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Rifapentine + isoniazid to prevent TB
among people living with HIV:
interim data and pending issues
The PREVENT TB Study
TB Trials Consortium Study 26
AIDS Clinical Trials Group 5259
Sterling TR, Benson CA, Shang N, Miro JM,
Grinsztejn B, Chaisson RE, Lucchetti A, Sanchez J,
Benator D, Scott N, Villarino ME
Background
• HIV is the strongest risk factor for
progressing from latent M. tuberculosis
infection to active tuberculosis
• 9 months of daily INH is efficacious, but
has low completion rates, limiting its
effectiveness
– Most common adverse effect: hepatotoxicity
Background
• 3 months of once-weekly rifapentine 900 mg
+ INH 900 mg under direct observation (3HP)
(PREVENT TB study)
– At least as effective as 9 months of daily INH 300
mg self-administered (9H)
– Higher treatment completion rate than 9H
• Only 3% of study participants were HIV+
– Enrollment of HIV+ persons was extended to
adequately assess tolerability in this population
Sterling TR. N Engl J Med 2011;365:2155-66.
Overview
• Effectiveness of 3HP in the PREVENT TB
study, with focus on HIV-infected TB cases
– Risk factor analysis for TB
• Tolerability of 3HP in HIV-infected persons
• Rifampin resistance in TB cases
The PREVENT TB Study Inclusion Criteria
• Persons > 2 years old who were:
– Tuberculin skin-test (TST)-positive close contacts of a
culture-confirmed TB case
– TST-converters
• Documented negative positive within 2 years
– TST-positive, fibrosis on chest radiograph consistent
with prior untreated TB
– Children 2-4 years old with + TST or close contact
with a culture-confirmed TB case
– HIV-infected with
• Positive TST
• Close contact to TB case regardless of TST
The PREVENT TB Study Exclusion Criteria
• Confirmed or suspected TB
• TB resistant to INH or rifampin in source case
• History of treatment with
– > 14 consecutive days with a rifamycin
– > 30 days with INH
• Prior treatment of TB or M. tuberculosis infection in HIV-
uninfected persons
• Intolerance to INH or rifamycins
• Aspartate aminotransferase (AST) > 5x upper limit if AST
determined
• Pregnant or lactating females
• Weight < 10 kg
• HIV-1 antiretroviral therapy < 90 days after enrollment
The PREVENT TB Study Summary
• 8,053 persons enrolled
– United States, Canada, Brazil, Spain
– June 2001-February 2008
– 33 months of follow-up
• 7,731 in modified intention-to-treat (MITT)
– Enrolled in the study, and eligible
• Tuberculosis risk (cumulative)
– 3HP: 7 / 3,986 (0.19%)
– 9H: 15 / 3,745 (0.43%)
– Rate difference: -0.24%
– Upper limit of 95% CI of difference: 0.01%
– Pre-defined non-inferiority margin: 0.75%
.
Difference in TB rates between the 2 study arms, and non-inferiority “delta”
Modified Intention to Treat Population; A33 analysis
Cumulative TB Rate 33 months from enrollment—MITT
Log-rank P-value: 0.06
Summary of TB Cases PREVENT TB Study
3HP 9H
HIV-infected 105 100
HIV-uninfected/unknown 3,881 3,645
Primary endpoint Culture + TB in adults; culture +/- in children
N=7 N=15
HIV-infected 2 2
HIV-uninfected 2 8
HIV-unknown 3 5
Secondary endpoint Culture – TB in adults
N=2 N=2
HIV-infected 0 1
HIV-uninfected 1 1
HIV-unknown 1 0
Risk Factor Analysis-for TB Univariate
Characteristic Reference group HR (95% CI) P-value
Regimen (3RPT/INH) 9INH 0.43 (0.18, 1.07) 0.07
Age (10 years) 10 years younger 0.87 (0.65, 1.17) 0.37
Male sex Female 1.50 (0.63, 3.58) 0.36
Black race White race 1.56 (0.64, 3.81) 0.33
HIV + HIV negative 7.00 (2.19, 22.30) 0.001
BMI (1 unit) 1 unit lower 0.85 (0.78, 0.93) 0.0006
EtOH abuse No EtOH 4.84 (1.58, 14.78) 0.006
Current smoking No smoking 4.73 (1.98, 11.27) 0.0005
IDU No IDU 1.29 (0.17, 9.59) 0.80
High school Completed 1.21 (0.51, 2.85) 0.66
Jail/prison No jail/prison 3.12 (0.92, 10.54) 0.07
Unemployed Not unemployed 2.55 (0.94, 6.92) 0.07
No interaction between treatment arm and above variables.
