Efficacy and Safety of Concomitant Use of Nevirapine and Rifampicin With HIV-TB ("NVP")
|First Received Date ICMJE||March 1, 2013|
|Last Updated Date||March 25, 2013|
|Start Date ICMJE||June 2007|
|Primary Completion Date||December 2012 (final data collection date for primary outcome measure)|
|Current Primary Outcome Measures ICMJE
||Virological suppression at 48 weeks. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
All patients underwent a detailed physical examination. Their body weight and height will be measured and their body mass index (BMI) was calculated. Haemoglobin, complete blood counts, erythrocyte sedimentation rate, fasting blood glucose, renal function tests, liver function tests, serum albumin, serum uric acid and routine urinalysis will be done for all patients.
Patients will be assessed at day 14 after the start of ART, then at day 28, 42 and every 4 weeks thereafter through 48 weeks. A complete haemogram, liver and kidney function tests will be obtained at all these visits. CD4 counts will be measured at 8 weeks, 24 weeks and 48 weeks after the start of ART. HIV plasma viral load will be measured at baseline, at 24 weeks and at the end of 48 weeks only in the cases. Trough nevirapine concentrations were assessed at day 14, day 28, day 42 and day 180, 12 hours after the evening dose of nevirapine.
|Original Primary Outcome Measures ICMJE||Same as current|
|Change History||Complete list of historical versions of study NCT01805258 on ClinicalTrials.gov Archive Site|
|Current Secondary Outcome Measures ICMJE
||Number of Participants with Adverse Events especially Hepatotoxicity as a measure of Safety. [ Time Frame: 5 years ] [ Designated as safety issue: Yes ]
Drug associated toxicities specially hepatitis were assessed in the subjects by performing liver function tests every 4 weeks during follow-up.
|Original Secondary Outcome Measures ICMJE||Same as current|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||Efficacy and Safety of Concomitant Use of Nevirapine and Rifampicin With HIV-TB|
|Official Title ICMJE||Efficacy and Safety of Concomitant Use of Nevirapine and Rifampicin in Antiretroviral Naive Patients Co-infected With HIV and Tuberculosis in India.|
The purpose of the study is to evaluate the efficacy and safety of Nevarapine and Rifampicin vs Efavirenz and Rifampicin in antiretroviral naive patients co-infected with HIV and TB and to investigate whether Rifampicin co-administration in clinical practice leads to a clinically relevant decrease of Nevirapine plasma concentrations in Indian patients co-infected with HIV and Tuberculosis and to characterize drug-associated toxicities (especially hepatic).
Drug interactions complicate concurrent treatment of HIV and Mycobacterium tuberculosis co-infection. Drug therapy for HIV and tuberculosis each consists of combined regimens with three or four drugs. Tuberculosis (TB) is the most significant co-infection of HIV patients in resource-limited settings. Application of antiretroviral (ARV) therapy in co-infected patients will require care providers who are appropriately trained in the use of ARV and TB drugs. Over 40 million people worldwide are currently living with HIV/AIDS, of which 90% live in the developing world, co-infected with TB. There are an estimated 12 million persons with TB/HIV co-infection. According to UNAIDS estimates, 5 million people have acquired HIV/AIDS in 2003. India is estimated to have 5.1 million HIV individuals by the end of 2002. TB is among the most frequent HIV-related opportunistic infections in developing countries, and is associated with substantial morbidity and mortality. In India, there were estimated 1.85 million HIV individuals co-infected with HIV and TB. In patients infected with both HIV and TB, the lifetime risk of developing the active tuberculosis has been estimated to be at least 60%, compared to approximately 10% in persons infected with TB who do not have HIV infection. It is well established that HIV increases the risk for TB (acquisition, reactivation and reinfection), alters its clinical presentation, and reduces survival compared to patients with TB and no HIV infection. Multiple epidemiologic studies have shown that co-infection with TB results in reduced survival, increased risk for opportunistic infections and elevations in HIV replication. Increased HIV replication is attributed to activation of latently infected cells and promotion of infection in uninfected lymphocytes and macrophages. HIV genetic diversity is also increased in the presence of active TB infection. Mortality rates in HIV-infected patients with TB are extraordinarily high in resource- limited settings. Therefore, it is essential to treat patients with HIV and TB co-infection for both infections. In India large numbers of HIV positive patients suffering with HIV/Tuberculosis co-infection. However, limited data are available for concomitant use of Nevirapine and Rifampicin in patients co-infected with HIV and Tuberculosis in India. No concrete data available about whether or not Nevirapine and Rifampicin can be safely co-administered without the plasma concentration of Nevirapine falling below therapeutic levels.
