The antiretroviral efficacy of highly active antiretroviral therapy and plasma nevirapine concentrations in HIV-TB co-infected Indian patients receiving rifampicin based antituberculosis treatment

Abstract

BackgroundRifampicin reduces the plasma concentrations of nevirapine in human immunodeficiency virus (HIV) and tuberculosis (TB) co-infected patients, who are administered these drugs concomitantly. We conducted a prospective interventional study to assess the efficacy of nevirapine-containing highly active antiretroviral treatment (HAART) when co-administered with rifampicin-containing antituberculosis treatment (ATT) and also measured plasma nevirapine concentrations in patients receiving such a nevirapine-containing HAART regimen.Methods63 cases included antiretroviral treatment naïve HIV-TB co-infected patients with CD4 counts less than 200 cells/mm3 started on rifampicin-containing ATT followed by nevirapine-containing HAART. In control group we included 51 HIV patients without tuberculosis and on nevirapine-containing HAART. They were assessed for clinical and immunological response at the end of 24 and 48 weeks. Plasma nevirapine concentrations were measured at days 14, 28, 42 and 180 of starting HAART.Results97 out of 114 (85.1%) patients were alive at the end of 48 weeks. The CD4 cell count showed a mean increase of 108 vs.113 cells/mm3 (p=0.83) at 24 weeks of HAART in cases and controls respectively. Overall, 58.73% patients in cases had viral loads of less than 400 copies/ml at the end of 48 weeks. The mean (± SD) Nevirapine concentrations of cases and control at 14, 28, 42 and 180 days were 2.19 ± 1.49 vs. 3.27 ± 4.95 (p = 0.10), 2.78 ± 1.60 vs. 3.67 ± 3.59 (p = 0.08), 3.06 ± 3.32 vs. 4.04 ± 2.55 (p = 0.10) respectively and 3.04 μg/ml (in cases).ConclusionsGood immunological and clinical response can be obtained in HIV-TB co-infected patients receiving rifampicin and nevirapine concomitantly despite somewhat lower nevirapine trough concentrations. This suggests that rifampicin-containing ATT may be co administered in resource limited setting with nevirapine-containing HAART regimen without substantial reduction in antiretroviral effectiveness. Larger sample sized studies and longer follow-up are required to identify populations of individuals where the reduction in nevirapine concentration may result in lower ART response or shorter response duration.

Tuberculosis and HIV Coinfection

“…The daily dosing of efavirenz and its coformulation with tenofovir and emtricitabine into a oncedaily pill (Atripla, Bristol-Myers Squibb, New York, NY) is also an important tool to enhance adherence given the already high pill count of anti-TB therapy. Rifampin causes a greater reduction of nevirapine levels than efavirenz levels, [98][99][100][101] but it is unclear if this results in more HIV virological failure, 99,[102][103][104] making nevirapine an acceptable alternative when efavirenz is unavailable (►Table 1).…”

Outcomes of highly active antiretroviral therapy and its predictors: a cohort study focusing on tuberculosis co-infection in South West Ethiopia

“…In this study, when the mean increases in CD4 cells count were compared the difference was not significant for both groups of PLWHs in contrary to what had been reported as starting ART, particularly early during TB treatment, could jeopardize adherence to treatment and hence worsening of the immune response [ 20 ]. Hung et al [ 10 ], Sharma and colleagues [ 21 ], Sinha et al [ 12 ] and Lipman et al [ 11 ] also showed similar findings. According to one study the additional increment in CD4 count in patients with co-infection following treatment suggest that CD4 suppression at the onset of TB may be the direct result of mycobacterium growth and inflammation as well as interaction between TB and HIV in addition to the effect of HIV alone [ 21 ].…”

“…However, there are limited literatures which compared outcomes of ART in adult people living with HIV who are TB co-infected with that of PLWH without TB co-infection. Amongst those few literatures available, majority of them are from developed countries [ 10 – 12 ] and published works on this issue in resource poor setting like Ethiopia is scarce [ 13 – 15 ].…”

Immunologic and Virologic Responses to Nevirapine Based Antiretroviral Therapy (ART) Among HIV-tuberculosis Co-infected Ugandan Children on Rifampicin Based Anti-tubercular Treatment

“…19 Both adult and paediatric studies done in Africa, Thailand and India have shown varying levels of the effect on NVP plasma levels as a result of the drug-drug interaction during concomitant use of a rifampicin containing anti-TB regimen and a NVP based ART regimen. [4][5][6]8,[20][21][22][23] An intensive pharmacokinetic study of standarddose NVP with and without rifampicin in South African adults found sub-therapeutic NVP levels in 6 of 16 patients during rifampicin dosing. 8 A pharmacokinetic sub analysis conducted on 20 of the children in this study as reported by Barlow Mosha et al also found that NVP trough concentration was significantly reduced in children who received rifampicin and NVP concurrently.…”