Objective To compare the safety/tolerability of abacavir and nevirapine in HIV-infected

Objective To compare the safety/tolerability of abacavir and nevirapine in HIV-infected adults starting antiretroviral (ARV) therapy in Uganda. cent completed 24 weeks: 4% died and 1% were lost to follow-up. Thirty-seven SAEs occurred on blinded drug in 36 participants. Twenty events [6 (2.0%) abacavir 14 (4.7%) nevirapine participants] were considered serious adverse reactions definitely/probably/uncertain whether related to blinded abacavir/nevirapine [HR = 0.42 (95% CI 0.16-1.09) = 0.06]. Only 2.0% of abacavir participants [six patients (0.7-4.3%)] experienced a suspected hypersensitivity reaction (HSR). In total 14 (4.7%) abacavir and 30 (10.0%) nevirapine participants discontinued blinded abacavir/nevirapine (= 0.02): because of toxicity (6A 15 = 0.07 all rash/possible HSR and/or hepatotoxicity) anti-tuberculosis therapy (6A 13 or for other reasons (2A 2 BMS-806 Conclusions There was a trend towards a lower rate of serious adverse reactions in Ugandan adults with low CD4 starting ARV regimens with abacavir than with nevirapine. This suggests that abacavir could be used more widely in resource-limited settings without major safety concerns. 2003 Montaner 2003). They are severe life-threatening or fatal in 2-5% subjects (van Leeuwen 2003) and cause discontinuation in around 7% (Knobel 2004; van Leth 2004). First-line therapy with 2NRTI/NNRTI is limited by interactions between NNRTIs and anti-tuberculosis treatment; hepatotoxicity of nevirapine in those with higher CD4 counts [particularly women (van Leth 2005) for whom efavirenz is usually contraindicated if they wish to become pregnant] or those co-infected with BMS-806 hepatitis C. Triple NRTI regimens have potential advantages over standard NNRTI-based first-line regimens in Africa BMS-806 as they avoid drug interactions with TB therapy can be taken by women who may become pregnant and those with higher CD4 counts consist of fewer pills and spare two classes for second-line after immunological/clinical failure where drug resistance is likely. Whilst it is generally acknowledged that triple NRTI regimens have poorer virological efficacy than NNRTI or protease inhibitor (PI)-based therapy (Gulick 2004; Bartlett 2006) a ‘simplification strategy’ for managing NNRTI toxicity and drug-drug interactions by substituting with a third NRTI either abacavir or tenofovir is also evolving (Gilks 2006). Abacavir is also an important potential backbone NRTI combined with NNRTIs (WHO 2006). However 3 of patients receiving abacavir in clinical studies in industrialized countries develop a suspected HSR (Brothers 2005) characterized by fever rash gastrointestinal and/or respiratory symptoms and lethargy or malaise which usually appear within 6 weeks. Symptoms worsen with continued therapy but usually resolve on discontinuation. Restarting abacavir results in a prompt return of symptoms which may be more severe you need to include life-threatening hypotension and loss of life. Regular practice in industrialized countries is certainly to avoid abacavir for symptoms in keeping with hypersensitivity rather than restart the medication. Although genetic variants in HLA-B have already been connected with abacavir HSRs in a few populations (Hughes 2004) such exams are improbable to be accessible throughout Africa to steer its use. Hence whilst prices of abacavir HSR will tend to be low in Africa than in BMS-806 Rabbit Polyclonal to APOL4. industrialized countries due to competition and lower pre-ART Compact disc4 (Brothers 2006) high prices of feasible reactions that can’t be verified or could be baffled with malaria or various other infections or immune system reconstitution disease could render abacavir complicated to make use of in Africa or significantly reduce its make use BMS-806 of. Nevirapine OR Abacavir (NORA) was as a result designed to measure the protection of abacavir weighed against nevirapine in previously neglected African people with advanced HIV disease initiating ARVs within a placing where all sufferers had been under close scientific supervision inside the DART trial. Strategies Trial style Nevirapine OR Abacavir was a 24-week randomized double-blind trial executed in two centres in Uganda (the Joint Clinical Analysis Centre Kampala as well as the MRC/UVRI Uganda Analysis Unit on Helps Entebbe Uganda) being a nested substudy within DART (Reid 2004). NORA individuals were allocated within a 1:1.