Risk Factor Analysis-for TB Multivariate
Characteristic Reference group HR (95% CI) P-value
Regimen (3RPT/INH) 9INH 0.38 (0.15, 0.99) 0.05
Age (10 years) 10 years younger
Male sex Female
Black race White race
HIV + HIV neg/unknown 4.07 (1.26, 3.16) 0.01
BMI (1 unit) 1 unit lower 0.81 (0.73, 0.90) 0.0002
EtOH abuse EtOH use or none
Smoking-current Smoke last 5 yrs/never 4.89 (1.90, 12.58) 0.001
IDU No IDU
High school Completed
Jail/prison No jail/prison
Unemployed Not unemployed
Primary Aim of the HIV Sub-Study
• Compare the tolerability of weekly 3HP vs. daily
9H in HIV-infected persons
• Endpoints
– Treatment completion
– Permanent drug discontinuation for any reason
– Drug discontinuation due to adverse drug reaction
– Grade 3 or 4 toxicity
– Grade 5 toxicity (death)
Enrollment of HIV-infected Persons
• United States, Brazil, Spain, Peru,
Canada, Hong Kong China
• Enrolled June 2001 – December 2010
• Follow-up for TB endpoints continues
through September 2013
– Treatment effectiveness data are pending
– This analysis focuses on tolerability
Analysis Populations HIV-infected Persons
• Of 4,242 participants enrolled with known HIV
status, 403 were HIV+
• Enrolled (ITT) 403
• Eligible (MITT) 394
– 9H 193
– 3HP 201
• Received > 1 dose of study drug 393
– 9H 186
– 3HP 207
Clinical and Demographic Characteristics MITT Population
Characteristic 9H
N=193
3HP
N=201
Age (median, IQR) 36 (29-44) 36 (30-44)
Male sex 131 (68) 145 (72)
Race
White 73 (38) 75 (37)
Black 75 (39) 71 (35)
Asian/Pac. Island 3 (2) 6 (3)
Am./Can. Indian 4 (2) 5 (3)
Multiracial 38 (20) 44 (22)
Ethnicity (US/Can)
Hispanic 22 (11) 26 (13)
Non-Hispanic 74 (38) 62 (31)
Clinical and Demographic Characteristics MITT Population
Characteristic 9H
N=193
3HP
N=201
CD4 (median, IQR) 514 (404-699) 493 (379-685)
BMI (median, IQR) 25 (22-28) 25 (23-28)
Site of recruitment
U.S./Canada 96 (50) 89 (44)
Brazil/Spain/Peru 97 (50) 112 (56)
Completed high school 118 (61) 120 (60)
Jail/prison ever 24 (12) 16 (8)
Unemployed 47 (24) 38 (19)
Hx EtOH at enrollment 120 (62) 112 (56)
Hx IDU at enrollment 33 (17) 27 (13)
Current tobacco 90 (47) 81 (40)
Clinical and Demographic Characteristics MITT Population
Characteristic 9H
N=193
3HP
N=201
Indication for TLI
Close contact 25 (13) 20 (10)
Recent TST converter 5 (3) 9 (5)
HIV-infected 163 (85) 172 (86)
Fibrosis on CXR 0 (0) 0 (0)
Co-morbid liver disease
HCV 26 (14) 22 (11)
HBV 19 (10) 11 (6)
Tolerability MITT population
Outcome 9H
N=193
3HP
N=201
P-value
Treatment
completion
125 (65%) 178 (89%) < 0.0001
Permanent drug d/c-
any reason
68 (35%) 23 (11%) < 0.0001
Permanent drug d/c-
due to an adverse
event
8 (4%)
7 (4%)
0.8
Death 4 (2%) 2 (1%) 0.44
Adverse Events by Toxicity Grade Among persons receiving > 1 dose
During treatment or within 60 days of the last dose
Attributable to study drug
Toxicity 9H
N=186
3HP
N=207
P-value
Grade 1-2
51 (26) 28 (13) 0.001
Grade 3
20 (10) 16 (8) 0.39
Grade 4
10 (5) 4 (2) 0.10
Adverse Events by Category Among persons receiving > 1 dose
During treatment or within 60 days of the last dose
Toxicity 9H
N=186
3HP
N=207
P-value
SAE 21 (11%) 8 (4%) 0.006
> 1 AE 75 (40%) 45 (22%) <0.001
