HIV-Resistant Gene Modified Stem Cells and Chemotherapy in Treating Patients With Lymphoma With HIV Infection

PRIMARY OBJECTIVES: I. To determine the safety and feasibility of infusing C46/CCR5/P140K lentiviral vector-transduced autologous hematopoietic stem progenitor cells (HSPC) (gene modified, HIV-protected HSPC) after standard first line treatment of lymphoma in patients with HIV infection. II. To determine the dose of carmustine (BCNU) in combination with O6-benzylguanine (O6BG) that results in selection in vivo of gene-modified HIV resistant cells with minimal toxicity. III. To estimate the effect of HIV infection on the presence of HIV-resistant blood cells as measured by genetic marking for vector sequences before and after highly active antiretroviral therapy (HAART) interruption. SECONDARY OBJECTIVES: I. Evaluate the molecular and clonal composition of gene-modified cells after standard first line treatment. II. Evaluate the molecular and clonal composition of gene-modified cells after O6BG/BCNU. III. Determine the correlation between the level of MGMT(P140K) marking with toxicity and response to O6BG/BCNU chemotherapy. IV. Characterize the toxicity associated with in vivo selection. V. Describe time to disease progression, progression-free survival, treatment-related mortality, time to neutrophil and platelet recovery, and incidence of infections. TERTIARY OBJECTIVES: I. Effect of procedure on the latent HIV reservoir. II. Effect of procedure on HIV-specific immune reconstitution. OUTLINE: MOBILIZATION AND HSPC COLLECTION: Between the second and the last course of planned standard chemotherapy, patients undergo mobilization of peripheral blood stem cells with filgrastim subcutaneously (SC) beginning the day after the last dose of chemotherapy in the previous cycle. If CD34 cell count in peripheral blood at least 24 hours after recovery from nadir is \>= 40 CD34 cells/mcL, patients will undergo apheresis collection the next day. If CD34 cell count is \< 40 CD34 cells/mcL, plerixafor SC will be administered and patients will undergo apheresis collection the next day. Patients undergo apheresis until a total apheresis product of \>= 4.0 x 10\^6 CD34+ cells/kg are collected. STEM CELL INFUSION: Patients receive CD34+ gene-modified C46/CCR5/P140K lentiviral vector-transduced autologous HSPC intravenously (IV) within 2 to 8 days, but no later than 28 days, after completion of the last cycle of first line treatment for lymphoma. IN VIVO SELECTION WITH O6-BENZYLGUANINE AND CARMUSTINE: Between 28-180 days after infusion of gene-modified HSPC and after hematopoietic recovery from first line treatment, patients with \>= 1% and \< 10% gene marked cells receive O6-benzylguanine IV over 1 hour, immediately followed by carmustine IV, and followed 7-8 hours later by O6-benzylguanine IV over 1 hour. Treatment continues for an additional course provided that gene marked cells does not meet or exceed 10% of peripheral blood cells and in the absence of unacceptable toxicity. STRUCTURED TREATMENT INTERRUPTION (STI): Patients achieving \>= 10% gene marked cells for 2 consecutive months following infusion of gene-modified HSPC and with CD4+ cell counts and total lymphocyte counts at baseline begin STI of HAART for up to 12 weeks. Patients resume HAART if one of the following criteria occurs: 1) CD4 count \< 350 cells/mcL or decline in percent CD4+ cells by \> 33% from baseline for three consecutive evaluations; 2) increase in HIV RNA \> 100,000 copies/mL on two consecutive evaluations; 3) 12 weeks have passed since discontinuation of HAART; or 4) at the discretion of the infectious disease (ID) consultant or principal investigator (PI). \* If patient is not on an efavirenz-containing regimen, HAART is discontinued simultaneously. If patient is on an efavirenz-containing regimen, patients will switch from efavirenz to an integrase inhibitor for at least 2 weeks and then discontinue HAART simultaneously. After completion of study treatment, patients are followed up for 2 years, every 6 months for 3 years and then annually for 15 years.