Safety and Antiretroviral Effectiveness of Concomitant Use of Rifampicin and Efavirenz for Antiretroviral-Naive Patients in India Who Are Coinfected With Tuberculosis and HIV-1

Chief Division of Infectious Disease, Sterling Hospital, Ahmedabad, India.
JAIDS Journal of Acquired Immune Deficiency Syndromes (Impact Factor: 4.56). 09/2004; 37(1):1166-9. DOI: 10.1097/01.qai.0000135956.96166.f0
Source: PubMed


To study the safety and antiretroviral effectiveness of concomitant use of rifampicin and efavirenz for antiretroviral-naïve patients in India who are coinfected with tuberculosis (TB) and HIV-1.
The study was an observational longitudinal cohort investigation. HIV-1-infected patients with CD4 cell counts of < or = 200/microL who attended the Infectious Disease Clinic of Sterling Hospital (Ahmedabad, India) from June 2001 to December 2002 were recruited for the study. Patients were divided in 2 groups: group A, patients with active TB (n = 126); and group B, patients without TB (n = 129). Group A patients were given efavirenz with 2 nucleoside reverse transcriptase inhibitors along with rifampicin-containing anti-TB treatment. Group B patients were treated for presenting opportunistic infections and started therapy with efavirenz plus 2 nucleoside reverse transcriptase inhibitors. The nucleoside reverse transcriptase inhibitors were either zidovudine and lamivudine (n = 30) or stavudine and lamivudine (n = 225). Patients self-funded their investigations and medications (antiretroviral, anti-TB, and other opportunistic infection-related agents). Indian generic medications were used.
Efavirenz-based highly active antiretroviral therapy with rifampicin for HIV/TB-coinfected patients resulted in an immunologic response that was comparable with that of the group not receiving rifampicin. Median CD4 cell counts at baseline, 3 months, 6 months, and 9 months in group A were 84/microL (range, 5-200/microL), 225/microL (range, 26-528/microL), 251/microL (range, 65-775/microL), and 275/microL (range, 61-611/microL), respectively, and in group B, these values were 118/microL (range, 2-200/microL), 244/microL (range, 38-881/microL), 294/microL (range, 23-1322/microL), and 295/microL (range, 26-991/microL), respectively. The overall increase in CD4 cell count was greater in group A than in group B at 9 months (190 vs. 176/microL, respectively). Patients in both groups tolerated the therapy well; the adverse effects profile was comparable except that group A patients had a higher incidence of hepatitis than group B patients (13.49% vs. 0, respectively; P < 0.0001).
Clinical and immunologic benefits are comparable for patients receiving efavirenz-based antiretroviral therapy with or without rifampicin.

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    • "Overall, virological suppression was achieved in 97% of patients at week 50. In various settings, excellent virological efficacy was also observed with 600 mg efavirenz co-administered daily with rifampicin, which again supports the lack of potent drug-drug interaction between rifampicin-based standard tuberculosis treatment [32], [33], [34], [35], [36], [37], [38]. Our observation that women were at reduced risk of having lower efavirenz concentrations is in keeping with Burger et al [39]. "
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    ABSTRACT: To assess efavirenz plasma concentrations and their association with treatment efficacy and tolerance of efavirenz 600 mg daily in HIV-tuberculosis co-infected patients. HIV-infected adults with CD4+ T cell count ≤200/mm3 received standard 6-month tuberculosis treatment and antiretroviral therapy including a daily-dose of 600 mg of efavirenz, irrespective of their body weight. Mid-dose blood samples were drawn both on tuberculosis treatment (week +2 and week +6 after antiretroviral therapy initiation, and week 22 of follow-up) and off tuberculosis treatment (week 50 of follow-up). Considered therapeutic range was 1,000 to 4,000 ng/mL. Multivariate analysis was performed to evaluate the association between efavirenz concentration below 1,000 ng/mL and virological failure. Linear regression was used to test the association between efavirenz exposure and CD4+ T cell gain. Severe side effects potentially related to efavirenz were described and their association with efavirenz exposure was tested by multivariate analysis. Efavirenz plasma concentrations were available in 540 patients. Median [interquartile range] efavirenz concentrations were 2,674 ng/mL [1,690-4,533], 2,667 ng/mL [1,753-4,494] and 2,799 ng/mL [1,804-4,744] at week +2, week +6, week 22, respectively, and 2,766 ng/mL [1,941-3,976] at week 50. Efavirenz concentrations were lower at week 50 (off rifampicin) compared to week 22 (on rifampicin) (p<0.001). Late attendance to study visit and low hemoglobinemia were the only factors associated with an increased risk of efavirenz concentration below 1,000 ng/mL. Efavirenz concentration below 1,000 ng/mL was not associated with treatment failure. Efavirenz concentration above 4,000 ng/mL was associated with higher risk of central nervous system side effects (p<0.001) and of hepatotoxicity (p<0.001). Body weight and tuberculosis treatment were not associated with low efavirenz concentrations or treatment failure, supporting the 600 mg daily-dose of efavirenz in HIV-tuberculosis co-infected patients. High efavirenz concentrations were related to a higher risk of central nervous system side effects and hepatotoxicity. NCT01300481.
    PLoS ONE 03/2014; 9(3):e90350. DOI:10.1371/journal.pone.0090350 · 3.23 Impact Factor
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    • "We and others have previously reported the association of ART-associated TB with lower CD4 recovery (Lawn et al. 2005; Hermans et al. 2010). TB diagnosed before ART initiation was associated with impaired immune reconstitution in South Africa (Bassett et al. 2012), but not in Asia (Patel et al. 2004; Breen et al. 2006; Zhou et al. 2010). When analysing patients with prevalent and ART-associated TB together, a "
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    Tropical Medicine & International Health 11/2012; 17(12). DOI:10.1111/tmi.12001 · 2.33 Impact Factor
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    • "Gradual increase in CD4 cell counts and weight gain from baseline to 12 weeks indicates that clinical and immunologic benefits were comparable among patients receiving efavirenz based HAART with or without rifampicin [49]. Unlike other studies that show an older age group, alcohol consumption and use of Fluconazole tablets as a risk factor for the development of DILI, in this study no such association was observed [50], [51]. "
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    PLoS ONE 07/2012; 7(7):e40180. DOI:10.1371/journal.pone.0040180 · 3.23 Impact Factor
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