Related to drug 19 (10) 16 (8) 0.48
Hepatotoxicity 11 (6) 3 (2) 0.03
Possible HS 0 (0) 1(0.5) 1.0
Rash only 0 (0) 1(0.5) 1.0
Other 8 (4) 11 (5) 0.81
Not related 65 (35) 34 (16) <0.0001
HS: hypersensitivity reaction
Tolerability of 9H and 3HP by HIV Status MITT Population
9H 3HP
Toxicity HIV-pos
N=193
HIV-neg
N=1,848
P-value HIV-pos
N=201
HIV-neg
N=1,862
P-value
Perm drug d/c
any reason
68 (35) 603 (33) 0.46 23 (11) 365 (20) 0.004
Perm drug d/c
due to AE
8 (4) 63 (3) 0.54 7 (4) 99 (5) 0.32
Death
4 (2) 20 (1) 0.28 2 (1) 17 (1) 0.71
Tolerability of 9H and 3HP by HIV Status Among persons receiving > 1 dose
During treatment or within 60 days of the last dose
9H 3HP
Toxicity HIV-pos
N=186
HIV-neg
N=1,847
P-value HIV-pos
N=207
HIV-neg
N=1,888
P-value
SAE 21 (11) 60 (3) <0.001 8 (4) 41 (2) 0.14
AE related to
study drug
19 (10) 98 (5) 0.01 16 (8) 181 (10) 0.45
Hepatotoxicity 11 (6) 49 (3) 0.02 3 (2) 11 (1) 0.15
Possible HS 0 (0) 10 (0.5) 0.61 1 (0.5) 85 (5) 0.003
HS: hypersensitivity reaction
Drug Resistance Among TB cases
9H
N=12
3HP
N=7
INH
resistant
2 0
Rifampin
resistant
0 1*
* M. bovis in an HIV-infected person who had treatment interruptions
and completed therapy late. CD4 = 271 at enrollment.
Cases of Tuberculosis, Culture-Confirmed Cases, and Drug-Resistant Isolates, According to Treatment Group.
Martinson NA et al. N Engl J Med 2011;365:11-20.
Limitations
• Sample size relatively small
– Though sufficient for tolerability assessment
• Patients could not receive antiretroviral therapy
for first 90 days after enrollment
– Drug interactions with rifapentine not well-
characterized
– Limited the number of eligible participants
• Data on effectiveness pending until late 2013
– In PREVENT TB, HIV+ TB cases equally distributed
Conclusions
• Among HIV-infected persons with high CD4
counts and not on antiretroviral therapy,
3HP had higher treatment completion rates
and was better tolerated than 9H for
treatment of latent M. tuberculosis infection
• 3HP was at least as well-tolerated in HIV-
infected than HIV-uninfected persons
Conclusions
• 9H was less well-tolerated in HIV-infected
than HIV-uninfected persons
• Smoking was associated with TB risk that
was at least as high as that with HIV infection
• Insufficient number of TB cases to determine
whether risk of rifampin resistance was
increased among persons who develop TB
after 3HP
Study Sites and Investigators Agencia de Salut Publica – Barcelona, Spain and UNTHSC (70)
Joan A. Cayla, MD, PhD, Jose M. Miró, MD, PhD, Maria Antonia Sambeat, MD, PhD, Jose L.
López Colomés, MD, José A. Martinez, MD, Xavier Martinez-Lacasa MD, PhD, Angels Orcau,
MD, Paquita Sanchez, MD, Cecilia Tortajada, MD, PhD, Imma Ocana, MD, PhD, Juan P.
Millet, MD, MPH, Antonio Moreno, MD, Jeanne Nelson, MPH, Omar Sued, MD, Mª Luiza de
Souza, MD, María A. Jiménez, MD, Lucía del Baño RN, Laia Fina MSc.
IPEC Evandro Chagas (FIOCRUZ) (42)
Beatriz Grinsztejn, MD, Guilherme Calvet, MD, MSc, Sandra Wagner Cardoso, MD, Thiago
Silva Torres, R.PH., M.Sc., Ronaldo Moreira, Deise Faria, Leandro Amparo de Xouza,
Alexandre Souza, Paula Leite Cruz dos Santos, Janaina Vieira.
