Abstract
The treatment of childhood and adolescent obesity is difficult and the outcome of behavioral interventions remains unsatisfactory. Several pharmacological approaches, used in conjunction with comprehensive behavioral interventions designed to improve diet and decrease inactivity have been developed and extensively studied, mainly in adults. Orlistat is a lipase inhibitor that reduces dietary fat absorption by a third. It is the only pharmacological agent approved in the pediatric age group for the treatment of obesity. The goal of this article is to review the efficacy and safety of orlistat in adolescents, with emphasis on its effects on weight and body mass index, body composition and liposoluble vitamins during growth.
Highlights
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are an important category of drugs for both chemotherapy and prevention of human immunodeficiency virus type 1 (HIV-1) infection
The challenge viruses for these models should mimic HIV mucosal transmission predominantly using CCR5 coreceptor, express HIV-1 genes such as RT that are appropriate as therapeutic targets, and induce rapid and readily detectable systemic infection that progress to AIDS-like illness
Three viruses exhibited similar replication kinetics as evidenced by the production of viral core antigen in the culture supernatants. These results indicate that RT-SHIV revealed the characteristics of a highly infectious and rapid replicating CCR5-tropic virus
Summary
Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are an important category of drugs for both chemotherapy and prevention of human immunodeficiency virus type 1 (HIV-1) infection. Current non-human primate (NHP) models utilizing simian immunodeficiency virus (SIV) or commonly used chimeric SHIV (SIV expressing HIV-1 envelope) are inadequate due to the insensitivity to NNRTIs. To develop a NHP model for evaluation of NNRTI compounds, we characterized a RT-SHIV virus that was assembled by replacing the SIVmac239 reverse transcriptase (RT) with that of HIV-1HXB2. Since RT-SHIV exhibited in vitro characteristics of high infectivity, CCR5-usage, and sensitivity to HIV-1 specific NNRTIs, this virus was thought to be suitable for mucosal transmission and was used to carry out a vaginal transmission study in pigtail macaques (Macaca nemestrina). While SIV and HIV-2 are well suited to study lentivirus infection and pathogenesis in Asian macaques, they cannot be used to evaluate virus control by HIV-1 specific NNRTI compounds. It is known that prior administration of DMPA enhances mucosal viral transmission by thinning of the vaginal epithelium [37] and possibly by suppression of antiviral immune response [38]
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