(taken from abstract of application) The presentation and course of HIV-infection have changed significantly in the current era of antiviral therapy. Loss of lean body mass and reduced functional capacity occurs in a substantial number of HIV-infected patients, despite protease inhibitor therapy. For such patients, development of effective anabolic strategies is critical to reverse sarcopenia and increase functional capacity. In this proposal, these investigators build upon preliminary data using testosterone and progressive resistance training (PRT) to increase muscle mass and strength in HIV-infected men. They have previously shown potent independent and maximal combined effects of short-term testosterone and PRT in HIV-infected men with wasting and significant sarcopenia. They will now investigate whether long-term PRT effects are maximized by high dose induction anabolic therapy and are sustainable using sequential low dose maintenance testosterone therapy. The development of novel, combined anabolic and PRT strategies is proposed also for women with AIDS wasting, a population with unique body composition changes for whom there are little data. They have previously shown that androgen administration to such patients is safe and, at high doses, results in increased lean body mass. They will assess whether combined androgen and PRT will maximally increase muscle mass and function in HIV-infected women. In addition to muscle loss, a significant percentage of HIV-infected patients experience fat redistribution, characterized by truncal adiposity, and loss of extremity fat in associate with hyperlipidemia and insulin resistance. In preliminary data they have shown significant truncal and visceral adiposity in such patients, which is highly correlated with hyperinsulinemia. Of concern, is that these changes will result in increased long-term cardiovascular morbidity and mortality. The novel use of combined testosterone and aerobic-resistance raining (men) and training alone (women) is proposed for HIV-infected patients with the lipodystrophy syndrome. No therapy as yet exists for this growing population of patients. In this renewal application, they propose: 1) specific resistance training strategies targeted at muscle accrual for HIV-infected men and women in combination with testosterone administration, and 2) development of novel aerobic/anabolic strategies to reverse lipodystrophy. The strategies outlined in this grant proposal will provide critically needed information to optimize muscle mass and function and redistribution of abnormal regional fat deposition among HIV-infected men and women in the new era of HIV-therapy.
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