeutic
pancreatitis Replace EFV
failure failure Replace NFV
with NFV
with SQV/r
Replace ZDV Replace d4T
with ddI with ddI Second-line
Second-line If severe If severe
If renal regimen dyslipidaemia If severe regimen dislipidaemia
failure Replace LPV/r
Replace
TDF + ddI + LPV/r with NFV Replace anaemia TDF + ddI + LPV/r Replace LPV/r
TDF TDF with NFV
with with
TB/HIV If severe gastrointestinal intolerance TB/HIV If severe gastrointestinal intolerance
ABC Replace LPV/r ABC Replace LPV/r
with SQV/r Replace ddI with ABC with SQV/r Replace ddI with ABC
72
Document 6.4

purpose of the exercise is to analyze the provision of antiretroviral therapy services in
Fictitia, identify gaps and propose activities to address these gaps.
• Read pages 140-148 in the report from Fictitia in Annex 1.
• Analyse what the national HIV/AIDS programme has done so far in the
country in relation to WHO recommendations for a public health approach,
with special focus on:
1) eligibility for antiretroviral therapy;
2) the skills available through the health system for delivering antiretroviral
therapy services;
3) the capacity of the laboratory network to comply with the requirements for
antiretroviral therapy monitoring; and
4) the management of people coinfected with TB/HIV.
• Identify gaps in the programme (especially in terms of strengthening the

capacity of the health system) and propose priorities for your planning.
73
Unit 7: Drug management for controlling

TB and HIV/AIDS
___________________________________________________________
Objectives
___________________________________________________________
By the end of this unit, participants will be able:
1) to discuss the various aspects of TB and HIV drug
management using a logical framework;
2) to identify the differences between the procurement
practices for TB and HIV/AIDS drugs; and
3) to identify gaps and priorities in the procurement of TB and
HIV/AIDS drugs and to propose solutions to facilitate drug
management in implementing collaborative TB/HIV
activities.
___________________________________________________________
Methods
___________________________________________________________
Plenary presentation: Drug management for controlling TB and
HIV/AIDS
Exercise
Plenary discussion
___________________________________________________________
Materials
___________________________________________________________
Document 7.1: Drug management for controlling TB and HIV/AIDS
(slides)
___________________________________________________________
74
Document 7.1
Drug management for controlling TB Objectives of the unit

and HIV/AIDS • To discuss the various aspects of TB/HIV drug
Document No. 7.1
management using a logical framework
• To identify the differences between procurement

practices for TB and HIV/AIDS drugs
• To identify gaps and priorities in procurement of

TB/HIV course for managers at the national TB and HIV/AIDS drugs and to propose solutions
and subnational levels to facilitate the implementation of collaborative
TB/HIV activities in drug management
1 2
Open
Pharmaceutical management cycle Pharmaceutical management is

the set of practices aimed at
Selection
ensuring the timely availability
and appropriate use of safe,
Management
Use
support
Procurement
effective and high-quality
medicines and related products
Distribution
and services in any health care
Policy, regulations and laws
setting
3 4
Standardized treatment regimens and uninterrupted

drug supply are basic principles of the DOTS Strategy
Levels Private sector Public sector Partners
• Political commitment to programme, including normative,

International Multinational suppliers International procurement
agencies / GLC / GDF
Donors/
GFATM GDF
financial, planning, surveillance, training and supervision
National functions
Local
Regulatory manufacturers
agencies Government supply services
National TB programme
TB institutes
• Case detection among people presenting with symptoms, using
Third-party Wholesalers
payers NGOs low-cost tools
Regional Distributors Regional facilities NGOs • Standardized treatment with direct observation
CMS flow
District Shops and District facilities
pharmacies
Alternative flow
Information flow
• System for uninterrupted supply of high-quality TB drugs
Primary care
Community Private
Prescribers facilities
NGOs • Recording and reporting system allowing accountability and
outcome evaluation
Medicine users 5 6
75
Management of HIV supplies Key principles
TB drug supply
HIV-related drugs and diagnostics are ordinary
• There are key rules for estimating drug needs (based supplies, but …
on previous consumption and/or on notifications)
• Regimens are standardized • Treatment is for life, and treatment interruptions (supply
interruptions) have to be avoided at all cost.
• Fixed-drug combinations and /or blister packs are • The supply system has to cater for the various treatment
recommended regimens and the changing proportions to which these are
• The cost of one first-line regimen is about US$ 15 used over time
• The Global Drug Facility (GDF) is fully operational • Antiretroviral drugs are relatively expensive and in high
demand.
to support the procurement of quality drugs at the
• Antiretroviral therapy receives high-level government and
lowest possible price donor support and scrutiny.
• Low-cost second-line drugs are available for Green • Antiretroviral drugs and test kits may require cold storage
Light Committee (GLC) programmes and often have short shelf lives.
7 8
Selection Procurement: quantification

• Fixed number of people receiving antiretroviral therapy per year
• National consensus: a committee + guidelines (regimen, weight band,
• Previous antiretroviral consumption times 2 – existing stock
strength, loose or combined, box or blister or kit)
• Previous activity: number of people receiving antiretroviral therapy times
• Curative drugs: antiretroviral drugs, opportunistic infections, palliative
number of drugs per year times 2 – existing stock
care, AIDS-related cancer, opioid dependence
• Morbidity: HIV prevalence rate times the population covered
• Preventive drugs: isoniazid, co-trimoxazole
Notes:
• HIV diagnosis kit – Isoniazid preventive therapy must be quantified
• CD4, viral load and drug resistance equipment – Number of HIV/AIDS cases is harder to predict than for TB, as quarterly TB reporting
is systematized
Notes: – Lack of expertise for appropriate quantification of antiretroviral drugs during scaling-up
– More people need to change regimens for HIV/AIDS (because of failure or side- (unlike TB drugs)
effects) than for TB (30% versus 2%) – Antiretroviral drugs and tests have short shelf lives (eight months)
– Recommendations to shift from first- to second-line standardized for TB but are under – Complex procurement due to multiple sources of funds
constant revision for antiretroviral drugs – Manufacturers and suppliers unable to meet demand (shortages of stavudine and
9 10
efavirenz)
Distribution Use
• Health unit provider or home delivery (by health staff)
• Port clearing (document, testing and taxes) • Drug provision (daily, weekly or monthly)
• Storage: separate versus common, bulk versus shelves, • Adherence
expiry dates, temperature and accountability (register – Recording (patient card, register and report)
and bin card) – DOT, weekly observation
– Blister, kit or combined tablets