Johns Hopkins University (38)
Richard Chaisson, MD, Susan Dorman, MD, Jim Fisher, Gina Maltas, RN, Judith
Hackman, RN.
Impacta San Miguel, Peru (33)
Rosa Infante, MD, Aldo Lucchetti, MD, Fanny García Velarde, RN, Carmen Rosa, Yance de la
Cruz, Pharm, Carmela Ganoza, MD, Jesus Peinado, MD, Jessica Rios, Rosemery Gutierrez,
Anabeli Tataje Candiotti, MD, Mónica Isabel Sánchez Castañeda, Pharm, Melissa Meneses
Civico.
Impacta, Lima, Peru (32)
Jorge Sánchez Fernandez, MD, Alberto La Rosa, MD, Bertha Ramirez, MD, Carmela Ganoza,
Md, Esmellin, Perez, Pharm, Victor Malpartida, Oscar Cevallos lopez, Juan Hurtado, Juan
Guanira, Javier Lama, David Ruben Iglesias, Erick Ramos, Juanita Calderon, Fanny Rosas
Bonancio.
Study Sites and Investigators University of North Texas Health Science Center at Ft. Worth (UNTHSC) (30)
Stephen E. Weis, D.O., Michel Fernandez, MD, Barbara King, RN, Lee Turk, RN, Norma
Shafer, Gloria Stevenson, RN, Guadalupe Bayona, MD, Randy Dean, RN, Joseph Helal,
MS, RPh, Gerry Burgess, RN.
Emory University Department of Medicine (19)
Susan M. Ray, MD , David P. Holland, MD, Deirdre Dixon, Omar Mohamed, Kanoa Folami,
Jane Bush, MA, Cheryl D. Simpson, BS, Gibson Barika, Wenona N. Favors, Nicole Snow
Hospital Nossa Senhora do Conceicao Porto Alegre (17)
Breno Riegel Santos, MD, Rita Lira, MD, Elizabeth Magalhaes, Pharm, Rui Flores, Kelin,
Zabtoski.
University of California, San Diego Medical Center (UCSD) (15)
Antonino Catanzaro, MD, Philip LoBue, MD, Kathleen Moser, MD, Mark Tracy, MD, Peach
Francisco, RN, Judy Davis.
Hospital Universitario Clementino Fraga Filho – Rio de Janeiro, Brazil, Johns Hopkins (14)
Marcus B. Conde, MD, Fernanda C. Q. Mello, MD, Anne Efron, MSN, MPH, Carla Loredo,
RN, Millene Barty S. Fortuna, Michelle Cailleaux-Cezar, MD, Renata L. Guerra, MD, Gisele
Mota, RN, Cristina Felix, RN, Afranio Kritski, PhD, Valéria de Oliveira, Claudeci dos Santos
Sacramento.
Study Sites and Investigators
Denver Public Health Department (13)
William Burman, MD, Randall Reves, MD, Robert Belknap, MD, David Cohn, MD, Jan Tapy,
RN, Grace Sanchez, CCA, Laurie Luna, RN.
Boston University Medical Center (11)
John Bernardo, MD, Jussi Saukkonen, MD, Claire Murphy, RN, Denise Brett-Curran, RN.
University of Southern California/LA County (10)
Brenda E. Jones, MD, Patricio Escalante, MD, Peregrina Molina, RN, Claudia Silva, RN,
Angela Grbic, RN, Maria Brown, MPH, Bonifacia Oamar, RN, Ermelinda Rayos, CW, Celia
Luken.
Duke University (7)
Carol Dukes Hamilton, MD, Jason Stout, MD, MHS, Ann Mosher, RN, MPH, FNP-BC, Emily
J. Hecker, RN, MSN, Brenda Ho, RN, Elle Rich, RN, MPH.
Harlem Hospital Center (7)
Wafaa M. El-Sadr, MD, MPH, Mary Klein, RN, Cyrus Badshah, MD, John Salazar Schicchi,
MD, Yael Hirsh-Moverman, MPH.
Study Sites and Investigators
Vanderbilt University Medical Center and Nashville Metro Public Health Department (6)
Timothy Sterling, MD, Linda R. Hammock RN, Amy Kerrigan, RN MSN, Alicia Wright, Belinda
Redd, LPN, Ingrid Montgomery, RN, Kathleen Miller, RN.
