TB Notes Newsletter
No. 3, 2005
Clinical and Health Systems Research Branch Updates
Tuberculosis Trials Consortium
(TBTC) Study 27 and 28 Update
TBTC Study 27, “An Evaluation of the Activity and Tolerability
of Moxifloxacin During the First 2 Mos. of Treatment for Pulmonary
Tuberculosis,” enrolled its first patient on July 25, 2003, and
completed enrollment on March 14, 2005. Initially proposed to study
300 patients and to take 3 years to complete, the final enrollment
was 336 patients. Findings from preliminary analyses were presented
at the TBTC meeting and American Thoracic Society (ATS) conference
in May 2005.Approximately half of the enrollments occurred at the
TBTC site in Kampala, Uganda,
with the next largest enrollment occurring at the site in Durban,
At the end of study enrollment, a large amount of generic ethambutol,
good through November 2005, remained from the original bulk purchase
from Versapharm. The surplus was offered to the African sites, whose
high case rates would enable them to use it quickly in their routine
clinical practice; the offer was accepted by the Uganda
site. At the end of March, after completing the necessary paperwork,
the CDC pharmacy sent 36,000 400 mg ethambutol tablets to Uganda,
where they were very much appreciated. For readers who may wonder,
matching placebo tablets that were also left over from Study 27
were destroyed according to CDC pharmacy drug services protocol.
TBTC Study 27 compared moxifloxacin with ethambutol during the
first 2 months of therapy. Study 28, “Evaluation of a Moxifloxacin-Based,
Isoniazid-Sparing Regimen for Tuberculosis Treatment,” will compare
moxifloxacin with isoniazid during the first 2 months of therapy.
It has been approved by the CDC IRB and is in the process of IRB
review locally by consortium sites. Enrollment starts in early fall
See TB Notes No. 4, 2004, for more detail on TBTC Study 27 and 28
—Reported by Stefan Goldberg, MD
Div of TB Elimination
Collaboration to Improve TB Services
for HIV-Infected Persons
In persons with latent TB infection (LTBI), coinfection with HIV
is one of the highest risk factors for development of active TB.
In August 2003, the Health Systems Research Team in the Clinical
and Health Systems Research Branch of DTBE began a collaborative
project with the HIV/AIDS Bureau of the Health Resources and Services
Administration (HRSA). The purpose of the collaboration is to help
improve the provision of TB services to HIV-infected persons who
receive care through Ryan White Comprehensive AIDS Resources Emergency
(CARE) Act grantees. The overall aim of the project is to help reduce
TB incidence among persons living with HIV/AIDS by facilitating
improvements in the detection and treatment of TB and LTBI.
Guidelines have been issued by the US Public Health Service (USPHS)
and the Infectious Diseases Society of America (IDSA) for preventing
opportunistic infections among HIV-infected persons.1,2
Individuals newly diagnosed with HIV infection should receive a
tuberculin skin test (TST) soon after HIV diagnosis and be clinically
evaluated for TB disease if they have a positive TST result or have
TB symptoms. If there is no evidence of TB disease (and no history
of treatment for TB or LTBI), persons with a positive TST result
should receive LTBI treatment (recent contacts to TB patients should
be treated regardless of TST result). The guidelines also recommend
annual repeat testing for persons with negative TST results who
may be at a substantial risk of TB exposure. Clinicians should also
consider repeat testing if immune function has improved owing to
Currently, there is limited information concerning the extent to
which TB screening and treatment services are being implemented
by HIV service providers throughout the United
States. A study at three US
sites by Lee revealed that about 50% of HIV-infected persons were
screened for LTBI, with a mean time of 6 months between HIV diagnosis
and TST.3 Approximately 7% had positive TST reactions,
and 59% of these individuals were given LTBI treatment. In a study
among New York City HIV clinics, Sackoff et al. revealed that 56%
of patients with an indication for a TST had a current test result.
They found that 41% of patients with TST-positive results completed
a 12-month regimen for LTBI.4 Finally, the CDC Supplement
to HIV/AIDS Surveillance project found that from 1995 to 1999, 80%
of eligible HIV/AIDS patients from 12 state or local health departments
reported ever receiving a TST.5 Of the 8% who had a positive
TST, 27% did not receive LTBI treatment. The researchers concluded
that current rates of LTBI testing and treatment did not fully meet
the USPHS/IDSA guidelines.
The HIV/AIDS Bureau (HAB) of HRSA administers the Ryan White CARE
Act. The CARE Act funds primary health care and support services
through four titles for approximately 571,000 persons per year,
or possibly 75% of HIV-infected persons who know their HIV status.
Those who receive services through CARE Act grantees are likely
to be persons with limited access to health care and may be at high
risk for TB. Because HRSA/HAB has access to this high-risk population
and because DTBE has prioritized TB prevention among HIV-infected
persons, the two agencies joined together in this collaborative
project. The relationship between HRSA/HAB and DTBE was formalized
in a Memorandum of Understanding (MOU), which facilitates study
collaboration and enables the exchange of information and resources.
The project is divided into two parts. Part One, recently
completed, identified the HRSA/HAB policies, procedures, and baseline
levels of TB screening and treatment through extant data reported
to HRSA/HAB by CARE Act grantees. The specific study questions for
Part One were
- What written policies are in place for HAB grantees to provide
- What is the current rate of TB screening and treatment of HIV-infected
clients at HAB grantees?
- Based on data from CARE Act Data Reports and earlier Title III
Program Data Reports, which HAB grantees have achieved high rates
of TB screening and treatment?
