The study will be a pilot, prospective, single-center, open-label, non-randomized, non-controlled clinical trial. 15 HIV-infected kidney transplant recipients will be enrolled in the study. Recruitment will be conducted through the renal transplant and infectious diseases outpatient clinics at the University of Maryland.
The study will include patients with stable glomerular filtration rates (GFRs) \>25 with suppressed HIV with CD4 counts \>200. These patients will be recruited from the University of Maryland's transplant nephrology and infectious diseases clinics. The transplant nephrology clinic is a multidisciplinary clinic that incorporates nephrologists, pharmacists to aid in medication management, and coordinators to assist the patients in coordination of care.
All patients will be screened either at the Institute of Human Virology (IHV) Clinical Research Unit or in the transplant nephrology or infectious disease clinics. At this visit, all patients will sign an informed consent as approved by our institutional review board (IRB), have a history and physical examination, and have screening clinical and research labs drawn. Additional requirements will be Trofile testing prior to enrollment. Eligibility will be determined based upon these results.
Study drugs will be prescribed (if the patient is not already taking them) starting on day 0 after an interval history and physical examination is performed and safety labs (and pregnancy tests for women of childbearing potential) are checked. The medications will be filled by the patient's pharmacy, using their insurance as these are both Food and Drug Administration (FDA) approved drugs.
Patients will be initially monitored weekly for sirolimus levels and renal function, until their sirolimus is at the pre-determined (by their transplant nephrologist) steady state. They will then be followed at week 4, and then every 12 weeks while they are on the new medication combination. Safety labs (blood counts, renal and liver function), HIV viral loads, cluster of differentiation 4 (CD4) counts, and rapamycin levels will be reviewed at each of these visits and if not checked within the specified time period these labs will be repeated at the study visit. Patients will also be advised about study adherence and monitored for adverse events.
Safety and adverse event monitoring will occur each study visit. Research nurses will inquire about adverse events that may or may not be related to study drugs. Any unfavorable medical occurrences will be recorded, whether or not considered related to the patient's participation in the research or temporally associated with the patient's participation in the research. Any grade 3 or 4 AEs and all serious adverse events (SAEs) will be reviewed as they occur by the study team. Adverse events (AEs) classified as grade 3 or higher occurring at a frequency greater than that expected by the study team will be reported to the IRB and principal investigator.
The end of treatment visit will occur at week 96. Clinical safety labs (blood counts, renal and liver function), HIV viral load, CD4 counts and rapamycin levels will be performed at this visit if not done in the pre-specified time period. Patients will be given the option, in conjunction with their transplant nephrologist and their infectious disease provider, to discontinue or continue the new medications at this time.