University of California, San Francisco (6)
Payam Nahid, MD, MPH, Philip Hopewell, MD, Charles Daley, MD, Robert Jasmer, MD, Cindy
Merrifield, RN, William Stanton, RN, Irina Rudoy, MD, Jill Israel, RN.
Washington DC Veterans Affairs Medical Center (4)
Fred Gordin, MD, Debra Benator, MD, Donna S. Conwell, RN.
University of Medicine and Dentistry New Jersey (UMDNJ) (4)
Bonita T. Mangura, MD, Lee B. Reichman, MD, George McSherry MD, Alfred Lardizabal, MD,
Maria Corazon Leus, RN, Marilyn Owens, RN, Eileen Napolitano, Laurie Kellert, RN, Veronica
Anokute, RN.
Montreal Chest Institute (3)
Richard I. Menzies, MD, Kevin Schwartzman, MD, MPH, Christina Greenaway, MD, Larry
Lands, MD, Sharyn Mannix, MD, Paul Brassard, MD, MSc, Bérénice Mortezai, MD, Barry
Rabinovitch, MD, Marthe Pelletier, Chantal Valiquette, Joanne Tremblay, Paul Anglade Plaisir,
Rebecca Binet, BSc.
Study Sites and Investigators
Hospital Dos Servidores Do Estado (2)
Maria Leticia Santos Cruz, MD, MSc, Esau Joao, Leon Claude Sidi, MD, José Carlos
Cruz, Fellipe Lattanzi, Elaine Santos, Deisi Scheiner Torgecki.
TB and Chest Services of Hong Kong (2)
Chi-Chiu Leung, MBBS, Kowk-Chiu Chang, MBBS, MSc, Sik-Wai Tam, Cheuk-Ming Tam,
Sau-Yin Tam, Ida Ka-Yun, Mak, Ka-Lin Fong, Nai-Chung Lee, Kai-Man, Kam, Chi-Wai
Yip, Judy Yee-Man Lam, Chi-Wai Ng, Oi-Wah Fong, Edman Tin-Keung Lam, Michelle
Chung-Ying Wong.
Public Health – Seattle and King County Public Health (2)
Masa Narita, MD, Charles M. Nolan, MD, Stefan Goldberg, MD, Debra Schwartz, RN,
Linh Deretsky, Marcia Stone, RN, MPH, Connie Friedly, RN.
The Miriam Hospital, Providence, RI (2)
Karen Tashima, MD, Aadia Rana, MD, Awe Kwara, MD, Pamela Poethke, RN, BSN,
Deborah Good, Renee Fraatz, Pharm.D, Virginia Patrick, Deborah Perez, RN, Helen
Patterson.
University of Manitoba (2)
Wayne Kepron, MD, Earl Hershfield, MD, Marian Roth, RN, Gerry A. Izon, RN.
University of Texas Health Science Center Houston (2)
Roberto Arduino, MD, Hilda Cuervo, Grady Douglas, Maria Insignares, Maria Martinez,
Martine Diez
Study Sites and Investigators
VA Houston Texas – Ben Taub General Hospital (2)
Elizabeth Guy, MD, Christopher Lahart, MD, Terry Scott, RN, Ruby Nickson, RN, Denise
Dunbar, Richard Hamill, MD, Michael George, Pharm D, BCPS.
VA Little Rock, Arkansas – Arkansas Department of Health (1)
Iram Bakhtawar, MD, Frank Wilson, MD, Pauline Wassler, RN, Annette Arnold, APN,
Kathy Haden, RN, Jamie Owens, HPN.
Jesse Brown VA Medical Center, Chicago (1)
Mondira Bhattacharya, MD, Susan Lippold, MD, MPH, William Clapp, MD, Julie Fabre,
RN, MPH.
Edward Hines Jr. VA Medical Center Chicago (1)
Constance T. Pachucki, MD, Anna Lee, MD, Susan Marantz MD, Mary Poly Samuel, RN,
Ana Zulaga BS, MPH.
Instituto Emilio Ribas-Sao Paolo (1)
Marinella Della Negra, MD, Gustavo Fadel, MSc, Luziane Flora Figueira, Wladimir
Queiroz, MD, Denise Pacola, Yu Ching Lian, Roberio Aves Cameiro.