• Push or pull system (consumption, activity and order
– Patient education and support ( psychological)
forms)
– Patient cost (free of charge, contribution or unofficial)
• Transport (frequency, separate versus common) Notes
Notes: – Antiretroviral therapy is more expensive for families and programmes than
TB (tests, drugs and programme)
– Small but sufficient stock to avoid expiry at the local level – Continuous (lifetime) motivation necessary for antiretroviral therapy
– Coordinated TB/HIV drug distribution based on model used – Accurate training on side-effects for Antiretroviral drugs necessary
– Security for antiretroviral drugs (more expensive) is a priority – Irrational use of antiretroviral drugs leads to greater wasting of resources
– Cold chain needed for some antiretroviral drugs – Lack of expertise in managing antiretroviral therapy and formulations for
11
children 12
76
Procurement: tender Procurement: generic versus
• Open tender: too long originator (1)
• Restricted tender: market information on price and quality: • TRIPS (Trade-Related Aspects of Intellectual Property
www.who.int/medicines, www.accessmed-msf.org Rights) Agreement of 1995 of the World Trade
Organization related to antiretroviral drugs
– Prequalified products: “Access to HIV/AIDS drugs and diagnosis of
acceptable quality” January 2004 • Doha Declaration 2001 (TRIPS and public health)
– Indicative price: “Sources and prices of selected medicines and Flexibility, such as compulsory licensing, is introduced to
ensure that the TRIPS Agreement does not prevent members
diagnosis for people living with HIV/AIDS” June 2003 from taking measures to protect public health.
– Untangling the web of price reductions, December 2003
• Government can allow companies to make patented
• Selected tender: national manufacturer or supplier, patented product under licence without the consent of the patent
owner for the domestic market (antiretroviral drugs
or generic only)
13 14
Procurement: generic versus originator (2) Making commodities available for

countries: the WHO AIDS Medicines
WTO member government decision of 30 August 2003:
and Diagnostics Service
the DOHA Declaration effectively limited the ability
of countries that cannot make pharmaceutical products • The AIDS Medicines and Diagnostics Service
from importing cheaper generics from countries where (AMDS) was launched in December 2003 as the
pharmaceuticals are patented. access and supply arm of the “3 by 5” Initiative.
The decision allows any member country to export • The objective of the AMDS is to expand access to
pharmaceutical products made under compulsory high-quality, effective treatments for HIV/AIDS by
license. improving the supply of antiretroviral drugs and
Twenty-three countries announced that they would diagnostics to developing countries
voluntarily refrain from using the system for import. 15 16
Making commodities available for countries:

the WHO AIDS Medicines and Diagnostics Service What the AMDS offers
Group of partners
• United Nations agencies • Governments, NGOs: intelligence for
• WHO (EDM, EHT, CPS and Essential Drugs units and HIV regional
advisers in regional offices), UNICEF, World Bank, UNAIDS, UNFPA, making informed choices on procurement
UNDP (prices of drugs and diagnostics and
• Technical organizations and donor agencies
• Canadian Committee on Antimicrobial Resistance, Clinton HIV/AIDS information on regulations and intellectual
Initiative, Commonwealth Pharmaceutical Association, Crown Agents,
Ecumenical Pharmaceutical Network, ESTHER (Ensemble pour une
property rights)
Solidarité Thérapeutique Hospitalière En Réseau), Global Fund to Fight
AIDS, Tuberculosis and Malaria, International Dispensary Association, • Governments, NGOs: capacity-building for
International Pharmaceutical Federation, John Snow Inc. (JSI),
Management Sciences for Health and Mission for Essential Drug Supply
managing procurement and supply
• Observers • Manufacturers: information necessary for
• MSF, United States Department of State (President’s Emergency Plan for
AIDS Relief), United States Agency for International Development forecasting volumes to be produced (not yet
• Secretariat available)
• AMDS unit of Department of HIV/AIDS of WHO 17 18
What the AMDS can provide to countries
• Technical country support for the pharmaceutical

management cycle
• Guidance on selection of core antiretroviral drugs.
• Guidance on legal issues related to importing generic

medicines
• Prequalification of drugs and diagnostics
• Information on product specification to be used in tenders
• Guidance and training in local production and quality

assurance
19
77
Document 7.2

purpose of the exercise is to estimate the antiretroviral therapy and TB services needed
in a given country or region, to identify gaps and propose activities to address these
gaps.
• Select one specific country (or a region within the country) representing the
group members.
• Provide figures (or estimates) on:

1) the number of people infected with HIV and coinfected with TB and HIV
living in the country (or region);
2) the number of people eligible for antiretroviral therapy in the country (or
region) and the number of people requiring TB treatment and isoniazid
preventive therapy;
3) the number of people infected with HIV and coinfected with TB and HIV
currently receiving antiretroviral therapy, TB treatment regimen and
isoniazid preventive therapy in the country (or region);
4) the target year for universal access to antiretroviral therapy in the country
(or region);
5) the number of people receiving antiretroviral therapy at the end of the year
in the country (or region); and
6) the number of people receiving isoniazid preventive therapy at the end of
the year in the country (or region).
• Discuss the figures or estimates.
• List three priority interventions to improve the pharmaceutical management

cycle to achieve universal access to antiretroviral therapy in the country (or
region).
78
Unit 8: The Interim policy on

collaborative TB/HIV activities
___________________________________________________________
Objectives
___________________________________________________________
1) to describe the main elements of the interim policy on
collaborative TB/HIV activities; and
2) to discuss the main problems, constraints and opportunities
found in implementing collaborative TB/HIV activities at
the country level.
___________________________________________________________
Methods
___________________________________________________________
Plenary presentation: The Interim policy on collaborative TB/HIV
activities
Exercise
Plenary discussion
___________________________________________________________
Materials
___________________________________________________________
Document 8.1: The Interim policy on collaborative TB/HIV activities
(slides)
Document 8.3: Interim policy on collaborative TB/HIV activities (6)
Document 8.4: Guidelines for implementing collaborative TB and HIV
programme activities (7)
Document 8.5: Strategic framework to decrease the burden of TB/HIV
(8)
___________________________________________________________
79
Document 8.1
The Interim policy on collaborative Objectives of the unit

TB/HIV activities
Document No. 8.1
• To describe the main elements of the interim
policy on collaborative TB/HIV activities
• To discuss the main problems, constraints

and opportunities found in implementing
TB/HIV course for managers at the national collaborative TB/HIV activities at the
and subnational levels country level
1 2
Open
Background on AIDS and ProTEST ProTEST
• 1981 AIDS reported in the United States • WHO initiative to promote testing for HIV using
• 1984 AIDS in Africa voluntary counselling and testing as an entry point
• 1984 TB in AIDS to a range of prevention and care interventions
related to TB/HIV and sexually transmitted
• 1989+ Descriptive studies of HIV and TB
infections
• 1991 Thiacetazone and HIV
• 1992 HIV-related mortality, relapse and
• Objective of ProTEST:
morbidity in TB
To develop a more cohesive response to TB in
• 1997 ProTEST and other projects settings with high HIV prevalence through
conceived collaboration between TB and HIV control
• 2000 Interventions defined programmes.
3 4
ProTEST ProTEST
Interventions: Results:
• Collaboration between stakeholders and the health • TB/HIV collaboration was feasible
service • Improved human resources capacity
• Improved access to high-quality voluntary counselling
and testing • Increased access to high-quality voluntary
• Intensified case-finding and treatment of active TB counselling and testing (VCT) services
among people living with HIV/AIDS • Improved TB case-finding
• Isoniazid preventive therapy to treat latent TB • Isoniazid preventive therapy (IPT) and co-
• Co-trimoxazole preventive therapy to reduce morbidity trimoxazole preventive therapy (CPT) introduced
and mortality from opportunistic infections
• HIV prevention (including condoms and management • HIV prevention activities introduced or enhanced
of sexually transmitted infections) • Community involvement developed
• Improved clinical care for people living with • Profile of TB/HIV raised
HIV/AIDS 5 6
80
ProTEST Rationale for joint TB/HIV activities
Lessons learned: • HIV drives TB incidence and mortality in areas with a
• Involvement of all stakeholders is critical high HIV prevalence: 11–50% of people living with
HIV/AIDS die from TB
• Additional staff are essential
• DOTS alone is insufficient to control TB in these areas
• Technical support is essential • Joint TB/HIV interventions, jointly delivered, are
• More operational research and cultural needed to control HIV-associated TB, expand DOTS
understanding are required to increase adherence and control HIV
to preventive treatments • TB control system can be a major partner for delivery
of antiretroviral therapy and thus for “3 by 5”, the
• Standard monitoring and evaluation tools are United States President’s Emergency Plan for AIDS
needed Relief etc.
• Joint TB/HIV work sets stage for antiretroviral
therapy TB is not just part of the problem; it is also part of the
7
solution 8
Principles Sequence of TB/HIV policy development

• “Two diseases, one patient” • Builds on field experience with ProTEST (Malawi, South
– Patient focuses in care delivery for both diseases at the Africa and Zambia) and other TB/HIV pilot projects
same time (Botswana, Cote d’Ivoire, Kenya, Rwanda, Thailand, etc.)
• There is an ongoing catastrophe, therefore: • Complements the Strategic framework to decrease the burden
– No more “projects” of TB/HIV, which provides a complete rationale and mentions
what could be done
– Immediate scale up of what works
• Complements the Guidelines for implementing collaborative
– Revise as more evidence becomes available TB and HIV programme activities, which show how to organize
• No separate programme at the national and district levels
– Collaborative activities add to existing strategies for
controlling TB and HIV/AIDS The Interim policy on collaborative TB/HIV activities states what
• Policy needs to be global countries should do
9 10
Goal and objectives

Process for the interim policy
Goal
To decrease the burden of TB and HIV in dually
• Under the auspices of the Global TB/HIV
Working Group affected populations
Objectives
• Iterative drafting process by: A. to establish the mechanisms for collaboration
– technical experts from TB and HIV between TB and HIV/AIDS programmes
– health management policy-makers, B. to decrease the burden of TB among people living
– people living with HIV/AIDS and their advocates, with HIV/AIDS
– international and national TB and HIV programme C. to decrease the burden of HIV in Tuberculosis
patients
managers and donor agencies
11 12
81
Collaborative TB/HIV activities Collaborative TB/HIV activities
A. Establish mechanisms for collaboration
1. Set up coordinating bodies for TB/HIV activities at all levels
A. Establish mechanisms for collaboration
2. Conduct surveillance of HIV prevalence among tuberculosis patients
3. Carry out joint TB/HIV planning 1. Set up coordinating bodies for TB/HIV activities at all levels
4. Conduct monitoring and evaluation
2. Conduct surveillance of HIV prevalence among TB patients
B. Decrease the burden of TB among people living with HIV/AIDS (guidelines available)
1. Establish intensified TB case-finding
2. Introduce isoniazid preventive therapy 3. Carry out joint TB/HIV planning
3. Ensure TB infection control in health care and congregate settings
Resource mobilization for TB/HIV
TB/HIV capacity-building, including training
C. Decrease the burden of HIV among tuberculosis patients TB/HIV communication: advocacy, programme communication and
1. Provide HIV testing and counselling social mobilization
2. Introduce HIV prevention methods Enhancing community involvement in collaborative TBHIV activities
3. Introduce co-trimoxazole preventive therapy Operational research
4. Ensure HIV/AIDS care and support
5. Introduce antiretroviral therapy 4. Conduct monitoring and evaluation (guidelines available)
13 14
Collaborative TB/HIV activities Collaborative TB/HIV activities

B. Decrease the burden of TB among people C. Decrease the burden of HIV among TB patients
living with HIV/AIDS
1. Provide HIV testing and counselling
1. Establish intensified TB case-finding
2. Introduce HIV prevention methods
2. Introduce isoniazid preventive therapy 3. Introduce co-trimoxazole preventive therapy
4. Ensure HIV/AIDS care and support

3. Ensure TB infection control in health care and
congregate settings 5. Introduce antiretroviral therapy
15 16
Thresholds for collaborative TB/HIV activities

Category Recommendation
Category I
Countries with national adult HIV prevalence
rate ≥1% Implement all recommended collaborative
TB/HIV activities
OR
Countries in which national HIV prevalence
among tuberculosis patients is ≥ 5%.
Category II
rate below 1% Implement all recommended collaborative
AND TB/HIV activities in administrative aras with
HIV prevalence > 1% and in other areas as in
Administrative areas that have adult HIV
Category III
prevalence rate ≥1%
Category III
rate below 1% HIV surveillance among TB patients
AND Activities to decrease the burden of TB in people
living with HIV/AIDs (with special emphasis on
No administrative areas with adult HIV
high HIV risk groups)
prevalence rate ≥ 1%
17
82
Targets for collaborative TB/HIV
Usual position
activities
• By 2005, all category I and II countries will have
established at least a national TB/HIV coordinating TB
body. Gulf HIV
VCT
By 2007, all category I and II countries will have IEC
• DOTS STIs
developed joint TB/HIV implementation plans. ARVs etc.
• By 2007, all category I and II countries will have General health services
established a system for HIV surveillance among
TB patients.
18 19
Possible HIV/TB structure and

Joint TB/HIV activities referral flows at the district level
Preventing
Voluntary
mother-to-
counselling
child
TB clinic
Start and testing
transmission
TB TB/HIV HIV +HIV testing
antiretroviral
therapy
Post-TB-therapy
DOTS Intensified
VCT + TB antiretroviral
+VCT case-finding screening Monitor during
therapy
management
+Condoms Isoniazid IEC
antiretroviral
therapy
AIDS ARV
+HIV preventive
therapy STIs clinic/day
surveillance care centre
ARVs Home-based
care
Co-trimoxazole preventive therapy
programme
Home- and community-based care Outpatient General

department wards
General health services
20
Keep in mind:
• It is high time for TB and HIV/AIDS
programmes to work together
• Much synergy is possible
• Many missed opportunities would be
prevented
• Universal access to antiretroviral therapy,
Stop TB strategy and other approaches and
initiatives provide many opportunities for
TB/HIV collaboration – we must take
advantage of them
22
83
Document 8.2

For this exercise, your facilitator will divide the participants into four groups. The
purpose of the exercise is to review in detail the activities proposed in the Interim
policy on collaborative TB/HIV activities.
• Each group is assigned three or four activities from the Interim policy on
collaborative TB/HIV activities as follows:
Group 1: A1; B2; B3; C5;
Group 2: A2; B1; C4;
Group 3: A3, C3; and
Group 4: A4; C1; C2.
• Familiarize yourself with the assigned activities.
• Discuss within the group and provide an example of how each of the assigned
activities could be implemented in one of the countries or regions represented in
the group.
• Brainstorm within the group on the constraints and opportunities found in

implementing collaborative TB/HIV activities at the country level.
84
Unit 9: Recording and reporting for the

implementation of collaborative TB/HIV
activities
___________________________________________________________
Objectives
___________________________________________________________
1) to describe how recording and reporting is organized for
controlling TB;
2) to describe how recording and reporting is organized for
controlling HIV/AIDS; and
3) to discuss relevant country experiences on TB/HIV
recording and reporting and how existing recording and
reporting systems can be harmonized to serve the
implementation of collaborative TB/HIV activities.
___________________________________________________________
Methods
___________________________________________________________
Plenary presentations: Recording and reporting for controlling TB and
HIV/AIDS
Plenary discussion
___________________________________________________________
Materials
___________________________________________________________
Document 9.1: Recording and reporting for controlling TB (slides)
Document 9.2: Recording and reporting for controlling HIV/AIDS
(slides)
Document 9.3: TB and HIV/AIDS forms (handout)
___________________________________________________________
85
Document 9.1
Recording and reporting for

Objectives of the presentation
controlling TB
Document No. 9.1
• To describe how recording and reporting are
organized for controlling TB
• To discuss relevant country experiences on

