Publications by authors named "Khalilullah Arefi"

2 Publications

  • Page 1 of 1

Mechanisms of anti-retroviral drug resistance: implications for novel drug discovery and development.

Infect Disord Drug Targets 2013 Oct;13(5):330-6

Iranian Research Center for HIV/AIDS (IRCHA), Imam Khomeini Hospital, Keshavarz Blvd, Tehran, Iran.

Anti-retroviral drug resistance evolves as an inevitable consequence of expanded combination Anti-retroviral Therapy (cART). According to each drug class, resistance mutations may occur due to the infidel nature of HIV reverse transcriptase (RT) and inadequate drug pressures. Correspondingly, resistance to Nucleoside Reverse Transcriptase Inhibitors (NRTIs) occurs due to incorporation impairment of the agent or its removal from the elongating viral DNA chain. With regard to Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs), resistance mutations may alter residues of the RT hydrophobic pocket and demonstrate high level of cross resistance. However, resistance to Protease Inhibitors requires complex accumulation of primary and secondary mutations that substitute amino acids in proximity to the viral protease active site. Resistance to novel entry inhibitors may also evolve as a result of mutations that affect the interactions between viral glycoprotein and CD4 or the chemokine receptors. According to the current studies, future drug initiative programs should consider agents that possess higher genetic barrier toward resistance for ascertaining adequate drug efficacy among patients who have failed first-line regimens.
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October 2013

Risk factors for postoperative recurrence of Crohn's disease.

Middle East J Dig Dis 2012 Oct;4(4):199-205

Digestive Disease Research Center, Shariati Hospital, Tehran University of Medical sciences ,Tehran Iran.

Background: Postoperative relapse is a common feature of Crohn's disease (CD) in Western countries but its frequency and risk factors have not been studied in the Middle East where there is a rapid upsurge in the incidence of CD. This study aims to research the frequency and risk factors of its recurrence after surgery among 566 Iranian patients with CD in Tehran, Iran.

Methods: All 566 patients diagnosed with Crohn's disease that enrolled in Digestive Diseases Research Center (DDRC) Inflammatory Bowel Disease (IBD) from April 1991 until November 2011 were included in our study. We reviewed clinical data that included time of surgery, possible risk factors and follow up after surgery. Multivariate regression analysis was performed to seek possible risk factors for early postoperative recurrence.

Results: The mean age of patients was 30.85 (range: 12-88) years at the onset of enrollment. During a mean follow up of 55 months, 139 (24.5%) out of 566 Crohn's disease patients underwent at least one surgery while 32 (23%) required additional surgery during the period after their first surgical intervention. Cigarette smoking was a risk factor for both initial (p=0.001) and additional surgery (p<0.0001). The penetrating behavior of Crohn's disease, in addition to its effect on surgery (p<0.001), showed a significant influence on disease recurrence (p<0.0007) along with perianal involvement which was significantly associated with relapse (p=0.001). Although disease duration of more than ten years was a significant risk factor for surgery (p=0.043) its effect on recurrence was insignificant (p=0.059).

Conclusion: The rate of initial and additional surgery is much lower in this region of the world, which is partially due to the relatively new occurrence of Crohn's disease in the Middle East. Cigarette smoking, disease duration over ten years, penetrating behavior of CD, and perianal disease were the main risk factors for surgery.
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October 2012