Rifamycins are frequently used for the treatment of tuberculosis. Rifamycins can interact with several antiretrovirals. In decreasing order of potency, rifampin, rifapentine and rifabutin have an inducing effect on drug metabolism mediated through cytochrome P450 isoenzyme 3A4 (CYP3A4). Non-nucleoside reverse transcriptase inhibitors and protease inhibitors are metabolized through CYP3A4 and thus the plasma concentrations of these antiretrovirals may decrease in the presence of rifamycins. Additionally, the non-nucleoside reverse transcriptase inhibitors are metabolized by CYP2B6. Drug-drug interactions may lead to suboptimal drug exposure, loss of viral suppression and selection of resistant HIV strains. Interactions between nucleoside analogue reverse transcriptase inhibitors and rifamycins occur at the level of glucuronidation and amination, as was described between rifampin or rifabutin and zidovudine, but is not considered to be clinically significant.
Coinfection of HIV-1 and tuberculosis mainly concerns developing countries like India where both infections are epidemic. Access to antiretrovirals may be difficult in developing countries because of limited availability or high cost. To improve pricing and accessibility, generic antiretroviral agents are manufactured in countries such as Brazil, India, Thailand and South Africa. Fixed-dose combinations of these generic agents are widely used as well. The most often-used generic fixed-dose combination is a twice-daily regimen with stavudine, lamivudine and nevirapine. Fixed-dose combinations are attractive regimens for patient care. Adherence to therapy may be improved because of low pill burden and the reduced possibility of incorrect dosing. Furthermore, the fixed-dose combinations simplify drug logistics. Compact drug quantities facilitate storage and distribution to hospitals, pharmacies and patients. Important for resource constraint settings is that fixed-dose combinations make improvements in public health care management possible. With respect to treatment of HIV/tuberculosis-coinfected patients, a clinically significant drug-drug interaction may be expected when nevirapine and rifamycin are co-administered. Treatment with rifabutin is preferred because of a more favourable interaction profile, but in most developing countries rifabutin is not available or too expensive. Tuberculosis treatment with a regimen that includes rifampicin is usually the only option. Reports in the literature have shown decreases in nevirapine plasma concentrations ranging from 31% to 58%. Rifampicin plasma concentrations are not influenced by nevirapine. Low nevirapine plasma concentrations may negatively affect virological outcome of antiretroviral therapy. Previous studies have documented higher plasma concentrations of nevirapine in Thai patients compared with patients in other countries, suggesting that even though the concomitant use of rifampicin lowers the nevirapine levels considerable, still most patients would still retain nevirapine plasma concentrations above a concentration of 3.1mg/l. The present study will be performed to investigate whether rifampicin co-administration in clinical practice leads to a clinically relevant decrease of nevirapine plasma concentrations in North Indian patients co-infected with HIV/Tuberculosis.
|Study Type ICMJE||Interventional|
|Study Phase||Phase 3|
|Study Design ICMJE||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||HIV/TB Co-infection|
|Study Arm (s)||
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Completed|
|Completion Date||February 2013|
|Primary Completion Date||December 2012 (final data collection date for primary outcome measure)|
|Eligibility Criteria ICMJE||
|Ages||18 Years to 60 Years|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||India|
|NCT Number ICMJE||NCT01805258|
|Other Study ID Numbers ICMJE||SKS/NACO-1/2006-07|
|Has Data Monitoring Committee||No|
|Responsible Party||S.K.SHARMA, All India Institute of Medical Sciences, New Delhi|
|Study Sponsor ICMJE||All India Institute of Medical Sciences, New Delhi|
|Collaborators ICMJE||National AIDS Control Organisation|
|Information Provided By||All India Institute of Medical Sciences, New Delhi|
|Verification Date||March 2013|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP