Funding was removed.

Therapy for non-Hodgkin lymphoma (NHL) is in evolution as new molecular pathways and targeted therapies are identified. Although most NHLs respond to currently available therapies, the majority of patients relapse and many never have a complete response to therapy. In the investigators attempts to further understand the pathogenesis of NHLs, the investigators have identified and characterized expression of human endogenous retroviruses (HERVs) at the DNA, RNA and protein levels in association with the presence of NHLs (and other neoplastic diseases). The investigators preclinical evidence suggests a correlation with the level of HERV-K (a particular family of HERVs) expression and NHL disease activity, leading us to hypothesize that HERV-K expression may contribute to the development of the disease and/or to its recurrence. If this hypothesis is correct, then drugs that inhibit HERV-K expression may prevent recurrence of disease and/or may provide a novel therapeutic approach for NHLs.

To test this hypothesis, the investigators eventually intend to study the use of anti-retroviral therapies in patients with NHL. The investigators in vitro studies have demonstrated that HERV-K expression decreases in response to the currently FDA-approved and available, anti-HIV drugs, Lamivudine and tenofovir disoproxil fumarate (tenofovir). These medications are tolerated well in HIV patients, but it is unknown how the combination of Lamivudine and Tenofovir will be tolerated by patients with NHL. To further test the investigators hypotheses, the investigators propose the following Specific Aims of the current study: (1) To evaluate the tolerability, toxicity and safety of administering Lamivudine and Tenofovir in combination to patients with relapsed or refractory NHL; (2) To evaluate the effects of the combination of lamivudine and tenofovir on HERV-K plasma viral RNA load; and (3) To monitor the response rate of the NHL to treatment with the combination of lamivudine and tenofovir.

The investigators study will recruit adult patients with relapsed or refractory NHL whom the investigators have identified as having expression of HERV-K. Volunteer participants will be administered the combination of lamivudine and tenofovir and monitored for tolerability, toxicity, compliance, changes in viral RNA load and disease response.

Inclusion Criteria:

• Patients must have a histologically confirmed diagnosis of non-Hodgkin lymphoma (NHL)
• Must have HERV-K(HML2) viral load of ≥1x103 using a gag primer reverse transcriptase polymerase chain reaction (RT-PCR) assay.
• Must have bi-dimensionally measurable disease.
• Patients with lymphomas that are felt to be incurable with any therapy and for whom there are no standard treatments that would be anticipated to be necessary or beneficial within the next 5 months. These patients can have received any amount of prior chemotherapy to enter this trial.
• All previous therapies must have been discontinued at least 4 weeks prior to initiation of the administration of this study's drugs.
• HIV negative by standard blood testing.
• Have an expected life expectancy of at least 5 months.
• Have an Eastern Cooperative Oncology Group (ECOG) performance scale status of 0 - 2l) Must have a serum creatinine <2.0 and creatinine clearance >30 ml/min/m2. Other organ dysfunction is eligible at the discretion of the PI.
• Agree to use a reliable method of birth control prior to drug initiation and for the duration of their study participation.

Exclusion Criteria:

• a) Have received chemotherapy or radiotherapy within 4 weeks
• Have not recovered from the adverse effects or toxicities of lymphoma therapy most recently administered.
• Currently receiving any other investigational medication or therapy.
• Patients with a second malignancy that might interfere with interpretation of the results of this study.
• Patients with known allergic reaction to lamivudine or tenofovir disoproxil fumarate (DF).
• Patients on drugs that interfere with renal function or drugs that compete with tenofovir for active binding sites (i.e. intravenous cidofovir, acyclovir, ganciclovir, and valganciclovir).
• Uncontrolled concurrent illnesses, including, but not limited to, active/ongoing infection, symptomatic congestive heart failure, unstable angina pectoris.
• Women who are pregnant, become pregnant, or are breast-feeding.
• Standard blood tests that are positive for HIV infection