Standard-dose efavirenz vs. Standard-dose nevirapine in antiretroviral regimens among HIV-1 and tuberculosis co-infected patients who received rifampicin

Bamrasnaradura Infectious Diseases Institute, Ministry of Public Health, Nonthaburi, Thailand.
HIV Medicine (Impact Factor: 3.99). 05/2008; 9(5):294-9. DOI: 10.1111/j.1468-1293.2008.00563.x
Source: PubMed


There is limited comparative data between efavirenz (EFV) 600 mg/day and nevirapine (NVP) 400 mg/day-based antiretroviral therapy (ART) among HIV-1 patients with tuberculosis (TB) and receiving rifampicin.
A retrospective cohort study was conducted in all ART-naïve patients who were receiving rifampicin between January 2002 and December 2005.
Of 188 patients, 77 and 111 patients were initiated on EFV-based ART (EFV group) and NVP-based ART (NVP group), respectively. Overall, median [interquartile range (IQR)] CD4 count was 36 (15-77) cells/microL and median (IQR) viral load was 5.6 (5.2-5.9) HIV-1 RNA log copies/mL. At 48 weeks, 77.9% (60/77) in the EFV group and 67.6% (75/111) in the NVP group achieved HIV-1 RNA <50 copies/mL (P=0.140, odds ratio=0.590, 95% confidence interval=0.302-1.153). At 24 and 48 weeks, respective median CD4 counts were 174 and 254 cells/muL in the EFV group and 156 and 218 cells/microL in the NVP group (P>0.05). By binary logistic regression, treatment group was not associated with HIV-1 RNA <50 copies/mL (P>0.05). No patient in the EFV group and eight (7.2%) patients in the NVP group discontinued ART because of adverse reactions (P=0.084).
For HIV-TB co-infected patients who receive rifampicin, efficacy of 600 mg EFV-based and 400 mg NVP-based ART may be similar, although adverse events tend to be higher in NVP-based ART.