TB/HIV recording and reporting and how existing
recording and reporting systems can be
TB/HIV course for managers at the national harmonized to serve the implementation of
and subnational levels collaborative TB/HIV activities
1 2
Open
TB determinants and case definitions Core package for TB recording and reporting
Registers and forms Content and purpose
Smear- Individual record of diagnosis, treatment and follow-up of each TB
Positive Treatment card (TB 01)
patient for proper case management at treatment unit
Pulmonary No New Case
Smear- Personal record of diagnosis, treatment and follow-up for information
TB Case Identity card (TB 02)
Negative to the TB patient
Extra- Yes Defaulter
Record of diagnosis, treatment and follow-up of each TB patient in
Pulmonary Relapse Case District register (TB 03)
the district or equivalent catchment area
Failure Case
Chronic Case Laboratory register (TB 04) Record of each sputum acid-fast bacillus microscopy examination at
laboratory
Smear Site of Previous Sputum examination Request for sputum acid-fast bacillus microscopy to laboratory with
Severity
Microscopy Disease Treatment request/report form (TB 05) report of results to requesting unit
Severe Case if: Smear-Pos. if: Pulmonary if: Case as: Culture and susceptibility
• meningitis • 2 sputa +ve lung Request for TB culture or susceptibility test to laboratory, with report
New = previous treatment less than 1 month test request/report form
• miliary or parenchyma of results to requesting unit
(TB 06)
• pericarditis • 1 sputum +ve
Defaulter = after stop treatment for 2 months Consolidated quarterly report of the TB cases (new pulmonary TB+,
• peritonitis and Quarterly report on case-
• bilat./extensive X-ray suspect relapses of pulmonary TB+, new pulmonary TB–, new
Relapse = before full treatment and cured finding (TB 07)
• pleural effusion and extrapulmonary TB) registered in a quarter
physician Quarterly report on Consolidated quarterly report of final treatment results in the new
• spinal Failure = after 5 months treatment
or treatment results (TB 08) pulmonary TB+, other pulmonary TB+ and new pulmonary TB–
• intestinal
• genito-urinary • 1 sputum +ve cases registered in a quarter
Chronic = after full re-treatment course
and Referral/transfer form Form to refer or transfer person with TB to other unit
culture +ve (TB 09)
3 An additional register for TB suspects and form to evaluate sputum smear conversion 4
had been recently introduced.
Core package for TB recording and reporting Indicators for analysing TB case-finding
Monitoring the programme Indicator Calculation Some possible interpretations
at the central level Less than xx per 100 000 population (70% of
• Laboratory request/report New pulmonary TB+ registered in one year xx/100 000 estimated incidence of new
New pulmonary TB+
(TB 06) notification rate
times 100 000 pulmonary TB+ in the country): low sputum
------------------------------------------- examination of symptomatic people, poor
(per 100 000 population) Total population
• Treatment card (TB 01) quality of smear examination, poor registration
of cases and poor accessibility of services
• Referral/transfer form • Quarterly report Less than 70% (target for TB control): as above
New pulmonary TB+ New pulmonary TB+ registered in one year
(TB 09) new cases and times 100
detection rate
relapses (TB 07) (percentage)
-------------------------------------------
• Identity card (TB 02) New pulmonary TB+ expected in one year
• Quarterly report New pulmonary TB+ Male new pulmonary TB+ in one year If large difference: as above for gender
Managing of treatment ratio M:F ----------------------------------------
the people outcome (TB 08) (in whole numbers) Female new pulmonary TB+ in one year
with TB Pulmonary TB+ (new + relapse) in one quarter Less than 65%: poor quality of sputum smear
Proportion of total
disease pulmonary TB who are
times 100 examination, over-diagnosis of pulmonary TB-
---------------------------------------------- through X-ray
positive (percentage) Total pulmonary TB in one quarter
• Laboratory register (TB 04) New pulmonary TB+ New pulmonary TB+ in one quarter More than 1:1 over-diagnosis of pulmonary
Monitoring the programme versus other new TB ratio
---------------------------------------------
TB+
• Treatment register (TB 03) New pulmonary TB– and extra pulmonary TB
at the district level (in whole numbers) in one quarter
5 6
vital if underlined
86
Indicators for analysing TB treatment results
Indicator Calculation Some possible interpretations
a
New pulmonary TB+ in one quarter who became Less than 85%: absence of follow-up
negative after intensive phase treatment times 100 sputum smear examination, poor DOT,
Smear conversion rate
----------------------------------------------------- excess of deaths and transfers out, poor
(percentage) New pulmonary TB+ registered in the same investigation about previous TB treatment,
quarter drug resistance or poor reporting
New pulmonary TB+ cured in one quarterb times Less than 85% cure: as above
100
Cure rate (percentage) --------------------------------------------------
New pulmonary TB+ registered in the same
quarter
New pulmonary TB+ in one quarter cured and Less than: 85% (target for TB control):
completed treatmentc times 100 poor overall programme performance
Programme success rate
--------------------------------------------------
(percentage) New pulmonary TB+ registered in the same
quarter
aThesame is applied to relapse of pulmonary TB+. bThe same is applied to other treatment result rates in new
pulmonary TB+ and relapse pulmonary TB+. cThe same is applied to calculate the other rates in new pulmonary
TB+ and relapse pulmonary TB+.
Cohort analysis Results expected in a good TB

programme
In a foot race: In a TB programme:
A group of people with TB • Success rate >85%

A group of people start
➨ disease start treatment
together a 10-km foot race
within one quarter
• Death rate <5%
How many people

➨
How many patients • Unsatisfactory outcomes (default or failure)
completed the race? completed this treatment?
<10%
8 9
TB forms and HIV/AIDS (1) TB forms and HIV/AIDS (2)
Additional information that will have to be • Main issue: confidentiality of HIV test
captured in TB recording and reporting forms: results in the TB register.
•Offered HIV test • The response: the TB register already
•Counselled and tested contains confidential patient information that
•Test result positive or negative should be treated with the same level of
•Given co-trimoxazole confidentiality as HIV results.
•Referred for HIV care and support • The solution is not to hide HIV results but
•Given antiretroviral therapy during or at the rather to improve the confidentiality of the
end of TB treatment TB register.
10 11
87
Document 9.2
Recording and reporting for Objectives of the presentation

controlling HIV/AIDS
Document No. 9.2
• To describe how recording and reporting is
organized for controlling HIV/AIDS
• To discuss relevant country experiences on

