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Safety and Early Virologic Response of Zidovudine + Lamivudine + Abacavir for Patients Co-infected with HIV and TB in Uganda
Padmini Srikantiah*1, M Walusimbi2, H Kayanja3, H Mayanja-Kizza2, R Mugerwa2, R Lin1, E Charlebois1, H Boom3, C Whalen3, and D Havlir1
1Univ of California, San Francisco, US; 2Makerere Univ, Kampala, Uganda; and 3Case Western Reserve Univ, Cleveland, OH, US
Background: Current World Health Organization (WHO)
guidelines recommend initiation of ART for patients co-infected with tuberculosis
(TB) and HIV at CD4 counts ≤350 cells/mm3. Triple nucleoside
therapy is an alternative ART regimen for co-infected patients because it can
be used at higher CD4 cell counts where nevirapine (NVP)
toxicity risks may be increased, it is compatible with rifampin,
and it is safe in pregnancy. Among
TB/HIV co-infected patients in Africa who
received zidovudine (ZDV) + lamivudine
(3TC) + abacavir (ABC), we evaluated early virologic and CD4 response, and development of immune
reconstitution syndrome and ABC hypersensitivity reaction.
Methods: ART-naïve adults with smear-positive pulmonary
TB and CD4 count ≥350 cells/mm3 were initiated on fixed-dose
ZDV+3TC+ABC 2 to 4 weeks after starting anti-TB therapy in a prospective
clinical trial. Subjects received directly observed ART and anti-TB therapy for
6 months. CD4 count and HIV RNA were assessed at baseline and at 12, and 24
weeks. Subjects were evaluated for immune reconstitution syndrome and ABC hypersensitivity
reaction monthly
and at patient-initiated clinic visits. Laboratory toxicity monitoring was
conducted at 2, 4, 8, 12, and 24 weeks.
Results: Among 23 patients who completed 24 weeks of
ZDV+3TC+ABC, median baseline CD4 count was 523 cells/mm3 (range 364
to 852), and baseline HIV RNA was 4.7 log copies/mL
(range 3.23 to 5.88). At 24 weeks, 20 (87%) patients achieved virologic suppression to <400 copies/mL.
Of 16 patients with HIV RNA <400 copies/mL tested
with a more sensitive assay, 14 (88%) achieved a viral load <50 copies/mL at 24 weeks. Among all 23 patients, the median CD4
increase at 24 weeks was 87 cells/mm3 (range –303 to
841 cells/mm3). Despite virologic
suppression at 24 weeks, 7 of 20 patients (35%) had CD4 increases of
<50 cells/mm3, 5 of whom had CD4 decline from baseline. No cases
of TB-associated immune reconstitution syndrome were observed. Dose reduction
of ZDV was required in 3 patients for grade 3 or 4 neutropenia.
Of 23 patients, 1 became pregnant during ART and continued to tolerate ZDV+3TC+ABC.
Of the 3 subjects evaluated for suspected ABC hypersensitivity reaction, none
met the case definition for definitive hypersensitivity reaction, and none
required ABC discontinuation.
Conclusions: ZDV+3TC+ABC was well tolerated and
exhibited potent anti-viral response at 24 weeks among patients with TB/HIV
co-infection in Uganda.
Patients exhibited heterogeneous CD4 response despite virologic
success, suggesting that TB may alter the ability to predict virologic failure by immunologic response to ART in this
setting.
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