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PLoS One. 2015 May 12;10(5):e0122587. doi: 10.1371/journal.pone.0122587. eCollection 2015.

Efficacy and Safety of Antiretroviral Therapy Initiated One Week after Tuberculosis Therapy in Patients with CD4 Counts < 200 Cells/μL: TB-HAART Study, a Randomized Clinical Trial.

Author information

1
Department of Medicine, Division of Infectious Diseases, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden; Department of Internal Medicine, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
2
Department of Internal Medicine, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
3
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Huddinge C1: 68, Karolinska Institute, Stockholm, Sweden; Department of Pharmacology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
4
Department of Pharmacology, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
5
School of Public Health, Addis Ababa University, Addis Ababa, Ethiopia.
6
Department of Medicine, Division of Infectious Diseases, Karolinska Institute at Karolinska University Hospital Huddinge, Stockholm, Sweden.
7
Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital, Huddinge C1: 68, Karolinska Institute, Stockholm, Sweden.

Abstract

BACKGROUND:

Given the high death rate the first two months of tuberculosis (TB) therapy in HIV patients, it is critical defining the optimal time to initiate combination antiretroviral therapy (cART).

METHODS:

A randomized, open-label, clinical trial comparing efficacy and safety of efavirenz-based cART initiated one week, four weeks, and eight weeks after TB therapy in patients with baseline CD4 count < 200 cells/μL was conducted. The primary endpoint was all-cause mortality rate at 48 weeks. The secondary endpoints were hepatotoxicity-requiring interruption of TB therapy, TB-associated immune reconstitution inflammatory syndrome, new AIDS defining illnesses, CD4 counts, HIV RNA levels, and AFB smear conversion rates. All analyses were intention-to-treat.

RESULTS:

We studied 478 patients with median CD4 count of 73 cells/μL and 5.2 logs HIV RNA randomized to week one (n = 163), week four (n = 160), and week eight (n = 155). Sixty-four deaths (13.4%) occurred in 339.2 person-years. All-cause mortality rates at 48 weeks were 25 per 100 person-years in week one, 18 per 100 person-years in week four and 15 per 100 person-years in week eight (P = 0.2 by the log-rank test). All-cause mortality incidence rate ratios in subgroups with CD4 count below 50 cells/μL versus above were 2.8 in week one (95% CI 1.2-6.7), 3.1 in week four (95% CI 1.2-8.6) and 5.1 in week eight (95% CI 1.8-16). Serum albumin < 3 gms/dL (adjusted HR, aHR = 2.3) and CD4 < 50 cells/μL (aHR = 2.7) were independent predictors of mortality. Compared with similar subgroups from weeks four and eight, first-line TB treatment interruption was high in week one deaths (P = 0.03) and in the CD4 subgroup <50 cells/μL (P = 0.02).

CONCLUSIONS:

Antiretroviral therapy one week after TB therapy doesn't improve overall survival. Despite increased mortality with CD4 < 50 cells/μL, we recommend cART later than the first week of TB therapy to avoid serious hepatotoxicity and treatment interruption.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT 01315301.

PMID:
25966339
PMCID:
PMC4429073
DOI:
10.1371/journal.pone.0122587
[Indexed for MEDLINE]
Free PMC Article

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