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

Abstract

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. MethodsA retrospective cohort study was conducted in all ART-naïve patients who were receiving rifampicin between January 2002 and December 2005. ResultsOf 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/mL 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 o50 copies/mL (P 5 0.140, odds ratio 5 0.590, 95% confidence interval 5 0.302-1.153). At 24 and 48 weeks, respective median CD4 counts were 174 and 254 cells/mL in the EFV group and 156 and 218 cells/mL in the NVP group (P40.05). By binary logistic regression, treatment group was not associated with HIV-1 RNA o50 copies/mL (P40.05). No patient in the EFV group and eight (7.2%) patients in the NVP group discontinued ART because of adverse reactions (P 5 0.084). ConclusionsFor 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.Keywords: efavirenz, HIV, nevirapine, standard dose, tuberculosis Received: 23 November 2007, accepted 1 February 2008 Introduction Tuberculosis (TB) and HIV-1 are the two leading causes of infectious disease-associated mortality worldwide. The accessibility of effective combined antiretroviral therapy (ART) has been associated with dramatic declines in the incidence of new AIDS cases and various opportunistic infections (OIs) among HIV-1-infected patients in many countries [1][2][3][4]. ART based on non-nucleoside reverse transcriptase inhibitors (NNRTIs) is a widely used regimen, particularly in resource-limited countries [5,6]. In most patients, CD4 cell counts rise with immune recovery after ART. Besides the appropriate timing of ART initiation, pill burdens, patients' adherence and overlapping toxicities, drug-drug interactions are also a major concern for treatment in HIV-1-infected patients with active TB [7]. To date, rifamycins are still the key drug class needed in the treatment of TB. Rifabutin is a weak cytochrome P450 enzyme inducer. Unfortunately, this drug is not available in many resource-limited countries, including Thailand. Therefore, rifampicin, a potent cytochrome P450 enzyme inducer, is still a key drug used for treatment of TB in these countries [8]. Moreover, current evidence shows clearly that relapse of TB in HIV-1-infected patients is minimized by a regimen containing rifampicin throughout the course of treatment [9]. DOI: 10.1111/j.1468-1293.2008.00563.x HIV Medicine (2008, 9, 294-299 r 2008 British HIV Association 294The drug-drug interactions of rifampicin and either NNRTIs or protease inhibitors (PIs) cause decre...

CYP2B6 G516T Polymorphism but Not Rifampin Coadministration Influences Steady-State Pharmacokinetics of Efavirenz in Human Immunodeficiency Virus-Infected Patients in South India

“…This is in agreement with that suggested by others, who observed excellent clinical outcomes when giving EFV at 600 mg/day to patients receiving RMP (11,22,27,28). A study conducted with HIV-TB patients receiving EFV at 600 mg/day and RMP reported virological success in about 80% of the patients studied at 48 weeks of treatment (24). In a comparative study of two groups of HIV-infected patients receiving EFV at 600 and 800 mg/day, Manosuthi et al did not observe any difference in plasma EFV levels and time to virological success (23).…”

Outcomes of Nevirapine- and Efavirenz-Based Antiretroviral Therapy When Coadministered With Rifampicin-Based Antitubercular Therapy

“…A recent Malawian study 30 found that 59% of patients coinfected with HIV and tuberculosis had subtherapeutic nevirapine concentrations during the lead-in dosing phase. A Thai study that compared patients initiating efavirenz-based or nevirapinebased ART with concurrent tuberculosis reported an OR between these groups for achieving a viral load lower than 50 copies/mL at 48 weeks of 0.590 (95% CI, 0.302-1.153) 22 but was based on smaller numbers of patients.…”

“…9,[11][12][13][14][15][16] Nevirapine has a higher risk of hepatotoxicity than efavirenz, althoughonlyasmallproportionofpatients develop clinical hepatitis. [17][18][19] There are 3 small published studies (32 patients fromSpain 20 and70patients 21 and111pa-tients from Thailand 22 ) that suggest that nevirapine can be safely and effectively coadministeredwithrifampicin.However, thefindingsfromtheThaistudiesmaynot be generalizable to other populations due to ethnic differences in drug effects and the low body weight of the patients, and the Spanish study was retrospective without a comparison group. Thus a need for more studies exists, particularly from Africa where approximately 85% of HIV-associated cases of tuberculosis occur.…”

HIV and tuberculosis in India

“…Regimens recommended for use in India for patients with concomitant TB are a combination of 2 NRTI's with Efavirenz or less commonly Nevirapine. The NRTI combinations used commonly are Zidovudine with Lamivudine, Stavudine with Lamivudine, Tenofovir with Lamivudine, and rarely Abacavir with Lamivudine or Didanosine with Lamivudine (only the fi rst two combinations are available in the national program) (National AIDS Control Organization 2007) There is some preliminary data to suggest that nevirapine can be safely given with rifampicin, but results of ongoing clinical trials are awaited (Manosuthi et al 2006(Manosuthi et al , 2008Cohen et al 2008). Among the PI's, nelfi navir, saquinavir, lopinavir and ritonavir can be used but additive hepatoxicity may occur with anti-TB drugs requiring close monitoring of liver function.…”