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Available from: Somnuek Sungkanuparph, Dec 18, 2014
    • "Thus, the clinical significance of NVP-RMP pharmacokinetic interaction resulting in reduced NVP concentrations during concomitant RMP treatment, and the cut-off values currently accepted, remain unclear. Several studies have reported on the lower efficacy of NVP-containing regimen compared to the EFV-containing regimen among HIV-infected TB patients62021. However, the role of sub-therapeutic plasma NVP during RMP co-administration in making the NVP regimen less effective remains a matter of conjecture. "
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    ABSTRACT: Background & objectives: Among patients with HIV-associated tuberculosis (TB), reduced plasma non-nucleoside reverse transcriptase inhibitors (NNRTI) concentrations during rifampicin (RMP) co-administration could lead to HIV treatment failure. This study was undertaken to examine the association between plasma nevirapine (NVP) and efavirenz (EFV) concentrations and virological outcomes in patients infected with HIV-1 and TB. Methods: This was a nested study undertaken in a clinical trial of patients with HIV-1 and TB, randomized to two different once-daily antiretroviral treatment (ART) regimens along with anti-TB treatment (ATT). Trough concentrations of plasma NVP and EFV were estimated at months 1 (during ATT and ART) and 6 months (ART only) by HPLC. Plasma HIV-1 RNA level >400 copies/ml or death within 6 months of ART were considered as unfavourable outcomes. Genotyping of CYP2B6 516G>T polymorphism was performed. Results: Twenty nine per cent of patients in NVP arm had an unfavourable outcome at 6 months compared to 9 per cent in EFV arm (P<0.08). The mean NVP and EFV levels estimated at 1 and 6 months did not significantly differ between favourable and unfavourable responders. Logistic regression analysis showed CYP2B6 516G>T polymorphism significantly associated with virologic outcome in patients receiving EFV–based regimen. Interpretation & conclusions: Trough plasma concentrations of NVP and EFV did not show any association with response to ART in patients on ATT and once-daily ART. CYP2B6 516G>T polymorphism was associated with virologic outcome among patients on EFV.
    No preview · Article · Dec 2013 · The Indian Journal of Medical Research
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    • "This open-label, randomised clinical trial demonstrated that, in HIV infected individuals with tuberculosis co-infection receiving rifampicin based ATT, there was no significant difference between twice daily nevirapine based ART and efavirenz based ART with respect to mortality, or immunological, virological and clinical response or side effect profile. There are multiple observational and retrospective studies comparing the clinical efficacy of nevirapine and efavirenz based ART in HIV/TB co-infected patients; however, results of this study were found contradictory to those [9,14-16]. The South African study [14] showed some difference between the two treatments, while the studies from Botswana [17] and Thailand [9,15] failed to demonstrate the difference. "
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    ABSTRACT: Administration of rifampicin along with nevirapine reduces the plasma concentration of nevirapine in human immunodeficiency virus positive individuals with concomitant tuberculosis (HIV-TB patients). Nevirapine is a much cheaper drug than its alternative efavirenz, and might be beneficial in resource constrained settings. A randomised open label trial was conducted at All India Institute of Medical Sciences, New Delhi, India. During the regimen of an antiretroviral therapy (ART), naive HIV-TB patients were randomly assigned to receive either nevirapine or efavirenz based ART with concomitant rifampicin based anti-tubercular therapy (ATT). Participants were followed for 24 months after starting ART. The end points were virological, immunological and clinical responses, and progression of HIV disease marked by failure of ART. Of the 135 HIV-TB patients, who were receiving rifampicin based ATT, 68 were selected randomly to receive efavirenz based ART and 67 to receive nevirapine based ART. The virological failure rates in the overall population, and the nevirapine and efavirenz groups were 14 . 1% (19/135); 14.9% (10/67) and 13.2% (9/68), respectively (p = 0.94). No significant difference was found between the groups in the rate of clinical, immunological or virological failures. The overall mortality was 17% with no significant difference between the two groups. Except for the lead in period on day 14, the mean nevirapine concentration remained above 3 mg/L. No association was found between plasma levels of nevirapine and incidence of unfavourable outcomes in this group. Outcome of ART in HIV-TB patients on rifampicin based ATT showed no significant difference, irrespective of whether efavirenz or nevirapine was used. Therefore, nevirapine based ART could be an alternative in the resource limited settings in patients with HIV and tuberculosis co-infection.Trial Registration: Trial Registration: Clinical Trials NCT01805258.
    Full-text · Article · Oct 2013 · BMC Infectious Diseases
    • "While once-daily nevirapine was shown to be inferior to efavirenz, with higher virological failure and mortality rates, this was probably due to the sub-therapeutic levels achieved during the lead-in period, in a situation of induced liver enzymes leading to faster metabolism of nevirapine86. Manosuthi et al94 demonstrated comparable efficacy with ATT and concomitantly administered twice-daily NVP and efavirenz. In their study comparing plasma levels of NVP and treatment outcomes between patients treated with rifampicin based and non-rifampicin based regimens, the level of NVP was low in the former compared to non-rifampicin containing regimens but the virological and immunological outcomes were similar95. "
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    ABSTRACT: Human immunodeficiency virus (HIV) associated tuberculosis (TB) remains a major global public health challenge, with an estimated 1.4 million patients worldwide. Co-infection with HIV leads to challenges in both the diagnosis and treatment of tuberculosis. Further, there has been an increase in rates of drug resistant tuberculosis, including multi-drug (MDR-TB) and extensively drug resistant TB (XDRTB), which are difficult to treat and contribute to increased mortality. Because of the poor performance of sputum smear microscopy in HIV-infected patients, newer diagnostic tests are urgently required that are not only sensitive and specific but easy to use in remote and resource-constrained settings. The treatment of co-infected patients requires antituberculosis and antiretroviral drugs to be administered concomitantly; challenges include pill burden and patient compliance, drug interactions, overlapping toxic effects, and immune reconstitution inflammatory syndrome. Also important questions about the duration and schedule of anti-TB drug regimens and timing of antiretroviral therapy remain unanswered. From a programmatic point of view, screening of all HIV-infected persons for TB and vice-versa requires good co-ordination and communication between the TB and AIDS control programmes. Linkage of co-infected patients to antiretroviral treatment centres is critical if early mortality is to be prevented. We present here an overview of existing diagnostic strategies, new tests in the pipeline and recommendations for treatment of patients with HIV-TB dual infection.
    No preview · Article · Dec 2011 · The Indian Journal of Medical Research
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