TB/HIV recording and reporting and how
existing recording and reporting systems can
TB/HIV course for managers at the national be harmonized to serve the implementation
and subnational levels of TB/HIV collaborative activities
1 2
Open
Contribution of patient tracking to the
Patient tracking data serve
milestones on universal access to
multiple needs antiretroviral therapy
• Direct patient care Level of Milestone Data collection
– Clinical team caring for group of patients monitoring
and
– Facilitates shift from acute to chronic care evaluation
• Monitoring drug supply and preparing facility Outcome 9. Children, women and men Country reports, site reporting,
with advanced HIV receiving industry, nongovernmental
drug orders antiretroviral therapy organizations; patient tracking –
current on antiretroviral therapy
• Summarizing and reporting data to meet district (numerator), once established
and national programme needs and to track
progress to targets 11. Survival on antiretroviral Patient tracking, once established
therapy
3 4
HIV care (pre–antiretroviral therapy) register

TB experience …
To record data on: Provides a link with antiretroviral
therapy register:
• Standardized treatment card
• Patients’ data • Date eligible
• Standardized register • Date of HIV diagnosis
• Reason for eligibility
• Isoniazid prophylaxis
• Globally standardized definitions • Co-trimoxazole prophylaxis • Date eligible and ready
• Deliberately constrains the data collected • Fluconazole prophylaxis • Date antiretroviral therapy
• TB treatment started
• Based on long experience • Pregnancy • Unique antiretroviral therapy
• Recently, new TB/HIV indicators • Clinical staging system
number
• Outcome
• Disease-specific (vertical) – antiretroviral therapy
– lost to follow-up
5 – death 6
88
Antiretroviral therapy register
(linked with pre–antiretroviral therapy register)
Consistent definitions for why an
antiretroviral drug or regimen is changed
To record data on: Follow-up:
1. Toxicity or side-effects
• Status when antiretroviral • Status at end of month
therapy starts – 24 months at least
2. Pregnancy
– Clinical
• Functioning and CD4
3. Risk of pregnancy
– Immune
• Isoniazid prophylaxis – 0, 6, 12 and 24 months 4. New TB
• Co-trimoxazole prophylaxis 5. New drug available
• TB treatment 6. Drug out of stock
• Pregnancy 7. Other reason (specify)
• Antiretroviral therapy 8. Clinical treatment failure
regimens
– First line 9. Immune failure
– Second line 10. Viral failure
– Reason for change
7 8
Consistent definitions Consistent definitions for why antiretroviral

Follow-up status (outcomes) therapy is stopped – reason codes
1 Toxicity or side-effects
• Alive and on antiretroviral therapy 2 Pregnancy – planned treatment interruption
• Specify current regimen 3 Treatment failure
4 Poor adherence
• Alive and stopped antiretroviral therapy
5 Illness or hospitalization
• Alive and restart 6 Drug out of stock
• Lost (not the same as TB default) 7 Patient lacked financial resources
8 Other patient decision
• Dead
9 Planned treatment interruption (record reason, such as early
• Transfer in or transfer out with records pregnancy)
10 Other
9 10
HIV care registers Cohort analysis report:

Receiving antiretroviral therapy for 6 months,
12 months, yearly
Allow the measurement of: • Proportion working, ambulatory or bedridden
• Proportion alive and receiving antiretroviral therapy at 6 and
12 months (survival indicator)
• Medically eligible people
• Proportion still on a first-line regimen
• Eligible and ready people • Proportion still on an original first-line regimen
• Start of first-line therapy • Proportion who have substituted an alternative first-line
regimen
• Proportion switched to a second-line (or higher) regimen
• Median CD4 count (optional)
11 12
89
Cohort analysis report:
Receiving antiretroviral therapy for 6 months,
12 months, yearly
• Optional:
Malawi experience
– Reasons for switching regimen
– Reasons for stopping
13 14
Antiretroviral therapy patient Cohort analysis

master card
Every three months, update the
register from the master card data
• Every three months, each cohort is analysed
for its treatment outcomes
[this allows survival analysis to be conducted]
Antiretroviral therapy
facility register
Every three months, perform • Every three months, all the cohort case
quarterly cohort analysis from the
updated register
numbers and treatment outcomes are
combined together
[this allows cumulative up-to-date data]
Antiretroviral therapy patient
cohort analysis
15 16
Antiretroviral therapy quarterly cohort analysis form

NAME OF TREATMENT UNIT_____________ Thyolo DH
COHORT [specify the year and the quarter] __________ 2003, Q2
Total number of patients initially registered in the cohort___ 116
Year in which evaluation is taking place:_______________________ 2003
Date on which evaluation is taking place _______________________ 10 July
Of the total number registered in the cohort:

Number Alive and on antiretroviral therapy___________ 106 (91%)
[Alive and on first-line regimen_______________ 101]
[Alive and on alternative first-line regimen______ 5]
[Alive and on second-line regimen______________ 0]
Dead ______________________________________ 6
Defaulted__________________________________ 0
Stopped____________________________________ 4
Transferred out to another treatment unit__________ 0
Of those alive:
Number Ambulatory ___________ 106
At work ___________ No information
With side-effects ___________ 14
With pill count in bottle 8 or less________ 63/63
17
(Note: pill count in bottle 8 or less is equivalent to 95% adherence)
90
Document 9.3
Course organizers will hand out the type

of TB and HIV forms used in the
country or area where the course is
conducted.
91
Unit 10: Surveillance of HIV prevalence

among people with TB disease
___________________________________________________________
Objectives
___________________________________________________________
1) to describe surveillance of HIV prevalence among
people with TB disease; and
2) to discuss the main problems, constraints and
opportunities for implementing coordinated TB/HIV
surveillance.
___________________________________________________________
Methods
___________________________________________________________
Plenary presentation: Surveillance of HIV prevalence among people
with TB disease
Exercise
Plenary discussion
___________________________________________________________
Materials
___________________________________________________________
Document 10.1: Surveillance of HIV prevalence among people with TB
disease (slides)
Document 10.3: Guidelines for HIV surveillance among tuberculosis
patients (9)
___________________________________________________________
92
Document 10.1
Surveillance of HIV prevalence among