The methods employed for Part One included the establishment of
the MOU; interviews with HRSA/HAB headquarters staff about TB services,
policies, and reporting; and an informal collection of written policies,
procedures, and training curricula from Title III and IV clinics.
Title III supports outpatient primary medical care and early intervention
services to people living with HIV/AIDS through grants to public
and private nonprofit organizations. Title IV supports coordinated
primary care services and access to research for children, youth,
and women with HIV disease and their families. CDC project staff
also analyzed data from all reporting grantees through the CARE
Act Data Report (CADR) on TB screening and treatment services. TB
variables included the number of clients who received a TST, received
treatment owing to a positive TST, or were diagnosed with active
TB in the reporting year. HAB has revised its CADR as of 2005 to
include additional TB variables, such as completion of LTBI treatment,
partly as a result of this project. The results of Part One were
presented at the 2005 National TB Controllers Association in Atlanta,
The primary objective of Part Two is to facilitate improvement
in the detection and treatment of LTBI and TB by developing knowledge
of successful TB services provision at selected CARE Act Title III
grantees, strengthening the capacity of Title III service providers,
and improving collaboration between Title III grantees and TB providers.
Proposed study questions for Part Two are
- How do the selected Title III grantees successfully provide
TB prevention services?
- What ecological and program characteristics and activities are
associated with higher rates of TB screening and treatment at
the selected Title III HIV clinics?
- How much does it cost to provide TB screening and treatment
services at the selected Title III HIV clinics?
A total of six CARE Act Title III grantees in New York City, Los
Angeles, and Miami, all areas with high HIV/TB co-morbidity, will
participate in the case studies. Using qualitative and quantitative
methods, CDC project staff will document the range of program designs
and practices that have achieved success in TB service provision.
Methods will include 1) key informant interviews with HIV clinic
staff; 2) chart abstractions of a random sample of Title III HIV-infected
clients; 3) a review of written TB policies, protocols, and other
documents relevant to TB services provision; 4) interviews with
clinic staff about cost of providing TB screening and treatment
services; 5) focus groups with a randomly selected sample of clients;
6) observation of program operations; 7) and if appropriate, interviews
with staff members from collaborating TB programs.
After results are shared with HAB and study sites, HAB in coordination
with CDC will develop a dissemination strategy that identifies potential
users and targets findings and mechanisms appropriate for each group.
Depending on the nature of the findings, the dissemination strategy
may involve HAB’s AIDS Education and Training Centers (AETCs). Study
findings will reach a wider audience through CDC and HAB publications
and a peer-reviewed journal.
In the final phase, HAB project staff will develop an implementation
strategy in collaboration with CDC. It is intended that this strategy
will promote the use of study findings by Title III HIV providers
beyond what could be expected from publication in a peer-reviewed
journal. Linkages between Title III HIV providers, AETCs, and DTBE
may be established to develop protocols or guidelines for TB services
provision improvement. Findings from the study will be considered
for incorporation into training and technical assistance activities
by HAB’s 11 regional AETCs and their local performance sites as
deemed appropriate given the study results. Findings may also be
incorporated into training materials and curricula developed by
the TB Regional Training and Medical Consultation Centers for broad
use by TB providers. DTBE’s Field Services and Evaluation Branch
will be consulted to help establish referral mechanisms between
HIV providers and local TB providers. Lastly, ongoing information
exchange mechanisms will be developed between CDC and HAB for sharing
of TB screening and treatment data to monitor TB services provision
In summary, HAB’s access to this at-risk population provides an
opportunity to prevent TB morbidity and mortality and to improve
TB services for people living with HIV/AIDS. This collaborative
project addresses priorities of both CDC and HAB, as well as the
Institute of Medicine6 and the Federal TB Task Force.7
In addition, this collaboration provides an opportunity for staff
members from HAB and CDC to build professional relationships and
sets the stage for future partnerships that further both agencies’
—Reported by Heather Joseph, MPH, Cathy Rawls, MPH,
CHES, and Suzanne Marks, MPH
Div of TB Elimination
For additional information about this study, please contact the
Suzanne Marks (SMarks@cdc.gov) or Heather Joseph (HJoseph1@cdc.gov) at DTBE or Alice Kroliczak
José Rafael Morales (firstname.lastname@example.org)
- CDC. Guidelines for preventing opportunistic infections among
HIV-infected persons—2002: Recommendations of the US Public Health
Service and the Infectious Diseases Society of America. MMWR.
- Prevention and treatment of tuberculosis among patients infected
with human immunodeficiency virus: Principles of therapy and revised
recommendations. MMWR 1998; 47(RR-20).
- Lee LM, Buskin SE, and Morse A. Low rates of tuberculin skin
testing among persons with diagnosed HIV infection, US, 1995-1997.
Presented at the 14th International AIDS Conference.
Barcelona, Spain; July
- Sackoff JE, Torian LV, Frieden TR, Brudney KF, Menzies IB. Purified
protein derivative testing and tuberculosis preventive therapy
for HIV-infected patients in New York City. AIDS. 1998;12:2017-2023.
- Campsmith ML, Nakashima AK, and Burgess D. Self-reported TB
testing and preventive therapy in an HIV-infected population:
Results from an interview project in the United
States. Presented at CDC. Atlanta, GA, 2000.
- Institute of Medicine. Ending Neglect: The Elimination of
Tuberculosis in the United States.
Washington, DC: National Academy Press. 2000.
- CDC. Federal Tuberculosis Task Force Plan in Response to
the Institute of Medicine Report,
Ending Neglect: The Elimination of Tuberculosis in the United
States. September 2003. IOM Recommendation