Columbia University College of Physcians and Surgeons, NYC Dept of Health (1)
Neil Schluger, MD, Joseph Burzynski, MD, Vilma Lozano, RN, Magda Wolk, RN, Marta
Scotto, RPh.
Study Sites and Investigators
Audie L. Murphy VA Hospital, San Antonio, TX (1)
Marc Weiner, MD, Melissa Engle, CRT, CCRC, Jose A. Jimenez, BS, Hipolito Pavon,
MPH, Victoria Rodriguez, RN, Col. Kevin B. West, MD, Col. David Dooley, MD, Col.
Duane Hospenthal, MD, PhD.
Universidade de Sao Paulo de Rebeirao Preto (1)
Marisa Márcia Mussi-Pinhata, MD, Marcia de Lima Isaac, MD, Hugo Lopes Gomes, MSc,
Julio Cesar Gabaldi, Pharm, Adriana Tiraboschi Barbaro, MD, Bento De Moura Negrini,
MD Fernanda Sturzbecher.
The University of British Columbia (1)
J. Mark Fitzgerald, MD, Kevin Elwood, MD, Eduardo Hernandez, MD, Banafsheh
Peyvandi, MD, Kadria Alasaly, MD.
Potential Conflicts of Interest
Analysis Populations
• Enrolled before February 15, 2008 – Completed 33 months of follow-up by September 30, 2010
• Intention-to-treat (ITT) – All persons enrolled in the study
• Modified intention-to-treat (MITT) – Enrolled in the study
– Eligible
• Per protocol (PP) – All persons enrolled in the study who were eligible
– Completed study drug within targeted time period
– Or developed TB or died but completed > 75% of expected doses prior to event
– All follow-up time counted; did not require reaching 33 months
Definitions
• Adverse Event (AE):
– As reported by local investigators
• Serious Adverse Events (SAE):
– Deaths on study drug or < 60 days after last
dose, life-threatening events, hospitalization,
disability or permanent damage, congenital
anomalies or birth defects
• Hepatotoxicity:
– As reported by local investigators, excluding
cases attributable to acute hepatitis A, B, or C
Definitions
• Possible Drug Hypersensitivity
– Hypotension, urticaria, angioedema, acute
bronchospasm, or conjunctivitis that occurred
in relation to study drug
– > 4 of the following (one of which had to be >
grade 2) that occurred in relation to study
drug: weakness, fatigue, nausea, vomiting,
headache, fever, aches, sweats, dizziness,
shortness of breath, flushing, or chills.
Reason for Ineligibility N=9 (of 403)
Reason Frequency %
Source TB case resistant to
INH or RIF
4 44.4
Source TB case culture-
negative for M. tuberculosis
3 33.3
Positive TST not confirmed 1 11.1
No susceptibility testing for
index case
0 0.0
TB at enrollment 1 11.1
Total 100%
Causes of Death
• 9H
– Hypertensive cardiovascular disease
– AIDS with dementia
– Chronic liver disease or cirrhosis
– Unknown
• 3HP
– Non-Hodgkins lymphoma
– Unknown
Population study
arms
# of
patients
# TB cases
TB per
100 p-y
Cumulative TB
rate (%)
Difference in
cumulative TB
rate
Upper bound of
95% CI of difference
in cumulative TB
rates*
MITT 9H 3,745 15 0.16 0.43 -0.24 0.01
3HP 3,986 7 0.07 0.19
Per
Protocol
9H 2,585 8 0.11 0.32 -0.19 0.06
3HP 3,273 4 0.05 0.13
Event rate estimates and the non-inferiority test for A33
33 months of follow-up from time of randomization
* non-inferiority margin (delta) = 0.75%
Once-weekly INH + rifapentine for 3 months HIV +/PPD+ Adults. Soweto, South Africa
• Rifapentine 900 mg + INH 900 mg – once-weekly for 3 months
• Rifampin 600 mg + INH 600 mg – twice-weekly for 3 months
• INH 300 mg – daily continuous
• INH 300 mg – daily for 6 months
Superiority trial—compared to 6 months of INH
All patients received B6 25 mg with each dose
Patients did not receive HAART
Martinson NA. N Engl J Med 2011.
Rates of Study End Points According to Treatment Group.
Martinson NA et al. N Engl J Med 2011;365:11-20
Adverse Events, Including Those Occurring after Discontinuation of Study Medications, and Status of Study Medications after the Adverse Events.
Martinson NA et al. N Engl J Med 2011;365:11-20