Objectives of the unit
people with TB disease
Document No. 10.1
• To describe surveillance of HIV
prevalence among people with TB
disease
• To discuss the main problems,

constraints and opportunities for
TB/HIV course for managers at the national
and subnational levels implementing coordinated TB/HIV
surveillance
1 2
Open
Guidelines for HIV surveillance among tuberculosis Why is surveillance of HIV prevalence
patients, 2nd edition
among people with TB disease important?
Other sources of
information (prevention
First edition: of mother-to-child
transmission, voluntary • HIV prevalence among people with TB
Guidelines for HIV counselling and testing,
surveillance among TB blood banks, TB disease is a sensitive indicator for the
patients. World Health research, etc.) spreading of HIV into the general population.
Organization, Geneva, Ethical concerns
1994 (informed consent and
(WHO/TB/94.180) access to voluntary
counselling and testing)
• Advocates increasing commitment to provide
comprehensive HIV/AIDS care and support,
• From experience in sub-Saharan Africa including antiretroviral therapy, to HIV-
• Unlinked, anonymous seroprevalence survey of HIV
infection among adults with newly diagnosed TB
positive people with TB disease.
3 4
Surveillance methods for use in different HIV

Surveillance methods and TB prevalence settings
Category Criteria Recommended surveillance method
The three main methods for surveillance of I Countries with national adult Routine testing
plus
HIV among people with TB disease: HIV prevalence rate ≥1%
Sentinel or special surveys to
calibrate the results of routine testing
1. Data from routine patient care II Countries with national adult
HIV prevalence rate below 1% Routine testing
BUT or
HIV prevalence rate ≥5% in Sentinel or periodic surveys
2. Sentinel surveillance groups with high-risk behaviour
III Countries with national adult
HIV prevalence rate below 1%
3. Periodic (special) surveys AND
Sentinel or periodic surveys
if
No population group with HIV Routine testing not in use
prevalence rate ≥5%
5 6
93
Methods for measuring HIV prevalence among people
Periodic (special) survey (1)
with TB disease
How:
Surveillance Description: cross-sectional survey in sample of people with TB disease
method Description Eligibility: all new TB cases or new cases and relapses (only if survey <2–3
Periodic Cross-sectional HIV seroprevalence surveys among a sample of people months) or only new adult (15–59 years) smear-positive cases; unlinked
with TB disease within a country. anonymous testing or linked anonymous testing or testing with informed
(special)
To include all newly registered TB cases; easier to focus on adult cases
surveys with smear-positive disease. consent
A predetermined number of people with TB disease are routinely tested Data collection: sample size, sampling procedure (random, systematic,
at selected sentinel sites. people with TB disease are used as a sentinel consecutive, cluster); <8–12 weeks (point prevalence) or <6 months (period
Sentinel
group within a general HIV sentinel surveillance system. prevalence); to repeat after 2–3 years
surveillance To include all newly registered TB cases; easier to focus on adult cases
with smear-positive disease. Specimen tested: blood, sputum (only with HIV prevalence >10%)
Data collected from routine care of people with TB disease who are HIV testing: blood or sputum (only if HIV prevalence >10%); 1 enzyme-linked
Data from tested for HIV on a voluntary and confidential basis, through notification immunosorbent assay (ELISA) (if HIV prevalence >10%), ELISA or ELISA
forms (TB or HIV/AIDS) or registers (TB; special TB + HIV; co-
routine care trimoxazole; isoniazid preventive therapy; voluntary counselling and + ELISA or another assay with different antigen (if HIV prevalence <10%) or
testing; voluntary counselling and testing + TB) or cross-matching of 2 ELISA + Western blot (if HIV prevalence <5%)
HIV and TB notification systems (computerized). Data management: standard reporting, confidentiality, quality, analysis and
7 8
feedback
Periodic (special) surveys (2) Ethical issues in HIV surveillance

• An unlinked anonymous method is used to reduce bias caused by people
Advantages Disadvantages refusing to be tested (based on testing blood drawn for other purposes).
This is ethical only if it is both anonymous and unlinked. The ethical
• Simple, no need for new infrastructure • May be expensive and time-consuming concern is that it limits access to antiretroviral therapy. All people with
TB disease included in unlinked anonymous seroprevalence surveys
• Established method • Problems if sample not taken routinely should have access to actively proposed, free, voluntary, confidential
counselling and testing for HIV infection.
• If representative, gives reliable HIV • Ethical concerns
• If leftover blood not available, each person with TB should give informed
estimates • If sample too small, no detailed consent. Alternatively, linked anonymous testing can be used in which
• Can identify biases in sentinel or analyses only person with TB knows the result.
routine surveillance • If poor testing, inconsistent results • Security and confidentiality policies and procedures in the transfer of
information: minimal storage and retention of unnecessary or redundant
• If infrequent, no information on trends paper or electronic reports; names removed from surveillance records
when this no longer serves the public health purpose; records located in
security area; electronic data protected by coded passwords and computer
encryption.
9 10
Methodological issues Sentinel surveillance

Use of sputum samples in HIV surveillance
Advantages Disadvantages
• HIV tests other than on serum or blood (principally gingival secretions)
are available and being further developed. In most countries sputum is
• Simple and inexpensive • Possible conflict of responsibility
routinely collected as part of the preliminary diagnostic investigations for
all people with TB disease. In some settings this may favour the testing of
• Focuses on easily accessible people • Problems if sample not taken routinely
sputum specimens over blood samples, especially if unlinked anonymous
methods are followed (for example for sputum testing).
• Often part of a well-established HIV • Ethical concerns
• The current sensitivity and specificity of HIV tests favours the use of
sentinel system • Low representativity of sentinel sites
blood testing over sputum testing. Even when unlinked methods are used,
the current sensitivity and specificity of sputum testing methods (93.5–
• Good information on trends • Possible selection biases
97.1% sensitivity and 99.7–100.0% specificity, respectively) are still not
sufficiently high to avoid having a low positive predictive value (71.9%) in
• If poor testing, inconsistent results
countries with low HIV prevalence (5%).
• Their use in HIV surveillance among people with TB disease is not

recommended unless these tests have been validated in the country against
gold-standard sero-HIV tests and found to be sufficiently reliable.
11 12
94
Data collection form for HIV prevalence surveys or sentinel
HIV testing from routine care surveillance among people with TB disease
Demographic data form*
Study site:
Advantages Disadvantages Date of patient visit:____ / ____ / ______ (dd/mm/yyyy)
• Access to HIV prevention and care • Need for large infrastructure (time, Patient ID number:
Age: __________ (years)

