RESUMO
BACKGROUND: Although general practitioners (GPs) play a central role in responding to human immunodeficiency virus (HIV) in Australia, the social history of their contribution in the early years has remained largely untold. METHODS: In-depth interviews were conducted with 21 GPs who provided HIV care between 1982 and 1996. De-identified transcripts were broadly coded in NVivo, then analysed for themes regarding GP experiences during the early years. RESULTS: Participants recalled a time of death, fear and prejudice, with large numbers of patients diagnosed with and dying from a highly stigmatised disease. An enduring emotional legacy resulted, with GPs developing survival strategies such as better managing relationships with patients, seeking mental health support and reducing working hours. DISCUSSION: These GPs represent the first generation of GPs in Australia caring for people with HIV. Understanding their experiences can inform and inspire the next generation, who inherit a much brighter future for HIV care.
Assuntos
Síndrome da Imunodeficiência Adquirida/história , Medicina Geral/história , Síndrome da Imunodeficiência Adquirida/diagnóstico , Austrália , Feminino , Clínicos Gerais/psicologia , História do Século XX , Humanos , Entrevistas como Assunto , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The protease inhibitor darunavir has been shown to be efficacious in highly treatment-experienced patients with HIV infection, but needs to be assessed in patients with a broader range of treatment experience. We did a randomised, controlled, phase III trial (TITAN) to compare 48-week efficacy and safety of darunavir-ritonavir with that of lopinavir-ritonavir in treatment-experienced, lopinavir-naive patients. METHODS: Patients received optimised background regimen plus non-blinded treatment with darunavir-ritonavir 600/100 mg twice daily or lopinavir-ritonavir 400/100 mg twice daily. The primary endpoint was non-inferiority (95% CI lower limit for the difference in treatment response -12% or greater) for HIV RNA of less than 400 copies per mL in plasma at week 48 (per-protocol analysis). TITAN (TMC114-C214) is registered with ClinicalTrials.gov, number NCT00110877. FINDINGS: Of 595 patients randomised and treated, 187 (31%) were protease inhibitor naive; 476 of 582 (82%) were susceptible to four or more protease inhibitors. At week 48, significantly more darunavir-ritonavir than lopinavir-ritonavir patients had HIV RNA of less than 400 copies per mL (77% [220 of 286] vs 68% [199 of 293]; estimated difference 9%, 95% CI 2-16). Fewer virological failures treated with darunavir-ritonavir than with lopinavir-ritonavir developed primary protease inhibitor mutations (21% [n=6] vs 36% [n=20]) and nucleoside analogue-associated mutations (14% [n=4] vs 27% [n=15]). Safety data were generally similar between the groups; grade 3 or 4 adverse events occurred in 80 (27%) darunavir-ritonavir and 89 (30%) lopinavir-ritonavir patients. INTERPRETATION: In lopinavir-naive, treatment-experienced patients, darunavir-ritonavir was non-inferior to lopinavir-ritonavir treatment in terms of our virological endpoint, and should therefore be considered as a treatment option for this population.
Assuntos
Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/efeitos dos fármacos , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Terapia Antirretroviral de Alta Atividade , Darunavir , Feminino , Inibidores da Protease de HIV/efeitos adversos , Humanos , Lopinavir , Masculino , Pessoa de Meia-Idade , Pirimidinonas/efeitos adversos , RNA Viral/sangue , Ritonavir/efeitos adversos , Sulfonamidas/efeitos adversosRESUMO
Ritonavir, a protease inhibitor (PI), is a potent inhibitor of cytochrome P450 3A4. This pharmacological effect, even at low doses (=200 mg/d), is used to "boost" levels of other PIs in the treatment of HIV infection and facilitate once or twice daily dosing with reduced pill burden. Six patients with preexisting HIV-lipodystrophy developed symptomatic Cushing's syndrome when treated with inhaled fluticasone at varying doses for asthma while concurrently treated with low-dose ritonavir-boosted PI antiretroviral therapy (ART) regimens for HIV infection. There was evidence of adrenal suppression in all patients on stimulation studies. After the withdrawal of inhaled fluticasone, four patients became symptomatic of hypocortisolism, and three required oral corticosteroid support for several months. Other complications included evidence of osteoporosis (n = 3), crush fractures (n = 1), and exacerbation of preexisting type 2 diabetes mellitus (n = 1). In part, the diagnosis of fluticasone-induced Cushing's syndrome was delayed because all patients had preexisting body composition changes of ART-associated lipodystrophy, masking the Cushing's features. Practitioners should be aware of the impact on the adrenal axis of coadministration of PI-based ART regimens with inhaled corticosteroids and the potential for exacerbating or even inducing other metabolic conditions, such as osteoporosis or diabetes.