36bLB
Novel Regimens for Treating Latent TB in HIV-infected Adults in South Africa: A Randomized Clinical Trial
Neil Martinson*1, G Barnes2, R Msandiwa1, L Moulton2, G Gray1, J McIntyre1, H Hausler3, M Ram2, and R Chaisson2
1Univ of the Witwatersrand, Johannesburg, South Africa; 2Johns Hopkins Univ, Baltimore, MD, US; and 3TB Care Assn, Cape Town, South Africa
Background: Treatment of latent TB in HIV-infected
individuals is efficacious, but few patients are treated in high-burden
countries. We compared standard isoniazid (H) preventive therapy with
alternative regimens that might be more potent, more durable or less likely to
contribute to resistance.
Methods: A randomized trial was performed in
HIV-infected, tuberculin positive (³5
mm) South African adults without active TB recruited at a perinatal HIV clinic
in Soweto. Patients were block-randomized 2:2:1:2 to receive rifapentine (RPT)
900 mg plus isoniazid (INH) 900 mg once weekly for 12 weeks (RPT/INH-3);
rifampin (RIF) 600 mg plus INH 900 mg twice weekly for 12 weeks (RIF/INH-3);
INH 300 mg daily continuously for the duration of the trial (INH-cont); or INH
300 mg daily for 6 months (INH-6, control arm). All patients also received
pyridoxine. The RPT/INH and RIF/INH regimens were supervised in the clinic and
all patients were followed at least monthly while on study treatment. The
primary endpoints were TB incidence and TB-free survival.
Results: We randomized 1150 patients. The median age
was 30 years and the majority were female (83%) and black African (99.5%).
Baseline median CD4 count was 485, viral load 4.2 log and TST reaction 15 mm.
The median follow-up was 3.9 years and adherence in the trial was high, with
average reported rates >80%. There were no statistically significant
differences in TB rates between the treatment arms (all p >0.2).
There were significantly more grade 3/4 toxicities in the INH-cont arm than in
the other study arms. Overall, 28% of patients began antiretroviral therapy
during the trial. Of 54 TB isolates tested, 5 had drug resistance (1 RIF monoresistance [RPT/INH arm], 1 streptomycin, and 3 MDR [1 INH-cont and 2 RPT/INH
arm]).
|
Outcome
|
RPT/INH-3
(n = 329)
|
RIF/INH-3
(n = 329)
|
INH-cont
(n = 164)
|
INH-6
(n = 328)
|
|
Median F/U (years)
|
3.98
|
3.99
|
3.81
|
3.78
|
|
TB Cases
|
23
|
24
|
8
|
20
|
|
TB incidence
|
1.94
|
1.97
|
1.43
|
1.77
|
|
Rate ratio
95%CI
|
1.10
0.57 to 2.1
|
1.11
0.59 to 2.1
|
0.81
0.31 to 1.9
|
1 (ref)
|
|
TB or death
|
3.03
|
2.87
|
2.67
|
3.53
|
|
Rate ratio
95%CI
|
0.86
0.53 to 1.4
|
0.81
0.50 to 1.3
|
0.76
0.39 to 1.4
|
1 (ref)
|
Conclusions: Alternative, short-course,
rifamycin-based regimens and continuous INH for latent TB in HIV-infected
adults were as efficacious as 6 months of INH. The development of
RIF-resistance and MDR TB in patients in the weekly RPT/INH arm is of concern.
We conclude that these novel regimens may improve the treatment of latent TB in
HIV-infected patients in high-burden settings.
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