• Estimates the burden of HIV-related costs)
Sex: Male: [ ] Female: [ ]
disease and demand for care • If low coverage (<80%) of testing,
Clinical
presentation: Pulmonary: [ ] Extrapulmonary: [ ]
unreliable HIV prevalence estimates;
If pulmonary: Sputum smear positive: [ ] Sputum smear negative: [ ]
if poor testing, inconsistent results
(If relapse cases are included)
New: [ ] Relapse: [ ]
• May reflect more the access to health
Laboratory form*
care services than the prevalence of
Patient ID number:
HIV within the TB population Results test 1: Positive: [ ] Negative: [ ] Doubtful: [ ] Not done: [ ]
Results test 2: Positive: [ ] Negative: [ ] Doubtful: [ ] Not done: [ ] (if undertaken)

13 14
Methodological issues
Costs Challenges to TB/HIV surveillance
Direct
– Specimen collection equipment
– Transport of specimens Organizational and financial
– Specimen testing kits
– Laboratory staff time
– Travel costs of staff – Low awareness of importance: lack of political
– Costs of data entry and analysis commitment to surveillance and insufficient
– Dissemination of information (printing of reports, investment
postage, presentations etc.)
– Suffers from gaps in the TB/HIV initiative
Indirect – Lack of skilled epidemiological personnel
– Investment of staff time at all levels in activities, ranging – Lack of feedback to those involved in
from specimen collection to the overall coordination of
surveillance activities surveillance activities
15 16
Concluding remarks
• HIV surveillance among people with TB disease is a key

TB/HIV activity
• It should be part of a plan for joint TB/HIV activity with

proper allocation of funds
• Surveillance methods in countries should vary according to

the underlying HIV epidemic state and TB burden
• Considering ethical issues and any possible organizational

constraints is important
• A guideline to provide a framework for this activity is now

available
17
95
Document 10.2

For this exercise, your facilitator will divide the participants into four groups. The
purpose of the exercise is to discuss how to implement surveillance of HIV among
people with TB disease.
• Read pages 140-148 in the report on Fictitia in Annex 1.
• Review the available information on the epidemiological situation and

surveillance system in Fictitia.
• Identify gaps in the surveillance component, in particular with relation to

surveillance of HIV among people with TB disease, and propose priorities for
addressing the gaps.
• Estimate the sample size and costs for a special survey to be conducted in
Fictitia to estimate the prevalence of HIV among people with TB disease.
96

Unit 5, Part 1: The DOTS Strategy For Controlling TB: Objectives

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Unit 5, part 1: The DOTS strategy for

The DOTS strategy for controlling TB Objectives of the sub-

• To describe the DOTS strategy (the

• To discuss the implications of the

Aspects of DOTS Aspects of DOTS

Aspects of DOTS Three phases to gradual DOTS

• Policy formulation 2. An expansion phase

• Resource mobilization 3. A maintenance phase

Treatment outcomes by WHO region:

Progress towards the 70/85 targets WHO-

Pursuing expansion and enhancement of high-quality DOTS

60 Brazil 1. Addressing TB/HIV and multi-drug-resistant TB

4. Empowering patients and communities

9 Standardized treatment, under proper case management conditions,

9 An efficient monitoring system for supervising and evaluating

The other five components of the

2. Addressing TB/HIV, multi-drug-resistant TB and other special

3. Contributing to strengthening health systems by collaborating

4. Engaging all care providers, public, nongovernmental and private, by

5. Empowering patients and communities by scaling up community TB

6. Enabling and promoting research to improve programme performance

Quality TB care for all: ensure a high standard

• The foundation of DOTS is effective patient care that alleviates

• A standard of care for TB exists already, and is evidence-

• Simply, each care provider, public or private, should:

• If all providers did the right thing, TB would be controlled.

Unit 5, part 2: Clinical management

Clinical management of TB Objectives of the subunit

• To describe how the clinical management

Diagnosis versus case detection Diagnosis versus case detection

Case detection Case detection

Case detection Case detection

• In high-risk groups • Many attend for other reasons (including child

Case detection Case detection: definitions

Standardized TB treatment regimens

• Food, rest, specialists not critical

• Accessible, acceptable, allows work

Organization of treatment (3) Treatment delivery process

Continuation phase alternatives • Integrated activity including:

Introduction to the exercise for Unit 5

• Read pages 140-148 in the report from Fictitia in Annex 1

• Identify immediate gaps in the programme (especially in terms of

• Prepare to present the group work in the plenary session.

Unit 6, part 1: Universal access to

Universal access to antiretroviral Objectives of the subunit

• To discuss the implications of universal

Antiretroviral therapy coverage in low- and middle-income

Geographical region Number of people

1000 North Africa and the Middle East

People receiving ARV therapy (thousands)

Percentage of patient-days on antiretroviral therapy

Yearly deaths as a proportion of 1995 values

5 Death s per 100 P er so n-Y ears

0.5 Introduction of highly active antiretroviral therapy

Prices (US$ per year) of a first-line antiretroviral Guiding principles

• Universal and equitable access

12 000 Paying attention to vulnerable groups

Involving people living with HIV/AIDS

• Country in the driving seat

• Innovation, learning and sharing

Strategic framework Accelerating prevention

Technical assistance needs identified Conclusions